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Sample records for e1 m1 e2

  1. E1M1 and E1E2 transition probabilities in one-electron ions

    Science.gov (United States)

    Labzowsky, L. N.; Shonin, A. V.

    2004-12-01

    The quantum electrodynamical (QED) theory of the two-photon transitions in hydrogenlike ions is presented. The emission probability for 2s→2γ(E1)+1s transitions is calculated and compared to the results of the previous calculations. The emission probabilities 2p→γ(E1)+γ(E2)+1s and 2p→γ(E1)+γ(M1)+1s are also calculated for the nuclear charge Z values 1⩽Z⩽100. This is the first calculation of the two latter probabilities. The results are given in two different gauges.

  2. E1M1 and E1E2 transition probabilities in one-electron ions

    Energy Technology Data Exchange (ETDEWEB)

    Labzowsky, L.N. [Institute of Physics, St. Petersburg State University, Uljanovskaya 1, Petrodvorets, 198904 St. Petersburg (Russian Federation) and Petersburg Nuclear Physics Institute, Gatchina, 188350 St. Petersburg (Russian Federation)]. E-mail: leonti@landau.phys.spbu.ru; Shonin, A.V. [Institute of Physics, St. Petersburg State University, Uljanovskaya 1, Petrodvorets, 198904 St. Petersburg (Russian Federation)

    2004-12-06

    The quantum electrodynamical (QED) theory of the two-photon transitions in hydrogenlike ions is presented. The emission probability for 2s1/2->2{gamma}(E1)+1s1/2 transitions is calculated and compared to the results of the previous calculations. The emission probabilities 2p1/2->{gamma}(E1)+{gamma}(E2)+1s1/2 and 2p1/2->{gamma}(E1)+{gamma}(M1)+1s1/2 are also calculated for the nuclear charge Z values 1=

  3. E1, M1, E2 transition energies and probabilities of W$^{54+}$ ions

    CERN Document Server

    Ding, Xiao-bin; Liu, Jia-xin; Koike, Fumihiro; Murakami, Izumi; Kato, Daiji; Sakaue, Hiroyuki A; Nakamura, Nobuyuki; Dong, Chen-zhong

    2016-01-01

    A comprehensive theoretical study of the E1, M1, E2 transitions of Ca-like tungsten ions is presented. Using multi-configuration Dirac-Fock (MCDF) method with a restricted active space treatment, the wavelengths and probabilities of the M1 and E2 transitions between the multiplets of the ground state configuration ([Ne]3s$^{2}$3p$^{6}$3d$^{2}$) and of the E1 transitions between [Ne]3s$^{2}$3p$^{5}$3d$^{3}$ and [Ne]3s$^{2}$3p$^{6}$3d$^{2}$ have been calculated. The results are in reasonable agreement with available experimental data. The present E1 and M1 calculations are compared with previous theoretical values. For E2 transitions, the importance of electron correlation from 3s and 3p orbitals is pointed out. Several strong E1 transitions are predicted, which have potential advantage for plasma diagnostics.

  4. Radiative rates for E1, E2, M1, and M2 transitions in Br-like ions with 43 $\\le$ Z $\\le$ 50

    CERN Document Server

    Aggarwal, K M

    2015-01-01

    Energies and lifetimes are reported for the eight Br-like ions with 43 $\\le$ Z $\\le$ 50, namely Tc ~IX, Ru~X, Rh~XI, Pd~XII, Ag~XIII, Cd~XIV, In~XV, and Sn~XVI. Results are listed for the lowest 375 levels, which mostly belong to the 4s$^2$4p$^5$, 4s$^2$4p$^4$4$\\ell$, 4s4p$^6$, 4s$^2$4p$^4$5$\\ell$, 4s$^2$4p$^3$4d$^2$, 4s4p$^5$4$\\ell$, and 4s4p$^5$5$\\ell$ configurations. Extensive configuration interaction among 39 configurations (generating 3990 levels) has been considered and the general-purpose relativistic atomic structure package ({\\sc grasp}) has been adopted for the calculations. Radiative rates are listed for all E1, E2, M1, and M2 transitions involving the lowest 375 levels. Previous experimental and theoretical energies are available for only a few levels of three, namely Ru~X, Rh~XI and Pd~XII. Differences with the measured energies are up to 4\\% but the present results are an improvement (by up to 0.3 Ryd) in comparison to other recently reported theoretical data. Similarly for radiative rates and ...

  5. The E2/M1 ratio in {Delta} photoproduction

    Energy Technology Data Exchange (ETDEWEB)

    Hoblit, S. [Brookhaven National Lab., Upton, NY (United States). Physics Dept.]|[Univ. of Virginia, Charlottesville, VA (United States). Dept. of Physics; Blanpied, G. [Univ. of South Carolina, Columbia, SC (United States). Dept. of Physics; Blecher, M. [Virginia Polytechnic Inst. and State Univ., Blacksburg, VA (United States). Physics Dept.] [and others; LEGS Collaboration

    1997-10-01

    New high-precision measurements of p({rvec {gamma}}, {pi}) and p({rvec {gamma}}, {gamma}) cross sections and beam asymmetries have been combined with other polarization ratios in a simultaneous analysis of both reactions. The E2/M1 mixing ratio for the n {r_arrow} {Delta} transition extracted from this analysis is EMR = {minus}3.0% {+-} 0.3 (stat+sys) {+-} 0.2 (model).

  6. The E2/M1 ratio in {Delta} photoproduction

    Energy Technology Data Exchange (ETDEWEB)

    Sandorfi, A.M. [Brookhaven National Lab., Upton, NY (United States). Physics Dept.; Blanpied, G. [Univ. of South Carolina, Columbia, SC (United States). Dept. of Physics; Blecher, M. [Virginia Polytechnic Inst. and State Univ., Blacksburg, VA (United States). Physics Dept.] [and others; LEGS Collaboration

    1997-08-01

    The properties of the transition from the nucleon to the {Delta}(1232) serve as a benchmark for models of nucleon structure. To first order, N {r_arrow} {Delta} photo-excitation is dominated by a simple M1 quark spin-flip transition. At higher order, small L = 2 components in the N and {Delta} wavefunctions allow this excitation to proceed via an electric quadrupole transition. Since Nucleon models differ greatly on the mechanisms used to generate these L = 2 components,, the ratio of E2/M1 transitions (EMR) provides a sensitive test for structure models. Here, new high-precision measurements of p({rvec {gamma}}, {pi}) and p({rvec {gamma}}, {gamma}) cross sections and beam asymmetries have been combined with other polarization ratios in a simultaneous analysis of both reactions. Compton scattering has provided two important new constraints on the photo-pion amplitude. The E2/M1 mixing ratio for the N {r_arrow} {Delta} transition extracted from this analysis is EMR = {minus}3.0% {+-} 0.3 (stat+sys) {+-} 0.2 (model).

  7. E1 and M1 strength functions at low energy

    Directory of Open Access Journals (Sweden)

    Schwengner Ronald

    2017-01-01

    Full Text Available We report photon-scattering experiments using bremsstrahlung at the γELBE facility of Helmholtz-Zentrum Dresden-Rossendorf and using quasi-monoenergetic, polarized γ beams at the HIγS facility of the Triangle Universities Nuclear Laboratory in Durham. To deduce the photoabsorption cross sections at high excitation energy and high level density, unresolved strength in the quasicontinuum of nuclear states has been taken into account. In the analysis of the spectra measured by using bremsstrahlung at γELBE, we perform simulations of statistical γ-ray cascades using the code γDEX to estimate intensities of inelastic transitions to low-lying excited states. Simulated average branching ratios are compared with model-independent branching ratios obtained from spectra measured by using monoenergetic γ beams at HIγS. E1 strength in the energy region of the pygmy dipole resonance is discussed in nuclei around mass 90 and in xenon isotopes. M1 strength in the region of the spin-flip resonance is also considered for xenon isotopes. The dipole strength function of 74Ge deduced from γELBE experiments is compared with the one obtained from experiments at the Oslo Cyclotron Laboratory. The low-energy upbend seen in the Oslo data is interpreted as M1 strength on the basis of shell-model calculations.

  8. Effects of E2 and E1-E2 Interference on Coulomb Dissociation of 19C

    Institute of Scientific and Technical Information of China (English)

    Rajesh Kharab; Pardeep Singh; Ravinder Kumar

    2007-01-01

    We investigate the effects of higher order multipole transitions, in particular electric quadrupole (E2) and E1-E2interference, on the Coulomb dissociation of 19 C within the framework of the first order eikonal approximation.The sensitivity of the total Coulomb breakup cross section and the longitudinal momentum distribution of the core fragment to these effects are checked. The breakup occurs predominately through the dipole transition and the contribution of E2 transition to the total cross section is found to be within the range from 1 to 3% of that of E1. It is further observed that the E1-E2 interference term contributes nothing to the integrated cross section.On the other hand, the longitudinal momentum distribution is observed to be insensitive to the E2 transition while the E1-E2 interference introduces a small asymmetry in its shape.

  9. Energies and E1, M1, E2, and M2 transition rates for states of the 2s22p3, 2s2p4, and 2p5 configurations in nitrogen-like ions between F III and Kr XXX

    Science.gov (United States)

    Rynkun, P.; Jönsson, P.; Gaigalas, G.; Froese Fischer, C.

    2014-03-01

    Based on relativistic wavefunctions from multiconfiguration Dirac-Hartree-Fock and configuration interaction calculations, E1, M1, E2, and M2 transition rates, weighted oscillator strengths, and lifetimes are evaluated for the states of the (1s2)2s22p3,2s2p4, and 2p5 configurations in all nitrogen-like ions between F III and Kr XXX. The wavefunction expansions include valence, core-valence, and core-core correlation effects through single-double multireference expansions to increasing sets of active orbitals. The computed energies agree very well with experimental values, with differences of only 300-600 cm-1 for the majority of the levels and ions in the sequence. Computed transitions rates are in close agreement with available data from MCHF-BP calculations by Tachiev and Froese Fischer [G.I. Tachiev, C. Froese Fischer, A&A 385 (2002) 716].

  10. Structural models of the membrane anchors of envelope glycoproteins E1 and E2 from pestiviruses

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jimin, E-mail: jimin.wang@yale.edu; Li, Yue; Modis, Yorgo, E-mail: yorgo.modis@yale.edu

    2014-04-15

    The membrane anchors of viral envelope proteins play essential roles in cell entry. Recent crystal structures of the ectodomain of envelope protein E2 from a pestivirus suggest that E2 belongs to a novel structural class of membrane fusion machinery. Based on geometric constraints from the E2 structures, we generated atomic models of the E1 and E2 membrane anchors using computational approaches. The E1 anchor contains two amphipathic perimembrane helices and one transmembrane helix; the E2 anchor contains a short helical hairpin stabilized in the membrane by an arginine residue, similar to flaviviruses. A pair of histidine residues in the E2 ectodomain may participate in pH sensing. The proposed atomic models point to Cys987 in E2 as the site of disulfide bond linkage with E1 to form E1E2 heterodimers. The membrane anchor models provide structural constraints for the disulfide bonding pattern and overall backbone conformation of the E1 ectodomain. - Highlights: • Structures of pestivirus E2 proteins impose constraints on E1, E2 membrane anchors. • Atomic models of the E1 and E2 membrane anchors were generated in silico. • A “snorkeling” arginine completes the short helical hairpin in the E2 membrane anchor. • Roles in pH sensing and E1E2 disulfide bond formation are proposed for E1 residues. • Implications for E1 ectodomain structure and disulfide bonding pattern are discussed.

  11. Structural analysis and evolution of specificity of the SUMO UFD E1-E2 interactions

    Science.gov (United States)

    Liu, Bing; Lois, L. Maria; Reverter, David

    2017-01-01

    SUMO belongs to the ubiquitin-like family (UbL) of protein modifiers. SUMO is conserved among eukaryotes and is essential for the regulation of processes such as DNA damage repair, transcription, DNA replication and mitosis. UbL modification of proteins occurs via a specific enzymatic cascade formed by the crosstalk between the E1-activating enzyme, the E2-conjugating enzyme and the E3-ligase. An essential discrimination step in all UbL modifiers corresponds to the interaction between E1 and E2 enzymes, which is mediated by the recruitment of the E2 to the UFD domain (Ubiquitin-Fold Domain) of the E1 enzyme. To gain insights in the properties of this interface, we have compared the structures of the complexes between E1 UFD domain and E2 in human and yeast, revealing two alternative UFD platforms that interact with a conserved E2. Comparative sequence analysis of the E1 UFD domain indicates that the E2 binding region has been conserved across phylogenetic closely related species, in which higher sequence conservation can be found in the E2 binding region than in the entire UFD domain. These distinctive strategies for E1-E2 interactions through the UFD domain might be the consequence of a high selective pressure to ensure specificity of each modifier conjugation system. PMID:28165030

  12. A MUB E2 structure reveals E1 selectivity between cognate ubiquitin E2s in eukaryotes

    Science.gov (United States)

    Lu, Xiaolong; Malley, Konstantin R.; Brenner, Caitlin C.; Koroleva, Olga; Korolev, Sergey; Downes, Brian P.

    2016-08-01

    Ubiquitin (Ub) is a protein modifier that controls processes ranging from protein degradation to endocytosis, but early-acting regulators of the three-enzyme ubiquitylation cascade are unknown. Here we report that the prenylated membrane-anchored ubiquitin-fold protein (MUB) is an early-acting regulator of subfamily-specific E2 activation. An AtMUB3:AtUBC8 co-crystal structure defines how MUBs inhibit E2~Ub formation using a combination of E2 backside binding and a MUB-unique lap-bar loop to block E1 access. Since MUBs tether Arabidopsis group VI E2 enzymes (related to HsUbe2D and ScUbc4/5) to the plasma membrane, and inhibit E2 activation at physiological concentrations, they should function as potent plasma membrane localized regulators of Ub chain synthesis in eukaryotes. Our findings define a biochemical function for MUB, a family of highly conserved Ub-fold proteins, and provide an example of selective activation between cognate Ub E2s, previously thought to be constitutively activated by E1s.

  13. CK2 phosphorylation inactivates DNA binding by the papillomavirus E1 and E2 proteins.

    Science.gov (United States)

    Schuck, Stephen; Ruse, Cristian; Stenlund, Arne

    2013-07-01

    Papillomaviruses have complex life cycles that are understood only superficially. Although it is well established that the viral E1 and E2 proteins play key roles in controlling viral transcription and DNA replication, how these factors are regulated is not well understood. Here, we demonstrate that phosphorylation by the protein kinase CK2 controls the biochemical activities of the bovine papillomavirus E1 and E2 proteins by modifying their DNA binding activity. Phosphorylation at multiple sites in the N-terminal domain in E1 results in the loss of sequence-specific DNA binding activity, a feature that is also conserved in human papillomavirus (HPV) E1 proteins. The bovine papillomavirus (BPV) E2 protein, when phosphorylated by CK2 on two specific sites in the hinge, also loses its site-specific DNA binding activity. Mutation of these sites in E2 results in greatly increased levels of latent viral DNA replication, indicating that CK2 phosphorylation of E2 is a negative regulator of viral DNA replication during latent viral replication. In contrast, mutation of the N-terminal phosphorylation sites in E1 has no effect on latent viral DNA replication. We propose that the phosphorylation of the N terminus of E1 plays a role only in vegetative viral DNA replication, and consistent with such a role, caspase 3 cleavage of E1, which has been shown to be necessary for vegetative viral DNA replication, restores the DNA binding activity to phosphorylated E1.

  14. E2 and M1 Transition Probabilities in Odd Mass Hg Nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Berg, V.; Baecklin, A.; Fogelberg, B.; Malmskog, S.G.

    1969-10-15

    L- and M-subshell ratios have been measured for the 39.5 keV transition in {sup 193}Hg and the 37.1 and 16.2 keV transitions in {sup 195}Hg yielding 0.38 {+-} 0.12 , <0.02 and 0.08 {+-} 0.03 per cent E2, respectively. The half-lives of the 39.5 keV level in {sup 193}Hg and the 53.3 and 37.1 keV levels in {sup 195}Hg have been measured by the delayed coincidence method, yielding values of 0.63 {+-} 0.03, 0.72 {+-} 0.03 and <0.05 nsec respectively. A systematic compilation of reduced E2 and M1 transition probabilities in odd mass Pt, Hg and Pb nuclei is given and compared to theoretical predictions.

  15. Ubiquitination independent of E1 and E2 enzymes by bacterial effectors

    Energy Technology Data Exchange (ETDEWEB)

    Qiu, Jiazhang; Sheedlo, Michael J.; Yu, Kaiwen; Tan, Yunhao; Nakayasu, Ernesto S.; Das, Chittaranjan; Liu, Xiaoyun; Luo, Zhao-Qing

    2016-04-06

    Signaling by ubiquitination regulates virtually every cellular process in eukaryotes. Covalent attachment of ubiquitin to a substrate is catalyzed by the E1, E2 and E3 three-enzyme cascade 1, which links the C terminus of ubiquitin via an isopeptide bond mostly to the ε-amino group of a lysine of the substrate. Given the essential roles of ubiquitination in the regulation of the immune system, it is not surprising that the ubiquitination network is a common target for diverse infectious agents 2. For example, many bacterial pathogens exploit ubiquitin signaling using virulence factors that function as E3 ligases, deubiquitinases 3 or as enzymes that directly attack ubiquitin 4. The bacterial pathogen Legionella pneumophila utilizes approximately 300 effectors that modulate diverse host processes to create a niche permissive for its replication in phagocytes 5. Here we demonstrate that members of the SidE effector family (SidEs) of L. pneumophila ubiquitinate multiple Rab small GTPases associated with the endoplasmic reticulum (ER). Moreover, we show that these proteins are capable of catalyzing ubiquitination without the need for the E1 and E2 enzymes. The E1/E2-independent ubiquitination catalyzed by these enzymes requires NAD but not ATP and Mg2+. A putative mono ADP-ribosyltransferase (mART) motif critical for the ubiquitination activity is also essential for the role of SidEs in intracellular bacterial replication in a protozoan host. These results establish that ubiquitination can be catalyzed by a single enzyme.

  16. Ubiquitination independent of E1 and E2 enzymes by bacterial effectors.

    Science.gov (United States)

    Qiu, Jiazhang; Sheedlo, Michael J; Yu, Kaiwen; Tan, Yunhao; Nakayasu, Ernesto S; Das, Chittaranjan; Liu, Xiaoyun; Luo, Zhao-Qing

    2016-05-01

    Signalling by ubiquitination regulates virtually every cellular process in eukaryotes. Covalent attachment of ubiquitin to a substrate is catalysed by the E1, E2 and E3 three-enzyme cascade, which links the carboxy terminus of ubiquitin to the ε-amino group of, in most cases, a lysine of the substrate via an isopeptide bond. Given the essential roles of ubiquitination in the regulation of the immune system, it is not surprising that the ubiquitination network is a common target for diverse infectious agents. For example, many bacterial pathogens exploit ubiquitin signalling using virulence factors that function as E3 ligases, deubiquitinases or as enzymes that directly attack ubiquitin. The bacterial pathogen Legionella pneumophila utilizes approximately 300 effectors that modulate diverse host processes to create a permissive niche for its replication in phagocytes. Here we demonstrate that members of the SidE effector family of L. pneumophila ubiquitinate multiple Rab small GTPases associated with the endoplasmic reticulum. Moreover, we show that these proteins are capable of catalysing ubiquitination without the need for the E1 and E2 enzymes. A putative mono-ADP-ribosyltransferase motif critical for the ubiquitination activity is also essential for the role of the SidE family in intracellular bacterial replication in a protozoan host. The E1/E2-independent ubiquitination catalysed by these enzymes is energized by nicotinamide adenine dinucleotide, which activates ubiquitin by the formation of ADP-ribosylated ubiquitin. These results establish that ubiquitination can be catalysed by a single enzyme, the activity of which does not require ATP.

  17. Identification of Interactions in the E1E2 Heterodimer of Hepatitis C Virus Important for Cell Entry*

    Science.gov (United States)

    Maurin, Guillemette; Fresquet, Judith; Granio, Ophélia; Wychowski, Czeslaw; Cosset, François-Loïc; Lavillette, Dimitri

    2011-01-01

    Several conserved domains critical for E1E2 assembly and hepatitis C virus entry have been identified in E1 and E2 envelope glycoproteins. However, the role of less conserved domains involved in cross-talk between either glycoprotein must be defined to fully understand how E1E2 undergoes conformational changes during cell entry. To characterize such domains and to identify their functional partners, we analyzed a set of intergenotypic E1E2 heterodimers derived from E1 and E2 of different genotypes. The infectivity of virions indicated that Con1 E1 did not form functional heterodimers when associated with E2 from H77. Biochemical analyses demonstrated that the reduced infectivity was not related to alteration of conformation and incorporation of Con1 E1/H77 E2 heterodimers but rather to cell entry defects. Thus, we generated chimeric E1E2 glycoproteins by exchanging different domains of each protein in order to restore functional heterodimers. We found that both the ectodomain and transmembrane domain of E1 influenced infectivity. Site-directed mutagenesis highlighted the role of amino acids 359, 373, and 375 in transmembrane domain in entry. In addition, we identified one domain involved in entry within the N-terminal part of E1, and we isolated a motif at position 219 that is critical for H77 function. Interestingly, using additional chimeric E1E2 complexes harboring substitutions in this motif, we found that the transmembrane domain of E1 acts as a partner of this motif. Therefore, we characterized domains of E1 and E2 that have co-evolved inside a given genotype to optimize their interactions and allow efficient entry. PMID:21555519

  18. New probe of M1 and E1 strengths in GDR regions

    Energy Technology Data Exchange (ETDEWEB)

    Hayakawa, T. [Japan Atomic Energy Agency and National Astronomical Observatory in Japan (Japan); Ogata, K. [RCNP, Osaka University (Japan); Miyamoto, S.; Mochizuki, T.; Horikawa, K.; Amano, S. [University of Hyogo (Japan); Imazaki, K.; Li, D.; Izawa, Y. [Institute for Laser Technology (Japan); Chiba, S. [Tokyo Institute of Technology (Japan)

    2014-05-02

    The M1 strengths (or level density of 1{sup +} states) are of importance for estimation of interaction strengths between neutrinos and nuclei for the study of the supernova neutrino-process. In 1957, Agodi predicted theoretically angular distribution of neutrons emitted from states excited via dipole transitions with linearly polarized gamma-ray beam at the polar angle of θ=90° should be followed by a simple function, a + b cos(2φ), where φ, is azimuthal angel. However, this theoretical prediction has not been verified over the wide mass region except for light nuclei as deuteron. We have measured neutron angular distributions with (polarized gamma, n) reactions on Au, Nal, and Cu. We have verified the Agodi's prediction for the first time over the wide mass region. This suggests that (polarized gamma, n) reactions may be useful tools to study M1 strengths in giant resonance regions.

  19. pRB-E2F1 complexes are resistant to adenovirus E1A-mediated disruption.

    Science.gov (United States)

    Seifried, L A; Talluri, S; Cecchini, M; Julian, L M; Mymryk, J S; Dick, F A

    2008-05-01

    Disruption of pRB-E2F interactions by E1A is a key event in the adenoviral life cycle that drives expression of early viral transcription and induces cell cycle progression. This function of E1A is complicated by E2F1, an E2F family member that controls multiple processes besides proliferation, including apoptosis and DNA repair. Recently, a second interaction site in pRB that only contacts E2F1 has been discovered, allowing pRB to control proliferation separately from other E2F1-dependent activities. Based on this new insight into pRB-E2F1 regulation, we investigated how E1A affects control of E2F1 by pRB. Our data reveal that pRB-E2F1 interactions are resistant to E1A-mediated disruption. Using mutant forms of pRB that selectively force E2F1 to bind through only one of the two binding sites on pRB, we determined that E1A is unable to disrupt E2F1's unique interaction with pRB. Furthermore, analysis of pRB-E2F complexes during adenoviral infection reveals the selective maintenance of pRB-E2F1 interactions despite the presence of E1A. Our experiments also demonstrate that E2F1 functions to maintain cell viability in response to E1A expression. This suggests that adenovirus E1A's seemingly complex mechanism of disrupting pRB-E2F interactions provides selectivity in promoting viral transcription and cell cycle advancement, while maintaining cell viability.

  20. Hepatitis C Virus E1 and E2 Proteins Used as Separate Immunogens Induce Neutralizing Antibodies with Additive Properties.

    Science.gov (United States)

    Beaumont, Elodie; Roch, Emmanuelle; Chopin, Lucie; Roingeard, Philippe

    2016-01-01

    Various strategies involving the use of hepatitis C virus (HCV) E1 and E2 envelope glycoproteins as immunogens have been developed for prophylactic vaccination against HCV. However, the ideal mode of processing and presenting these immunogens for effective vaccination has yet to be determined. We used our recently described vaccine candidate based on full-length HCV E1 or E2 glycoproteins fused to the heterologous hepatitis B virus S envelope protein to compare the use of the E1 and E2 proteins as separate immunogens with their use as the E1E2 heterodimer, in terms of immunogenetic potential and the capacity to induce neutralizing antibodies. The specific anti-E1 and anti-E2 antibody responses induced in animals immunized with vaccine particles harboring the heterodimer were profoundly impaired with respect to those in animals immunized with particles harboring E1 and E2 separately. Moreover, the anti-E1 and anti-E2 antibodies had additive neutralizing properties that increase the cross-neutralization of heterologous strains of various HCV genotypes, highlighting the importance of including both E1 and E2 in the vaccine for an effective vaccination strategy. Our study has important implications for the optimization of HCV vaccination strategies based on HCV envelope proteins, regardless of the platform used to present these proteins to the immune system.

  1. Hepatitis C Virus E1 and E2 Proteins Used as Separate Immunogens Induce Neutralizing Antibodies with Additive Properties

    Science.gov (United States)

    Beaumont, Elodie; Roch, Emmanuelle; Chopin, Lucie; Roingeard, Philippe

    2016-01-01

    Various strategies involving the use of hepatitis C virus (HCV) E1 and E2 envelope glycoproteins as immunogens have been developed for prophylactic vaccination against HCV. However, the ideal mode of processing and presenting these immunogens for effective vaccination has yet to be determined. We used our recently described vaccine candidate based on full-length HCV E1 or E2 glycoproteins fused to the heterologous hepatitis B virus S envelope protein to compare the use of the E1 and E2 proteins as separate immunogens with their use as the E1E2 heterodimer, in terms of immunogenetic potential and the capacity to induce neutralizing antibodies. The specific anti-E1 and anti-E2 antibody responses induced in animals immunized with vaccine particles harboring the heterodimer were profoundly impaired with respect to those in animals immunized with particles harboring E1 and E2 separately. Moreover, the anti-E1 and anti-E2 antibodies had additive neutralizing properties that increase the cross-neutralization of heterologous strains of various HCV genotypes, highlighting the importance of including both E1 and E2 in the vaccine for an effective vaccination strategy. Our study has important implications for the optimization of HCV vaccination strategies based on HCV envelope proteins, regardless of the platform used to present these proteins to the immune system. PMID:26966906

  2. Hepatitis C Virus E1 and E2 Proteins Used as Separate Immunogens Induce Neutralizing Antibodies with Additive Properties.

    Directory of Open Access Journals (Sweden)

    Elodie Beaumont

    Full Text Available Various strategies involving the use of hepatitis C virus (HCV E1 and E2 envelope glycoproteins as immunogens have been developed for prophylactic vaccination against HCV. However, the ideal mode of processing and presenting these immunogens for effective vaccination has yet to be determined. We used our recently described vaccine candidate based on full-length HCV E1 or E2 glycoproteins fused to the heterologous hepatitis B virus S envelope protein to compare the use of the E1 and E2 proteins as separate immunogens with their use as the E1E2 heterodimer, in terms of immunogenetic potential and the capacity to induce neutralizing antibodies. The specific anti-E1 and anti-E2 antibody responses induced in animals immunized with vaccine particles harboring the heterodimer were profoundly impaired with respect to those in animals immunized with particles harboring E1 and E2 separately. Moreover, the anti-E1 and anti-E2 antibodies had additive neutralizing properties that increase the cross-neutralization of heterologous strains of various HCV genotypes, highlighting the importance of including both E1 and E2 in the vaccine for an effective vaccination strategy. Our study has important implications for the optimization of HCV vaccination strategies based on HCV envelope proteins, regardless of the platform used to present these proteins to the immune system.

  3. Improved energy of the 21.5 keV M1 + E2 nuclear transition in {sup 151}Eu

    Energy Technology Data Exchange (ETDEWEB)

    Inoyatov, A.Kh. [JINR, Laboratory of Nuclear Problems, Dubna, Moscow Region (Russian Federation); National University, Institute of Applied Physics, Tashkent (Uzbekistan); Kovalik, A. [JINR, Laboratory of Nuclear Problems, Dubna, Moscow Region (Russian Federation); Nuclear Physics Institute of the ASCR, Rez near Prague (Czech Republic); Filosofov, D.V.; Perevoshchikov, L.L. [JINR, Laboratory of Nuclear Problems, Dubna, Moscow Region (Russian Federation); Rysavy, M. [Nuclear Physics Institute of the ASCR, Rez near Prague (Czech Republic); Baimukhanova, A. [JINR, Laboratory of Nuclear Problems, Dubna, Moscow Region (Russian Federation); Institute of Nuclear Physics, Almaty (Kazakhstan)

    2016-05-15

    Using internal conversion electron spectroscopy, improved energy 21 541.5±0.5 eV was determined for the 21.5 keV M1+E2 nuclear transition in {sup 151}Eu populated in the electron capture decay of {sup 151}Gd. This value was found to agree well with the present adopted value but is much more accurate. A value of 0.0305±0.0011 derived for the E2 admixture parameter vertical stroke δ(E2/M1) vertical stroke from the measured conversion electron line intensities corresponds to the present adopted value. A possible effect of nuclear structure on the multipolarity of the 21.5 keV transition was also investigated. (orig.)

  4. Study of thermally excited nuclei through E1 and E2 decay from collective modes

    Energy Technology Data Exchange (ETDEWEB)

    Million, B.; Bracco, A.; Benzoni, G.; Leoni, S.; Camera, F.; Wieland, O. [Dipartimento di Fisica, Universita di Milano and INFN, via Celoria 16, 20133, Milano (Italy); Maj, A.; Kmiecik, M. [Niewodniczanski Institute of Nuclear Physics, 31-342, Krakow (Poland); Gadea, A. [Laboratori Nazionali di Legnaro, via Romea, Legnaro (Italy); Herskind, B. [The Niels Bohr Institute, Blegdamsvej 15-17, 2100, Copenhagen (Denmark)

    2004-04-01

    The nuclear system at the limit of excitation energy and angular momentum is here studied in the case of the superdeformed nucleus {sup 143}Eu using {gamma}-spectroscopy techniques. The data are based on a EUROBALL experiment using the reaction {sup 37}Cl+{sup 110}Pd{yields}{sup 143}Eu+4n. The influence of thermal energy on superdeformed configurations is investigated through the analysis of the quasi-continuum spectra formed by E2 transitions among states of excited rotational bands with energy extending up to 4-5 MeV above the yrast line. In particular, the effective lifetimes of the discrete rotational bands forming ridge structures in {gamma}-{gamma} coincidence matrices is measured by a Doppler Shift Attenuation Method. The deduced quadrupole deformation of Q{sub t} {approx}10 eb indicates that the nucleus maintains its collectivity with increasing excitation energy, supporting the superdeformed character of the excited nuclear rotation. The obtained number of superdeformed discrete bands forming the ridge structures is found in good agreement with microscopic cranked shell model calculations including the decay-out process into the lower deformation minimum. In addition, the nuclear properties at higher excitation energies are investigated through the E1 {gamma}-decay of the giant dipole resonance (GDR). It is found that the intensity of the superdeformed yrast and excited bands increases by a factor of approximately 1.6 when a coincidence with a high-energy {gamma}-ray is required, showing the importance of the E1 cooling in the feeding mechanism of the superdeformed states. (orig.)

  5. The Deacetylase SIRT1 Regulates the Replication Properties of Human Papillomavirus 16 E1 and E2.

    Science.gov (United States)

    Das, Dipon; Smith, Nathan; Wang, Xu; Morgan, Iain M

    2017-05-15

    Human papillomaviruses (HPV) replicate their genomes in differentiating epithelium using the viral proteins E1 and E2 in association with host proteins. While the roles of E1 and E2 in this process are understood, the host factors involved and how they interact with and regulate E1-E2 are not. Our previous work identified the host replication and repair factor TopBP1 as an E2 partner protein essential for optimal E1-E2 replication and for the viral life cycle. The role of TopBP1 in host DNA replication is regulated by the class III deacetylase SIRT1; activation of the DNA damage response prevents SIRT1 deacetylation of TopBP1, resulting in a switch from DNA replication to repair functions for this protein and cell cycle arrest. Others have demonstrated an essential role for SIRT1 in regulation of the HPV31 life cycle; here, we report that SIRT1 can directly regulate HPV16 E1-E2-mediated DNA replication. SIRT1 is part of the E1-E2 DNA replication complex and is recruited to the viral origin of replication in an E1-E2-dependent manner. CRISPR/Cas9 was used to generate C33a clones with undetectable SIRT1 expression and lack of SIRT1 elevated E1-E2 DNA replication, in part due to increased acetylation and stabilization of the E2 protein in the absence of SIRT1. The results demonstrate that SIRT1 is a member of, and can regulate, the HPV16 replication complex. We discuss the potential role of this protein in the viral life cycle.IMPORTANCE HPV are causative agents in a number of human diseases, and currently only the symptoms of these diseases are treated. To identify novel therapeutic approaches for combating these diseases, the viral life cycle must be understood in more detail. This report demonstrates that a cellular enzyme, SIRT1, is part of the HPV16 DNA replication complex and is brought to the viral genome by the viral proteins E1 and E2. Using gene editing technology (CRISPR/Cas9), the SIRT1 gene was removed from cervical cancer cells. The consequence of this

  6. Comparison of osteogenic potentials of human rat BMP4 and BMP6 gene therapy using [E1-] and [E1-,E2b-] adenoviral vectors

    Directory of Open Access Journals (Sweden)

    Hongwei Li, Jin Zhong Li, Debra D. Pittman, Andy Amalfitano, Gerald R. Hankins, Gregory A. Helm

    2006-01-01

    Full Text Available Osteogenic potentials of some recombinant human bone morphogenetic protein (BMP first-generation adenoviral vectors (ADhBMPs are significantly limited in immunocompetent animals. It is unclear what role expression of viral proteins and foreign proteins transduced by adenoviral vectors play in the host immune response and in ectopic bone formation. In this study two sets of experiments were designed and performed. First, rat BMP6 cDNA were amplified, sequenced, and recombined in first-generation adenoviral vector (ADrBMP6. A comparison of human and rat BMP6 adenoviral vectors demonstrated identical osteogenic activities in both immunodeficient and immunocompetent rats. Second, the activities of recombinant human BMP6 in E1- (ADhBMP6 and [E1-,E2b-] ( [E1-,E2b-]ADGFP&hBMP6, and [E1-,E2b-]ADhBMP6 adenoviral vectors were compared in both in vitro and in vivo models. Similar activities of these two generations of BMP adenoviral vectors were found in all models. These results indicate that the amount of viral gene expression and the source of the BMP cDNA are not major factors in the interruption of osteogenic potentials of recombinant BMP6 adenoviral vectors in immunocompetent animals.

  7. Salmonid alphavirus glycoprotein E2 requires low temperature and E1 for virion formation and induction of protective immunity.

    Science.gov (United States)

    Hikke, Mia C; Braaen, Stine; Villoing, Stephane; Hodneland, Kjartan; Geertsema, Corinne; Verhagen, Lisa; Frost, Petter; Vlak, Just M; Rimstad, Espen; Pijlman, Gorben P

    2014-10-29

    Salmonid alphavirus (SAV; also known as Salmon pancreas disease virus; family Togaviridae) causes pancreas disease and sleeping disease in Atlantic salmon and rainbow trout, respectively, and poses a major burden to the aquaculture industry. SAV infection in vivo is temperature-restricted and progeny virus is only produced at low temperatures (10-15 °C). Using engineered SAV replicons we show that viral RNA replication is not temperature-restricted suggesting that the viral structural proteins determine low-temperature dependency. The processing/trafficking of SAV glycoproteins E1 and E2 as a function of temperature was investigated via baculovirus vectors in Sf9 insect cells and by transfection of CHSE-214 fish cells with DNA constructs expressing E1 and E2. We identified SAV E2 as the temperature determinant by demonstrating that membrane trafficking and surface expression of E2 occurs only at low temperature and only in the presence of E1. Finally, a vaccination-challenge model in Atlantic salmon demonstrates the biological significance of our findings and shows that SAV replicon DNA vaccines encoding E2 elicit protective immunity only when E1 is co-expressed. This is the first study that identifies E2 as the critical determinant of SAV low-temperature dependent virion formation and defines the prerequisites for induction of a potent immune response in Atlantic salmon by DNA vaccination.

  8. Muscarinic M1 receptor inhibition reduces gastroduodenal bicarbonate secretion and promotes gastric prostaglandin E2 synthesis in healthy volunteers

    DEFF Research Database (Denmark)

    Mertz-Nielsen, A; Hillingsø, Jens; Eskerod, O

    1995-01-01

    The selective muscarinic M1 receptor antagonist, pirenzepine, considerably stimulates duodenal mucosal bicarbonate secretion in the rat and increases gastric luminal release of prostaglandin E2 (PGE2) in humans. This study, therefore, looked at the effect of pirenzepine on bicarbonate secretion...... sham feeding and acid exposure (HCl 0.1 M; 20 ml; 5 min) of the duodenal bulb increased mucosal bicarbonate secretion from 191 (14) mumol/cm x h to 266 (27) mumol/cm x h (p Pirenzepine (10 mg/h intravenously) reduced basal and vagally...... stimulated gastric and basal duodenal bicarbonate secretion by about 50% (p pirenzepine. In conclusion, human gastroduodenal mucosal bicarbonate secretion is regulated...

  9. Effects of the spin-orbit and tensor interactions on the M1 and E2 excitations in light nuclei

    CERN Document Server

    Fayache, M S; Zamick, L; Von Neumann-Cosel, P; Richter, A

    1996-01-01

    The effects of varying the spin-orbit and tensor components of a realistic interaction on M1 excitation rates and B(E2)'s are studied on nuclei in the 0p and 1s-0d shells. Not only the total M1 but also the spin and orbital parts separately are studied. The single-particle energies are first calculated with the same interaction that is used between the valence nucleons. Later this stringent condition is relaxed somewhat and the 1s level is raised relative to 0d. For nuclei up to ^{28}Si, much better results i.e stronger B(M1) rates are obtained by increasing the strength of the spin-orbit interaction relative to the free value. This is probably also true for ^{32}S, but ^{36}Ar presents some difficulties. The effects of weakening the tensor interaction are also studied. On a more subtle level, the optimum spin-orbit interaction in the lower half of the s-d shell, as far as M1 excitations are concerned, is substantially larger than the difference E(J=3/2^+)_1-E(J=5/2^+)_1=5.2~MeV in ^{17}O. A larger spin-orbit...

  10. The first human epitope map of the alphaviral E1 and E2 proteins reveals a new E2 epitope with significant virus neutralizing activity.

    Directory of Open Access Journals (Sweden)

    Ann R Hunt

    2010-07-01

    Full Text Available Venezuelan equine encephalitis virus (VEEV is responsible for VEE epidemics that occur in South and Central America and the U.S. The VEEV envelope contains two glycoproteins E1 (mediates cell membrane fusion and E2 (binds receptor and elicits virus neutralizing antibodies. Previously we constructed E1 and E2 epitope maps using murine monoclonal antibodies (mMAbs. Six E2 epitopes (E2(c,d,e,f,g,h bound VEEV-neutralizing antibody and mapped to amino acids (aa 182-207. Nothing is known about the human antibody repertoire to VEEV or epitopes that engage human virus-neutralizing antibodies. There is no specific treatment for VEE; however virus-neutralizing mMAbs are potent protective and therapeutic agents for mice challenged with VEEV by either peripheral or aerosol routes. Therefore, fully human MAbs (hMAbs with virus-neutralizing activity should be useful for prevention or clinical treatment of human VEE.We used phage-display to isolate VEEV-specific hFabs from human bone marrow donors. These hFabs were characterized by sequencing, specificity testing, VEEV subtype cross-reactivity using indirect ELISA, and in vitro virus neutralization capacity. One E2-specific neutralizing hFAb, F5n, was converted into IgG, and its binding site was identified using competitive ELISA with mMAbs and by preparing and sequencing antibody neutralization-escape variants.Using 11 VEEV-reactive hFabs we constructed the first human epitope map for the alphaviral surface proteins E1 and E2. We identified an important neutralization-associated epitope unique to the human immune response, E2 aa115-119. Using a 9 A resolution cryo-electron microscopy map of the Sindbis virus E2 protein, we showed the probable surface location of this human VEEV epitope.The VEEV-neutralizing capacity of the hMAb F5 nIgG is similar to that exhibited by the humanized mMAb Hy4 IgG. The Hy4 IgG has been shown to limit VEEV infection in mice both prophylactically and therapeutically. Administration

  11. The first human epitope map of the alphaviral E1 and E2 proteins reveals a new E2 epitope with significant virus neutralizing activity.

    Directory of Open Access Journals (Sweden)

    Ann R Hunt

    Full Text Available BACKGROUND: Venezuelan equine encephalitis virus (VEEV is responsible for VEE epidemics that occur in South and Central America and the U.S. The VEEV envelope contains two glycoproteins E1 (mediates cell membrane fusion and E2 (binds receptor and elicits virus neutralizing antibodies. Previously we constructed E1 and E2 epitope maps using murine monoclonal antibodies (mMAbs. Six E2 epitopes (E2(c,d,e,f,g,h bound VEEV-neutralizing antibody and mapped to amino acids (aa 182-207. Nothing is known about the human antibody repertoire to VEEV or epitopes that engage human virus-neutralizing antibodies. There is no specific treatment for VEE; however virus-neutralizing mMAbs are potent protective and therapeutic agents for mice challenged with VEEV by either peripheral or aerosol routes. Therefore, fully human MAbs (hMAbs with virus-neutralizing activity should be useful for prevention or clinical treatment of human VEE. METHODS: We used phage-display to isolate VEEV-specific hFabs from human bone marrow donors. These hFabs were characterized by sequencing, specificity testing, VEEV subtype cross-reactivity using indirect ELISA, and in vitro virus neutralization capacity. One E2-specific neutralizing hFAb, F5n, was converted into IgG, and its binding site was identified using competitive ELISA with mMAbs and by preparing and sequencing antibody neutralization-escape variants. FINDINGS: Using 11 VEEV-reactive hFabs we constructed the first human epitope map for the alphaviral surface proteins E1 and E2. We identified an important neutralization-associated epitope unique to the human immune response, E2 aa115-119. Using a 9 A resolution cryo-electron microscopy map of the Sindbis virus E2 protein, we showed the probable surface location of this human VEEV epitope. CONCLUSIONS: The VEEV-neutralizing capacity of the hMAb F5 nIgG is similar to that exhibited by the humanized mMAb Hy4 IgG. The Hy4 IgG has been shown to limit VEEV infection in mice both

  12. NEW ORBITS FOR COMETS C/1960 M1 (HUMASON, C/1980 E1 (BOWELL, AND MUSINGS ON EXTRASOLAR COMETS

    Directory of Open Access Journals (Sweden)

    Richard L. Branham Jr.

    2013-01-01

    Full Text Available Se calculan órbitas nuevas para los cometas Humason (C/1960 M1 y Bowell (C/1980 E1. La órbita de Humason se basa en 34 observaciones hechas durante 348 días y para Bowell en 203 observaciones hechas durante ocho años. Integraciones hacia atrás indican que ambos cometas tenían órbitas originalmente muy elípticas, que fueron cambiadas a hipérbolas por la adición de energía desde el Sistema Solar. Puesto que sus distancias del perihelio son mayores de 3 AU, la posibilidad de fuerzas no gravitatorias es remota. Para el cometa Secchi (C/1853 E1, sin embargo, la órbita es hiperbólica a una distancia de más de 100000 AU del Sol y sin evidencia alguna de fuerzas no gravitatorias. Si la órbita permanece hiperbólica a esa distancia, quizás su origen sea fuera de la nube de Oort.

  13. Microarray-based analysis and clinical validation identify ubiquitin-conjugating enzyme E2E1 (UBE2E1 as a prognostic factor in acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Hongmei Luo

    2016-11-01

    Full Text Available Abstract Background Previous research suggested that single gene expression might be correlated with acute myeloid leukemia (AML survival. Therefore, we conducted a systematical analysis for AML prognostic gene expressions. Methods We performed a microarray-based analysis for correlations between gene expression and adult AML overall survival (OS using datasets GSE12417 and GSE8970. Positive findings were validated in an independent cohort of 50 newly diagnosed, non-acute promyelocytic leukemia (APL AML patients by quantitative RT-PCR and survival analysis. Results Microarray-based analysis suggested that expression of eight genes was each associated with 1-year and 3-year AML OS in both GSE12417 and GSE8970 datasets (p < 0.05. Next, we validated our findings in an independent cohort of AML samples collected in our hospital. We found that ubiquitin-conjugating enzyme E2E1 (UBE2E1 expression was adversely correlated with AML survival (p = 0.04. Multivariable analysis showed that UBE2E1 high patients had a significant shorter OS and shorter progression-free survival after adjusting other known prognostic factors (p = 0.03. At last, we found that UBE2E1 expression was negatively correlated with patients’ response to induction chemotherapy (p < 0.05. Conclusions In summary, we demonstrated that UBE2E1 expression was a novel prognostic factor in adult, non-APL AML patients.

  14. Crystal Structure of UBA2[superscript ufd]-Ubc9: Insights into E1-E2 Interactions in Sumo Pathways

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jing; Taherbhoy, Asad M.; Hunt, Harold W.; Seyedin, Steven N.; Miller, David W.; Miller, Darcie J.; Huang, Danny T.; Schulman, Brenda A. (SJCH)

    2012-04-30

    Canonical ubiquitin-like proteins (UBLs) such as ubiquitin, Sumo, NEDD8, and ISG15 are ligated to targets by E1-E2-E3 multienzyme cascades. The Sumo cascade, conserved among all eukaryotes, regulates numerous biological processes including protein localization, transcription, DNA replication, and mitosis. Sumo conjugation is initiated by the heterodimeric Aos1-Uba2 E1 enzyme (in humans called Sae1-Uba2), which activates Sumo's C-terminus, binds the dedicated E2 enzyme Ubc9, and promotes Sumo C-terminal transfer between the Uba2 and Ubc9 catalytic cysteines. To gain insights into details of E1-E2 interactions in the Sumo pathway, we determined crystal structures of the C-terminal ubiquitin fold domain (ufd) from yeast Uba2 (Uba2{sup ufd}), alone and in complex with Ubc9. The overall structures of both yeast Uba2{sup ufd} and Ubc9 superimpose well on their individual human counterparts, suggesting conservation of fundamental features of Sumo conjugation. Docking the Uba2{sup ufd}-Ubc9 and prior full-length human Uba2 structures allows generation of models for steps in Sumo transfer from Uba2 to Ubc9, and supports the notion that Uba2 undergoes remarkable conformational changes during the reaction. Comparisons to previous structures from the NEDD8 cascade demonstrate that UBL cascades generally utilize some parallel E1-E2 interaction surfaces. In addition, the structure of the Uba2{sup ufd}-Ubc9 complex reveals interactions unique to Sumo E1 and E2. Comparison with a previous Ubc9-E3 complex structure demonstrates overlap between Uba2 and E3 binding sites on Ubc9, indicating that loading with Sumo and E3-catalyzed transfer to substrates are strictly separate steps. The results suggest mechanisms establishing specificity and order in Sumo conjugation cascades.

  15. The Competitive Relationships of SN2, SN1, E2, E1 Reactions in Organic Chemistry%有机化学中SN2,SN1,E2,E1反应的相互竞争关系

    Institute of Scientific and Technical Information of China (English)

    颜志明; 潘英明

    2014-01-01

    有机化学中的SN2,SN1,E2,E1反应在学习中有着重要的作用,同时也是学习中易混淆的知识点.通过总结它们的反应机理、反应影响因素和反应相互竞争关系图,并利用竞争关系图解答了一些典型考研真题,方便读者理解和掌握SN2,SN1,E2,E1反应的相互竞争关系.

  16. DNA Damage Reduces the Quality, but Not the Quantity of Human Papillomavirus 16 E1 and E2 DNA Replication

    Directory of Open Access Journals (Sweden)

    Molly L. Bristol

    2016-06-01

    Full Text Available Human papillomaviruses (HPVs are causative agents in almost all cervical carcinomas. HPVs are also causative agents in head and neck cancer, the cases of which are increasing rapidly. Viral replication activates the DNA damage response (DDR pathway; associated proteins are recruited to replication foci, and this pathway may serve to allow for viral genome amplification. Likewise, HPV genome double-strand breaks (DSBs could be produced during replication and could lead to linearization and viral integration. Many studies have shown that viral integration into the host genome results in unregulated expression of the viral oncogenes, E6 and E7, promoting HPV-induced carcinogenesis. Previously, we have demonstrated that DNA-damaging agents, such as etoposide, or knocking down viral replication partner proteins, such as topoisomerase II β binding protein I (TopBP1, does not reduce the level of DNA replication. Here, we investigated whether these treatments alter the quality of DNA replication by HPV16 E1 and E2. We confirm that knockdown of TopBP1 or treatment with etoposide does not reduce total levels of E1/E2-mediated DNA replication; however, the quality of replication is significantly reduced. The results demonstrate that E1 and E2 continue to replicate under genomically-stressed conditions and that this replication is mutagenic. This mutagenesis would promote the formation of substrates for integration of the viral genome into that of the host, a hallmark of cervical cancer.

  17. Native Folding of a Recombinant gpE1/gpE2 Heterodimer Vaccine Antigen from a Precursor Protein Fused with Fc IgG.

    Science.gov (United States)

    Logan, Michael; Law, John; Wong, Jason Alexander Ji-Xhin; Hockman, Darren; Landi, Amir; Chen, Chao; Crawford, Kevin; Kundu, Juthika; Baldwin, Lesley; Johnson, Janelle; Dahiya, Anita; LaChance, Gerald; Marcotrigiano, Joseph; Law, Mansun; Foung, Steven; Tyrrell, Lorne; Houghton, Michael

    2017-01-01

    A recombinant strain HCV1 (hepatitis C virus [HCV] genotype 1a) gpE1/gpE2 (E1E2) vaccine candidate was previously shown by our group to protect chimpanzees and generate broad cross-neutralizing antibodies in animals and humans. In addition, recent independent studies have highlighted the importance of conserved neutralizing epitopes in HCV vaccine development that map to antigenic clusters in E2 or the E1E2 heterodimer. E1E2 can be purified using Galanthis nivalis lectin agarose (GNA), but this technique is suboptimal for global production. Our goal was to investigate a high-affinity and scalable method for isolating E1E2. We generated an Fc tag-derived (Fc-d) E1E2 that was selectively captured by protein G Sepharose, with the tag being removed subsequently using PreScission protease. Surprisingly, despite the presence of the large Fc tag, Fc-d E1E2 formed heterodimers similar to those formed by GNA-purified wild-type (WT) E1E2 and exhibited nearly identical binding profiles to HCV monoclonal antibodies that target conserved neutralizing epitopes in E2 (HC33.4, HC84.26, and AR3B) and the E1E2 heterodimer (AR4A and AR5A). Antisera from immunized mice showed that Fc-d E1E2 elicited anti-E2 antibody titers and neutralization of HCV pseudotype viruses similar to those with WT E1E2. Competition enzyme-linked immunosorbent assays (ELISAs) showed that antisera from immunized mice inhibited monoclonal antibody binding to neutralizing epitopes. Antisera from Fc-d E1E2-immunized mice exhibited stronger competition for AR3B and AR5A than the WT, whereas the levels of competition for HC84.26 and AR4A were similar. We anticipate that Fc-d E1E2 will provide a scalable purification and manufacturing process using protein A/G-based chromatography.

  18. Deacylation of the transmembrane domains of Sindbis virus envelope glycoproteins E1 and E2 does not affect low-pH-induced viral membrane fusion activity

    NARCIS (Netherlands)

    Smit, JM; Bittman, R; Wilschut, J

    2001-01-01

    The envelope glycoproteins E1 and E2 of Sindbis virus are palmitoylated at cysteine residues within their transmembrane domains (E1 at position 430, and E2 at positions 388 and 390), Here, we investigated the in vitro membrane fusion activity of Sindbis virus variants (derived from the Tote 1101 inf

  19. Specifically Binding of L-ficolin to N-glycans of HCV Envelope Glycoproteins E1 and E2 Leads to Complement Activation

    Institute of Scientific and Technical Information of China (English)

    Jun Liu; Mohammed A.M.Ali; Yinghua Shi; Yinglan Zhao; Fenglin Luo; Jin Yu; Tian Xiang; Jie Tang; Dongqing Li; Quan Hu; Wenzhe Ho; Xiaolian Zhang

    2009-01-01

    L-ficolin and HCV E1 and E2 glycoproteins was attributed to the N-glycans of E1 and E2.These findings provide new insights into the biological functions of L-ficolin in clinically important hepatic viral diseases.

  20. Structure, dynamics, and interaction of Mycobacterium tuberculosis (Mtb DprE1 and DprE2 examined by molecular modeling, simulation, and electrostatic studies.

    Directory of Open Access Journals (Sweden)

    Isha Bhutani

    Full Text Available The enzymes decaprenylphosphoryl-β-D-ribose oxidase (DprE1 and decaprenylphosphoryl-β-D-ribose-2-epimerase (DprE2 catalyze epimerization of decaprenylphosporyl ribose (DPR todecaprenylphosporyl arabinose (DPA and are critical for the survival of Mtb. Crystal structures of DprE1 so far reported display significant disordered regions and no structural information is known for DprE2. We used homology modeling, protein threading, molecular docking and dynamics studies to investigate the structural and dynamic features of Mtb DprE1 and DprE2 and DprE1-DprE2 complex. A three-dimensional model for DprE2 was generated using the threading approach coupled with ab initio modeling. A 50 ns simulation of DprE1 and DprE2 revealed the overall stability of the structures. Principal Component Analysis (PCA demonstrated the convergence of sampling in both DprE1 and DprE2. In DprE1, residues in the 269-330 area showed considerable fluctuation in agreement with the regions of disorder observed in the reported crystal structures. In DprE2, large fluctuations were detected in residues 95-113, 146-157, and 197-226. The study combined docking and MD simulation studies to map and characterize the key residues involved in DprE1-DprE2 interaction. A 60 ns MD simulation for DprE1-DprE2 complex was also performed. Analysis of data revealed that the docked complex is stabilized by H-bonding, hydrophobic and ionic interactions. The key residues of DprE1 involved in DprE1-DprE2 interactions belong to the disordered region. We also examined the docked complex of DprE1-BTZ043 to investigate the binding pocket of DprE1 and its interactions with the inhibitor BTZ043. In summary, we hypothesize that DprE1-DprE2 interaction is crucial for the synthesis of DPA and DprE1-DprE2 complex may be a new therapeutic target amenable to pharmacological validation. The findings have important implications in tuberculosis (TB drug discovery and will facilitate drug development efforts against

  1. Independent regions of adenovirus E1A are required for binding to and dissociation of E2F-protein complexes

    DEFF Research Database (Denmark)

    Fattaey, A R; Harlow, E; Helin, K

    1993-01-01

    overexpression of pRB or p107 in cells lacking a functional pRB leads to the repression of E2F activity. The products of the adenovirus E1A gene can disrupt E2F complexes and result in free and presumably active E2F transcription factor. The regions of E1A required for this function are also essential...

  2. Characterization of hepatitis C virus recombinants with chimeric E1/E2 envelope proteins and identification of single amino acids in the E2 stem region important for entry

    DEFF Research Database (Denmark)

    Carlsen, Thomas H R; Scheel, Troels K H; Ramirez, Santseharay

    2013-01-01

    The hepatitis C virus (HCV) envelope proteins E1 and E2 play a key role in host cell entry and represent important targets for vaccine and drug development. Here, we characterized HCV recombinants with chimeric E1/E2 complexes in vitro. Using genotype 1a/2a JFH1-based recombinants expressing 1a...... in particle density. In addition, the 1b-E2 exchange led to a decrease in secreted core protein of 25 to 50%, which was further reduced by the E2 stem region mutations. These findings indicated that compensatory mutations permitted robust infectious virus production, without increasing assembly...

  3. Human liver estrone (E1), Estradiol (E2) and dehydroepiandrosterone (DHEA) sulfotransferases (STs): Comparison with thermostable (TS) and thermolabile (TL) phenol sulfotransferase (PST) activities

    Energy Technology Data Exchange (ETDEWEB)

    Hernandez, J.S.; Watson, R.W.G.; Weinshilboum, R.M. (Mayo Clinic/Mayo Foundation, Rochester, MN (United States))

    1991-03-11

    Sulfation plays an important role in the metabolism of E1, E2 and DHEA in humans. The relationship between the enzymes that catalyze the sulfation of E1, E2 and DHEA and TS and TL PST is unclear. The authors compared thermal stability, sensitivity to inhibition by 2,6-dichloro-4-nitrophenol (DCNP) and individual variation in the regulation of these steroid ST activities with those of TS PST and TL PST in the human liver. E2 ST and TS PST had very similar thermal stabilities. The thermal inactivation profile of E1 ST suggested that this activity might be related to both DHEA ST and TS PST. DCNP inhibition studies also showed similar profiles for E2 ST and TS PST, with a small resistant component for E2 ST. A multiphasic profile for DCNP inhibition of E1 ST activity was found. Finally, studies performed with human liver sample showed significant correlations between E2 ST and TS PST, E1 ST and DHEA ST, E2 St and E1 ST, and, to a lesser degree, between E1 ST and TS PST and E2 ST and DHEA ST. TL PST was not correlated significantly with any of the other activities. These results suggest that the sulfation of E2 in human liver is catalyzed predominantly by TS PST, although DHEA ST may also play a role. Their results also suggest that the sulfation of E1 is catalyzed by DHEA ST and by TS PST, although other ST(s) could also be involved.

  4. Effect of prostaglandins E1, E2, and F2 alpha on osteoclast formation in mouse bone marrow cultures

    Energy Technology Data Exchange (ETDEWEB)

    Collins, D.A.; Chambers, T.J. (St. George' s Hospital Medical School, London (United Kingdom))

    1991-02-01

    Prostaglandins (PG) act as direct inhibitors of mature osteoclasts, but although resorption-inhibition is also observed initially PG increase bone resorption in organ culture. This suggests that PG influence bone resorption in organ culture through actions on cell types other than mature osteoclasts. We have therefore tested the effects of PG E1, E2, and F2 alpha on the differentiation of osteoclastic phenotype in mouse bone marrow cultures using bone resorption and calcitonin receptors (CTR) as markers of osteoclastic differentiation. We found that PGE2 (10{sup {minus} 6}-10{sup {minus} 9} M) and PGE1 (10{sup {minus} 6} - 10{sup {minus} 7} M) induced a significant increase in CTR-positive cell numbers, to levels five to eight times those seen in controls and similar to the number induced by 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3). Bone resorption was increased (10{sup {minus} 7} M PGE2 and 10{sup {minus} 6} M PGE1) in association with the increased CTR-positive cell numbers, suggesting that the PG also induced resorptive function. 1,25-(OH)2D3 increased both the number of CTR-positive cells and the extent of resorption per cell; the additional presence of PG did not affect the number of CTR-positive cells but did reduce bone resorption compared with 1,25-(OH)2D3 alone. PGF2 alpha had no significant effect on CTR-positive cell induction or bone resorption. The results suggest that PGE1 and E2 induce osteoclastic differentiation in mouse bone marrow cultures and inhibit the function of the osteoclasts thus formed.

  5. E2F activates late-G1 events but cannot replace E1A in inducing S phase in terminally differentiated skeletal muscle cells

    DEFF Research Database (Denmark)

    Pajalunga, D; Tognozzi, D; Tiainen, M

    1999-01-01

    We have previously shown that the adenovirus E1A oncogene can reactivate the cell cycle in terminally differentiated cells. Current models imply that much or all of this E1A activity is mediated by the release of the E2F transcription factors from pocket-protein control. In contrast, we show here...

  6. Rigorous Photogrammetric Processing of CHANG'E-1 and CHANG'E-2 Stereo Imagery for Lunar Topographic Mapping

    Science.gov (United States)

    Di, K.; Liu, Y.; Liu, B.; Peng, M.

    2012-07-01

    Chang'E-1(CE-1) and Chang'E-2(CE-2) are the two lunar orbiters of China's lunar exploration program. Topographic mapping using CE-1 and CE-2 images is of great importance for scientific research as well as for preparation of landing and surface operation of Chang'E-3 lunar rover. In this research, we developed rigorous sensor models of CE-1 and CE-2 CCD cameras based on push-broom imaging principle with interior and exterior orientation parameters. Based on the rigorous sensor model, the 3D coordinate of a ground point in lunar body-fixed (LBF) coordinate system can be calculated by space intersection from the image coordinates of con-jugate points in stereo images, and the image coordinates can be calculated from 3D coordinates by back-projection. Due to uncer-tainties of the orbit and the camera, the back-projected image points are different from the measured points. In order to reduce these inconsistencies and improve precision, we proposed two methods to refine the rigorous sensor model: 1) refining EOPs by correcting the attitude angle bias, 2) refining the interior orientation model by calibration of the relative position of the two linear CCD arrays. Experimental results show that the mean back-projection residuals of CE-1 images are reduced to better than 1/100 pixel by method 1 and the mean back-projection residuals of CE-2 images are reduced from over 20 pixels to 0.02 pixel by method 2. Consequently, high precision DEM (Digital Elevation Model) and DOM (Digital Ortho Map) are automatically generated.

  7. Noncanonical E2 recruitment by the autophagy E1 revealed by Atg7-Atg3 and Atg7-Atg10 structures

    Energy Technology Data Exchange (ETDEWEB)

    Kaiser, Stephen E; Mao, Kai; Taherbhoy, Asad M; Yu, Shanshan; Olszewski, Jennifer L; Duda, David M; Kurinov, Igor; Deng, Alan; Fenn, Timothy D; Klionsky, Daniel J; Schulman, Brenda A [Cornell; (Stanford); (Michigan); (Tennessee-HSC); (SJCH)

    2012-11-11

    Core functions of autophagy are mediated by ubiquitin-like protein (UBL) cascades, in which a homodimeric E1 enzyme, Atg7, directs the UBLs Atg8 and Atg12 to their respective E2 enzymes, Atg3 and Atg10. Crystallographic and mutational analyses of yeast (Atg7–Atg3)2 and (Atg7–Atg10)2 complexes reveal noncanonical, multisite E1-E2 recognition in autophagy. Atg7's unique N-terminal domain recruits distinctive elements from the Atg3 and Atg10 'backsides'. This, along with E1 and E2 conformational variability, allows presentation of 'frontside' Atg3 and Atg10 active sites to the catalytic cysteine in the C-terminal domain from the opposite Atg7 protomer in the homodimer. Despite different modes of binding, the data suggest that common principles underlie conjugation in both noncanonical and canonical UBL cascades, whereby flexibly tethered E1 domains recruit E2s through surfaces remote from their active sites to juxtapose the E1 and E2 catalytic cysteines.

  8. Lettuce-produced hepatitis C virus E1E2 heterodimer triggers immune responses in mice and antibody production after oral vaccination.

    Science.gov (United States)

    Clarke, Jihong Liu; Paruch, Lisa; Dobrica, Mihaela-Olivia; Caras, Iuliana; Tucureanu, Catalin; Onu, Adrian; Ciulean, Sonya; Stavaru, Crina; Eerde, Andre; Wang, Yanliang; Steen, Hege; Haugslien, Sissel; Petrareanu, Catalina; Lazar, Catalin; Popescu, Costin-Ioan; Bock, Ralph; Dubuisson, Jean; Branza-Nichita, Norica

    2017-04-17

    The hepatitis C virus (HCV) is a major etiologic agent for severe liver diseases (e.g. cirrhosis, fibrosis and hepatocellular carcinoma). Approximately 140 million people have chronic HCV infections and about 500 000 die yearly from HCV-related liver pathologies. To date, there is no licensed vaccine available to prevent HCV infection and production of a HCV vaccine remains a major challenge. Here, we report the successful production of the HCV E1E2 heterodimer, an important vaccine candidate, in an edible crop (lettuce, Lactuca sativa) using Agrobacterium-mediated transient expression technology. The wild-type dimer (E1E2) and a variant without an N-glycosylation site in the E2 polypeptide (E1E2∆N6) were expressed, and appropriate N-glycosylation pattern and functionality of the E1E2 dimers were demonstrated. The humoral immune response induced by the HCV proteins was investigated in mice following oral administration of lettuce antigens with or without previous intramuscular prime with the mammalian HEK293T cell-expressed HCV dimer. Immunization by oral feeding only resulted in development of weak serum levels of anti-HCV IgM for both antigens; however, the E1E2∆N6 proteins produced higher amounts of secretory IgA, suggesting improved immunogenic properties of the N-glycosylation mutant. The mice group receiving the intramuscular injection followed by two oral boosts with the lettuce E1E2 dimer developed a systemic but also a mucosal immune response, as demonstrated by the presence of anti-HCV secretory IgA in faeces extracts. In summary, our study demonstrates the feasibility of producing complex viral antigens in lettuce, using plant transient expression technology, with great potential for future low-cost oral vaccine development. © 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and the Association of Applied Biologists and John Wiley & Sons Ltd.

  9. Adenovirus E4 open reading frame 4-induced dephosphorylation inhibits E1A activation of the E2 promoter and E2F-1-mediated transactivation independently of the retinoblastoma tumor suppressor protein

    DEFF Research Database (Denmark)

    Mannervik, M; Fan, S; Ström, A C

    1999-01-01

    Previous studies have shown that the cell cycle-regulated E2F transcription factor is subjected to both positive and negative control by phosphorylation. Here we show that in transient transfection experiments, adenovirus E1A activation of the viral E2 promoter is abrogated by coexpression...... of the viral E4 open reading frame 4 (E4-ORF4) protein. This effect does not to require the retinoblastoma protein that previously has been shown to regulate E2F activity. The inhibitory activity of E4-ORF4 appears to be specific because E4-ORF4 had little effect on, for example, E4-ORF6/7 transactivation...... of the E2 promoter. We further show that the repressive effect of E4-ORF4 on E2 transcription works mainly through the E2F DNA-binding sites in the E2 promoter. In agreement with this, we find that E4-ORF4 inhibits E2F-1/DP-1-mediated transactivation. We also show that E4-ORF4 inhibits E2 mRNA expression...

  10. Unitary ambiguity in the extraction of the {ital E}2/{ital M}1 ratio for the {gamma}{ital N}{leftrightarrow}{Delta} transition

    Energy Technology Data Exchange (ETDEWEB)

    Wilhelm, P.; Wilbois, T.; Arenhoevel, H. [Institut fuer Kernphysik, Johannes Gutenberg-Universitaet, D-55099 Mainz (Germany)

    1996-09-01

    The resonant electric quadrupole amplitude in the transition {gamma}{ital N}{leftrightarrow}{Delta}(1232) is of great interest for the understanding of baryon structure. Various dynamical models have been developed to extract it from the corresponding photoproduction multipole of pions on nucleons. It is shown that once such a model is specified, a whole class of unitarily equivalent models can be constructed, all of them providing exactly the same fit to the experimental data. However, they may predict quite different resonant amplitudes. Therefore, the extraction of the {ital E}2/{ital M}1({gamma}{ital N}{leftrightarrow}{Delta}) ratio (bare or dressed), which is based on a dynamical model using a largely phenomenological {pi}{ital N} interaction, is not unique. {copyright} {ital 1996 The American Physical Society.}

  11. Revised and extended calculations of level energies, M1 and E2 radiative rates for highly charged tungsten ions from W57+ to W60+

    Science.gov (United States)

    Singh, Gajendra; Puri, Nitin K.

    2016-10-01

    We have applied systematically enlarged multiconfiguration Dirac–Fock wavefunctions using Grasp2K to calculate the transition energies, oscillator strengths and transition probabilities for fine structure M1 and E2 transitions between the low-lying levels of the 3s23p5, 3s23p4, 3s23p3 and 3s23p2 configurations of highly charged tungsten ions from {{{W}}}57+ to {{{W}}}60+. Large wavefunction expansions are applied to calculate the transition probabilities, which are indispensable for calculating various plasma parameters accurately. In the present calculations, our theoretical data agrees well with that obtained in precise electron beam ion trap measurements, and is therefore important for the identification of weak forbidden lines for plasma diagnostic applications.

  12. Two novel epistatic mutations (E1:K211E and E2:V264A) in structural proteins of Chikungunya virus enhance fitness in Aedes aegypti.

    Science.gov (United States)

    Agarwal, Ankita; Sharma, Ajay Kumar; Sukumaran, D; Parida, Manmohan; Dash, Paban Kumar

    2016-10-01

    Expansion of CHIKV outbreaks with appearance of novel mutations are reported from many parts of the world. Two novel mutations viz. E1:K211E and E2:V264A in background of E1:226A are recently identified from Aedes aegypti dominated areas of India. In this study, the role of these mutations in modulation of infectivity, dissemination and transmission by two different Aedes species was studied. Mutations were sequentially constructed in CHIKV genome and female Ae. aegypti and Aedes albopictus mosquitoes were orally infected with eight different CHIKV mutants. Double mutant virus containing E1:K211E and E2:V264A mutations in background of E1:226A revealed remarkably higher fitness for Ae. aegypti, as indicated by significant increase in virus infectivity (13 fold), dissemination (15 fold) and transmission (62 fold) compared to parental E1:226A virus. These results indicate that adaptive mutations in CHIKV are leading to efficient CHIKV circulation in Ae. aegypti endemic areas, contributing and sustaining the major CHIKV outbreaks. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Head and Tail Deformations, Torsional Coriolis Coupling, and E(1d)-E(2d) Vibrational Mixing in Ethane-Like Molecules.

    Science.gov (United States)

    Lattanzi; di Lauro C

    1999-12-01

    The mechanism of torsional Coriolis interaction of E(1d) and E(2d) vibrational modes in ethane-like molecules is investigated, and it is shown that this coupling can drastically affect the torsional splitting in the degenerate vibrational states. A basic point of our treatment is that the sets of coordinates of head and tail which combine with the + sign to generate E(1d) normal coordinates are in general different from those which combine with the - sign to generate E(2d) normal coordinates. It is shown that the zeta(gamma) torsional Coriolis coefficients calculated by the usual methods of normal mode analysis are related to the vibrational angular momenta within head and tail referred to the internal rotor axis systems. With knowledge of the L and L(-1) matrices it is possible to transform these coefficients for reference to the molecule-fixed frame. It is peculiar that torsional Coriolis matrix elements occur between E(1d) and E(2d) vibrational components with the same x or y orientation in the molecule-fixed frame. The matrix elements of the torsional Coriolis operator and other operators responsible for the end-to-end coupling are determined, and a method for calculating vibration-torsion energies, and then torsional splittings, in degenerate vibrational states is outlined. Detailed calculations require a global model, involving all the degenerate vibrational basis states in a complex mechanism of interactions, but it is shown that useful information can be obtained by means of simplified models. Our semiempirical rule that degenerate vibrational states with a large negative value of the diagonal vibration-rotation Coriolis coefficient are likely to deviate much from the behavior of E(1d) or E(2d) vibrational states, with a sensible decrease of the torsional splittings, is confirmed. Copyright 1999 Academic Press.

  14. Atg8 Transfer from Atg7 to Atg3: A Distinctive E1-E2 Architecture and Mechanism in the Autophagy Pathway

    Energy Technology Data Exchange (ETDEWEB)

    Taherbhoy, Asad M.; Tait, Stephen W.; Kaiser, Stephen E.; Williams, Allison H.; Deng, Alan; Nourse, Amanda; Hammel, Michal; Kurinov, Igor; Rock, Charles O.; Green, Douglas R.; Schulman, Brenda A. (Cornell); (LBNL); (SJCH)

    2012-07-11

    Atg7 is a noncanonical, homodimeric E1 enzyme that interacts with the noncanonical E2 enzyme, Atg3, to mediate conjugation of the ubiquitin-like protein (UBL) Atg8 during autophagy. Here we report that the unique N-terminal domain of Atg7 (Atg7{sup NTD}) recruits a unique 'flexible region' from Atg3 (Atg3{sup FR}). The structure of an Atg7{sup NTD}-Atg3{sup FR} complex reveals hydrophobic residues from Atg3 engaging a conserved groove in Atg7, important for Atg8 conjugation. We also report the structure of the homodimeric Atg7 C-terminal domain, which is homologous to canonical E1s and bacterial antecedents. The structures, SAXS, and crosslinking data allow modeling of a full-length, dimeric (Atg7 {approx} Atg8-Atg3){sub 2} complex. The model and biochemical data provide a rationale for Atg7 dimerization: Atg8 is transferred in trans from the catalytic cysteine of one Atg7 protomer to Atg3 bound to the N-terminal domain of the opposite Atg7 protomer within the homodimer. The studies reveal a distinctive E1 {approx} UBL-E2 architecture for enzymes mediating autophagy.

  15. Quasispecies Sequence Analyses of Envelope Protein E1/E2 Coding Genes from four Chinese HCV Patients and Identification of a Novel Insertion Mutation of HCV%四份中国HCV阳性血清中包膜蛋白E1/E2准种基因的序列分析及新型插入突变的发现

    Institute of Scientific and Technical Information of China (English)

    李从力; 张玲; 鲁健; 刘晓明; 邓瑶; 王岳; 沈晓玲; 谭文杰

    2012-01-01

    为分析四份中国丙型肝炎病毒(HCV)阳性血清中包膜蛋白E1/E2基因的准种特征.本研究对从4份中国HCV阳性血清(1b亚型:274、366和383;2a亚型:283)中提取的HCV核酸,采用逆转录-聚合酶反应扩增编码全长E1/E2蛋白(191~764aa)的基因片段,随机挑取多个克隆测序.根据E1/E2基因核苷酸的序列与其他相关序列(来自于GenBank)构建亲缘性关系进化树,进行核苷酸与氨基酸同源性分析并对重要的基因位点进行分析.共获得阳性克隆序列43个(274株10个,283株12个,366株13个,383株8个),发现高变区HVR1、HVR2的基因异质性高,而其他抗体中和表位及跨膜区I、Ⅱ及N末端糖基化位点相对保守.并首次发现在HCV 2a亚型(283血清)中多个准种序列存在1 279nt(E1区,313aa)处单碱基插入优势基因突变,导致HCV包膜蛋白编码突变与中断(E2区,398aa).本研究对中国HCV代表株包膜蛋白E1/E2编码基因的准种多样性及一种新型插入突变进行了描述,可为进一步研究HCV免疫逃避与慢性化机制提供重要信息.%This paper investigated the envelope protein E1/E2 quasispecies genetic characterization of 4 HCV positive sera (Genotype 1b:274,366,383; Genotype 2a;283) in China. Nucleotide acid was extracted and glycoprotein E1/E2 (191~764aa) coding genes were obtained by RT-PCR, positive clones were randomly selected for sequencing. The phylogenetic relationships and the homology of nucleotide and amino acid were analyzed based on E1/E2 coding genes, and some vital functional regions of E1/E2 were characterized. A total of 43 sequences (274 : 10;283 : 12;366 : 13; 383 : 8) were obtained showing high genetic heterogeneity in HVR1 and HVR2 regions, while sequences of the neutralizing epitopes, transmembrane domain I,II and N-terminal ectodomain were comparatively conservative. Single base(C)insertion mutation at ntl279 ( El region, aa313),resulting in a mutated El coding protein (beginning at aa 313) and

  16. HCV E1E2-MF59 vaccine in chronic hepatitis C patients treated with PEG-IFNα2a and Ribavirin: a randomized controlled trial.

    Science.gov (United States)

    Colombatto, P; Brunetto, M R; Maina, A M; Romagnoli, V; Almasio, P; Rumi, M G; Ascione, A; Pinzello, G; Mondelli, M; Muratori, L; Rappuoli, R; Rosa, D; Houghton, M; Abrignani, S; Bonino, F

    2014-07-01

    Hepatitis C virus (HCV) vaccines may be able to increase viral clearance in combination with antiviral therapy. We analysed viral dynamics and HCV-specific immune response during retreatment for experienced patients in a phase Ib study with E1E2MF59 vaccine. Seventy-eight genotype 1a/1b patients [relapsers (30), partial responders (16) and nonresponders (32) to interferon-(IFN)/ribavirin-(RBV)] were randomly assigned to vaccine (V:23), Peg-IFNα2a-180-ug/qw and ribavirin 1000-1200-mg/qd for 48 weeks (P/R:25), or their combination (P/R + V:30). Vaccine (100 μg/0.5 mL) was administered intramuscularly at week 0-4-8-12-24-28-32-36. Neutralizing of binding (NOB) antibodies and lymphocyte proliferation assay (LPA) for E1E2-specific-CD4 + T cells were performed at week 0-12-16-48. Viral kinetics were analysed up to week 16. The vaccine was safe, and a sustained virological response (SVR) was achieved in 4 P/R + V and 2 P/R patients. Higher SVR rates were observed in prior relapsers (P/R + V = 27.3%; P/R = 12.5%). Higher NOB titres and LPA indexes were found at week 12 and 16 in P/R + V as compared to P/R patients (P = 0.023 and 0.025, P = 0.019 and <0.001, respectively). Among the 22 patients with the strongest direct antiviral effects of IFN (ε ≥ 0.800), those treated with P/R + V (10) reached lower HCV-RNA levels (P = 0.026) at week 16. HCV E1E2MF59 vaccine in combination with Peg-IFNα2a + RBV was safe and elicited E1E2 neutralizing antibodies and specific CD4 + T cell proliferation. Upon early response to IFN, vaccinations were associated with an enhanced second phase viral load decline. These results prompt phase II trials in combination with new antiviral therapies.

  17. 激光金等离子体中Au50+离子E1M1跃迁的理论研究%E1 and M1 transitions of Au50+ in Au laser plasma

    Institute of Scientific and Technical Information of China (English)

    徐敏; 闫安英; 蒋刚

    2015-01-01

    根据全相对论组态相互作用(RCI)方法和多组态Dirac-Fock (MCDF)方法,考虑量子电动力学(QED)效应和Breit修正,选取重要的电子组态,系统计算了激光金等离子体中类铜Au50+离子nl−n′l′(n=4,l=s, p, d, f;n′=4,5,l′=s, p, d, f)电偶极(E1)跃迁和磁偶极(M1)跃迁的跃迁波长、跃迁几率和振子强度,并得到Au50+离子部分激发态能级结构。计算得到的能级与波长与其他已有的理论和实验结果进行了比较,得到了较为满意的结果。分别采用长度规范和速度规范对电偶极(E1)跃迁参数进行了计算和比较,得到了很好的收敛。计算结果还表明,对于高 Z高离化态离子,某些禁戒跃迁占有重要地位。%Using the fully relativistic configuration interaction (RCI) method and the multi-configuration Dirac-Fock (MCDF) method and taking quantum electrodynamical (QED) effect and Breit correction into account, wavelengths, transition probabilities and oscillator strengths were calculated for electric dipole (E1) transitions and magnetic dipole (M1) transitions in Au50+ ion. The obtained energy levels of some excited states and wavelengths of transitions in Au50+ ion from the method were compared with other theoretical and experimental results, and a good agreement with other results was shown. The calculated transition probabilities and oscillator strengths in E1 transitions using the velocity and length gauges respectively confirmed the accuracy of our calculations. The calculation results indicated that for high-Z highly ionized atom, some forbidden transitions could be very important.

  18. Theoretical study of forbidden M1, M2, E2 transitions for highly charged Ni-like ions%类镍等电子系列离子M1,M2,E2禁戒跃迁特性的理论研究

    Institute of Scientific and Technical Information of China (English)

    万建杰; 颉录有; 董晨钟; 蒋军; 颜君

    2007-01-01

    利用基于全相对论框架下的多组态Dirac-Fock理论方法发展起来的程序包GRASP92和新发展的处理辐射跃迁过程的程序REOS99,计算了类镍等电子系列离子(Z=45-95)的基组态3s23p63d10 1S0以及低激发组态3s23p63d94l,3s23p53d104l和3s3p63d104 l(l=s,p,d,f)的能级及其向基态的M1,M2,E2禁戒跃迁概率.通过分析高离化类镍离子在特定的原子序数范围内由于存在能级交叉而产生的强组态相互作用,解释了高离化类镍离子禁戒跃迁概率的反常变化现象,探讨了禁戒跃迁概率受强组态相互作用影响而变化的一般规律.

  19. Allelic combinations of soybean maturity Loci E1, E2, E3 and E4 result in diversity of maturity and adaptation to different latitudes.

    Directory of Open Access Journals (Sweden)

    Bingjun Jiang

    Full Text Available Soybean cultivars are extremely diverse in time to flowering and maturation as a result of various photoperiod sensitivities. The underlying molecular genetic mechanism is not fully clear, however, four maturity loci E1, E2, E3 and E4 have been molecularly identified. In this report, cultivars were selected with various photoperiod sensitivities from different ecological zones, which covered almost all maturity groups (MG from MG 000 to MG VIII and MG X adapted from latitude N 18° to N 53°. They were planted in the field under natural daylength condition (ND in Beijing, China or in pots under different photoperiod treatments. Maturity-related traits were then investigated. The four E maturity loci were genotyped at the molecular level. Our results suggested that these four E genes have different impacts on maturity and their allelic variations and combinations determine the diversification of soybean maturity and adaptation to different latitudes. The genetic mechanisms underlying photoperiod sensitivity and adaptation in wild soybean seemed unique from those in cultivated soybean. The allelic combinations and functional molecular markers for the four E loci will significantly assist molecular breeding towards high productivity.

  20. Allelic combinations of soybean maturity Loci E1, E2, E3 and E4 result in diversity of maturity and adaptation to different latitudes.

    Science.gov (United States)

    Jiang, Bingjun; Nan, Haiyang; Gao, Youfei; Tang, Lili; Yue, Yanlei; Lu, Sijia; Ma, Liming; Cao, Dong; Sun, Shi; Wang, Jialin; Wu, Cunxiang; Yuan, Xiaohui; Hou, Wensheng; Kong, Fanjiang; Han, Tianfu; Liu, Baohui

    2014-01-01

    Soybean cultivars are extremely diverse in time to flowering and maturation as a result of various photoperiod sensitivities. The underlying molecular genetic mechanism is not fully clear, however, four maturity loci E1, E2, E3 and E4 have been molecularly identified. In this report, cultivars were selected with various photoperiod sensitivities from different ecological zones, which covered almost all maturity groups (MG) from MG 000 to MG VIII and MG X adapted from latitude N 18° to N 53°. They were planted in the field under natural daylength condition (ND) in Beijing, China or in pots under different photoperiod treatments. Maturity-related traits were then investigated. The four E maturity loci were genotyped at the molecular level. Our results suggested that these four E genes have different impacts on maturity and their allelic variations and combinations determine the diversification of soybean maturity and adaptation to different latitudes. The genetic mechanisms underlying photoperiod sensitivity and adaptation in wild soybean seemed unique from those in cultivated soybean. The allelic combinations and functional molecular markers for the four E loci will significantly assist molecular breeding towards high productivity.

  1. Comparison of HCV core and coreE1E2 virus-like particles generated by stably transfected Leishmania tarentolae for stimulation of Th1 immune responses in mice.

    Science.gov (United States)

    Bolhassani, Azam; Davoudi, Noushin; Agi, Elnaz; Motevalli, Fatemeh

    2017-01-25

    Virus-like particles (VLPs) could be improved into successful immunogens as well as a potent delivery vehicle, but however, the current expression systems for VLPs production have some limitations. Recently, we developed a novel strategy to produce two HCV VLPs containing core or coreE1E2 proteins using stably transfected Leishmania tarentolae promastigotes. Then, BALB/c mice were injected by both viral like particles in different immunization strategies such as homologous DNA-, homologous VLP-, and heterologous DNA/ VLP-based immunizations. TEM microscopy indicated HCV core and HCV coreE1E2 VLP assembly with average size of 30-40 and 40-60 nm after purification, respectively. Our results showed that homologous immunizations with both HCV core or coreE1E2 VLPs significantly induced anti-core or anti-coreE1E2 antibody responses, respectively as well as secretion of IFN-γ cytokine as compared to other strategies. Moreover, DNA-prime/VLP-boost regimens significantly elicited higher levels of IFN-γ and antibody responses in comparison with homologous DNA/DNA regimens. The groups immunized with homologous or heterologous coreE1E2 VLPs showed markedly higher immune responses as compared to groups immunized with core VLP regimens against coreE1E2 protein. The crude HCV VLPs generated by Leishmania expression system could elicit a Th1-type response as a promising vaccine candidate against HCV infections.

  2. Effects of intraluteal implants of prostaglandin E1 or E2 on angiogenic growth factors in luteal tissue of Angus and Brahman cows.

    Science.gov (United States)

    Weems, Yoshie S; Ma, Yan; Ford, Stephen P; Nett, Terry M; Vann, Rhonda C; Lewis, Andrew W; Neuendorff, Don A; Welsh, Thomas H; Randel, Ronald D; Weems, Charles W

    2014-12-01

    Previously, it was reported that intraluteal implants containing prostaglandin E1 or E2 (PGE1 and PGE2) in Angus or Brahman cows prevented luteolysis by preventing loss of mRNA expression for luteal LH receptors and luteal unoccupied and occupied LH receptors. In addition, intraluteal implants containing PGE1 or PGE2 upregulated mRNA expression for FP prostanoid receptors and downregulated mRNA expression for EP2 and EP4 prostanoid receptors. Luteal weight during the estrous cycle of Brahman cows was reported to be lesser than that of Angus cows but not during pregnancy. The objective of this experiment was to determine whether intraluteal implants containing PGE1 or PGE2 alter vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), angiopoietin-1 (ANG-1), and angiopoietin-2 (ANG-2) protein in Brahman or Angus cows. On Day 13 of the estrous cycle, Angus cows received no intraluteal implant and corpora lutea were retrieved, or Angus and Brahman cows received intraluteal silastic implants containing vehicle, PGE1, or PGE2 on Day 13 and corpora lutea were retrieved on Day 19. Corpora lutea slices were analyzed for VEGF, FGF-2, ANG-1, and ANG-2 angiogenic proteins via Western blot. Day-13 Angus cow luteal tissue served as preluteolytic controls. Data for VEGF were not affected (P > 0.05) by day, breed, or treatment. PGE1 or PGE2 increased (P Brahman cows when compared w Day-13 or Day-19 Angus controls. There was no effect (P > 0.05) of PGE1 or PGE2 on ANG-1 in Angus luteal tissue when compared with Day-13 or Day-19 controls, but ANG-1 was decreased (P Brahman cows when compared with Day-19 Brahman controls. ANG-2 was increased (P 0.05) of PGE1 or PGE2 on ANG-2 in Brahman cows. PGE1 or PGE2 may alter cow luteal FGF-2, ANG-1, or ANG-2 but not VEGF to prevent luteolysis; however, species or breed differences may exist. Published by Elsevier Inc.

  3. The Search for a Complex Molecule in a Selected Hot Core Region: A Rigorous Attempt to Confirm trans-Ethyl Methyl Ether toward W51 e1/e2

    CERN Document Server

    Carroll, P Brandon; Blake, Geoffrey A; Apponi, A J; Ziuyrs, L M; Remijan, Anthony

    2014-01-01

    An extensive search has been conducted to confirm transitions of \\textit{trans}-ethyl methyl ether (tEME, C$_2$H$_5$OCH$_3$), toward the high mass star forming region W51 e1/e2 using the 12 m Telescope of the Arizona Radio Observatory (ARO) at wavelengths from 2 mm and 3 mm. In short, we cannot confirm the detection of tEME toward W51 e1/e2 and our results call into question the initial identification of this species by \\citet{FuchsSpace}. Additionally, reevaluation of the data from the original detection indicates that tEME is not present toward W51 e1/e2 in the abundance reported by Fuchs and colleagues. Typical peak-to-peak noise levels for the present observations of W51 e1/e2 were between 10 - 30 mK, yielding an upper limit of the tEME column density of $\\leq$ 1.5 $\\times$ 10$^{15}$ cm$^{-2}$. This would make tEME at least a factor 2 times less abundant than dimethyl ether (CH$_3$OCH$_3$) toward W51 e1/e2. We also performed an extensive search for this species toward the high mass star forming region Sgr...

  4. Calculation of parity violating effects in the 6/sup 2/P/sub 1/2/-7/sup 2/P/sub 1/2/ forbidden M1 transition in thallium. [E1 amplitude, circular dichroism, parity violation, hyperfine structure

    Energy Technology Data Exchange (ETDEWEB)

    Neuffer, D.B.

    1977-05-01

    Calculations are presented of the E1 amplitude expected in forbidden M1 transitions of Tl and Cs if parity is violated in the neutral weak e-N interaction, as proposed in a number of gauge models, including that of Weinberg and Salam. Valence electron wave functions are generated as numerical solutions to the Dirac equation in a modified Tietz central potential. These wave functions are used to calculate allowed E1 transition rates, hfs splittings, and Stark E1 transition ampitudes. These results are compared with experiment and the agreement is generally good. The relativistic Tl 6/sup 2/P/sub 1/2/-7/sup 2/P/sub 1/2/ M1 transition amplitude M is also calculated, and corrections due to interconfiguration interaction, Breit interaction, and hfs mixing are included. The parity violating E1 amplitude E/sub PV/ is calculated and a value for the circular dichroism in the Weinberg model delta = -2.6 x 10/sup -3/ is obtained. Parity violating effects in other Tl transitions are discussed. Contributions to the M1 amplitude for the forbidden Cs 6/sup 2/S/sub 1/2/-7/sup 2/S/sub 1/2/ and 6/sup 2/S/sub 1/2/-8/sup 2/S/sub 1/2/ transitions and to the Cs 6/sup 2/S/sub 1/2/ g-factor anomaly from relativistic effects, Breit interaction, interconfiguration interaction, and hfs mixing are calculated, and it is found that this current theoretical description is not entirely adequate. The parity violating E1 amplitude E/sub PV/ for the 6S/sub 1/2/-7/sup 2/S/sub 1/2/ and 6S/sub 1/2/-8/sup 2/S/sub 1/2/ transitions is evaluated. With a measured value M/sub expt/ and the Weinberg value Q/sub W/ = -99, a circular dichroism delta = 1.64 x 10/sup -4/ for the 6/sup 2/S/sub 1/2/-7/sup 2/S/sub 1/2/ transition is found.

  5. 丙型肝炎病毒1a、1b 和2a 型 E1E2原核质粒的构建和序列分析

    Institute of Scientific and Technical Information of China (English)

    胥冰; 黄峰; 霍慧春

    2015-01-01

    目的:构建陕西地方株丙型肝炎病毒(HCV)1a、1b 和2a 型包膜糖蛋白 E1E2的原核质粒并测序比对。方法采用逆转录-巢式聚合酶链反应(RT-nest PCR)扩增获得 HCV 1a、1b 和2a 型 E1E2片段,与 pMD-18 simple vector 连接,转化感受态细菌 DH5α,小量提取质粒 DNA 并测序。测序结果与 Gene bank 中其他标准序列比对以获取同源性数据。同时重点分析 E2蛋白高变区(HVR)1和2氨基酸序列。 MEGA 4软件绘制种系进化树图。结果成功扩增约2 kb 的目的片段并构建原核质粒,测序结果正确。1b 亚型 E1E2的核苷酸和氨基酸序列的同源性最差。 HCV E2的HVR1和2的序列比对显示,同种基因亚型在 HVR 1的变异性最大,而 HVR 2的序列变异性不显著。不同基因亚型的毒株在 HVR 1和2的变异性极大,而1b 亚型在 HVR 1和2的变异性比1a 和2a 型突出。结论陕西地方株 HCV 1b 型 E1E2区比1a 和2a 型更易发生突变,1b 型 E2的 HVR 变异性更显著。

  6. THE SEARCH FOR A COMPLEX MOLECULE IN A SELECTED HOT CORE REGION: A RIGOROUS ATTEMPT TO CONFIRM TRANS-ETHYL METHYL ETHER TOWARD W51 e1/e2

    Energy Technology Data Exchange (ETDEWEB)

    Carroll, P. Brandon; McGuire, Brett A. [Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125 (United States); Blake, Geoffrey A. [Division of Chemistry and Chemical Engineering and Division Geological and Planetary Sciences, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125 (United States); Apponi, A. J.; Ziurys, L. M. [Departments of Chemistry and Astronomy, University of Arizona, 933 North Cherry Avenue, Tucson, AZ 85721 (United States); Remijan, Anthony, E-mail: pcarroll@caltech.edu [National Radio Astronomy Observatory, 520 Edgemont Road, Charlottesville, VA 22901-2475 (United States)

    2015-01-20

    An extensive search has been conducted to confirm transitions of trans-ethyl methyl ether (tEME, C{sub 2}H{sub 5}OCH{sub 3}), toward the high-mass star forming region W51 e1/e2 using the 12 m Telescope of the Arizona Radio Observatory at wavelengths from 2 mm and 3 mm. In short, we cannot confirm the detection of tEME toward W51 e1/e2 and our results call into question the initial identification of this species by Fuchs et al. Additionally, re-evaluation of the data from the original detection indicates that tEME is not present toward W51 e1/e2 in the abundance reported by Fuchs and colleagues. Typical peak-to-peak noise levels for the present observations of W51 e1/e2 were between 10 and 30 mK, yielding an upper limit of the tEME column density of ≤1.5 × 10{sup 15} cm{sup –2}. This would make tEME at least a factor of two times less abundant than dimethyl ether (CH{sub 3}OCH{sub 3}) toward W51 e1/e2. We also performed an extensive search for this species toward the high-mass star forming region Sgr B2(N-LMH) with the National Radio Astronomy Observatory 100 m Green Bank Telescope. No transitions of tEME were detected and we were able to set an upper limit to the tEME column density of ≤4 × 10{sup 14} cm{sup –2} toward this source. Thus, we are able to show that tEME is not a new molecular component of the interstellar medium and that an exacting assessment must be carried out when assigning transitions of new molecular species to astronomical spectra to support the identification of large organic interstellar molecules.

  7. Screening concentration of E1, E2 and EE2 in sewage effluents and surface waters of the "Pampas" region and the "Río de la Plata" estuary (Argentina).

    Science.gov (United States)

    Valdés, María Eugenia; Marino, Damián José; Wunderlin, Daniel Alberto; Somoza, Gustavo Manuel; Ronco, Alicia Estela; Carriquiriborde, Pedro

    2015-01-01

    Concentrations of estrone (E1), 17β-estradiol (E2) and 17α-ethinylestradiol (EE2) were investigated for the first time in sewage effluents and receiving waters of the "Río de la Plata" estuary and neighboring areas by means of LC-MS/MS. E2 and EE2 were ubiquitous in the evaluated sewage effluent samples showing concentrations ranging between 122-631 and 65-187 ng/L, respectively. In surface waters, these estrogens were only detected in the "Girado" stream (Chascomús) at 369 and 43 ng/L, respectively. No significant relationship was found among the size of the served population and the concentration of the estrogens in the sewage effluent. The detection of these estrogens in receiving waters was dependent on the dilution capacity of the system. The studied estrogens were undetectable at the La Plata City water supply station. Conversely, concentrations found at the "Girado" stream indicate a potential ecotoxicological risk of these estrogens to the local aquatic biota.

  8. Persistent replication of a hepatitis C virus genotype 1b-based chimeric clone carrying E1, E2 and p6 regions from GB virus B in a New World monkey.

    Science.gov (United States)

    Suzuki, Saori; Mori, Ken-Ichi; Higashino, Atsunori; Iwasaki, Yuki; Yasutomi, Yasuhiro; Maki, Noboru; Akari, Hirofumi

    2016-01-01

    The development of effective hepatitis C virus (HCV) vaccines is essential for the prevention of further HCV dissemination, especially in developing countries. Therefore the aim of this study is to establish a feasible and immunocompetent surrogate animal model of HCV infection that will help in evaluation of the protective efficacy of newly developing HCV vaccine candidates. To circumvent the narrow host range of HCV, an HCV genotype 1b-based chimeric clone carrying E1, E2 and p6 regions from GB virus B (GBV-B), which is closely related to HCV, was generated. The chimera between HCV and GBV-B, named HCV/G, replicated more efficiently as compared with the HCV clone in primary marmoset hepatocytes. Furthermore, it was found that the chimera persistently replicated in a tamarin for more than 2 years after intrahepatic inoculation of the chimeric RNA. Although relatively low (virus. Our results will help establish a novel non-human primate model for HCV infection on the basis of the HCV/G chimera in the major framework of the HCV genome.

  9. Effects of the novel compound DK223 ([1E,2E-1,2-Bis(6-methoxy-2H-chromen-3-yl)methylene]hydrazine) on migration and proliferation of human keratinocytes and primary dermal fibroblasts.

    Science.gov (United States)

    Ho, Manh Tin; Kang, Hyun Sik; Huh, Jung Sik; Kim, Young Mee; Lim, Yoongho; Cho, Moonjae

    2014-07-23

    Wound healing plays an important role in protecting the human body from external infection. Cell migration and proliferation of keratinocytes and dermal fibroblasts are essential for proper wound healing. Recently, several studies have demonstrated that secondary compounds produced in plants could affect skin cells migration and proliferation. In this study, we identified a novel compound DK223 ([1E,2E-1,2-bis(6-methoxy-2H-chromen-3-yl)methylene]hydrazine) that concomitantly induced human keratinocyte migration and dermal fibroblast proliferation. We evaluated the regulation of epithelial and mesenchymal protein markers, such as E-cadherin and Vimentin, in human keratinocytes, as well as extracellular matrix (ECM) secretion and metalloproteinase families in dermal fibroblasts. DK223 upregulated keratinocyte migration and significantly increased the epithelial marker E-cadherin in a time-dependent manner. We also found that reactive oxygen species (ROS) increased significantly in keratinocytes after 2 h of DK223 exposure, returning to normal levels after 24 h, which indicated that DK223 had an early shock effect on ROS production. DK223 also stimulated fibroblast proliferation, and induced significant secretion of ECM proteins, such as collagen I, III, and fibronectin. In dermal fibroblasts, DK223 treatment induced TGF-β1, which is involved in a signaling pathway that mediates proliferation. In conclusion, DK223 simultaneously induced both keratinocyte migration via ROS production and fibroblast proliferation via TGF-β1 induction.

  10. Effects of the Novel Compound DK223 ([1E,2E-1,2-Bis(6-methoxy-2H-chromen-3-ylmethylene]hydrazine on Migration and Proliferation of Human Keratinocytes and Primary Dermal Fibroblasts

    Directory of Open Access Journals (Sweden)

    Manh Tin Ho

    2014-07-01

    Full Text Available Wound healing plays an important role in protecting the human body from external infection. Cell migration and proliferation of keratinocytes and dermal fibroblasts are essential for proper wound healing. Recently, several studies have demonstrated that secondary compounds produced in plants could affect skin cells migration and proliferation. In this study, we identified a novel compound DK223 ([1E,2E-1,2-bis(6-methoxy-2H-chromen-3-ylmethylene]hydrazine that concomitantly induced human keratinocyte migration and dermal fibroblast proliferation. We evaluated the regulation of epithelial and mesenchymal protein markers, such as E-cadherin and Vimentin, in human keratinocytes, as well as extracellular matrix (ECM secretion and metalloproteinase families in dermal fibroblasts. DK223 upregulated keratinocyte migration and significantly increased the epithelial marker E-cadherin in a time-dependent manner. We also found that reactive oxygen species (ROS increased significantly in keratinocytes after 2 h of DK223 exposure, returning to normal levels after 24 h, which indicated that DK223 had an early shock effect on ROS production. DK223 also stimulated fibroblast proliferation, and induced significant secretion of ECM proteins, such as collagen I, III, and fibronectin. In dermal fibroblasts, DK223 treatment induced TGF-β1, which is involved in a signaling pathway that mediates proliferation. In conclusion, DK223 simultaneously induced both keratinocyte migration via ROS production and fibroblast proliferation via TGF-β1 induction.

  11. 129Xe30+轰击Ni表面激发靶原子偶极跃迁和禁戒(M1E2)跃迁的特征光谱线%Atomic and ionic light emission spectra of dipole transition and forbidden transition induced by the impact of 126Xe30+ on Ni solid surface

    Institute of Scientific and Technical Information of China (English)

    张小安; 赵永涛; 李福利; 杨治虎; 肖国青; 詹文龙

    2004-01-01

    报道了用高电荷态离子129Xe30+(150keV) 轰击金属Ni表面,激发的200-1000nm NiⅠ和NiⅡ的特征光谱线的实验结果.实验结果表明:用电荷态足够高的离子作光谱激发源,无需很强的束流强度(nA量级),便可有效地产生原子和离子的复杂组态间跃迁所形成的可见光波段的特征谱线,特别是NiⅠ和NiⅡ偶极禁戒的电四极跃迁E2和磁偶极跃迁M1的特征光谱线.通过分析发现,在禁戒跃迁的谱线中,有些是电子组态相同而原子态不同的偶极禁戒跃迁光谱线而且NiⅡ的684.84nm谱线较强.

  12. Loop 7 of E2 enzymes

    DEFF Research Database (Denmark)

    Papaleo, Elena; Casiraghi, Nicola; Arrigoni, Alberto;

    2012-01-01

    The ubiquitin (Ub) system controls almost every aspect of eukaryotic cell biology. Protein ubiquitination depends on the sequential action of three classes of enzymes (E1, E2 and E3). E2 Ub-conjugating enzymes have a central role in the ubiquitination pathway, interacting with both E1 and E3...

  13. Loop 7 of E2 enzymes

    DEFF Research Database (Denmark)

    Papaleo, Elena; Casiraghi, Nicola; Arrigoni, Alberto

    2012-01-01

    The ubiquitin (Ub) system controls almost every aspect of eukaryotic cell biology. Protein ubiquitination depends on the sequential action of three classes of enzymes (E1, E2 and E3). E2 Ub-conjugating enzymes have a central role in the ubiquitination pathway, interacting with both E1 and E3...... hydrophobic and acidic residues in a finely orchestrate mechanism....

  14. Radiative rates for E1, E2, M1, and M2 transitions among the 3s$^2$3p$^5$, 3s3p$^6$, and 3s$^2$3p$^4$3d configurations of Cl-like W LVIII

    CERN Document Server

    Aggarwal, K M

    2014-01-01

    We report calculations of energy levels, radiative decay rates, and lifetimes for transitions among the 3s$^2$3p$^5$, 3s3p$^6$, and 3s$^2$3p$^4$3d configurations of Cl-like W LVIII. The general-purpose relativistic atomic structure package (GRASP) has been adopted for our calculations. Comparisons are made with the most recent results of Mohan et al. [Can. J. Phys. {\\bf 92} (2014) xxx] and discrepancies in lifetimes are noted, up to four orders of magnitude in some instances. Our energy levels are estimated to be accurate to better than 0.5\\%, whereas results for radiative rates and lifetimes should be accurate to better than 20\\%.

  15. Forbidden M1 and E2 transitions in monovalent atoms and ions

    CERN Document Server

    Safronova, U I; Johnson, W R

    2016-01-01

    We carried out a systematic high-precision relativistic study of the forbidden magnetic-dipole and electric-quadrupole transitions in Ca+, Rb, Sr+, Cs, Ba+, Fr, Ra+, Ac2+, and Th3+. This work is motivated by the importance of these transitions for tests of fundamental physics and precision measurements. The relative importance of the relativistic, correlation, Breit correction, and contributions of negative-energy states is investigated. Recommended values of reduced matrix elements are presented together with their uncertainties. The matrix elements and resulting lifetimes are compared with other theoretical values and with experiment where available.

  16. GSM(m,1)(m=1,2)模型的数值解%Numeriacl Solution of GSM (m, 1)(m= 1,2)Model

    Institute of Scientific and Technical Information of China (English)

    吴强; 刘炳琪

    2001-01-01

    The prediction accuracy can be improved by using the spline function to correct the residue of GM (m,1)(m=1,2). Numerical Solution of GSM (m,1)(m=1,2)Modle is given.%本文用样条函数对GM(m,1)(m=1,2)模型的残差序列进行插值拟合,得到GSM(m,1)(m=1,2)模型的数值解.

  17. Main: E2FAT [PLACE

    Lifescience Database Archive (English)

    Full Text Available tial E2F target genes; most potential E2F targets identified in silico show a cell cycle-regulated expression; Y=T/C; see S000366; E2F; cell cycle; Arabidopsis thaliana TYTCCCGCC ...

  18. The E(2) Particle

    CERN Document Server

    Ghosh, Subir

    2009-01-01

    Recently it has been advocated [1] that for describing nature within the minimal symmetry requirement, certain subgroups of Lorentz group (along with translation invariance) may play a fundamental role, (instead of the full Poincare group). One such group is E(2) which induces a Lie algebraic Non-Commutative spacetime [4]. In this new kind of Non-Commutative phase space, (which however is not translation invariant in all directions), we construct a point particle action. Interestingly, contrary to some of the other Lie algebraic Non-Commutative spacetimes, no change in the Einstein dispersion relation $p^2=m^2$ is needed. The model is constructed by exploiting a dual canonical phase space following the scheme developed by us earlier [8].

  19. Functional processing and secretion of Chikungunya virus E1 and E2 glycoproteins in insect cells

    NARCIS (Netherlands)

    S.W. Metz (Stefan); C. Geertsema (Corinne); B.E.E. Martina (Byron); P. Andrade (Paulina); J.G.M. Heldens; M.M. van Oers (Monique); J.M. Vlak (Just); G.P. Pijlman (Gorben)

    2011-01-01

    textabstractBackground: Chikungunya virus (CHIKV) is a mosquito-borne, arthrogenic Alphavirus that causes large epidemics in Africa, South-East Asia and India. Recently, CHIKV has been transmitted to humans in Southern Europe by invading and now established Asian tiger mosquitoes. To study the proce

  20. Functional processing and secretion of Chikungunya virus E1 and E2 glycoproteins in insect cells

    NARCIS (Netherlands)

    Metz, S.W.H.; Geertsema, C.; Martina, Byron E.; Andrade, Paulina; Heldens, J.; Oers, van M.M.; Goldbach, R.W.; Vlak, J.M.; Pijlman, G.P.

    2011-01-01

    Background - Chikungunya virus (CHIKV) is a mosquito-borne, arthrogenic Alphavirus that causes large epidemics in Africa, South-East Asia and India. Recently, CHIKV has been transmitted to humans in Southern Europe by invading and now established Asian tiger mosquitoes. To study the processing of en

  1. (E-1-Phenyl-2-({5-[(1E-(2-phenylhydrazin-1-ylidenemethyl]-2-thienyl}methylidenehydrazine

    Directory of Open Access Journals (Sweden)

    James L. Wardell

    2010-03-01

    Full Text Available The title molecule, C18H16N4S, adopts a U-shape with the aromatic groups lying syn and orientated in the same direction as the thiophene S atom. The conformation about each of the C=N bonds is E. Overall, the molecule is curved as seen in the dihedral angle of 30.26 (19° formed between the terminal benzene rings. In the crystal, supramolecular chains along the c axis are formed by a combination of N—H...N hydrogen bonds and N—H...π interactions.

  2. Functional processing and secretion of Chikungunya virus E1 and E2 glycoproteins in insect cells

    NARCIS (Netherlands)

    S.W. Metz (Stefan); C. Geertsema (Corinne); B.E.E. Martina (Byron); P. Andrade (Paulina); J.G.M. Heldens; M.M. van Oers (Monique); J.M. Vlak (Just); G.P. Pijlman (Gorben)

    2011-01-01

    textabstractBackground: Chikungunya virus (CHIKV) is a mosquito-borne, arthrogenic Alphavirus that causes large epidemics in Africa, South-East Asia and India. Recently, CHIKV has been transmitted to humans in Southern Europe by invading and now established Asian tiger mosquitoes. To study the proce

  3. (1E,2E-1,2-Bis(2,2-diphenylhydrazin-1-ylideneethane

    Directory of Open Access Journals (Sweden)

    Angel Mendoza

    2010-09-01

    Full Text Available In the crystal structure of the title compound, C26H22N4, the molecule is located on an inversion centre and shows an E configuration with respect to each C=N bond. The dihedral angle between the phenyl rings in the diphenylhydrazone group is 83.69 (11°. These two rings make dihedral angles of 30.53 (15 and 84.53 (16° with the central N—N=C—C=N—N dihydrazonoethane plane. Intermolecular C—H...π interactions are observed.

  4. Separation of Pygmy Dipole and M1 Resonances in Zr90 by a High-Resolution Inelastic Proton Scattering Near 0°

    Science.gov (United States)

    Iwamoto, C.; Utsunomiya, H.; Tamii, A.; Akimune, H.; Nakada, H.; Shima, T.; Yamagata, T.; Kawabata, T.; Fujita, Y.; Matsubara, H.; Shimbara, Y.; Nagashima, M.; Suzuki, T.; Fujita, H.; Sakuda, M.; Mori, T.; Izumi, T.; Okamoto, A.; Kondo, T.; Bilgier, B.; Kozer, H. C.; Lui, Y.-W.; Hatanaka, K.

    2012-06-01

    A high-resolution measurement of inelastic proton scattering off Zr90 near 0° was performed at 295 MeV with a focus on a pronounced strength previously reported in the low-energy tail of giant dipole resonance. A forest of fine structure was observed in the excitation energy region 7-12 MeV. A multipole decomposition analysis of the angular distribution for the forest was carried out using the ECIS95 distorted-wave Born approximation code with the Hartree-Fock plus random-phase approximation model of E1 and M1 transition densities and inclusion of E1 Coulomb excitation. The analysis separated pygmy dipole and M1 resonances in the forest at EPDR=9.15±0.18MeV with ΓPDR=2.91±0.64MeV and at EM1=9.53±0.06MeV with ΓM1=2.70±0.17MeV in the Lorentzian function, respectively. The B(E1)↑ value for pygmy dipole resonance over 7-11 MeV is 0.75±0.08e2fm2, which corresponds to 2.1±0.2% of the Thomas-Reiche-Kuhn sum rule.

  5. Reference: E2FBNTRNR [PLACE

    Lifescience Database Archive (English)

    Full Text Available E2FBNTRNR Chaboute ME, Clement B, Sekine M, Philipps G, Chaubet-Gigot N Cell cycle re...gulation of the tobacco ribonucleotide reductase small subunit gene is mediated by E2F-like elements Plant Cell 12: 1987-2000 (2000) PubMed: 11041892; ...

  6. M$_1$ - M* correlation in galaxy clusters

    CERN Document Server

    Trevese, D; Appodia, B

    1994-01-01

    Photographic F band photometry of a sample of 36 Abell clusters has been used to study the relation between the magnitude M_1 of the brightest cluster member and the Schechter function parameter M^*. Clusters appear segregated in the M_1-M^* plane according to their Rood \\& Sastry class. We prove on a statistical basis that on average, going from early to late RS classes, M_1 becomes brighter while M^* becomes fainter. The result agrees with the predictions of galactic cannibalism models, never confirmed by previous analyses.

  7. Gamma-ray spectrometer onboard Chang'E-2

    Science.gov (United States)

    Ma, T.; Chang, J.; Zhang, N.; Jian, W.; Cai, M. S.; Gong, Y. Z.; Tang, H. S.; Zhang, R. J.; Wang, N. S.; Yu, M.; Mao, J. P.; Hu, Y. M.; Xu, A. A.; Zhu, M. H.

    2013-10-01

    Chang'E-2 gamma-ray spectrometer (GRS) is included in the payload of Chinese second lunar mission Chang'E-2 that has been launched in October 2010. Specific objectives of the GRS are to map abundance of O, Si, Fe, Ti, U, Th, K, and, perhaps, Mg, Al, and Ca, to depth of about 20 cm. The energy resolution and detection efficiency were improved compared with Chang'E-1 GRS. We will describe the design of GRS, which used LaBr3 for its main detector, and present its performance in this paper. Moreover, the initial result of Chang'E-2 GRS is reported.

  8. Characterization of Compass M-1 signals

    NARCIS (Netherlands)

    Hauschild, A.; Montenbruck, O.; Sleewaegen, J.-M.; Huisman, L.; Teunissen, P.J.G.

    2011-01-01

    An analysis of observations from China’s first medium earth orbit satellite Compass M-1 is presented, with main focus on the first orbit and clock solution for this satellite. The orbit is computed from laser ranging measurements. Based on this orbit solution, the apparent clock offset is estimated

  9. Inactivation of cyclin E1 inhibits chemically induced hepatocarcinogenesis in mice

    OpenAIRE

    Moro, Nives

    2011-01-01

    E-type cyclins (CcnE) control the transition of quiescent cells into the cell cycle. Two E-type cyclins, CcnE1 and CcnE2 have been described. A variety of human cancers, including hepatocellular carcinoma (HCC), overexpress CcnE and this is frequently associated with reduced patient survival. The aim of the present study was to dissect the role of CcnE1 and CcnE2 for hepatocarcinogenesis induced by the carcinogen diethylnitrosamine (DEN) using CcnE1 and CcnE2 knockout mice. The central questi...

  10. Analytic closures for M1 neutrino transport

    Science.gov (United States)

    Murchikova, E. M.; Abdikamalov, E.; Urbatsch, T.

    2017-08-01

    Carefully accounting for neutrino transport is an essential component of many astrophysical studies. Solving the full transport equation is too expensive for most realistic applications, especially those involving multiple spatial dimensions. For such cases, resorting to approximations is often the only viable option for obtaining solutions. One such approximation, which recently became popular, is the M1 method. It utilizes the system of the lowest two moments of the transport equation and closes the system with an ad hoc closure relation. The accuracy of the M1 solution depends on the quality of the closure. Several closures have been proposed in the literature and have been used in various studies. We carry out an extensive study of these closures by comparing the results of M1 calculations with precise Monte Carlo calculations of the radiation field around spherically symmetric protoneutron star models. We find that no closure performs consistently better or worse than others in all cases. The level of accuracy that a given closure yields depends on the matter configuration, neutrino type and neutrino energy. Given this limitation, the maximum entropy closure by Minerbo on average yields relatively accurate results in the broadest set of cases considered in this work.

  11. M1 muscarinic receptor activation mediates cell death in M1-HEK293 cells.

    Science.gov (United States)

    Graham, E Scott; Woo, Kerhan K; Aalderink, Miranda; Fry, Sandie; Greenwood, Jeffrey M; Glass, Michelle; Dragunow, Mike

    2013-01-01

    HEK293 cells have been used extensively to generate stable cell lines to study G protein-coupled receptors, such as muscarinic acetylcholine receptors (mAChRs). The activation of M1 mAChRs in various cell types in vitro has been shown to be protective. To further investigate M1 mAChR-mediated cell survival, we generated stable HEK293 cell-lines expressing the human M1 mAChR. M1 mAChRs were efficiently expressed at the cell surface and efficiently internalised within 1 h by carbachol. Carbachol also induced early signalling cascades similar to previous reports. Thus, ectopically expressed M1 receptors behaved in a similar fashion to the native receptor over short time periods of analysis. However, substantial cell death was observed in HEK293-M1 cells within 24 h after carbachol application. Death was only observed in HEK cells expressing M1 receptors and fully blocked by M1 antagonists. M1 mAChR-stimulation mediated prolonged activation of the MEK-ERK pathway and resulted in prolonged induction of the transcription factor EGR-1 (>24 h). Blockade of ERK signalling with U0126 did not reduce M1 mAChR-mediated cell-death significantly but inhibited the acute induction of EGR-1. We investigated the time-course of cell death using time-lapse microscopy and xCELLigence technology. Both revealed the M1 mAChR cytotoxicity occurs within several hours of M1 activation. The xCELLigence assay also confirmed that the ERK pathway was not involved in cell-death. Interestingly, the MEK blocker did reduce carbachol-mediated cleaved caspase 3 expression in HEK293-M1 cells. The HEK293 cell line is a widely used pharmacological tool for studying G-protein coupled receptors, including mAChRs. Our results highlight the importance of investigating the longer term fate of these cells in short term signalling studies. Identifying how and why activation of the M1 mAChR signals apoptosis in these cells may lead to a better understanding of how mAChRs regulate cell-fate decisions.

  12. "m=1" coatings for neutron guides

    OpenAIRE

    Cooper-Jensen, C.P.; Vorobiev, A.; Klinkby, Esben Bryndt; Kapaklis, V.; Wilkens, H.; Rats, D.; Hjörvarsson, B.; Kirstein, O.; Bentley, Philip

    2014-01-01

    A substantial part of the price for a neutron guide is the shielding needed because of the gamma ray produced when neutrons are absorbed. This absorption occurs in the coating and the substrate of the neutron guides. Traditional m=1 coatings have been made of Ni and if reflectivity over the critical angle of Ni is needed one has used Ni58 or Ni/Ti multilayer coatings. Ni has one of the highest neutron scattering density but it also has a fairly high absorption cross section for cold and therm...

  13. The hepatitis C virus E1 glycoprotein undergoes productive folding but accelerated degradation when expressed as an individual subunit in CHO cells.

    Directory of Open Access Journals (Sweden)

    Valentina Botti

    Full Text Available Hepatitis C Virus E1E2 heterodimers are components of the viral spike. Although there is a general agreement on the necessity of the co-expression of both E1 and E2 on a single coding unit for their productive folding and assembly, in a previous study using an in vitro system we obtained strong indications that E1 can achieve folding in absence of E2. Here, we have studied the folding pathway of unescorted E1 from stably expressing CHO cells, compared to the folding observed in presence of the E2 protein. A DTT-resistant conformation is achieved by E1 in both situations, consistent with the presence of an E2-independent oxidative pathway. However, while the E1E2 heterodimer is stable inside cells, E1 expressed alone is degraded within a few hours. On the other hand, the oxidation and stability of individually expressed E2 subunits is dependent on E1 co-expression. These data are consistent with E1 and E2 assisting each other for correct folding via different mechanisms: E2 assists E1 by stabilizing a semi-native conformation meanwhile E1 drives E2 towards a productive folding pathway.

  14. "m=1" coatings for neutron guides

    DEFF Research Database (Denmark)

    Cooper-Jensen, C.P.; Vorobiev, A.; Klinkby, Esben Bryndt

    2014-01-01

    A substantial part of the price for a neutron guide is the shielding needed because of the gamma ray produced when neutrons are absorbed. This absorption occurs in the coating and the substrate of the neutron guides. Traditional m=1 coatings have been made of Ni and if reflectivity over...... the critical angle of Ni is needed one has used Ni58 or Ni/Ti multilayer coatings. Ni has one of the highest neutron scattering density but it also has a fairly high absorption cross section for cold and thermal neutrons and when a neutron is absorbed it emits a lot of gamma rays, some with energies above 9 Me......V. Materials like diamond and Be have higher neutron scattering density than Ni, have smaller absorption cross section and when a neutron is absorbed they emit much less gamma ray and at lower energies. We present results, both theoretically and experimentally, comparing Ni with Be and preliminary results...

  15. Hepatitis C Virus E2 Envelope Glycoprotein Core Structure

    Energy Technology Data Exchange (ETDEWEB)

    Kong, Leopold; Giang, Erick; Nieusma, Travis; Kadam, Rameshwar U.; Cogburn, Kristin E.; Hua, Yuanzi; Dai, Xiaoping; Stanfield, Robyn L.; Burton, Dennis R.; Ward, Andrew B.; Wilson, Ian A.; Law, Mansun

    2014-08-26

    Hepatitis C virus (HCV), a Hepacivirus, is a major cause of viral hepatitis, liver cirrhosis, and hepatocellular carcinoma. HCV envelope glycoproteins E1 and E2 mediate fusion and entry into host cells and are the primary targets of the humoral immune response. The crystal structure of the E2 core bound to broadly neutralizing antibody AR3C at 2.65 angstroms reveals a compact architecture composed of a central immunoglobulin-fold β sandwich flanked by two additional protein layers. The CD81 receptor binding site was identified by electron microscopy and site-directed mutagenesis and overlaps with the AR3C epitope. The x-ray and electron microscopy E2 structures differ markedly from predictions of an extended, three-domain, class II fusion protein fold and therefore provide valuable information for HCV drug and vaccine design.

  16. Cancer risks posed by aflatoxin M1.

    Science.gov (United States)

    Hsieh, D P; Cullen, J M; Hsieh, L S; Shao, Y; Ruebner, B H

    1985-01-01

    The suspect milk-borne carcinogen, aflatoxin M1 (AFM), was produced and isolated from the rice culture of the fungus Aspergillus flavus NRRL3251 for confirmation and determination of the potency of its carcinogenicity in the male adult Fischer rat. The carcinogen was mixed into an agar-based, semisynthetic diet at 0, 0.5, 5, and 50 ppb (microgram/kg) and was fed to groups of animals continuously for 19-21 months. Aflatoxin B1 (AFB), of which AFM is a metabolite, at 50 ppb was used as a positive control. Hepatocarcinogenicity of AFM was detected at 50 ppb, but not at 5 or 0.5 ppb, with a potency of 2-10% that of AFB. A low incidence of intestinal adenocarcinomas was found in the AFM 50 ppb group, but not in any other groups. At 0.5 ppb, the action level enforced by the U.S.A. Food and Drug Administration, AFM induced no liver lesions in the rats but stimulated the animals' growth. On the average, the rats in the 0.5 ppb group weighed 11% (p less than 0.001) more than those in the control group. This increased growth was associated with increased feed intake. Based on the biological activity of AFM at the relevant low doses and the estimated level of human exposure to AFM through consumption of milk, the cancer risk posed by this contaminant for human adults is assessed to be very low. For infants, further studies are warranted because milk constitutes the major ingredient of the infant diet and because infant animals have been shown to be more sensitive to the carcinogenicity of AFB than adult animals.

  17. Inhibition of E2F-1 transactivation by direct binding of the retinoblastoma protein

    DEFF Research Database (Denmark)

    Helin, K; Harlow, E; Fattaey, A

    1993-01-01

    to transcription factor E2F has provided a model for the mechanism of pRB-mediated growth regulation. Since adenovirus E1A proteins dissociate the pRB-E2F complexes and stimulate E2F-dependent transcription, it has been suggested that pRB inhibits E2F transactivation. Although some evidence for this hypothesis has...... been provided, it has not been possible to determine the mechanism of pRB-mediated inhibition of E2F transactivation. In this study, we constructed mutants of E2F-1 that do not bind to pRB yet retain the ability to transactivate the adenovirus E2 promoter through E2F DNA-binding sites. We demonstrated...

  18. Reference: E2F1OSPCNA [PLACE

    Lifescience Database Archive (English)

    Full Text Available E2F1OSPCNA Kosugi S, Ohashi Y E2F sites that can interact with E2F proteins cloned from rice are require...d for meristematic tissue-specific expression of rice and tobacco proliferating cell nuclear antigen promoters Plant J 29: 45-59 (2002) PubMed: 12060226; ...

  19. DNA-damage response control of E2F7 and E2F8

    OpenAIRE

    Panagiotis Zalmas, L.; Zhao, Xiujie; Graham, Anne L; FISHER Rebecca; Reilly, Carmel; Coutts, Amanda S; La Thangue, Nicholas B

    2008-01-01

    Here, we report that the two recently identified E2F subunits, E2F7 and E2F8, are induced in cells treated with DNA-damaging agents where they have an important role in dictating the outcome of the DNA-damage response. The DNA-damage-dependent induction coincides with the binding of E2F7 and E2F8 to the promoters of certain E2F-responsive genes, most notably that of the E2F1 gene, in which E2F7 and E2F8 coexist in a DNA-binding complex. As a consequence, E2F7 and E2F8 repress E2F target genes...

  20. Salmonid alphavirus glycoprotein E2 requires low temperature and E1 for virion formation and induction of protective immunity

    NARCIS (Netherlands)

    Hikke, M.C.; Braaen, S.; Villoing, S.; Hodneland, K.; Geertsema, C.; Verhagen, L.; Frost, P.; Vlak, J.M.; Rimstad, E.; Pijlman, G.P.

    2014-01-01

    Salmonid alphavirus (SAV; also known as Salmon pancreas disease virus; family Togaviridae) causes pancreas disease and sleeping disease in Atlantic salmon and rainbow trout, respectively, and poses a major burden to the aquaculture industry. SAV infection in vivo is temperature-restricted and

  1. (1E,2E-1,2-Bis(2,3-dihydro-1H-inden-1-ylidenehydrazine

    Directory of Open Access Journals (Sweden)

    Wolfgang Imhof

    2012-09-01

    Full Text Available In the title compound, C18H16N2, there are two independent half-molecules (A and B in the asymmetric unit, each molecule being completed by an inversion center situated in the mid-point of the central N—N bond. The molecules themselves therefore are essentially planar with r.m.s. deviations of 0.015 (1 and 0.020 (1 Å, respectively. In the crystal, molecules are connected via C—H...π interactions in which only type B molecules are donors, while both A and B molecules act as acceptors. As a result, type B molecules are linked into infinite chains along b, which are interconnected by molecules of type A.

  2. Salmonid alphavirus glycoprotein E2 requires low temperature and E1 for virion formation and induction of protective immunity

    NARCIS (Netherlands)

    Hikke, M.C.; Braaen, S.; Villoing, S.; Hodneland, K.; Geertsema, C.; Verhagen, L.; Frost, P.; Vlak, J.M.; Rimstad, E.; Pijlman, G.P.

    2014-01-01

    Salmonid alphavirus (SAV; also known as Salmon pancreas disease virus; family Togaviridae) causes pancreas disease and sleeping disease in Atlantic salmon and rainbow trout, respectively, and poses a major burden to the aquaculture industry. SAV infection in vivo is temperature-restricted and progen

  3. On the nonexistence of $[\\binom{2m}{m-1}, 2m, \\binom{2m-1}{m-1}]$, $m$ odd, complex orthogonal design

    CERN Document Server

    Li, Yuan

    2011-01-01

    Complex orthogonal designs (CODs) are used to construct space-time block codes. COD $\\mathcal{O}_z$ with parameter $[p, n, k]$ is a $p\\times n$ matrix, where nonzero entries are filled by $\\pm z_i$ or $\\pm z^*_i$, $i = 1, 2,..., k$, such that $\\mathcal{O}^H_z \\mathcal{O}_z = (|z_1|^2+|z_2|^2+...+|z_k|^2)I_{n \\times n}$. Adams et al. in "The final case of the decoding delay problem for maximum rate complex orthogonal designs," IEEE Trans. Inf. Theory, vol. 56, no. 1, pp. 103-122, Jan. 2010, first proved the nonexistence of $[\\binom{2m}{m-1}, 2m, \\binom{2m-1}{m-1}]$, $m$ odd, COD. Combining with the previous result that decoding delay should be an integer multiple of $\\binom{2m}{m-1}$, they solved the final case $n \\equiv 2 \\pmod 4$ of the decoding delay problem for maximum rate complex orthogonal designs. In this paper, we give another proof of the nonexistence of COD with parameter $[\\binom{2m}{m-1}, 2m, \\binom{2m-1}{m-1}]$, $m$ odd. Our new proof is based on the uniqueness of $[\\binom{2m}{m-1}, 2m-1, \\binom{...

  4. Main: E2F1OSPCNA [PLACE

    Lifescience Database Archive (English)

    Full Text Available E2F1OSPCNA S000396 21-May-2002 (last modified) uchi re2f-1 found in the promoter of rice PCN...ividing cells and tissue; E2F; PCNA; meristematic tissue; cell cycle; rice (Oryza sativa); tobacco (Nicotiana tabacum) GCGGGAAA ...

  5. The conformation of acetylated virginiamycin M1 and virginiamycin M1 in explicit solvents.

    Science.gov (United States)

    Ng, Chai Ann; Zhao, Wen; Dang, Jason; Bergdahl, Mikael; Separovic, Frances; Brownlee, Robert T C; Metzger, Robert P

    2007-05-01

    The three-dimensional structure of acetylated virginiamycin M(1) (acetylated VM1) in chloroform and in a water/acetonitrile mixture (83:17 v/v) have been established through 2D high resolution NMR experiments and molecular dynamics modeling and the results compared with the conformation of the antibiotic VM1 in the same and other solvents. The results indicated that acetylation of the C-14 OH group of VM1 caused it to rotate about 90 degrees from the position it assumed in non-acetylated VM1. The conformation of both VM1 and acetylated VM1 appear to flatten in moving from a nonpolar to polar solvent. However, the acetylated form has a more hydrophobic nature. The acetylated VM1 in chloroform and in water/acetonitrile solution had a similar configuration to that of VM1 bound to 50S ribosomes and to the Vat(D) active sites as previously determined by X-ray crystallography. Docking studies of VM1 to the 50S ribosomal binding site and the Vat(D) gave conformations very similar to those derived from X-ray crystallographic studies. The docking studies with acetylated VM1 suggested the possibility of a hydrogen bond from the acetyl carbonyl group oxygen of acetylated VM1 to the 2' hydroxyl group of ribose of adenosine 2538 at the ribosomal VM1 binding site. No hydrogen bonds between acetylated VM1 and the Vat(D) active sites were found; the loss of this binding interaction partly accounts for the release of the product from the active site.

  6. The Implementation of E1 Clock Recovery

    Directory of Open Access Journals (Sweden)

    Wang Ziyu

    2016-01-01

    Full Text Available Clock transform and recovery is of significant importance in microwave TDM service, and it is always extracted from the E1 line data stream in most cases. However, intrinsically uncertain delay and jitter caused by packet transmission of E1 data information, may lead to the indexes of the data recovery clock exceed the clock performance template. Through analysis of the E1 clock indexes and measuring methods, this paper proposes a new clock recovery method. The method employs two buffers, the first RAM is used as a buffer to deduct excess information, and the second FIFO is used as a buffer to recovery the clock and data. The first buffer has a feedback from the second one, and is able to actively respond to changes in the data link and requests from the second one. The test results validate the effectiveness of the method, and the corresponding scheme is also valuable for the other communication systems.

  7. Characterization of E2F8, a novel E2F-like cell-cycle regulated repressor of E2F-activated transcription

    DEFF Research Database (Denmark)

    Christensen, Jesper; Cloos, Paul; Toftegaard, Ulla

    2005-01-01

    . Sequence analysis of E2F8 predicts the presence of two distinct E2F-related DNA binding domains suggesting that E2F8 and, the recently, identified E2F7 form a subgroup within the E2F family. We show that E2F transcription factors bind the E2F8 promoter in vivo and that expression of E2F8 is being induced...... at the G1/S transition. Purified recombinant E2F8 binds specifically to a consensus E2F-DNA-binding site indicating that E2F8, like E2F7, binds DNA without the requirement of co-factors such as DP1. E2F8 inhibits E2F-driven promoters suggesting that E2F8 is transcriptional repressor like E2F7. Ectopic...

  8. Qualification Lab Testing on M1 Abrams Engine Oil Filters

    Science.gov (United States)

    2016-11-01

    UNCLASSIFIED QUALIFICATION LAB TESTING ON M1 ABRAMS ENGINE OIL FILTERS FINAL REPORT TFLRF No. 483 by Kristi K. Rutta U.S...the originator. UNCLASSIFIED QUALIFICATION LAB TESTING ON M1 ABRAMS ENGINE OIL FILTERS FINAL REPORT TFLRF No. 483 by Kristi K...TITLE AND SUBTITLE Qualification Lab Testing on M1 Abrams Engine Oil Filter 5a. CONTRACT NUMBER W56HZV-15-C-0030 5b. GRANT NUMBER 5c. PROGRAM

  9. Develop Efficient Leak Proof M1 Abrams Plenum Seal

    Science.gov (United States)

    2014-05-07

    UNCLASSIFIED UNCLASSIFIED ER-GLSV11389-001.docx Develop Efficient Leak Proof M1 Abrams Plenum Seal SBIR Phase I: Topic A13-061...Leak Proof M1 Abrams Plenum Seal Christian Muehfeld Steve Pennala Great Lakes Sound & Vibration, Inc. 47140 North Main Street Houghton, MI 49931 ER...061. The purpose of this report is to show the feasibility of developing an efficient, leak proof plenum seal for the M1 Abrams . It also shows the

  10. Moist convection scheme in Model E2

    CERN Document Server

    Kim, Daehyun; Yao, Mao-Sung

    2013-01-01

    This documentation describes the version of the Del Genio - Yao cumulus parameterization used in the NASA Goddard Institute for Space Studies Model E2 GCM. This version was used for the official GISS submissions to the CMIP5 archive.

  11. Bifunctional effect of E2 on macrophage

    Institute of Scientific and Technical Information of China (English)

    MinHONG; QuanZHU

    2004-01-01

    AIM: Our previous study showed that the effect of 1713-estradiol(E2) on macrophage does not strengthen when concentrationincreased. So the effect of E2 on cytokines, intracellular free Ca2+([Ca2+]i) and morphological change of macrophages at differentconcentrations were studied. METHODS: TNF-α was measured by MTT via L929 cell. Nitrate and nitrite level(NO) wasmeasured by the method of Griess. [Ca2+]i was examined by laser scanning confocal microscopy(LSCM). Fluorescent microscopy

  12. Theory of (e, 2e) reactions

    Science.gov (United States)

    Byron, F. W.; Joachain, C. J.

    1989-08-01

    A comprehensive survey is given of the theory of (e, 2e) reactions. We begin by discussing the kinematics of these reactions, with special attention devoted to the coplanar asymmetric (Ehrhardt-type) geometry and the fully symmetric geometry in which most of the recent (e, 2e) coincidence measurements have been performed. We then review the foundations of the theory of the ionization of atoms by electron impact, first for one-electron atoms and then for target atoms with N electrons. Next, we discussed the Wannier theory of threshold ionization and its excitations. We then turn to the analysis of (e, 2e) reactions at intermediate and high energies. The theory of fast coplanar asymmetric (e, 2e) reactions is analyzed and it is shown that the eikonal-Born series method successfully accounts for all the dynamical features of these reactions. In particular, it is shown that second order effects are essential in explaining all the features exhibited by the measured by the measured triple differential cross sections at intermediate energies. Finally, we review the theory of fast symmetric (e, 2e) reactions. We consider first the (e, 2e) spectroscopy regime in which the momentum transfer Δ is large, but the recoil momentum Q of the ion is small or moderate. We then turn to the regime of large Δ and large Q, for which second order effects are of paramount importance, so that the coplanar symmetric triple differential cross section exhibits a striking behaviour in the large angle region.

  13. E2F7, a novel E2F featuring DP-independent repression of a subset of E2F-regulated genes

    OpenAIRE

    Di Stefano, Luisa; Jensen, Michael Rugaard; Helin, Kristian

    2003-01-01

    The E2F family of transcription factors play an essential role in the regulation of cell cycle progression. In a screen for E2F-regulated genes we identified a novel E2F family member, E2F7. Like the recently identified E2F-like proteins of Arabidopsis, E2F7 has two DNA binding domains and binds to the E2F DNA binding consensus site independently of DP co-factors. Consistent with being an E2F target gene, we found that the expression of E2F7 is cell cycle regulated. Ectopic expression of E2F7...

  14. Quadrupole decay strength of the M1 scissors mode of {sup 156}Gd

    Energy Technology Data Exchange (ETDEWEB)

    Beck, T.; Beller, J.; Gayer, U.; Mertes, L.; Pai, H.; Pietralla, N.; Ries, P.; Romig, C.; Werner, V.; Zweidinger, M. [IKP, TU Darmstadt (Germany); Derya, V. [IKP, Universitaet zu Koeln (Germany); Isaak, J.; Loeher, B.; Savran, D. [EMMI, GSI, Darmstadt (Germany); FIAS, Frankfurt (Germany); Scheck, M. [IKP, TU Darmstadt (Germany); School of Engineering, UWS, Paisley (United Kingdom); SUPA, Glasgow (United Kingdom); Tornow, W.; Weller, H.R. [Duke University, Durham (United States)

    2015-07-01

    The isovector low-lying J{sup π}{sub K}=1{sup +}{sub 1} scissors mode of deformed nuclei has been studied extensively in (e,e{sup '}) and (γ,γ{sup '}) experiments over the last 30 years with the main focus on strong M1 transitions to the ground state band. In the framework of the semiclassical two-rotor-model it has its origin in quadrupole deformation. A considerable E2 matrix element between the rotational band of the scissors mode and the ground band is predicted which has not been addressed experimentally. A photon-scattering experiment with linearly-polarized quasi monoenergetic vector (γ)-rays has been performed at the High Intensity vector (γ)-ray Source (HIvector (γ)S) at Duke University, Durham, NC, exploiting the γ{sup 3} setup. We have measured an E2/M1-multipole mixing ratio for the 1{sup +}{sub sc}→2{sup +}{sub 1} transition for the first time. The Alaga rule is applicable and delivers a first estimate of the transition strength B(E2:2{sup +}{sub sc}→0{sup +}{sub 1}). A candidate for a 2{sup +}{sub sc}→2{sup +}{sub 1} transition is discussed.

  15. Genomic Characterization of Campylobacter jejuni strain M1

    DEFF Research Database (Denmark)

    Friis, Carsten; Wassenaar, Gertrude Maria; Javed, Muhammad A.

    2010-01-01

    publicly available. Compared to these, M1 is closest to strain 81116. Based on the 13 genome sequences, we have identified the C. jejuni pan-genome, as well as the core genome, the auxiliary genes, and genes unique between strains M1 and 81116. The pan-genome contains 2,427 gene families, whilst the core...

  16. FoxM1 Regulates Mammary Luminal Cell Fate

    Directory of Open Access Journals (Sweden)

    Janai R. Carr

    2012-06-01

    Full Text Available Elevated expression of FoxM1 in breast cancer correlates with an undifferentiated tumor phenotype and a negative clinical outcome. However, a role for FoxM1 in regulating mammary differentiation was not known. Here, we identify another function of FoxM1, the ability to act as a transcriptional repressor, which plays an important role in regulating the differentiation of luminal epithelial progenitors. Regeneration of mammary glands with elevated levels of FoxM1 leads to aberrant ductal morphology and expansion of the luminal progenitor pool. Conversely, knockdown of FoxM1 results in a shift toward the differentiated state. FoxM1 mediates these effects by repressing the key regulator of luminal differentiation, GATA-3. Through association with DNMT3b, FoxM1 promotes methylation of the GATA-3 promoter in an Rb-dependent manner. This study identifies FoxM1 as a critical regulator of mammary differentiation with significant implications for the development of aggressive breast cancers.

  17. E2F1 is crucial for E2F-dependent apoptosis

    DEFF Research Database (Denmark)

    Lazzerini Denchi, Eros; Helin, Kristian

    2005-01-01

    Loss of the retinoblastoma protein, pRB, leads to apoptosis, and several results have suggested that this is dependent on the E2F transcription factors. However, so far, the ability of the different E2F family members to contribute to apoptosis is controversial. Here, we show that ectopic...... expression of E2F3 results in apoptosis in both primary mouse fibroblasts and transgenic mice. Apoptosis induced by E2F3 is associated with the accumulation of E2F1 and, strikingly, we found that E2F3-induced apoptosis is dependent on E2F1. On the basis of these results, we propose that the accumulation...... of crucial levels of E2F1 activity, and not total E2F activity, is essential for the induction of apoptosis in response to a deregulated pRB pathway. These results are consistent with previous findings that E2F1, but not other E2Fs, can have tumour-suppressing activities....

  18. E1 strength in N = 82 nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Hartmann, T.; Volz, S.; Babilon, M.; Mohr, P.; Vogt, K.; Zilges, A

    2003-05-19

    Recently the importance of small contributions of electric dipole strength near the particle threshold to the production rates of atomic nuclei has become evident. Prior estimates concentrated on the Giant Dipole Resonance (GDR) which dominates photoabsorption in all nuclei. Extrapolations to smaller excitation energies were assumed to be sufficiently reliable. However, new measurements reveal that collective E1 strength can be found in the threshold region.

  19. On (2m + 1)-variable symmetric Boolean functions with submaximum algebraic immunity 2m-1

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    All (2m +1)-variable symmetric Boolean functions with submaximal algebraic immunity 2m-1 are described and constructed. The total number of such Boolean functions is 32 ·22m-3 +3m-2 · 24 - 2 for m≥2.

  20. Competing E2 and SN2 Mechanisms for the F(-) + CH3CH2I Reaction.

    Science.gov (United States)

    Yang, Li; Zhang, Jiaxu; Xie, Jing; Ma, Xinyou; Zhang, Linyao; Zhao, Chenyang; Hase, William L

    2017-02-09

    Anti-E2, syn-E2, inv-, and ret-SN2 reaction channels for the gas-phase reaction of F(-) + CH3CH2I were characterized with a variety of electronic structure calculations. Geometrical analysis confirmed synchronous E2-type transition states for the elimination of the current reaction, instead of nonconcerted processes through E1cb-like and E1-like mechanisms. Importantly, the controversy concerning the reactant complex for anti-E2 and inv-SN2 paths has been clarified in the present work. A positive barrier of +19.2 kcal/mol for ret-SN2 shows the least feasibility to occur at room temperature. Negative activation energies (-16.9, -16.0, and -4.9 kcal/mol, respectively) for inv-SN2, anti-E2, and syn-E2 indicate that inv-SN2 and anti-E2 mechanisms significantly prevail over the eclipsed elimination. Varying the leaving group for a series of reactions F(-) + CH3CH2Y (Y = F, Cl, Br, and I) leads to monotonically decreasing barriers, which relates to the gradually looser TS structures following the order F > Cl > Br > I. The reactivity of each channel nearly holds unchanged except for the perturbation between anti-E2 and inv-SN2. RRKM calculation reveals that the reaction of the fluorine ion with ethyl iodide occurs predominately via anti-E2 elimination, and the inv-SN2 pathway is suppressed, although it is energetically favored. This phenomenon indicates that, in evaluating the competition between E2 and SN2 processes, the kinetic or dynamical factors may play a significant role. By comparison with benchmark CCSD(T) energies, MP2, CAM-B3LYP, and M06 methods are recommended to perform dynamics simulations of the title reaction.

  1. Polymorphic genetic characterization of E2 gene of bovine viral diarrhea virus in China.

    Science.gov (United States)

    Lang, Yifei; Gao, Shandian; Du, Junzheng; Shao, Junjun; Cong, Guozheng; Lin, Tong; Zhao, Furong; Liu, Lihong; Chang, Huiyun

    2014-12-05

    Bovine viral diarrhea virus (BVDV) is one of the wide distributed pathogenic viruses of livestock and wild animals worldwide. E2 glycoprotein is a major structural component of the BVDV virion and plays a key role in viral attachment to host cells and inducing immune responses against viral infection. In order to gain detailed information of the E2 coding region of BVDV circulating in China, 46 positive samples were tested by RT-PCR for the E2 coding region. The 1122 nt nucleotide sequences of full-length E2 were harvested and analyzed. The results suggested that full-length E2 was an ideal target for BVDV genotyping and divided the domestic BVDV isolates into 9 subgenotypes, namely BVDV-1a, -1b1, -1c, -1d, -1o, -1m, -1p, -1q and BVDV-2a, showing great diversity. The difference of nonsynonymous and synonymous substitution rates (dN-dS) inferred both positive and purifying selection of the E2. However, combination of positive and purifying selection at different points indicated purifying selection within the complete E2. Protein properties analysis based on glycosylation sites and epitope prediction demonstrated that the biological character of E2 among individual BVDV subgenotype was similar, but may alter due to amino acid changes. For the first time, the comprehensive collection of E2 sequences of Chinese BVDV isolates was elucidated, which would provide information for future vaccine design and BVD control in China.

  2. Inhibition of human papillomavirus DNA replication by an E1-derived p80/UAF1-binding peptide.

    Science.gov (United States)

    Lehoux, Michaël; Fradet-Turcotte, Amélie; Lussier-Price, Mathieu; Omichinski, James G; Archambault, Jacques

    2012-04-01

    The papillomavirus E1 helicase is recruited by E2 to the viral origin, where it assembles into a double hexamer that orchestrates replication of the viral genome. We previously identified the cellular WD40 repeat-containing protein p80/UAF1 as a novel interaction partner of E1 from anogenital human papillomavirus (HPV) types. p80 was found to interact with the first 40 residues of HPV type 31 (HPV31) E1, and amino acid substitutions within this domain abrogated the maintenance of the viral episome in keratinocytes. In this study, we report that these p80-binding substitutions reduce by 70% the ability of E1 to support transient viral DNA replication without affecting its interaction with E2 and assembly at the origin in vivo. Microscopy studies revealed that p80 is relocalized from the cytoplasm to discrete subnuclear foci by E1 and E2. Chromatin immunoprecipitation assays further revealed that p80 is recruited to the viral origin in an E1- and E2-dependent manner. Interestingly, overexpression of a 40-amino-acid-long p80-binding peptide, derived from HPV31 E1, was found to inhibit viral DNA replication by preventing the recruitment of endogenous p80 to the origin. Mutant peptides defective for p80 interaction were not inhibitory, demonstrating the specificity of this effect. Characterization of this E1 peptide by nuclear magnetic resonance (NMR) showed that it is intrinsically disordered in solution, while mapping studies indicated that the WD repeats of p80 are required for E1 interaction. These results provide additional evidence for the requirement for p80 in anogenital HPV DNA replication and highlight the potential of E1-p80 interaction as a novel antiviral target.

  3. Diverse Effects on M1 Signaling and Adverse Effect Liability within a Series of M1 Ago-PAMs.

    Science.gov (United States)

    Rook, Jerri M; Abe, Masahito; Cho, Hyekyung P; Nance, Kellie D; Luscombe, Vincent B; Adams, Jeffrey J; Dickerson, Jonathan W; Remke, Daniel H; Garcia-Barrantes, Pedro M; Engers, Darren W; Engers, Julie L; Chang, Sichen; Foster, Jarrett J; Blobaum, Anna L; Niswender, Colleen M; Jones, Carrie K; Conn, P Jeffrey; Lindsley, Craig W

    2017-01-10

    Both historical clinical and recent preclinical data suggest that the M1 muscarinic acetylcholine receptor is an exciting target for the treatment of Alzheimer's disease and the cognitive and negative symptom clusters in schizophrenia; however, early drug discovery efforts targeting the orthosteric binding site have failed to afford selective M1 activation. Efforts then shifted to focus on selective activation of M1 via either allosteric agonists or positive allosteric modulators (PAMs). While M1 PAMs have robust efficacy in rodent models, some chemotypes can induce cholinergic adverse effects (AEs) that could limit their clinical utility. Here, we report studies aimed at understanding the subtle structural and pharmacological nuances that differentiate efficacy from adverse effect liability within an indole-based series of M1 ago-PAMs. Our data demonstrate that closely related M1 PAMs can display striking differences in their in vivo activities, especially their propensities to induce adverse effects. We report the discovery of a novel PAM in this series that is devoid of observable adverse effect liability. Interestingly, the molecular pharmacology profile of this novel PAM is similar to that of a representative M1 PAM that induces severe AEs. For instance, both compounds are potent ago-PAMs that demonstrate significant interaction with the orthosteric site (either bitopic or negative cooperativity). However, there are subtle differences in efficacies of the compounds at potentiating M1 responses, agonist potencies, and abilities to induce receptor internalization. While these differences may contribute to the differential in vivo profiles of these compounds, the in vitro differences are relatively subtle and highlight the complexities of allosteric modulators and the need to focus on in vivo phenotypic screening to identify safe and effective M1 PAMs.

  4. Characterization of E2F8, a novel E2F-like cell-cycle regulated repressor of E2F-activated transcription

    OpenAIRE

    Christensen, Jesper; Cloos, Paul; Toftegaard, Ulla; Klinkenberg, David; Bracken, Adrian P.; Trinh, Emmanuelle; Heeran, Mel; Di Stefano, Luisa; Helin, Kristian

    2005-01-01

    The E2F family of transcription factors are downstream effectors of the retinoblastoma protein, pRB, pathway and are essential for the timely regulation of genes necessary for cell-cycle progression. Here we describe the characterization of human and murine E2F8, a new member of the E2F family. Sequence analysis of E2F8 predicts the presence of two distinct E2F-related DNA binding domains suggesting that E2F8 and, the recently, identified E2F7 form a subgroup within the E2F family. We show th...

  5. E2F-4 and E2F-5, two members of the E2F family, are expressed in the early phases of the cell cycle.

    OpenAIRE

    Sardet, C; Vidal, M.; Cobrinik, D; Y. Geng; Onufryk, C; Chen, A; Weinberg, R A

    1995-01-01

    The E2F transcription factors play a role in regulating the expression of genes required for cell proliferation. Their activity appears to be regulated by association with the retinoblastoma protein (pRb) and the pRb-related proteins p107 and p130. In vivo, pRb is found in complex with a subset of E2F components--namely, E2F-1, E2F-2, and E2F-3. Here we describe the characterization of cDNAs encoding two unusual E2Fs, E2F-4 and E2F-5, each identified by the ability of their gene product to in...

  6. E2F7, a novel E2F featuring DP-independent repression of a subset of E2F-regulated genes.

    Science.gov (United States)

    Di Stefano, Luisa; Jensen, Michael Rugaard; Helin, Kristian

    2003-12-01

    The E2F family of transcription factors play an essential role in the regulation of cell cycle progression. In a screen for E2F-regulated genes we identified a novel E2F family member, E2F7. Like the recently identified E2F-like proteins of Arabidopsis, E2F7 has two DNA binding domains and binds to the E2F DNA binding consensus site independently of DP co-factors. Consistent with being an E2F target gene, we found that the expression of E2F7 is cell cycle regulated. Ectopic expression of E2F7 results in suppression of E2F target genes and accumulation of cells in G1. Furthermore, E2F7 associates with E2F-regulated promoters in vivo, and this association increases in S phase. Interestingly, however, E2F7 binds only a subset of E2F-dependent promoters in vivo, and in agreement with this, inhibition of E2F7 expression results in specific derepression of these promoters. Taken together, these data demonstrate that E2F7 is a unique repressor of a subset of E2F target genes whose products are required for cell cycle progression.

  7. Broad analgesic activity of a novel, selective M1 agonist.

    Science.gov (United States)

    Wood, Michael W; Martino, Giovanni; Coupal, Martin; Lindberg, Mattias; Schroeder, Patricia; Santhakumar, Vijayaratnam; Valiquette, Manon; Sandin, Johan; Widzowski, Daniel; Laird, Jennifer

    2017-09-01

    Although the muscarinic receptor family has long been a source of potentially compelling targets for small molecule drug discovery, it was difficult to achieve agonist selectivity within the family. A new class of M1 muscarinic agonists has emerged, and these compounds have been characterized as agonists that activate the receptor at an allosteric site. Members of this class of M1 agonists have been shown to be selective across the muscarinic receptors. However, upon introduction of a novel pharmacologic mechanism, it is prudent to ensure that no new off-target activities have arisen, particularly within the context of in vivo experiments. Reported here, is the in vitro and in vivo characterization of a novel M1 agonist tool compound, PPBI, and demonstrations that the primary biological effects of PPBI are mediated through M1. PPBI reverses d-amphetamine locomotor activity, but fails to do so in transgenic mice that do not express M1. PPBI also reverses a natural deficit in a rat cognition model at a level of exposure which also activates cortical circuitry. Most notably, PPBI is analgesic in a variety of rat and mouse models and the analgesic effect of PPBI is reversed by an M1-preferring antagonist and an M1-selective toxin. Finally, the pharmacokinetic/pharmacodynamic measures of PPBI are compared across multiple endpoints which highlights that activity in models of psychosis and pain require higher exposures than that required in the cognition model. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. E2F-5, a new E2F family member that interacts with p130 in vivo

    NARCIS (Netherlands)

    Hijmans, E.M.; Voorhoeve, P.M.; Beijersbergen, R.L.; Veer, L.J. van 't; Bernards, R.A.

    1995-01-01

    E2F DNA binding sites are found in a number of genes whose expression is tightly regulated during the cell cycle. The activity of E2F transcription factors is regulated by association with specific repressor molecules that can bind and inhibit the E2F transactivation domain. For E2F-1, E2F-2, and E2

  9. HPV-18 E2circumflexE4 chimera: 2 new spliced transcripts and proteins induced by keratinocyte differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Chye Ling [Papillomavirus Regulation and Cancer, Institute of Medical Biology, Agency for Science, Technology and Research (A-STAR), Biopolis, 8A Biomedical Grove, Immunos, Singapore 138648 (Singapore); Gunaratne, Jayantha [Mass Spectrometry and Systems Biology Laboratory, Institute of Molecular and Cell Biology, A-STAR, Biopolis, 61 Biopolis Drive, Proteos, Singapore 138673 (Singapore); Lai, Deborah [Papillomavirus Regulation and Cancer, Institute of Medical Biology, Agency for Science, Technology and Research (A-STAR), Biopolis, 8A Biomedical Grove, Immunos, Singapore 138648 (Singapore); Carthagena, Laetitia [UMR-S996, Universite Paris-Sud 11, 32 rue des Carnets, 92140 Clamart (France); Wang, Qian [MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London N10 3UE (United Kingdom); Xue, Yue Zhen; Quek, Ling Shih [Papillomavirus Regulation and Cancer, Institute of Medical Biology, Agency for Science, Technology and Research (A-STAR), Biopolis, 8A Biomedical Grove, Immunos, Singapore 138648 (Singapore); Doorbar, John [MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London N10 3UE (United Kingdom); Bachelerie, Francoise [UMR-S996, Universite Paris-Sud 11, 32 rue des Carnets, 92140 Clamart (France); Thierry, Francoise, E-mail: francoise.thierry@imb.a-star.edu.sg [Papillomavirus Regulation and Cancer, Institute of Medical Biology, Agency for Science, Technology and Research (A-STAR), Biopolis, 8A Biomedical Grove, Immunos, Singapore 138648 (Singapore); Bellanger, Sophie, E-mail: sophie.bellanger@imb.a-star.edu.sg [Papillomavirus Regulation and Cancer, Institute of Medical Biology, Agency for Science, Technology and Research (A-STAR), Biopolis, 8A Biomedical Grove, Immunos, Singapore 138648 (Singapore)

    2012-07-20

    The Human Papillomavirus (HPV) E4 is known to be synthesized as an E1circumflexE4 fusion resulting from splice donor and acceptor sites conserved across HPV types. Here we demonstrate the existence of 2 HPV-18 E2circumflexE4 transcripts resulting from 2 splice donor sites in the 5 Prime part of E2, while the splice acceptor site is the one used for E1circumflexE4. Both E2circumflexE4 transcripts are up-regulated by keratinocyte differentiation in vitro and can be detected in clinical samples containing low-grade HPV-18-positive cells from Pap smears. They give rise to two fusion proteins in vitro, E2circumflexE4-S and E2circumflexE4-L. Whereas we could not differentiate E2circumflexE4-S from E1circumflexE4 in vivo, E2circumflexE4-L could be formally identified as a 23 kDa protein in raft cultures in which the corresponding transcript was also found, and in a biopsy from a patient with cervical intraepithelial neoplasia stage I-II (CINI-II) associated with HPV-18, demonstrating the physiological relevance of E2circumflexE4 products.

  10. Selectivity of oxomemazine for the M1 muscarinic receptors.

    Science.gov (United States)

    Lee, S W; Woo, C W; Kim, J G

    1994-12-01

    The binding characteristics of pirenzepine and oxomemazine to muscarinic receptor were studied to evaluate the selectivity of oxomemazine for the muscarinic receptor subtypes in rat cerebral microsomes. Equilibrium dissociation constant (KD) of (-)-[3H]quinuclidinyl benzilate([3H]QNB) determined from saturation isotherms was 64 pM. Analysis of the pirenzepine inhibition curve of [3H]QNB binding to cerebral microsome indicated the presence of two receptor subtypes with high (Ki = 16 nM, M1 receptor) and low (Ki = 400 nM, M3 receptor) affinity for pirenzepine. Oxomemazine also identified two receptor subtypes with about 20-fold difference in the affinity for high (Ki = 84 nM, OH receptor) and low (Ki = 1.65 microM, OL receptor) affinity sites. The percentage populations of M1 and M3 receptors to the total receptors were 61:39, and those of OH and OL receptors 39:61, respectively. Both pirenzepine and oxomemazine increased the KD value for [3H]QNB without affecting the binding site concentrations and Hill coefficient for the [3H]QNB binding. Oxomemazine had a 10-fold higher affinity at M1 receptors than at M3 receptors, and pirenzepine a 8-fold higher affinity at OH receptors than at OL receptors. Analysis of the shallow competition binding curves of oxomemazine for M1 receptors and pirenzepine for OL receptors yielded that 69% of M1 receptors were of OH receptors and the remaining 31% of OL receptors, and that 29% of OL receptors were of M1 receptors and 71% of M3 receptors. However, M3 for oxomemazine and OH for pirenzepine were composed of a uniform population. These results suggest that oxomemazine could be classified as a selective drug for M1 receptors and also demonstrate that rat cerebral microsomes contain three different subtypes of M1, M3 and the other site which is different from M1, M2 and M3 receptors.

  11. M1.3--a small scaffold for DNA origami .

    Science.gov (United States)

    Said, Hassan; Schüller, Verena J; Eber, Fabian J; Wege, Christina; Liedl, Tim; Richert, Clemens

    2013-01-07

    The DNA origami method produces programmable nanoscale objects that form when one long scaffold strand hybridizes to numerous oligonucleotide staple strands. One scaffold strand is dominating the field: M13mp18, a bacteriophage-derived vector 7249 nucleotides in length. The full-length M13 is typically folded by using over 200 staple oligonucleotides. Here we report the convenient preparation of a 704 nt fragment dubbed "M1.3" as a linear or cyclic scaffold and the assembly of small origami structures with just 15-24 staple strands. A typical M1.3 origami is large enough to be visualized by TEM, but small enough to show a cooperativity in its assembly and thermal denaturation that is reminiscent of oligonucleotide duplexes. Due to its medium size, M1.3 origami with globally modified staples is affordable. As a proof of principle, two origami structures with globally 5'-capped staples were prepared and were shown to give higher UV-melting points than the corresponding assembly with unmodified DNA. M1.3 has the size of a gene, not a genome, and may function as a model for gene-based nanostructures. Small origami with M1.3 as a scaffold may serve as a workbench for chemical, physical, and biological experiments.

  12. Surface properties of new virginiamycin M(1) derivatives.

    Science.gov (United States)

    Nott, Katherine; Paquot, Michel; Dufour, Samuel; Eeman, Marc; Deleu, Magali

    2009-03-01

    Three kinds of derivatives of the M(1) factor of virginiamycin have been synthesised: esters with long chain fatty acids, oximes with modified polar amino acids and bis-derivatives with both the ester and oxime function. The study of the surface tension time dependence of M(1) and its derivatives has shown that it is necessary to enhance simultaneously the hydrophobicity and the hydrophilicity of M(1) to render M(1) surface-active. A structure/function relationship study of the surface-active bis-derivatives has shown that enhancing the hydrophobicity of the molecule led to slower adsorption kinetics, higher stability of the monolayers formed and a better capacity to penetrate a membrane model. The repulsive electrostatic forces due to the presence of charges on the amino acids linked to M(1) lead to higher surface tensions, a greater molecular area at the interface and lower penetration into a membrane model. This study has demonstrated that modifying systematically the hydrophobicity and hydrophilicity of a non surface-active molecule allows the production of surface-active derivatives.

  13. Genomic characterization of Campylobacter jejuni strain M1.

    Directory of Open Access Journals (Sweden)

    Carsten Friis

    Full Text Available Campylobacter jejuni strain M1 (laboratory designation 99/308 is a rarely documented case of direct transmission of C. jejuni from chicken to a person, resulting in enteritis. We have sequenced the genome of C. jejuni strain M1, and compared this to 12 other C. jejuni sequenced genomes currently publicly available. Compared to these, M1 is closest to strain 81116. Based on the 13 genome sequences, we have identified the C. jejuni pan-genome, as well as the core genome, the auxiliary genes, and genes unique between strains M1 and 81116. The pan-genome contains 2,427 gene families, whilst the core genome comprised 1,295 gene families, or about two-thirds of the gene content of the average of the sequenced C. jejuni genomes. Various comparison and visualization tools were applied to the 13 C. jejuni genome sequences, including a species pan- and core genome plot, a BLAST Matrix and a BLAST Atlas. Trees based on 16S rRNA sequences and on the total gene families in each genome are presented. The findings are discussed in the background of the proven virulence potential of M1.

  14. Investigation of aflatoxin M1 degradation in milk

    Directory of Open Access Journals (Sweden)

    Smajlović Ahmed

    2012-01-01

    Full Text Available Aflatoxin M1 is a highly toxic 4-hydroxylated metabolite of aflatoxins B1 and B2. It is one of the most potent hepatocarcinogens, mutagens, teratogens and immunosuppressors. Feed is often contaminated with aflatoxigenic moulds and aflatoxins with a high possibility of contaminating milk and dairy products with aflatoxin M1. Samples of artificially contaminated milk were exposed to the effects of physical conditions (temperature of -18oC and for microwaves in a microwave oven, time (during the period from 1 to 12 months and a combination of the above mentioned conditions. Following this, levels of aflatoxin M1 degradation were established by using the ELISA method. An insignificant decrease in concentration of toxin was observed which indicates that a temperature of -18°C does not significantly influence the concentration of aflatoxin M1 in the artificially contaminated milk. At the same time, treatment of milk with microwaves in a microwave oven showed an insignificant influence on the percentage of aflatoxin M1 absorbance.

  15. Novel functions for atypical E2Fs, E2F7 and E2F8, in polyploidization and liver cancer

    NARCIS (Netherlands)

    Pandit, Shusil Kumar

    2014-01-01

    Atypical E2F transcription factors, E2F7 and E2F8, function as transcriptional repressors of E2F target genes and are crucial for controlling the cell proliferation. In this thesis, we reveal that these two factors are crucial for liver cell polyploidization, embryonic development and prevention of

  16. E2F7, a novel E2F featuring DP-independent repression of a subset of E2F-regulated genes

    DEFF Research Database (Denmark)

    Di Stefano, Luisa; Jensen, Michael Rugaard; Helin, Kristian

    2003-01-01

    The E2F family of transcription factors play an essential role in the regulation of cell cycle progression. In a screen for E2F-regulated genes we identified a novel E2F family member, E2F7. Like the recently identified E2F-like proteins of Arabidopsis, E2F7 has two DNA binding domains and binds...... to the E2F DNA binding consensus site independently of DP co-factors. Consistent with being an E2F target gene, we found that the expression of E2F7 is cell cycle regulated. Ectopic expression of E2F7 results in suppression of E2F target genes and accumulation of cells in G1. Furthermore, E2F7 associates...... with E2F-regulated promoters in vivo, and this association increases in S phase. Interestingly, however, E2F7 binds only a subset of E2F-dependent promoters in vivo, and in agreement with this, inhibition of E2F7 expression results in specific derepression of these promoters. Taken together, these data...

  17. Concerning the Integral dx/x[superscript m] (1+x)

    Science.gov (United States)

    Walters, William; Huber, Michael

    2010-01-01

    Consider the integral dx/x[superscript m] (1+x). In the "CRC Standard Mathematical Tables," this integral can require repeated integral evaluations. Enter this integral into your favourite computer algebra system, and the results may be unrecognizable. In this article, we seek to provide a simpler evaluation for integrals of this form. We state up…

  18. Theory of the M = 1 Kink Mode in Toroidal Plasma

    NARCIS (Netherlands)

    de Blank, H. J.; Schep, T. J.

    1991-01-01

    The energy principle of ideal magnetohydrodynamics (MHD) is used to study the ideal MHD stability of the m = 1 internal kink mode in a toroidal plasma. The equilibrium configurations that are considered allow for a broad region where the safety factor q is close to unity. This region may extend to t

  19. Concerning the Integral dx/x[superscript m] (1+x)

    Science.gov (United States)

    Walters, William; Huber, Michael

    2010-01-01

    Consider the integral dx/x[superscript m] (1+x). In the "CRC Standard Mathematical Tables," this integral can require repeated integral evaluations. Enter this integral into your favourite computer algebra system, and the results may be unrecognizable. In this article, we seek to provide a simpler evaluation for integrals of this form. We state up…

  20. Adenovirus E1A/E1B Transformed Amniotic Fluid Cells Support Human Cytomegalovirus Replication

    Directory of Open Access Journals (Sweden)

    Natascha Krömmelbein

    2016-02-01

    Full Text Available The human cytomegalovirus (HCMV replicates to high titers in primary human fibroblast cell cultures. A variety of primary human cells and some tumor-derived cell lines do also support permissive HCMV replication, yet at low levels. Cell lines established by transfection of the transforming functions of adenoviruses have been notoriously resistant to HCMV replication and progeny production. Here, we provide first-time evidence that a permanent cell line immortalized by adenovirus type 5 E1A and E1B (CAP is supporting the full HCMV replication cycle and is releasing infectious progeny. The CAP cell line had previously been established from amniotic fluid cells which were likely derived from membranes of the developing fetus. These cells can be grown under serum-free conditions. HCMV efficiently penetrated CAP cells, expressed its immediate-early proteins and dispersed restrictive PML-bodies. Viral DNA replication was initiated and viral progeny became detectable by electron microscopy in CAP cells. Furthermore, infectious virus was released from CAP cells, yet to lower levels compared to fibroblasts. Subviral dense bodies were also secreted from CAP cells. The results show that E1A/E1B expression in transformed cells is not generally repressive to HCMV replication and that CAP cells may be a good substrate for dense body based vaccine production.

  1. Characterization of Autoantibodies against the E1 Subunit of Branched-Chain 2-Oxoacid Dehydrogenase in Patients with Primary Biliary Cirrhosis

    Directory of Open Access Journals (Sweden)

    Tsutomu Mori

    2012-01-01

    Full Text Available Primary biliary cirrhosis (PBC is characterized by antimitochondrial antibodies (AMAs that react with the lipoyl-containing E2 subunits of 2-oxoacid dehydrogenase complexes such as BCOADC and PDC. The lipoyl domains of E2 contain the major epitopes essential for immunopathology. However, the non-lipoyl-containing E1 subunits are also frequently targeted. Since anti-E1 antibodies always appear in combination with anti-E2 antibodies, the mechanisms underlying the autoimmunity against E1 may be linked to, but distinct from, those against E2. Here, we demonstrate that intermolecular and intramolecular determinant spreading underlies the autoimmunity against E1. We performed characterizations and epitope mapping for anti-BCOADC-E1 antibodies from both the intermolecular and intramolecular points of view. The antibody reactivities form a cluster against the BCOADC complex that is distinct from that against the PDC complex, and the anti-BCOADC-E1 antibodies arise as part of the cluster against the BCOADC complex. Multiple epitopes are present on the surface of the BCOADC-E1 molecule, and the major epitope overlaps with the active center. Sera with anti-BCOADC-E1 antibodies strongly inhibited the enzyme activity. These findings suggest that the E1 subunit as part of the native BCOADC complex is an immunogen, and that determinant spreading is involved in the pathogenesis of AMA production.

  2. In vitro characterization of the NAD+ synthetase NadE1 from Herbaspirillum seropedicae.

    Science.gov (United States)

    Laskoski, Kerly; Santos, Adrian R S; Bonatto, Ana C; Pedrosa, Fábio O; Souza, Emanuel M; Huergo, Luciano F

    2016-05-01

    Nicotinamide adenine dinucleotide synthetase enzyme (NadE) catalyzes the amination of nicotinic acid adenine dinucleotide (NaAD) to form NAD(+). This reaction represents the last step in the majority of the NAD(+) biosynthetic routes described to date. NadE enzymes typically use either glutamine or ammonium as amine nitrogen donor, and the reaction is energetically driven by ATP hydrolysis. Given the key role of NAD(+) in bacterial metabolism, NadE has attracted considerable interest as a potential target for the development of novel antibiotics. The plant-associative nitrogen-fixing bacteria Herbaspirillum seropedicae encodes two putative NadE, namely nadE1 and nadE2. The nadE1 gene is linked to glnB encoding the signal transduction protein GlnB. Here we report the purification and in vitro characterization of H. seropedicae NadE1. Gel filtration chromatography analysis suggests that NadE1 is an octamer. The NadE1 activity was assayed in vitro, and the Michaelis-Menten constants for substrates NaAD, ATP, glutamine and ammonium were determined. Enzyme kinetic and in vitro substrate competition assays indicate that H. seropedicae NadE1 uses glutamine as a preferential nitrogen donor.

  3. Heterodimerization of the transcription factors E2F-1 and DP-1 is required for binding to the adenovirus E4 (ORF6/7) protein

    DEFF Research Database (Denmark)

    Helin, K; Harlow, E

    1994-01-01

    Adenovirus infection leads to E1A-dependent activation of the transcription factor E2F. E2F has recently been identified in complexes with cellular proteins such as the retinoblastoma protein (pRB) and the two pRB family members p107 and p130. E1A dissociates E2F from these cellular proteins......, and another viral protein, E4 (ORF6/7), can bind to E2F. The binding of E4 to E2F induces the formation of a stable DNA-binding complex containing the two proteins, and stimulation of the adenovirus E2 early promoter can occur. Recent studies have shown that E2F is the combined activity of several proteins...

  4. Analysis of the human E2 ubiquitin conjugating enzyme protein interaction network

    Science.gov (United States)

    Markson, Gabriel; Kiel, Christina; Hyde, Russell; Brown, Stephanie; Charalabous, Panagoula; Bremm, Anja; Semple, Jennifer; Woodsmith, Jonathan; Duley, Simon; Salehi-Ashtiani, Kourosh; Vidal, Marc; Komander, David; Serrano, Luis; Lehner, Paul; Sanderson, Christopher M.

    2009-01-01

    In eukaryotic cells the stability and function of many proteins are regulated by the addition of ubiquitin or ubiquitin-like peptides. This process is dependent upon the sequential action of an E1-activating enzyme, an E2-conjugating enzyme, and an E3 ligase. Different combinations of these proteins confer substrate specificity and the form of protein modification. However, combinatorial preferences within ubiquitination networks remain unclear. In this study, yeast two-hybrid (Y2H) screens were combined with true homology modeling methods to generate a high-density map of human E2/E3-RING interactions. These data include 535 experimentally defined novel E2/E3-RING interactions and >1300 E2/E3-RING pairs with more favorable predicted free-energy values than the canonical UBE2L3–CBL complex. The significance of Y2H predictions was assessed by both mutagenesis and functional assays. Significantly, 74/80 (>92%) of Y2H predicted complexes were disrupted by point mutations that inhibit verified E2/E3-RING interactions, and a ∼93% correlation was observed between Y2H data and the functional activity of E2/E3-RING complexes in vitro. Analysis of the high-density human E2/E3-RING network reveals complex combinatorial interactions and a strong potential for functional redundancy, especially within E2 families that have undergone evolutionary expansion. Finally, a one-step extended human E2/E3-RING network, containing 2644 proteins and 5087 edges, was assembled to provide a resource for future functional investigations. PMID:19549727

  5. Effect of the radial plasma nonuniformity on the propagation of guided m = + 1 and m = - 1 modes in helicon discharges

    Science.gov (United States)

    Aliev, Yu. M.; Krämer, M.

    2016-10-01

    Theoretical as well as numerical analyses of the full set of Maxwell's equations is carried out to study non-axisymmetric ( m ≠ 0 ) guided modes in radially nonuniform helicon (HE) discharges. Unlike the axisymmetric (m = 0) modes, these modes reveal a non-reciprocal behavior with respect to the azimuthal direction. We develop the conditions for propagation and non-propagation of the various modes in the helicon parameter range, thereby focussing on the important role of the radial density gradient. Three types of modes occurring in different parameter ranges are described, i.e., the helicon (HE) mode, the electrostatic (ES) or Trivelpiece-Gould mode, and the locally coupled (LC) mode that is characterized by mode coupling (MC) in a certain region of the plasma density profile. In contrast to m = + 1 modes, the parameter range of m = - 1 modes is much more restricted as rather high densities are needed for the propagation of the helicon and LC modes. An important issue of the investigations is the rf power coupling and absorption via the various modes. Computations based on a simple antenna-plasma model show that the axial wavenumber of the antenna determines decisively which type of mode is excited. In case of LC mode excitation, the dominant role of the MC layer for the absorption is demonstrated. Finally, the rf power coupling to helicon modes is studied. The density limit for m = - 1 helicon mode propagation and the narrow magnetic field profiles of these modes are the main reasons why the rf power absorption in helicon discharges occurs via m = + 1 helicon modes.

  6. Electrochemical immunochip sensor for aflatoxin M1 detection.

    Science.gov (United States)

    Parker, Charlie O; Lanyon, Yvonne H; Manning, Mary; Arrigan, Damien W M; Tothill, Ibtisam E

    2009-07-01

    An investigation into the fabrication, electrochemical characterization, and development of a microelectrode array (MEA) immunosensor for aflatoxin M(1) is presented in this paper. Gold MEAs (consisting of 35 microsquare electrodes with 20 microm x 20 microm dimensions and edge-to-edge spacing of 200 microm) together with on-chip reference and counter electrodes were fabricated using standard photolithographic methods. The MEAs were then characterized by cyclic voltammetry, and the behavior of the on-chip electrodes were evaluated. The microarray sensors were assessed for their applicability to the development of an immunosensor for the analysis of aflatoxin M(1) directly in milk samples. Following the sensor surface silanization, antibodies were immobilized by cross-linking with 1,4-phenylene diisothiocyanate (PDITC). Surface characterization was conducted by electrochemistry, fluorescence microscopy, scanning electron microscopy (SEM), and atomic force microscopy (AFM). A competitive enzyme linked immunosorbent assay (ELISA) assay format was developed on the microarray electrode surface using the 3,3,5',5'-tetramethylbenzidine dihyrochloride (TMB)/H(2)O(2) electrochemical detection scheme with horseradish peroxidase (HRP) as the enzyme label. The performance of the assay and the microarray sensor were characterized in pure buffer conditions before applying to the milk samples. With the use of this approach, the detection limit for aflatoxin M(1) in milk was estimated to be 8 ng L(-1), with a dynamic detection range of 10-100 ng L(-1), which meets present legislative limits of 50 ng L(-1). The milk interference with the sensor surface was also found to be minimal. These devices show high potential for development of a range of new applications which have previously only been detected using elaborate instrumentation.

  7. A review of aflatoxin M1 in liquid milk

    OpenAIRE

    2015-01-01

    Mycotoxins continue to pose a health concern via human exposure to contaminated food. Aflatoxin M1 (AFM1), the hydroxylated metabolite of aflatoxin B1 (AFB1), may be found in the milk of dairy cattle and other mammals. In humans, AFM1 is excreted through the feces, urine, and in the case of lactating mothers, also in breast milk after consumption of aflatoxin contaminated food. Concentration of AFM1 in milk is a function of several factors, namely: animal type, milking day, milk yield, season...

  8. PEMBUATAN PROGRAM INTERFACE UNTUK PENGONTROLAN RV-M1

    Directory of Open Access Journals (Sweden)

    Endra Endra

    2007-10-01

    Full Text Available Article explores the making of interface of RV-M1 hand robot control that replaced the cosiprog program,a program that is able to help student in Mecatronica-1 Practice, and able to control the hand robot by localnetwork by two user or more. The used methods were literature study, and field study, that is design method. Theresearch result are control of hand robot on X,Y,Z axis and point to point, the use of local network to control thehand robot, save certain position, and use several user to control the robot.Keywords: interface program, robot, local network

  9. Identification of Aptamer-Binding Sites in Hepatitis C Virus Envelope Glycoprotein E2

    Directory of Open Access Journals (Sweden)

    Fan Chen

    2015-01-01

    Full Text Available Hepatitis C Virus (HCV encodes two envelope glycoproteins, E1 and E2. Our previous work selected a specific aptamer ZE2, which could bind to E2 with high affinity, with a great potential for developing new molecular probes as an early diagnostic reagents or therapeutic drugs targeting HCV. In this study, the binding sites between E2 and aptamer ZE2 were further explored. E2 was truncated to 15 peptides (P1 to P15 and these peptides were used to detect the affinity with ZE2 by ELISA respectively. The peptide with high affinity was then further truncated, detected and compared with six kinds of HCV genotypes. The basic amino acid in 500 aa bound to ZE2 with high affinity, while acidic amino acid in 501 aa reduced the reaction between E2 and ZE2. The results showed the 500 aa and 501 aa of E2 were the key sites that bound to ZE2.

  10. Main: 1E1E [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available 1E1E トウモロコシ Corn Zea mays L. Beta-Glucosidase, Chloroplast Precursor Name=Glu1; Zea...TDDAYASQEVNGPDGKPIGPPMGNPWIYMYPEGLKDLLMIMKNKYGNPPIYITENGIGDVDTKETPLPMEAALNDYKRLDYIQRHIATLKESIDLGSNVQGYFAWSLLDNFEWFAGFTERYGIVYVDRNNNCTRYMKESAKWLKEFNTAKKPSKKILTPA corn_1E1E.jpg ...

  11. Main: 1E1F [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available 1E1F トウモロコシ Corn Zea mays L. Beta-Glucosidase, Chloroplast Precursor Name=Glu1; Zea...QRHIATLKESIDLGSNVQGYFAWSLLDNFEWFAGFTERYGIVYVDRNNNCTRYMKESAKWLKEFNTAKKPSKKILTPA corn_1E1F.jpg ...

  12. E2F-6: a novel member of the E2F family is an inhibitor of E2F-dependent transcription

    DEFF Research Database (Denmark)

    Cartwright, P; Müller, H; Wagener, C;

    1998-01-01

    promoter (TTTCGCGC). In contrast to the other members of the E2F family, ectopic expression of E2F-6 inhibits transcription from promoters possessing E2F recognition sites rather than activating transcription. In addition, overexpression of E2F-6 suppresses the transactivational effects of coexpression......The E2F family of transcription factors are essential for the regulation of genes required for appropriate progression through the cell cycle. Five members of the E2F family have been previously reported, namely E2F1-5. All five are key elements in transcriptional regulation of essential genes......, and they can be divided into two functional groups, those that induce S-phase progression when overexpressed in quiescent cells (E2Fs 1-3), and those that do not (E2Fs 4-5). Here, we describe the identification of a novel member of this family, which we refer to as E2F-6. E2F-6 shares significant homology...

  13. E2F-5, a new E2F family member that interacts with p130 in vivo

    OpenAIRE

    Hijmans, E.M.; Voorhoeve, P.M.; Beijersbergen, R.L.; Veer, L J Van't; Bernards, R.A.

    1995-01-01

    E2F DNA binding sites are found in a number of genes whose expression is tightly regulated during the cell cycle. The activity of E2F transcription factors is regulated by association with specific repressor molecules that can bind and inhibit the E2F transactivation domain. For E2F-1, E2F-2, and E2F-3, the repressor is the product of the retinoblastoma gene, pRb. E2f-4 interacts with pRb-related p107 and not with pRb itself. Recently, a cDNA encoding a third member of the retinoblastoma gene...

  14. The isolation of the ectodomain of the alphavirus E1 protein as a soluble hemagglutinin and its crystallization.

    Science.gov (United States)

    Wengler, G; Wengler, G; Rey, F A

    1999-05-10

    Alphaviruses are isometric enveloped viruses approximately 70 nm in diameter. The viral surface contains 80 glycoprotein spikes arranged in a T = 4 lattice. Each of these spikes consists of three heterodimers of the viral membrane proteins E1 (approximately 49 kDa) and E2 (approximately 51 kDa). Cryoelectron microscopic analyses have shown that the spikes form a protein shell on the viral surface. We have made an attempt to isolate biologically active protein fragments from this surface and to grow crystals from such fragments. To this end membrane proteins were extracted with Nonidet-P40 from the Semliki Forest alphavirus and the proteins were separated from detergent by centrifugation. A protein complex containing the E1 and E2 molecules in quantitative yield was obtained by this procedure. This complex has the following properties: It sediments at approximately 30S, it chromatographs with an apparent molecular mass of approximately 580,000 Da during gel filtration, it cannot be dissociated by either nonionic detergents or 6 M urea, and at acid pH it is a highly active hemagglutinin. The data indicate that this 30S hemagglutinin complex, which has not been hitherto described for alphaviruses, may represent a variant form of the protein lattice present on the alphavirus surface. Cleavage of this complex by subtilisin selectively removes carboxy-terminal sequences from the E1 and E2 proteins, which contain the cytoplasmic and transmembrane segments of the proteins and a small part of their ectodomain. The remaining ectodomains are called E1DeltaS and E2DeltaS. This proteolysis also leads to dissociation of the 30S complex. The cleavage products accumulate in the form of a heterodimer of the E1DeltaS and E2DeltaS proteins. Treatment of the heterodimer with PNGase F leads to rapid removal of carbohydrate from the E2DeltaS protein and a dissociation of the complex into the constituent molecules, which can be separated by chromatography. The finding that the

  15. Presence of moulds and aflatoxin M1 in milk

    Directory of Open Access Journals (Sweden)

    Janković Vesna V.

    2009-01-01

    Full Text Available Aflatoxin M1 (AFM1 appears in milk or dairy products as a direct result of the cattle's ingestion of feed contaminated with aflatoxin B1 (AFB1. This study comprises mycological and mycotoxicological investigations of 23 milk samples (raw, infant food, pasteurized, whey and yoghurt. The mycological testing showed dominant presence of genus Geotrichum. G. candidum was found in 9 samples, with the highest contamination in the raw milk samples. The contamination level of AM1 is defined by using direct competitive enzyme- -linked immunosorbent assay (ELISA. AFM1 was found in 9 samples. AFM1 levels were lower than the recommended limits. However, as AFM1 is considered a probable human carcinogen (2B type, it is necessary to achieve a low level of AFM1 in milk. Therefore, cows' feed samples from various cowsheds are supposed to be evaluated routinely for aflatoxin, and kept away from fungal contamination as much as possible.

  16. Aflatoxin M1 Contamination in Ice-Cream

    Directory of Open Access Journals (Sweden)

    R. Kazemi Darsanaki

    2013-06-01

    Full Text Available Aflatoxin M1 (AFM1 is the hydroxylated metabolite of aflatoxin B1 (AFB1 that it can be found in milk and dairy products. In this study, ELISA (Enzyme Linked Immunosorbent Assay technique was used for detection of AFM1 in ice-cream in Guilan province (Northern Iran. A total of 90 ice-cream samples was randomly obtained from different supermarkets. In 62 of the 90 ice-cream samples examined (68.88%, the presence of AFM1 was detected in concentrations between 8.4 -147.7 ng/l. The mean level of AFM1 in positive samples was 40.36 ng/l. AFM1 levels in 11 samples (12.22% were higher than the maximum tolerance limit (50 ng/l accepted by ISIRI, European Community and Codex Alimentarius.

  17. [The BION-M1 project: overview and first results].

    Science.gov (United States)

    Sychev, V N; Ilyin, E A; Yarmanova, E N; Rakov, D V; Ushakov, I B; Kirilin, A N; Orlov, O I; Grigoriev, A I

    2014-01-01

    Biosatellite BION-M1 was launched on April 19 and landed on May 19, 2013. The mission program was largely a continuation of the earlier flown 11 BION projects, FOTON-M2 and FOTON-M3. The biosatellite was inhabited by a great variety of living organisms used for experiments and studies in gravitational physiology, gravitational biology, biotechnology, astrobiology and radiation biology, dosimetry and spectrometry. This was the first time in the history of national biology and physiology when male mice C57bl/6 were chosen for a long-term space experiment focused upon molecular biology investigations. Unfortunately, because of technical failures during the flight a part of the animals were lost. However, the major objectives were attained through reconsideration of biomaterial division among investigators and completion of virtually the total scope of investigations.

  18. The E1 protein is mandatory for pore formation by Semliki Forest virus spikes.

    Science.gov (United States)

    Dick, M; Barth, B U; Kempf, C

    1996-06-01

    Insect cells (Aedes albopictus, clone C6/36) were infected with various variants of Semliki Forest virus including the wild type using the SFV replicon system. The variants included deletion mutants lacking one of the structural proteins and a mutant with a point mutation in p62 (SQL). The latter mutation results in a failure to process p62 to E2 and E3. After infection of the cells with different variant viruses and subsequent expression of viral proteins in the host cell plasma membrane low pH-induced pore formation was detected by measuring the efflux of a radiolabeled compound. The results of these experiments clearly showed that the E1 protein is mandatory for the acid-induced pore formation. A participation of the 6K or C-protein could be excluded. Furthermore, results obtained with the SQL mutant suggest that dissociation of the E1/E2 heterodimer and subsequent homooligomerization of E1 are required for pore formation.

  19. Observation of an E2 (Ubc9)-homodimer by crystallography.

    Science.gov (United States)

    Alontaga, Aileen Y; Ambaye, Nigus D; Li, Yi-Jia; Vega, Ramir; Chen, Chih-Hong; Bzymek, Krzysztof P; Williams, John C; Hu, Weidong; Chen, Yuan

    2016-06-01

    Post-translational modifications by the small ubiquitin-like modifiers (SUMO), in particular the formation of poly-SUMO-2 and -3 chains, regulates essential cellular functions and its aberration leads to life-threatening diseases (Geoffroy and Hay, 2009) [1]. It was shown previously that the non-covalent interaction between SUMO and the conjugating enzyme (E2) for SUMO, known as Ubc9, is required for poly-SUMO-2/3 chain formation (Knipscheer et al., 2007) [2]. However, the structure of SUMO-Ubc9 non-covalent complex, by itself, could not explain how the poly-SUMO-2/3 chain forms and consequently a Ubc9 homodimer, although never been observed, was proposed for poly-SUMO-2/3 chain formation (Knipscheer et al., 2007) [2]. Here, we solved the crystal structure of a heterotrimer containing a homodimer of Ubc9 and the RWD domain from RWDD3. The asymmetric Ubc9 homodimer is mediated by the N-terminal region of one Ubc9 molecule and a surface near the catalytic Cys of the second Ubc9 molecule (Fig. 1A). This N-terminal surface of Ubc9 that is involved in the homodimer formation also interacts with the RWD domain, the ubiquitin-fold domain of the SUMO activating enzyme (E1), SUMO, and the E3 ligase, RanBP2 (Knipscheer et al., 2007; Tong et al.. 1997; Tatham et al., 2005; Reverter and Lima, 2005; Capili and Lima, 2007; Wang et al., 2009, 2010; Wang and Chen, 2010; Alontaga et al., 2015) [2], [3], [4], [5], [6], [7], [8], [9], [10]. The existence of the Ubc9 homodimer in solution is supported by previously published solution NMR studies of rotational correlation time and chemical shift perturbation (Alontaga et al., 2015; Yuan et al., 1999) [10], [11]. Site-directed mutagenesis and biochemical analysis suggests that this dimeric arrangement of Ubc9 is likely important for poly-SUMO chain formation (Fig. 1B and C). The asymmetric Ubc9 homodimer described for the first time in this work could provide the critical missing link in the poly-SUMO chain formation mechanism. The

  20. Observation of an E2 (Ubc9-homodimer by crystallography

    Directory of Open Access Journals (Sweden)

    Aileen Y. Alontaga

    2016-06-01

    Full Text Available Post-translational modifications by the small ubiquitin-like modifiers (SUMO, in particular the formation of poly-SUMO-2 and -3 chains, regulates essential cellular functions and its aberration leads to life-threatening diseases (Geoffroy and Hay, 2009 [1]. It was shown previously that the non-covalent interaction between SUMO and the conjugating enzyme (E2 for SUMO, known as Ubc9, is required for poly-SUMO-2/3 chain formation (Knipscheer et al., 2007 [2]. However, the structure of SUMO-Ubc9 non-covalent complex, by itself, could not explain how the poly-SUMO-2/3 chain forms and consequently a Ubc9 homodimer, although never been observed, was proposed for poly-SUMO-2/3 chain formation (Knipscheer et al., 2007 [2]. Here, we solved the crystal structure of a heterotrimer containing a homodimer of Ubc9 and the RWD domain from RWDD3. The asymmetric Ubc9 homodimer is mediated by the N-terminal region of one Ubc9 molecule and a surface near the catalytic Cys of the second Ubc9 molecule (Fig. 1A. This N-terminal surface of Ubc9 that is involved in the homodimer formation also interacts with the RWD domain, the ubiquitin-fold domain of the SUMO activating enzyme (E1, SUMO, and the E3 ligase, RanBP2 (Knipscheer et al., 2007; Tong et al.. 1997; Tatham et al., 2005; Reverter and Lima, 2005; Capili and Lima, 2007; Wang et al., 2009, 2010; Wang and Chen, 2010; Alontaga et al., 2015 [2–10]. The existence of the Ubc9 homodimer in solution is supported by previously published solution NMR studies of rotational correlation time and chemical shift perturbation (Alontaga et al., 2015; Yuan et al., 1999 [10,11]. Site-directed mutagenesis and biochemical analysis suggests that this dimeric arrangement of Ubc9 is likely important for poly-SUMO chain formation (Fig. 1B and C. The asymmetric Ubc9 homodimer described for the first time in this work could provide the critical missing link in the poly-SUMO chain formation mechanism. The data presented here are related

  1. A p53-independent apoptotic mechanism of adenoviral mutant E1A was involved in its selective antitumor activity for human cancer

    Science.gov (United States)

    Fang, Lin; Cheng, Qian; Zhao, Jingjing; Ge, Yan; Zhu, Qi; Zhao, Min; Zhang, Jie; Zhang, Qi; Li, Liantao; Liu, Junjie; Zheng, Junnian

    2016-01-01

    The conserved regions (CR) of adenoviral E1A had been shown to be necessary for disruption of pRb-E2F transcription factor complexes and induction of the S phase. Here we constructed a mutant adenoviral E1A with Rb-binding ability absent (E1A 30-60aa and 120-127aa deletion, mE1A) and investigated its antitumor capacities in vitro and in vivo. The mE1A suppressed the viability of tumor cells as efficiently as the wild type E1A, and there was no cytotoxic effect on normal cells. Although the mE1A arrested tumor cell cycle with the same manner as E1A, the former played a different role on cell cycle regulation compared with E1A in normal cells, which might contribute to its selective antitumor activity. E1A and mE1A had accumulated inactive p53, decreased the expression of mdm2, Cdkn1a (also named p21), increased p21's nuclear distribution and induced tumor cell apoptosis in a p53-indenpent manner. Further, E1A or mE1A significantly suppressed tumor growth in subcutaneous hepatocellular carcinoma xenograft models. Especially, tumor-bearing mice treated with mE1A had higher survival rate than those treated with E1A. Our data demonstrated that mutant adenoviral E1A significantly induced tumor cell apoptosis in a p53-indenpednt manner and had selective tumor suppressing ability. The observations of adenoviral E1A mutant had provided a novel mechanism for E1A's complex activities during infection. PMID:27340782

  2. Structure of a Pestivirus Envelope Glycoprotein E2 Clarifies Its Role in Cell Entry

    Directory of Open Access Journals (Sweden)

    Kamel El Omari

    2013-01-01

    Full Text Available Enveloped viruses have developed various adroit mechanisms to invade their host cells. This process requires one or more viral envelope glycoprotein to achieve cell attachment and membrane fusion. Members of the Flaviviridae such as flaviviruses possess only one envelope glycoprotein, E, whereas pestiviruses and hepacivirus encode two glycoproteins, E1 and E2. Although E2 is involved in cell attachment, it has been unclear which protein is responsible for membrane fusion. We report the crystal structures of the homodimeric glycoprotein E2 from the pestivirus bovine viral diarrhea virus 1 (BVDV1 at both neutral and low pH. Unexpectedly, BVDV1 E2 does not have a class II fusion protein fold, and at low pH the N-terminal domain is disordered, similarly to the intermediate postfusion state of E2 from sindbis virus, an alphavirus. Our results suggest that the pestivirus and possibly the hepacivirus fusion machinery are unlike any previously observed.

  3. Structure of the retinoblastoma protein bound to adenovirus E1A reveals the molecular basis for viral oncoprotein inactivation of a tumor suppressor

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xin; Marmorstein, Ronen (UPENN)

    2008-04-02

    The adenovirus (Ad) E1A (Ad-E1A) oncoprotein mediates cell transformation, in part, by displacing E2F transcription factors from the retinoblastoma protein (pRb) tumor suppressor. In this study we determined the crystal structure of the pRb pocket domain in complex with conserved region 1 (CR1) of Ad5-E1A. The structure and accompanying biochemical studies reveal that E1A-CR1 binds at the interface of the A and B cyclin folds of the pRb pocket domain, and that both E1A-CR1 and the E2F transactivation domain use similar conserved nonpolar residues to engage overlapping sites on pRb, implicating a novel molecular mechanism for pRb inactivation by a viral oncoprotein.

  4. Unstable $m=1$ modes of counter-rotating Keplerian discs

    CERN Document Server

    Gulati, Mamta; Sridhar, S

    2012-01-01

    We study the linear $m=1$ counter-rotating instability in a two-component, nearly Keplerian disc. Our goal is to understand these \\emph{slow} modes in discs orbiting massive black holes in galactic nuclei. They are of interest not only because they are of large spatial scale--and can hence dominate observations--but also because they can be growing modes that are readily excited by accretion events. Self-gravity being nonlocal, the eigenvalue problem results in a pair of coupled integral equations, which we derive for a two-component softened gravity disc. We solve this integral eigenvalue problem numerically for various values of mass fraction in the counter-rotating component. The eigenvalues are in general complex, being real only in the absence of the counter-rotating component, or imaginary when both components have identical surface density profiles. Our main results are as follows: (i) the pattern speed appears to be non negative, with the growth (or damping) rate being larger for larger values of the ...

  5. The conformational flexibility of the antibiotic virginiamycin M(1).

    Science.gov (United States)

    Dang, Jason; Metzger, Robert P; Brownlee, Robert T C; Ng, Chai Ann; Bergdahl, Mikael; Separovic, Frances

    2005-07-01

    The antibiotic virginiamycin is a combination of two molecules, virginiamycin M(1) (VM1) and virginiamycin S(1) (VS1) or analogues, which function synergistically by binding to bacterial ribosomes and inhibiting bacterial protein synthesis. Both VM1 and VS1 dissolve poorly in water and are soluble in more hydrophobic solvents. We have recently reported that the 3D conformation of VM1 in CDCl(3) solution differs markedly from the conformation bound to a VM1 binding enzyme and to 50S ribosomes as found by X-ray crystallographic studies. We now report the results of further NMR studies and subsequent molecular modeling of VM1 dissolved in CD(3)CN/H(2)O and compare the structure with that in CD(3)OD and CDCl(3). The conformations of VM1 in CD(3)CN/H(2)O, CD(3)OD and CDCl(3) differ substantially from one another and from the bound form, with the aqueous form most like the bound structure. We propose that the flexibility of the VM1 molecule in response to environmental conditions contributes to its effectiveness as an antibiotic.

  6. The m=1 amplituhedron and cyclic hyperplane arrangements

    CERN Document Server

    Karp, Steven N

    2016-01-01

    The (tree) amplituhedron A(n,k,m) is the image in the Grassmannian Gr(k,k+m) of the totally nonnegative part of Gr(k,n), under a (map induced by a) linear map which is totally positive. It was introduced by Arkani-Hamed and Trnka in 2013 in order to give a geometric basis for the computation of scattering amplitudes in N=4 supersymmetric Yang-Mills theory. When k+m=n, the amplituhedron is isomorphic to the totally nonnegative Grassmannian, and when k=1, the amplituhedron is a cyclic polytope. While the case m=4 is most relevant to physics, the amplituhedron is an interesting mathematical object for any m. In this paper we study it in the case m=1. We start by taking an orthogonal point of view and define a related "B-amplituhedron" B(n,k,m), which we show is isomorphic to A(n,k,m). We use this reformulation to describe the amplituhedron in terms of sign variation. We then give a cell decomposition of the amplituhedron A(n,k,1) using the images of a collection of distinguished cells of the totally nonnegative ...

  7. Abundances of Planetary Nebula M1-42

    CERN Document Server

    Pottasch, S R; Roellig, T L

    2007-01-01

    The spectra of the planetary nebula M1-42 is reanalysed using spectral measurements made in the mid-infrared with the Spitzer Space Telescope. The aim is to determine the chemical composition of this object. We also make use of ISO, IUE and ground based spectra. Abundances determined from the mid- and far-infrared lines, which are insensitive to electron temperature, are used as the basis for the determination of the composition, which are found to substantially differ from earlier results. High values of neon, argon and sulfur are found. They are higher than in other PN, with the exception of NGC6153, a nebula of very similar abundances. The high values of helium and nitrogen found indicate that the second dredge-up and hot bottom burning has occurred in the course of evolution and that the central star was originally more massive than 4Msun. The present temperature and luminosity of the central star is determined and at first sight may be inconsistent with such a high mass.

  8. Thermoelectric waste heat recovery from an M1 Abrams tank

    Science.gov (United States)

    Stokes, C. David; Thomas, Peter M.; Baldasaro, Nicholas G.; Mantini, Michael J.; Venkatasubramanian, Rama; Barton, Michael D.; Cardine, Christopher V.; Walker, Grayson W.

    2012-06-01

    The addition of advanced sensors, targeting systems and electronic countermeasures to military vehicles has created a strategic need for additional electric power. By incorporating a thermoelectric (TE) waste heat recovery system to convert available exhaust heat to electricity, increased electric power needs can be met without reducing the energy efficiency of the vehicle. This approach allows existing vehicles to be upgraded without requiring a complete re-design of the engine and powertrain to support the integration of advanced electronic sensors and systems that keep the performance at the state of the art level. RTI has partnered with General Dynamics Land Systems and Creare, Inc. under an Army Research Lab program to develop a thermoelectric exhaust waste heat recovery system for the M1 Abrams tank. We have designed a reduced-scale system that was retrofitted to the tank and generated 80W of electric power on the vehicle operating on a test track by capturing a portion of the exhaust heat from the Honeywell/Lycoming AGT-1500 gas turbine engine.

  9. The E2F family: specific functions and overlapping interests

    DEFF Research Database (Denmark)

    Attwooll, Claire; Lazzerini Denchi, Eros; Helin, Kristian

    2004-01-01

    The E2F transcription factors are key regulators of cell cycle progression and the E2F field has made rapid advances since its advent in 1986. Yet, while our understanding of the roles and functions of the E2F family has made enormous progress, with each discovery new questions arise. In this rev...

  10. Epistatic roles of E2 glycoprotein mutations in adaption of chikungunya virus to Aedes albopictus and Ae. aegypti mosquitoes.

    Directory of Open Access Journals (Sweden)

    Konstantin A Tsetsarkin

    Full Text Available Between 2005 and 2007 Chikungunya virus (CHIKV caused its largest outbreak/epidemic in documented history. An unusual feature of this epidemic is the involvement of Ae. albopictus as a principal vector. Previously we have demonstrated that a single mutation E1-A226V significantly changed the ability of the virus to infect and be transmitted by this vector when expressed in the background of well characterized CHIKV strains LR2006 OPY1 and 37997. However, in the current study we demonstrate that introduction of the E1-A226V mutation into the background of an infectious clone derived from the Ag41855 strain (isolated in Uganda in 1982 does not significantly increase infectivity for Ae. albopictus. In order to elucidate the genetic determinants that affect CHIKV sensitivity to the E1-A226V mutation in Ae. albopictus, the genomes of the LR2006 OPY1 and Ag41855 strains were used for construction of chimeric viruses and viruses with a specific combination of point mutations at selected positions. Based upon the midgut infection rates of the derived viruses in Ae. albopictus and Ae. aegypti mosquitoes, a critical role of the mutations at positions E2-60 and E2-211 on vector infection was revealed. The E2-G60D mutation was an important determinant of CHIKV infectivity for both Ae. albopictus and Ae. aegypti, but only moderately modulated the effect of the E1-A226V mutation in Ae. albopictus. However, the effect of the E2-I211T mutation with respect to mosquito infections was much more specific, strongly modifying the effect of the E1-A226V mutation in Ae. albopictus. In contrast, CHIKV infectivity for Ae. aegypti was not influenced by the E2-1211T mutation. The occurrence of the E2-60G and E2-211I residues among CHIKV isolates was analyzed, revealing a high prevalence of E2-211I among strains belonging to the Eastern/Central/South African (ECSA clade. This suggests that the E2-211I might be important for adaptation of CHIKV to some particular conditions

  11. Epistatic roles of E2 glycoprotein mutations in adaption of chikungunya virus to Aedes albopictus and Ae. aegypti mosquitoes.

    Science.gov (United States)

    Tsetsarkin, Konstantin A; McGee, Charles E; Volk, Sara M; Vanlandingham, Dana L; Weaver, Scott C; Higgs, Stephen

    2009-08-31

    Between 2005 and 2007 Chikungunya virus (CHIKV) caused its largest outbreak/epidemic in documented history. An unusual feature of this epidemic is the involvement of Ae. albopictus as a principal vector. Previously we have demonstrated that a single mutation E1-A226V significantly changed the ability of the virus to infect and be transmitted by this vector when expressed in the background of well characterized CHIKV strains LR2006 OPY1 and 37997. However, in the current study we demonstrate that introduction of the E1-A226V mutation into the background of an infectious clone derived from the Ag41855 strain (isolated in Uganda in 1982) does not significantly increase infectivity for Ae. albopictus. In order to elucidate the genetic determinants that affect CHIKV sensitivity to the E1-A226V mutation in Ae. albopictus, the genomes of the LR2006 OPY1 and Ag41855 strains were used for construction of chimeric viruses and viruses with a specific combination of point mutations at selected positions. Based upon the midgut infection rates of the derived viruses in Ae. albopictus and Ae. aegypti mosquitoes, a critical role of the mutations at positions E2-60 and E2-211 on vector infection was revealed. The E2-G60D mutation was an important determinant of CHIKV infectivity for both Ae. albopictus and Ae. aegypti, but only moderately modulated the effect of the E1-A226V mutation in Ae. albopictus. However, the effect of the E2-I211T mutation with respect to mosquito infections was much more specific, strongly modifying the effect of the E1-A226V mutation in Ae. albopictus. In contrast, CHIKV infectivity for Ae. aegypti was not influenced by the E2-1211T mutation. The occurrence of the E2-60G and E2-211I residues among CHIKV isolates was analyzed, revealing a high prevalence of E2-211I among strains belonging to the Eastern/Central/South African (ECSA) clade. This suggests that the E2-211I might be important for adaptation of CHIKV to some particular conditions prevalent in

  12. CYP2E1 Metabolism of Styrene Involves Allostery

    OpenAIRE

    2012-01-01

    We are the first to report allosterism during styrene oxidation by recombinant CYP2E1 and human liver microsomes. At low styrene concentrations, oxidation is inefficient because of weak binding to CYP2E1 (Ks = 830 μM). A second styrene molecule then binds CYP2E1 with higher affinity (Kss = 110 μM) and significantly improves oxidation to achieve a kcat of 6.3 nmol · min−1 · nmol CYP2E1−1. The transition between these metabolic cycles coincides with reported styrene concentrations in blood from...

  13. DcE2F, a functional plant E2F-like transcriptional activator from Daucus carota

    DEFF Research Database (Denmark)

    Albani, D; Mariconti, L; Ricagno, S;

    2000-01-01

    In animal cells the progression of the cell cycle through G(1)/S transition and S phase is under the control of the pRB/E2F regulatory pathway. The E2F transcription factors are key activators of genes coding for several regulatory proteins and for enzymes involved in nucleotide and DNA synthesis....... In this report we have detected the presence of E2F-like DNA binding activities in carrot nuclear extracts, and we have isolated a carrot cDNA (DcE2F) encoding a plant E2F homologue. The DcE2F gene is expressed in proliferating cells and is induced during the G(1)/S transition of the cell cycle. Supershift...... assays have revealed that DcE2F is a functional transcription factor that can transactivate, together with a DP partner, an E2F-responsive reporter gene in both plant and mammalian cells....

  14. CYP2E1 autoantibodies in liver diseases

    Science.gov (United States)

    Sutti, Salvatore; Rigamonti, Cristina; Vidali, Matteo; Albano, Emanuele

    2014-01-01

    Autoimmune reactions involving cytochrome P4502E1 (CYP2E1) are a feature of idiosyncratic liver injury induced by halogenated hydrocarbons and isoniazid, but are also detectable in about one third of the patients with advanced alcoholic liver disease (ALD) and chronic hepatitis C (CHC). In these latter the presence of anti-CYP2E1 auto-antibodies is an independent predictor of extensive necro-inflammation and fibrosis and worsens the recurrence of hepatitis following liver transplantation, indicating that CYP2E1-directed autoimmunity can contribute to hepatic injury. The molecular characterization of the antigens recognized by anti-CYP2E1 auto-antibodies in ALD and CHC has shown that the targeted conformational epitopes are located in close proximity on the molecular surface. Furthermore, these epitopes can be recognized on CYP2E1 expressed on hepatocyte plasma membranes where they can trigger antibody-mediated cytotoxicity. This does not exclude that T cell-mediated responses against CYP2E1 might also be involved in causing hepatocyte damage. CYP2E1 structural modifications by reactive metabolites and molecular mimicry represent important factors in the breaking of self-tolerance against CYP2E1 in, respectively, ALD and CHC. However, genetic or acquired interferences with the mechanisms controlling the homeostasis of the immune system are also likely to contribute. More studies are needed to better characterize the impact of anti-CYP2E1 autoimmunity in liver diseases particularly in relation to the fact that common metabolic alterations such as obesity and diabetes stimulates hepatic CYP2E1 expression. PMID:25462068

  15. Analysis list: E2f4 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available E2f4 Blood,Embryonic fibroblast,Liver,Muscle,Pluripotent stem cell + mm9 http://dba...rchive.biosciencedbc.jp/kyushu-u/mm9/target/E2f4.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/E2f4....5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/E2f4.10.tsv http://dbarchive.biosciencedbc....jp/kyushu-u/mm9/colo/E2f4.Blood.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/E2f4....Embryonic_fibroblast.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/E2f4.Liver.tsv,htt

  16. An E2-Substituted Chimeric Pestivirus With DIVA Vaccine Properties

    DEFF Research Database (Denmark)

    Rasmussen, Thomas Bruun; Uttenthal, Åse; Nielsen, Jens

    An advantage of the use of chimeric pestiviruses as modified live vaccines against classical swine fever (CSF) resides in their capacity to be manipulated to achieve the characteristics desired for safe and efficacious DIVA vaccines. We have recently generated a new chimeric virus, Riems26_E2gif...... engineered specifically for this purpose. The E2-substituted Riems26_E2gif was derived by homologues recombination of the complete E2 protein encoding genome region from Border disease strain Gifhorn into a bacterial artificial chromosome (BAC) harbouring the genome of the CSFV vaccine strain C......-Riems. The virulence, immunogenicity and vaccine properties of Riems26_E2gif were tested in a vaccine-challenge experiment in pigs. Riems26_E2gif vaccinated pigs could be differentiated from infected pigs using a CSFV-E2 specific ELISA. Following challenge infection with highly virulent CSFV strain Koslov, all...

  17. New insights into FoxE1 functions: identification of direct FoxE1 targets in thyroid cells.

    Directory of Open Access Journals (Sweden)

    Lara P Fernández

    Full Text Available BACKGROUND: FoxE1 is a thyroid-specific forkhead transcription factor essential for thyroid gland development, as well as for the maintenance of the thyroid differentiated state in adults. FoxE1 recognizes and binds to a short DNA sequence present in thyroglobulin (Tg and thyroperoxidase (Tpo promoters, but FoxE1 binding to regulatory regions other than Tg and Tpo promoters remains almost unexplored. Improving knowledge of the regulatory functions of FoxE1 is necessary to clarify its role in endocrine syndromes and cancer susceptibility. METHODOLOGY/PRINCIPAL FINDING: In order to further investigate downstream FoxE1 targets, we performed a genome-wide expression screening after knocking-down FoxE1 and obtained new insights into FoxE1 transcriptional networks in thyroid follicular cells. After validation, we confirmed Adamts9, Cdh1, Duox2 and S100a4 as upregulated genes and Casp4, Creld2, Dusp5, Etv5, Hsp5a, Nr4a2 and Tm4sf1 as downregulated genes when FoxE1 was silenced. In promoter regions of putative FoxE1-regulated genes and also in the promoters of the classical thyroid genes Nis, Pax8 and Titf1, we performed an in silico search of the FoxE1 binding motif that was in close proximity to the NF1/CTF binding sequence, as previously described for other forkhead factors. Using chromatin immunoprecipitation we detected specific in vivo FoxE1 binding to novel regulatory regions in two relevant thyroid genes, Nis and Duox2. Moreover, we demonstrated simultaneous binding of FoxE1 and NF1/CTF to the Nis upstream enhancer region, as well as a clear functional activation of the Nis promoter by both transcription factors. CONCLUSIONS/SIGNIFICANCE: In search for potential downstream mediators of FoxE1 function in thyroid cells, we identified two novel direct FoxE1 target genes. To our knowledge, this is the first evidence regarding the implication of Nis and Duox2 in executing the transcriptional program triggered by FoxE1. Furthermore, this study points

  18. Large low-energy M1 strength for ^{56,57}Fe within the nuclear shell model.

    Science.gov (United States)

    Brown, B Alex; Larsen, A C

    2014-12-19

    A strong enhancement at low γ-ray energies has recently been discovered in the γ-ray strength function of ^{56,57}Fe. In this work, we have for the first time obtained theoretical γ decay spectra for states up to ≈8  MeV in excitation for ^{56,57}Fe. We find large B(M1) values for low γ-ray energies that provide an explanation for the experimental observations. The role of mixed E2 transitions for the low-energy enhancement is addressed theoretically for the first time, and it is found that they contribute a rather small fraction. Our calculations clearly show that the high-ℓ(=f) diagonal terms are most important for the strong low-energy M1 transitions. As such types of 0ℏω transitions are expected for all nuclei, our results indicate that a low-energy M1 enhancement should be present throughout the nuclear chart. This could have far-reaching consequences for our understanding of the M1 strength function at high excitation energies, with profound implications for astrophysical reaction rates.

  19. 26 CFR 1.927(e)-1 - Special sourcing rule.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 10 2010-04-01 2010-04-01 false Special sourcing rule. 1.927(e)-1 Section 1.927... (CONTINUED) INCOME TAXES Earned Income of Citizens of United States § 1.927(e)-1 Special sourcing rule. (a... under section 925 with respect to such transaction applied to such transaction. This special sourcing...

  20. 26 CFR 1.514(e)-1 - Allocation rules.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 7 2010-04-01 2010-04-01 true Allocation rules. 1.514(e)-1 Section 1.514(e)-1... Allocation rules. Where only a portion of property is debt-financed property, proper allocation of the basis...)(iii) of § 1.514(b)-1 for illustrations of proper allocation....

  1. 26 CFR 1.642(e)-1 - Depreciation and depletion.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Depreciation and depletion. 1.642(e)-1 Section 1... (CONTINUED) INCOME TAXES Estates, Trusts, and Beneficiaries § 1.642(e)-1 Depreciation and depletion. An estate or trust is allowed the deductions for depreciation and depletion, but only to the extent...

  2. Garlic extract diallyl sulfide (DAS activates nuclear receptor CAR to induce the Sult1e1 gene in mouse liver.

    Directory of Open Access Journals (Sweden)

    Tatsuya Sueyoshi

    Full Text Available Constituent chemicals in garlic extract are known to induce phase I and phase II enzymes in rodent livers. Here we have utilized Car(+/+ and Car(-/- mice to demonstrate that the nuclear xenobiotic receptor CAR regulated the induction of the estrogen sulfotransferase Sult1e1 gene by diallyl sulfide (DAS treatment in mouse liver. DAS treatment caused CAR accumulation in the nucleus, resulting in a remarkable increase of SULT1E1 mRNA (3,200 fold and protein in the livers of Car(+/+ females but not of Car(-/- female mice. DAS also induced other CAR-regulated genes such as Cyp2b10, Cyp3a11 and Gadd45β. Compared with the rapid increase of these mRNA levels, which began as early as 6 hours after DAS treatment, the levels of SULT1E1 mRNA began increasing after 24 hours. This slow response to DAS suggested that CAR required an additional factor to activate the Sult1e1 gene or that this activation was indirect. Despite the remarkable induction of SULT1E1, there was no decrease in the serum levels of endogenous E2 or increase of estrone sulfate while the clearance of exogenously administrated E2 was accelerated in DAS treated mice.

  3. CYP2E1 Metabolism of Styrene Involves Allostery

    Science.gov (United States)

    Hartman, Jessica H.; Boysen, Gunnar

    2012-01-01

    We are the first to report allosterism during styrene oxidation by recombinant CYP2E1 and human liver microsomes. At low styrene concentrations, oxidation is inefficient because of weak binding to CYP2E1 (Ks = 830 μM). A second styrene molecule then binds CYP2E1 with higher affinity (Kss = 110 μM) and significantly improves oxidation to achieve a kcat of 6.3 nmol · min−1 · nmol CYP2E1−1. The transition between these metabolic cycles coincides with reported styrene concentrations in blood from exposed workers; thus, this CYP2E1 mechanism may be relevant in vivo. Scaled modeling of the in vitro-positive allosteric mechanism for styrene metabolism to its in vivo clearance led to significant deviations from the traditional model based on Michaelis-Menten kinetics. Low styrene levels were notably much less toxic than generally assumed. We interrogated the allosteric mechanism using the CYP2E1-specific inhibitor and drug 4-methylpyrazole, which we have shown binds two CYP2E1 sites. From the current studies, styrene was a positive allosteric effector on 4-methylpyrazole binding, based on a 10-fold increase in 4-methylpyrazole binding affinity from Ki 0.51 to Ksi 0.043 μM. The inhibitor was a negative allosteric effector on styrene oxidation, because kcat decreased 6-fold to 0.98 nmol · min−1 · nmol CYP2E1−1. Consequently, mixtures of styrene and other molecules can induce allosteric effects on binding and metabolism by CYP2E1 and thus mitigate the efficiency of their metabolism and corresponding effects on human health. Taken together, our elucidation of mechanisms for these allosteric reactions provides a powerful tool for further investigating the complexities of CYP2E1 metabolism of drugs and pollutants. PMID:22807108

  4. Crystal structure of ethyl 2-[2-((1E-{(1E-2-[2-(2-ethoxy-2-oxoethoxybenzylidene]hydrazin-1-ylidene}methylphenoxy]acetate

    Directory of Open Access Journals (Sweden)

    Joel T. Mague

    2015-01-01

    Full Text Available The complete molecule of the title compound, C22H24N2O6, is generated by crystallographic inversion symmetry and is approximately planar (r.m.s. deviation of the non-H atoms = 0.134 Å. The packing consists of inter-digitated sheets inclined at 25.9 (4° to one another and linked by short C—H...O hydrogen bonds.

  5. Pyrolysis of Aryl Sulfonate Esters in the Absence of Solvent: E1 or E2? A Puzzle for the Organic Laboratory

    Science.gov (United States)

    Nash, John J.; Leininger, Marnie A.; Keyes, Kurt

    2008-01-01

    The aryl sulfonate ester, menthyl N-acetylsulfanilate, is synthesized from N-acetylsulfanilyl chloride and menthol in pyridine, then pyrolyzed (thermally decomposed) at reduced pressure. The volatile (elimination) products of the reaction are analyzed using gas chromatography, and the resulting product distribution is used to determine whether the…

  6. Pyrolysis of Aryl Sulfonate Esters in the Absence of Solvent: E1 or E2? A Puzzle for the Organic Laboratory

    Science.gov (United States)

    Nash, John J.; Leininger, Marnie A.; Keyes, Kurt

    2008-01-01

    The aryl sulfonate ester, menthyl N-acetylsulfanilate, is synthesized from N-acetylsulfanilyl chloride and menthol in pyridine, then pyrolyzed (thermally decomposed) at reduced pressure. The volatile (elimination) products of the reaction are analyzed using gas chromatography, and the resulting product distribution is used to determine whether the…

  7. Oxido[2-{(E-[((1E-{(E-2-[1-(2-oxidophenylethylidene]hydrazin-1-ylidene}(prop-2-en-1-ylsulfanylmethylimino]methyl}phenolato]vanadium(IV

    Directory of Open Access Journals (Sweden)

    Reza Takjoo

    2012-08-01

    Full Text Available The VIV atom in the title complex, [V(C19H17N3O2SO], is coordinated by two N and two O atoms of the dianionic tetradentate Schiff base ligand and the terminal oxide O atom. The N2O3 donor set defines a square-pyramidal coordination geometry with the oxide O atom in the apical site. Some buckling in the tetradentate ligand is indicated by the dihedral angle of 17.92 (19° between the six-membered chelate rings. Supramolecular chains are formed along the b axis via C—H...O contacts in the crystal. The chains are connected into a layer in the ab plane via C—H...π interactions. The atoms comprising the –SCH2—CH=CH2 and methyl substituents were found to be disordered in a 0.916 (2:0.088 (2 ratio. The crystal studied was found to be twinned by nonmerohedry with a 28.1 (4% minor twin component.

  8. INSCRIPTION OF UYUK-ARJAN (E 2 E 2 - UYUK-ARJAN (Tuva YAZITI

    Directory of Open Access Journals (Sweden)

    Osman Fikri SERTKAYA

    2011-01-01

    Full Text Available Texts of the tombstone texts, known as Yenisei (Enisei inscriptions, which were found near the Yenisei river banks, are important in terms of Turkic philology and dialectology. The inscription Uyuk-Arjan (E-2, which was found in 1888 by J. R. Aspelin near the Uyuk riverbed, was published by Radloff, Orkun, Malov, Batmanov, Amonjolov and Kormushin previously. This paper is an attempt for the re-reading and re-interpretation of this tombstone text. To this paper resourches in the field are given a resource. Yenisey nehri kıyıları boyunca bulunan Yenisey yazıtlarının metinleri, genel olarak Eski Türk filolojisi, özel olarak da Eski Türk diyalektolojisi bakımından önemlidir. Bu yazıya konu olan mezar yazıtı Uyuk-Arjan (E 2, J. R. Aspelin tarafından 1888’de Uyuk nehri yatağı yakınlarında bulunmuş ve daha önce Radloff, Orkun, Malov, Batmanov, Amonjolov ve Kormuşin tarafından yayımlanmıştır. Bu makale, yazıt metninin yeniden okuma ve anlamlandırma denemesidir. Daha önceki okuma ve anlamlandırmalar da değerlendirilerek, alan araştırmacılarının dikkatlerine sunulmuştur.

  9. Modulation of Effects of Intermittent Theta Burst Stimulation Applied Over Primary Motor Cortex (M1) by Conditioning Stimulation of the Opposite M1

    Science.gov (United States)

    Ragert, Patrick; Camus, Mickael; Vandermeeren, Yves; Dimyan, Michael A.; Cohen, Leonardo G.

    2009-01-01

    The excitability of the human primary motor cortex (M1) as tested with transcranial magnetic stimulation (TMS) depends on its previous history of neural activity. Homeostatic plasticity might be one important physiological mechanism for the regulation of corticospinal excitability and synaptic plasticity. Although homeostatic plasticity has been demonstrated locally within M1, it is not known whether priming M1 could result in similar homeostatic effects in the homologous M1 of the opposite hemisphere. Here, we sought to determine whether down-regulating excitability (priming) in the right (R) M1 with 1-Hz repetitive transcranial magnetic stimulation (rTMS) changes the excitability-enhancing effect of intermittent theta burst stimulation (iTBS) applied over the homologous left (L) M1. Subjects were randomly allocated to one of four experimental groups in a sham-controlled parallel design with real or sham R M1 1-Hz TMS stimulation always preceding L M1 iTBS or sham by about 10 min. The primary outcome measure was corticospinal excitability in the L M1, as measured by recruitment curves (RCs). Secondary outcome measures included pinch force, simple reaction time, and tapping speed assessed in the right hand. The main finding of this study was that preconditioning R M1 with 1-Hz rTMS significantly decreased the excitability-enhancing effects of subsequent L M1 iTBS on RCs. Application of 1-Hz rTMS over R M1 alone and iTBS over L M1 alone resulted in increased RC in L M1 relative to sham interventions. The present findings are consistent with the hypothesis that homeostatic mechanisms operating across hemispheric boundaries contribute to regulate motor cortical function in the primary motor cortex. PMID:19474173

  10. Analysis list: E2f1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available E2f1 Blood,Liver + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/E2f1.1....tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/E2f1.5.tsv http://dbarchive.biosciencedbc.jp/kyus...hu-u/mm9/target/E2f1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/E2f1.Blood.tsv,http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/colo/E2f1.Liver.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/colo/Blood.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Liver.gml ...

  11. Analysis list: Gtf2e2 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Gtf2e2 Blood,Liver + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Gtf2e2.1.tsv http:...//dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Gtf2e2.5.tsv http://dbarchive.biosciencedbc.j...p/kyushu-u/mm9/target/Gtf2e2.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Gtf2e2.Blood.tsv,http:...//dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Gtf2e2.Liver.tsv http://dbarchiv...e.biosciencedbc.jp/kyushu-u/mm9/colo/Blood.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Liver.gml ...

  12. CYP2E1 impairs GLUT4 gene expression and function: NRF2 as a possible mediator.

    Science.gov (United States)

    Armoni, M; Harel, C; Ramdas, M; Karnieli, E

    2014-06-01

    Impaired GLUT4 function/expression in insulin target tissues is well-documented in diabetes and obesity. Cytochrome P450 isoform 2E1 (CYP2E1) induces oxidative stress, leading to impaired insulin action. CYP2E1 knockout mice are protected against high fat diet-induced insulin resistance and obesity; however the molecular mechanisms are still unclear. We examined whether CYP2E1 impairs GLUT4 gene expression and function in adipose and muscle cells. CYP2E1 overexpression in skeletal muscle-derived L6 cells inhibited insulin-stimulated Glut4 translocation and 2-deoxyglucose uptake, with the latter inhibition being blocked by vitamin E. CYP2E1 overexpression in L6 and primary rat adipose (PRA) cells suppressed GLUT4 gene expression at promoter and mRNA levels, whereas CYP2E1 silencing had opposite effects. In PRA, CYP2E1-induced suppression of GLUT4 expression was blocked by chlormethiazole (CYP2E1-specific inhibitor) and the antioxidants vitamin E and N-acetyl-l-cysteine. CYP2E1 effect was mediated by the transcription factor NF-E2-related factor 2 (NRF2), as evident from its complete reversal by a coexpressed dominant-negative, but not wild-type NRF2. GLUT4 transcription was suppressed by NRF2 overexpression, and enhanced by NRF2 silencing. Promoter and ChIP analysis showed a direct and specific binding of NRF2 to a 58-326 GLUT4 promoter region that was required to maintain CYP2E1 suppression; this binding was enhanced by CYP2E1 overexpression. We suggest a mechanism for CYP2E1 action that involves: a) suppression of GLUT4 gene expression that is mediated by NRF2; b) impairment of insulin-stimulated Glut4 translocation and function. CYP2E1 and NRF2 are introduced as negative regulators of GLUT4 expression and function in insulin-sensitive cells.

  13. E2F-1 as an anticancer drug target

    Directory of Open Access Journals (Sweden)

    Joseph R. Bertino

    2011-12-01

    Full Text Available Mounting evidence indicates that the E2F transcription factors play an essential role in all aspects of cellular functions. Many human malignancies have been shown to overexpress one or more of the ‘‘activating’’ E2Fs. In some circumstances, down regulation as well as overexpression of E2F-1, leads to inhibition of cell growth. The emphasis in this review is placed on new data implicating microRNAs in the regulation of E2F activity and the efforts thus far to target this activity in order to cause tumor regression.

  14. The TNM 8 M1b and M1c classification for non-small cell lung cancer in a cohort of patients with brain metastases.

    Science.gov (United States)

    Nieder, C; Hintz, M; Oehlke, O; Bilger, A; Grosu, A L

    2017-09-01

    According to the recent TNM 8 classification, patients with metastatic non-small cell lung cancer (NSCLC) and single extrathoracic metastasis should be classified as stage M1b, while those with 2 or more metastases comprise stage M1c. The purpose of this study was to analyze the impact of this classification in patients with brain metastases. This retrospective study included 172 patients treated with individualized approaches. Actuarial survival was calculated. Uni- and multivariate analyses were performed. Thirty patients (17%) were staged as M1b. Those with squamous cell cancer were more likely to harbor M1b disease (29%, adenocarcinoma 14%, other histology 17%, p = 0.16). Median survival was 5.4 months (8.0 months in case of M1b disease and 4.5 months in case of M1c disease, p = 0.001). Multivariate analysis confirmed the role of M1b stage. M1b patients managed with upfront surgery or radiosurgery had significantly longer median survival than those who received whole-brain irradiation (21.0 vs. 3.5 months, p = 0.0001) and the potential to survive beyond 5 years. We found the M1b classification to provide clinically relevant information. The multivariate analysis suggested that patients with M1b disease, better performance status and younger age have better survival.

  15. A distance regular graph of type E1 Ed

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    In this note, the distance regular graph of type E1 Ed is considered and some characterization of the type graph is given. The results generalize the characterization of tight distance regular graphs.

  16. Experimental Conditions: SE37_S18_M1_D1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available opes SE37_S18 PSEUDO: Unlabeled and labeled Medicago samples for metabolite annotation using ShiftedIonsFind...17_M1), and for Medicago samples labeled by 13C (S05_M1), 15N (S07_M1), 28O (S10_M1), and 34S (S13_M1) are used. SE37_DS4 Labeled peak search by ShiftedIonsFinder ...

  17. Recombinant modified vaccinia virus Ankara expressing glycoprotein E2 of Chikungunya virus protects AG129 mice against lethal challenge.

    Directory of Open Access Journals (Sweden)

    Petra van den Doel

    2014-09-01

    Full Text Available Chikungunya virus (CHIKV infection is characterized by rash, acute high fever, chills, headache, nausea, photophobia, vomiting, and severe polyarthralgia. There is evidence that arthralgia can persist for years and result in long-term discomfort. Neurologic disease with fatal outcome has been documented, although at low incidences. The CHIKV RNA genome encodes five structural proteins (C, E1, E2, E3 and 6K. The E1 spike protein drives the fusion process within the cytoplasm, while the E2 protein is believed to interact with cellular receptors and therefore most probably constitutes the target of neutralizing antibodies. We have constructed recombinant Modified Vaccinia Ankara (MVA expressing E3E2, 6KE1, or the entire CHIKV envelope polyprotein cassette E3E26KE1. MVA is an appropriate platform because of its demonstrated clinical safety and its suitability for expression of various heterologous proteins. After completing the immunization scheme, animals were challenged with CHIV-S27. Immunization of AG129 mice with MVAs expressing E2 or E3E26KE1 elicited neutralizing antibodies in all animals and provided 100% protection against lethal disease. In contrast, 75% of the animals immunized with 6KE1 were protected against lethal infection. In conclusion, MVA expressing the glycoprotein E2 of CHIKV represents as an immunogenic and effective candidate vaccine against CHIKV infections.

  18. Mechanism and disease association of E2-conjugating enzymes: lessons from UBE2T and UBE2L3.

    Science.gov (United States)

    Alpi, Arno F; Chaugule, Viduth; Walden, Helen

    2016-10-15

    Ubiquitin signalling is a fundamental eukaryotic regulatory system, controlling diverse cellular functions. A cascade of E1, E2, and E3 enzymes is required for assembly of distinct signals, whereas an array of deubiquitinases and ubiquitin-binding modules edit, remove, and translate the signals. In the centre of this cascade sits the E2-conjugating enzyme, relaying activated ubiquitin from the E1 activating enzyme to the substrate, usually via an E3 ubiquitin ligase. Many disease states are associated with dysfunction of ubiquitin signalling, with the E3s being a particular focus. However, recent evidence demonstrates that mutations or impairment of the E2s can lead to severe disease states, including chromosome instability syndromes, cancer predisposition, and immunological disorders. Given their relevance to diseases, E2s may represent an important class of therapeutic targets. In the present study, we review the current understanding of the mechanism of this important family of enzymes, and the role of selected E2s in disease.

  19. Recombinant E2 glycoprotein of bovine viral diarrhea virus induces a solid humoral neutralizing immune response but fails to confer total protection in cattle

    Directory of Open Access Journals (Sweden)

    S. Chimeno Zoth

    2007-06-01

    Full Text Available Two recombinant baculoviruses were produced in order to obtain a bovine viral diarrhea virus (BVDV immunogen: AcNPV/E2 expressing E2 glycoprotein, and AcNPV/E0E1E2 expressing the polyprotein region coding for the three structural proteins of BVDV (E0, E1, and E2. Mice were immunized with Sf9 cells infected with the recombinant baculoviruses in a water in oil formulation and the production of neutralizing antibodies was evaluated. Since E2 elicited higher neutralizing antibody titers than E0-E1-E2 polyprotein, it was selected to immunize cattle. Calves received two doses of recombinant E2 vaccine and were challenged with homologous BVDV 37 days later. The recombinant immunogen induced neutralizing titers which showed a mean value of 1.5 ± 0.27 on the day of challenge and reached a top value of 3.36 ± 0.36, 47 days later (84 days post-vaccination. On the other hand, sera from animals which received mock-infected Sf9 cells did not show neutralizing activity until 25 days post-challenge (62 days post-vaccination, suggesting that these antibodies were produced as a consequence of BVDV challenge. Even when no total protection was observed in cattle, in vitro viral neutralization assays revealed that the recombinant immunogen was able to induce neutralizing antibody synthesis against the homologous strain as well as against heterologous strains in a very efficient way.

  20. Concurrent Deletion of Cyclin E1 and Cyclin-Dependent Kinase 2 in Hepatocytes Inhibits DNA Replication and Liver Regeneration in Mice

    OpenAIRE

    Hu W; Nevzorova YA; Haas U; Moro N.; Sicinski P; Geng Y; Barbacid M; Trautwein C; Liedtke C.

    2014-01-01

    The liver has a strong regenerative capacity. After injury, quiescent hepatocytes can reenter the mitotic cell cycle to restore tissue homeostasis. This G0/G1-S cell-cycle transition of primed hepatocytes is regulated by complexes of cyclin-dependent kinase 2 (Cdk2) with E-type cyclins (CcnE1 or CcnE2). However, single genetic ablation of either E-cyclin or Cdk2 does not affect overall liver regeneration. Here, we systematically investigated the contribution of CcnE1, CcnE2, and Cdk2 for live...

  1. Laser altimetry data of Chang’E-1 and the global lunar DEM model

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The Laser AltiMeter (LAM), as one of the main payloads of Chang’E-1 probe, is used to measure the topography of the lunar surface. It performed the first measurement at 02:22 on November 28th, 2007. Up to December 4th 2008, the total number of measurements was approximately 9.12 million, covering the whole surface of the Moon. Using the LAM data, we constructed a global lunar Digtal Elevation Model (DEM) with 3 km spatial resolution. The model shows pronounced morphological characteristics, legible and vivid details of the lunar surface. The plane positioning accuracy of the DEM is 445 m (1σ), and the vertical accuracy is 60 m (1σ). From this DEM model, we measured the full range of the altitude difference on the lunar sur-face, which is about 19.807 km. The highest point is 10.629 km high, on a peak between crater Korolev and crater Dirichlet-Jackson at (158.656°W, 5.441°N) and the lowest point is -9.178 km in height, inside crater Antoniadi (172.413°W, 70.368°S) in the South Pole-Aitken Basin. By comparison, the DEM model of Chang’E-1 is better than the USA ULCN2005 in accuracy and resolution and is probably identical to the DEM of Japan SELENE, but the DEM of Chang’E-1 reveals a new lowest point, clearly lower than that of SELENE.

  2. Expression of Structural Protein E2 of Hepatitis C Virus

    Institute of Scientific and Technical Information of China (English)

    GUO Tai-lin; YE Lin-bo; MAO Can-quan

    2005-01-01

    The E2 glycoprotein is one of the structural components of the hepatitis C virus (HCV) virion. It elicits production of neutralising antibodies against the virus, and is involved in viral morphogenesis. The protein is considered as a major candidate for anti- HCV vaccine. Despitethis, little is known about this protein. Previous studies have focused on the and functional analysis of the glycosylated forms. This report describes expression of the E2 (recE2) in different forms and in different expression systems in Escherichia coli cells and in mammalian cells in order to obtain enough protein efficiently in vitro, in addition we also analysed the usage of rare codons in the genes of E2 and CORE. All results have shown that great efforts should be made to improve the expression efficiency of E2 in bacteria or mammalian cells.

  3. Anti-CD47 Treatment Stimulates Phagocytosis of Glioblastoma by M1 and M2 Polarized Macrophages and Promotes M1 Polarized Macrophages In Vivo.

    Directory of Open Access Journals (Sweden)

    Michael Zhang

    Full Text Available Tumor-associated macrophages (TAMs represent an important cellular subset within the glioblastoma (WHO grade IV microenvironment and are a potential therapeutic target. TAMs display a continuum of different polarization states between antitumorigenic M1 and protumorigenic M2 phenotypes, with a lower M1/M2 ratio correlating with worse prognosis. Here, we investigated the effect of macrophage polarization on anti-CD47 antibody-mediated phagocytosis of human glioblastoma cells in vitro, as well as the effect of anti-CD47 on the distribution of M1 versus M2 macrophages within human glioblastoma cells grown in mouse xenografts. Bone marrow-derived mouse macrophages and peripheral blood-derived human macrophages were polarized in vitro toward M1 or M2 phenotypes and verified by flow cytometry. Primary human glioblastoma cell lines were offered as targets to mouse and human M1 or M2 polarized macrophages in vitro. The addition of an anti-CD47 monoclonal antibody led to enhanced tumor-cell phagocytosis by mouse and human M1 and M2 macrophages. In both cases, the anti-CD47-induced phagocytosis by M1 was more prominent than that for M2. Dissected tumors from human glioblastoma xenografted within NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice and treated with anti-CD47 showed a significant increase of M1 macrophages within the tumor. These data show that anti-CD47 treatment leads to enhanced tumor cell phagocytosis by both M1 and M2 macrophage subtypes with a higher phagocytosis rate by M1 macrophages. Furthermore, these data demonstrate that anti-CD47 treatment alone can shift the phenotype of macrophages toward the M1 subtype in vivo.

  4. Anti-CD47 Treatment Stimulates Phagocytosis of Glioblastoma by M1 and M2 Polarized Macrophages and Promotes M1 Polarized Macrophages In Vivo

    Science.gov (United States)

    Kahn, Suzana A.; Azad, Tej D.; Gholamin, Sharareh; Xu, Chelsea Y.; Liu, Jie; Achrol, Achal S.; Richard, Chase; Sommerkamp, Pia; Schoen, Matthew Kenneth; McCracken, Melissa N.; Majeti, Ravi; Weissman, Irving; Mitra, Siddhartha S.; Cheshier, Samuel H.

    2016-01-01

    Tumor-associated macrophages (TAMs) represent an important cellular subset within the glioblastoma (WHO grade IV) microenvironment and are a potential therapeutic target. TAMs display a continuum of different polarization states between antitumorigenic M1 and protumorigenic M2 phenotypes, with a lower M1/M2 ratio correlating with worse prognosis. Here, we investigated the effect of macrophage polarization on anti-CD47 antibody-mediated phagocytosis of human glioblastoma cells in vitro, as well as the effect of anti-CD47 on the distribution of M1 versus M2 macrophages within human glioblastoma cells grown in mouse xenografts. Bone marrow-derived mouse macrophages and peripheral blood-derived human macrophages were polarized in vitro toward M1 or M2 phenotypes and verified by flow cytometry. Primary human glioblastoma cell lines were offered as targets to mouse and human M1 or M2 polarized macrophages in vitro. The addition of an anti-CD47 monoclonal antibody led to enhanced tumor-cell phagocytosis by mouse and human M1 and M2 macrophages. In both cases, the anti-CD47-induced phagocytosis by M1 was more prominent than that for M2. Dissected tumors from human glioblastoma xenografted within NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice and treated with anti-CD47 showed a significant increase of M1 macrophages within the tumor. These data show that anti-CD47 treatment leads to enhanced tumor cell phagocytosis by both M1 and M2 macrophage subtypes with a higher phagocytosis rate by M1 macrophages. Furthermore, these data demonstrate that anti-CD47 treatment alone can shift the phenotype of macrophages toward the M1 subtype in vivo. PMID:27092773

  5. Oncolytic Replication of E1b-Deleted Adenoviruses

    Directory of Open Access Journals (Sweden)

    Pei-Hsin Cheng

    2015-11-01

    Full Text Available Various viruses have been studied and developed for oncolytic virotherapies. In virotherapy, a relatively small amount of viruses used in an intratumoral injection preferentially replicate in and lyse cancer cells, leading to the release of amplified viral particles that spread the infection to the surrounding tumor cells and reduce the tumor mass. Adenoviruses (Ads are most commonly used for oncolytic virotherapy due to their infection efficacy, high titer production, safety, easy genetic modification, and well-studied replication characteristics. Ads with deletion of E1b55K preferentially replicate in and destroy cancer cells and have been used in multiple clinical trials. H101, one of the E1b55K-deleted Ads, has been used for the treatment of late-stage cancers as the first approved virotherapy agent. However, the mechanism of selective replication of E1b-deleted Ads in cancer cells is still not well characterized. This review will focus on three potential molecular mechanisms of oncolytic replication of E1b55K-deleted Ads. These mechanisms are based upon the functions of the viral E1B55K protein that are associated with p53 inhibition, late viralmRNAexport, and cell cycle disruption.

  6. Primary scientific results of Chang’E-1 lunar mission

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The strategic plan for the development of the unmanned Chinese Lunar Exploration Program is characterized by three distinct stages: "orbiting around", "landing on" and "returning from" the Moon. The first Chinese lunar probe, Chang’E-1, which was successfully launched on October 24th, 2007 at Xichang Satellite Launch Center, and guided to crash on the Moon on March 1st, 2009, at 52.36°E, 1.50°S, in the north of Mare Fecunditatis, is the first step towards the "orbiting around" stage. The Chang’E-1 mission lasted 495 days, exceeding the expected life-span by about four months. A total of 1.37 TB raw data was received from Chang’E-1. It was then processed into 4 TB scientific data products at various levels. Many scientific results have been obtained by analyzing these data, including especially the "global lunar image from the first Chinese lunar explora- tion mission". All scientific goals of Chang’E-1 have been achieved. It provides much useful materials for further advances of lunar sciences and planetary chemistry. Meanwhile, these results will serve as a firm basis for future Chinese lunar missions.

  7. Performance Analysis of Two Ethernet over E1 Schemes

    Institute of Scientific and Technical Information of China (English)

    CHEN Wentao; JIN Depeng; ZENG Lieguang

    2007-01-01

    The Ethernet over E1 approach,which takes advantage of widely deployed telecom networks,is an efficient and economical way to interconnect two Ethernets in different regions.Two Ethernet over E1 schemes, namely a byte granularity scheme and a frame granularity scheme are discussed. The byte granularity scheme partitions Ethernet frames into several pieces for transmission and has a strict requirement on the maximum delay difference of multiple E1 links. To solve this problem, the newly proposed frame granularity scheme transmits separately each frame through E1 links without any partitioning. The architecture designs of both schemes are presented. This paper evaluates the throughput and delay performances of both schemes, both analytically from results calculated from delay models and using test results from field programmable gate array (FPGA) implementation. Although the frame granularity scheme has a slightly worse delay performance, it has a higher throughput, and is the only choice able to overcome large delay differences of the E1 links.

  8. Common Structure of Rare Replication-Deficient E1-Positive Particles in Adenoviral Vector Batches

    Science.gov (United States)

    Murakami, Pete; Havenga, Menzo; Fawaz, Farah; Vogels, Ronald; Marzio, Giuseppe; Pungor, Erno; Files, Jim; Do, Linh; Goudsmit, Jaap; McCaman, Michael

    2004-01-01

    The use of the PER.C6 adenovirus packaging cell line in combination with a designated vector plasmid system, whereby the cell line and vector with E1 deleted have no sequence overlap, eliminates the generation of replication-competent adenovirus during vector production. However, we have found cytopathic effect (CPE)-inducing particles in 2 out of more than 40 large-scale manufacturing lots produced in PER.C6 cells. The CPE inducer was detected at a frequency of 1 event in 7.5 × 1012 vector particles. Despite amplification, it was not readily purified, indicating that the agent itself is replication deficient and requires the parental recombinant adenovirus serotype 5 (rAd5) vector for replication and packaging. Therefore, we designated the agent as a helper-dependent E1-positive region containing viral particle (HDEP). Here, we report the molecular structure of the HDEP genome, revealing an Ad comprised of E1 sequences derived from PER.C6 cells flanked by inverted terminal repeat, packaging signal, and transgene sequences. These sequences form a palindromic structure devoid of E2, E3, E4, and late genes. Since only 5 bp were shared between E1 sequences in the PER.C6 genome and viral vector sequences, the data strongly suggested that insertion of genomic DNA into an adenoviral genome had occurred essentially via nonhomologous recombination. HDEPs have been found in unrelated virus batches and appear to share a common structure that may explain their mechanism of generation. This finding allowed development of an HDEP assay to screen batches of rAd5 produced on the PER.C6 cell line and resulted in detection of seven HDEP agents from four different transgene-virus vector constructs in separate batches of Ad. PMID:15163713

  9. A Broad View of the Chang'e 2 Mission

    Institute of Scientific and Technical Information of China (English)

    Pang Dan

    2010-01-01

    @@ China's second lunar exploration satellite Chang'e 2 was launched on October 1 2010 from the Xichang Satellite Launch Center.The satellite was sent directly into an Earth-moon transfer orbit on a LM-3C launch vehicle.Five days later, the satellite reached a preliminary orbit 100km above the moon.All the payloads onboard Chang'e 2 have been operational since October 15,signifying a good start to Chang'e 2's six-month observation mission.

  10. Chang'e-1 Satellite Completed Its Preset Objectives

    Institute of Scientific and Technical Information of China (English)

    He Ying

    2008-01-01

    @@ By October 23, Chang'e-1 satellite with a one-year design lifetime has been operating in lunar orbit for one year, completed more than 4000 orbits, covering the entire moon 12 times. The satellite's platform works normally at present and all systems and equipment onboard work in their main mode. The satellite has obtained a large quantity of scientific data and achieved the preset objectives of precise orbit maneuver, successful moon orbiting, effective exploration and oneyear lifetime. The Chang'e-1 mission is a complete success.

  11. Energy Efficiency Management Platform (E2MP) Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The Energy Efficiency Management Platform (E2MP) is a power-aware, "Green" computing technology for managing energy consumption on High End Computing (HEC) systems...

  12. Nematicidal activity of (E,E)-2,4-decadienal and (E)-2-decenal from Ailanthus altissima against Meloidogyne javanica.

    Science.gov (United States)

    Caboni, Pierluigi; Ntalli, Nikoletta G; Aissani, Nadhem; Cavoski, Ivana; Angioni, Alberto

    2012-02-01

    Methanol extracts of various plant parts of Ailanthus altissima were tested against the root knot nematode Meloidogyne javanica . Extracts of bark (ABE), wood (AWE), roots (ARE), and leaves (ALE) from A. altissima were investigated against freshly hatched second-stage juveniles (J(2)). AWE was the most active extract, with EC(50/3d) of 58.9 mg/L, while ALE, ARE, and ABE did not show nematicidal activity. The chemical composition of the extracts of A. altissima was determined by gas chromatography-mass spectrometry, and (E,E)-2,4-decadienal, (E)-2-undecenal, (E)-2-decenal, hexanal, nonanal, and furfural were the most prominent constituents. (E,E)-2,4-Decadienal, (E)-2-decenal, and furfural showed the highest nematicidal activity against M. javanica , with EC(50/1d) = 11.7, 20.43, and 21.79 mg/L, respectively, while the other compounds were inactive at the concentrations tested. The results obtained showed that AWE and its constituents (E,E)-2,4-decadienal and (E)-2-decenal could be considered as potent botanical nematicidal agents.

  13. Chang'e 2's Journey to the Moon

    Institute of Scientific and Technical Information of China (English)

    Zong He

    2010-01-01

    @@ OCTOBER 1:INITIAL STAGE OF THE FLIGHT TO THE MOON At 18:59, October 1, 2010, a LM-3C launch vehicle blasted off from the Xichang Satellite Launch Center (XSLC) and precisely placed China's second lunar probe Chang'e 2 into the Earth-moon transfer orbit.Chang'e 2 began its 112-hour journey to the moon and the second phase of China Lunar Exploration Program was formally started.

  14. 26 CFR 31.3302(e)-1 - Successor employer.

    Science.gov (United States)

    2010-04-01

    ... TAXES AND COLLECTION OF INCOME TAX AT SOURCE EMPLOYMENT TAXES AND COLLECTION OF INCOME TAX AT SOURCE Federal Unemployment Tax Act (Chapter 23, Internal Revenue Code of 1954) § 31.3302(e)-1 Successor employer. (a) In general. In addition to the credits against the tax allowable under section 3302(a) and...

  15. A constitutively expressed pair of rpoE2-chrR2 in Azospirillum brasilense Sp7 is required for survival under antibiotic and oxidative stress.

    Science.gov (United States)

    Gupta, Namrata; Kumar, Santosh; Mishra, Mukti Nath; Tripathi, Anil Kumar

    2013-02-01

    Extracytoplasmic function (ECF) sigma factors (σ(E)) are known to bring about changes in gene expression to enable bacteria to adapt to different stresses. The Azospirillum brasilense Sp245 genome harbours nine genes encoding σ(E), of which two are adjacent to the genes encoding ChrR-type zinc-binding anti-sigma (ZAS) factors. We describe here the role and regulation of a new pair of rpoE-chrR, which was found in the genome of A. brasilense Sp7 in addition to the previously described rpoE-chrR pair (designated rpoE1-chrR1). The rpoE2-chrR2 pair is also cotranscribed, and their products show protein-protein interaction. The -10 and -35 promoter elements of rpoE2-chrR2 and rpoE1-chrR1 were similar but not identical. Unlike the promoter of rpoE1-chrR1, the rpoE2-chrR2 promoter was neither autoregulated nor induced by oxidative stress. Inactivation of chrR2 or overexpression of rpoE2 in A. brasilense Sp7 resulted in an overproduction of carotenoids. It also conferred resistance to oxidative stresses and antibiotics. By controlling the synthesis of carotenoids, initiation and elongation of translation, protein folding and purine biosynthesis, RpoE2 seems to play a crucial role in preventing and repairing the cellular damage caused by oxidative stress. Lack of autoregulation and constitutive expression of rpoE2-chrR2 suggest that RpoE2-ChrR2 may provide a rapid mechanism to cope with oxidative stress, wherein singlet oxygen ((1)O(2))-mediated dissociation of the RpoE2-ChrR2 complex might release RpoE2 to drive the expression of its target genes.

  16. Dimethyl fumarate blocks pro-inflammatory cytokine production via inhibition of TLR induced M1 and K63 ubiquitin chain formation

    Science.gov (United States)

    McGuire, Victoria A.; Ruiz-Zorrilla Diez, Tamara; Emmerich, Christoph H.; Strickson, Sam; Ritorto, Maria Stella; Sutavani, Ruhcha V.; Weiβ, Anne; Houslay, Kirsty F.; Knebel, Axel; Meakin, Paul J.; Phair, Iain R.; Ashford, Michael L. J.; Trost, Matthias; Arthur, J. Simon C.

    2016-01-01

    Dimethyl fumarate (DMF) possesses anti-inflammatory properties and is approved for the treatment of psoriasis and multiple sclerosis. While clinically effective, its molecular target has remained elusive - although it is known to activate anti-oxidant pathways. We find that DMF inhibits pro-inflammatory cytokine production in response to TLR agonists independently of the Nrf2-Keap1 anti-oxidant pathway. Instead we show that DMF can inhibit the E2 conjugating enzymes involved in K63 and M1 polyubiquitin chain formation both in vitro and in cells. The formation of K63 and M1 chains is required to link TLR activation to downstream signaling, and consistent with the block in K63 and/or M1 chain formation, DMF inhibits NFκB and ERK1/2 activation, resulting in a loss of pro-inflammatory cytokine production. Together these results reveal a new molecular target for DMF and show that a clinically approved drug inhibits M1 and K63 chain formation in TLR induced signaling complexes. Selective targeting of E2s may therefore be a viable strategy for autoimmunity. PMID:27498693

  17. 小鼠抗E2抗体在体外可以捕获丙型肝炎病毒%Murine antibody against E2 can capture hepatitis C virus in vitro

    Institute of Scientific and Technical Information of China (English)

    马文彬; 冯百芳; 陶其敏

    2001-01-01

    Objective To find neutralizing antibody candidates against hepatitis C virus (HCV) infection. Methods We constructed two eukaryotic expression vectors which contained the E1 and E2 gene of HCV, and detected their expression in mammalian cells with transient expression. BALB/c mice were given subculaneous injections of constructed vectors combined with the IL-2 gene intraepidermally and evaluated for induced humoral immune responses by enzyme-linked immunosorbent assay (ELISA). We used an antibody-virus interaction assay to analyze the interaction of the antisera and HCV viral particles in vitro. Results Anti E1 and anti-E2 antisera were obtained from immunized mice. The serum of mice immunized with the E2 gene immunoprecipitated the HCV isolate in source serum and reacted with the isolates unrelated to the original one. Conclusions Anti-E2 antibody in induced mice can cross-reactively capture HCV particles, highlighting the possibility of generating broadly reactive anti-E2 antibodies.%目的寻找可能存在的抗丙型肝炎病毒(HCV)感染的中和抗体。 方法构建两个分别含HCV E1E2抗原基因的真核表达载体, 用瞬时表达法检测其在哺乳动物细胞中的表达。将构建的载体连同IL-2基因一起经皮下给BalB/c小鼠进行注射,然后用ELISA法检测特异性抗体产生情况。最后通过研究抗体和病毒间的相互作用分析基因免疫诱导产生的抗血清在体外与HCV的相互作用情况。 结果经过基因免疫的小鼠分别产生了E-1E2抗体。其中,用含E2基因的质粒载体免疫的小鼠所产生的E2抗血清不仅可以免疫沉淀来源血清中的HCV病毒颗粒,而且可以和与来源株非相关的HCV病毒颗粒相互作用。 结论我们的研究表明基因免疫诱导小鼠产生的E2抗体可以和HCV病毒颗粒发生交叉反应,这使我们看到了诱导产生具有广泛针对性的E2抗体的希望。

  18. The retinoblastoma protein binds to a family of E2F transcription factors

    DEFF Research Database (Denmark)

    Lees, J A; Saito, M; Vidal, M;

    1993-01-01

    for E2F-2 and E2F-3 were mapped to 1p36 and 6q22, respectfully, confirming their independence from E2F-1. However, the E2F-2 and E2F-3 proteins are closely related to E2F-1. Both E2F-2 and E2F-3 bound to wild-type but not mutant E2F recognition sites, and they bound specifically to the retinoblastoma...

  19. Full-length core sequence dependent complex-type glycosylation of hepatitis C virus E2 glycoprotein

    Institute of Scientific and Technical Information of China (English)

    Li-Xin Zhu; Jing Liu; Ying-Chun Li; Yu-Ying Kong; Caroline Staib; Gerd Sutter; Yuan Wang; Guang-Di Li

    2002-01-01

    AIM: To study HCV polyprotein processing is important forthe understanding of the natural history of HCV and thedesign of vaccines against HCV. The purpose of this studyis to investigate the affection of context sequences onhepatitis C virus (HCV) E2 processingMETHODS: HCV genes of different lengths were expressedand compared in vaccinia virus/T7 system with homologouspatient serum S94 and mouse anti-serum ME2116 raisedagainst E. coli-derived E2 peptide, respectively.Deglycosylation analysis and GNA (Galanthus nivalus )lectin binding assay were performed to study the post-translational processing of the expressed products.RESULTS: E2 glycoproteins with different molecular weights( ~ 75kDa end ~ 60kDa) were detected using S94 and ME2116,respectively. Deglycosylation analysis showed that thisdifference was mainly due to different glycosylation. Endo Hresistance and its failure to bind to GNA lectin demonstratedthat the higher molecular weight form (75kDa) of E2 wascomplex-type glycosylated, which was readily recognized byhomologous patient serum S94. Expression of complex-typeglycosylated E2 could not be detected in all of the core-truncated constructs tested, but readily detected inconstructs encoding full-length core sequences.CONCLUSION: The upstream conserved full-length corecoding sequence was required for the production of E2glycoproteins carrying complex-type N-glycans whichreacted strongly with homologous patient serum andtherefore possibly represented more mature forms of E2. Ascomplex-type N-glycans indicated modification by Golgienzymes, the results suggest that the presence of full-lengthcore might be critical for E1/E2 complex to leave ER. Ourdata may contribute to a better understanding of theprocessing of HCV structural proteins as well as HCVmorphogenesis.

  20. Interaction of NCOR/SMRT Repressor Complexes with Papillomavirus E8^E2C Proteins Inhibits Viral Replication.

    Science.gov (United States)

    Dreer, Marcel; Fertey, Jasmin; van de Poel, Saskia; Straub, Elke; Madlung, Johannes; Macek, Boris; Iftner, Thomas; Stubenrauch, Frank

    2016-04-01

    Infections with high-risk human papillomaviruses (HR-HPV) such as HPV16 and 31 can lead to ano-genital and oropharyngeal cancers and HPV types from the beta genus have been implicated in the development of non-melanoma skin cancer. HPV replicate as nuclear extrachromosomal plasmids at low copy numbers in undifferentiated cells. HPV16 and 31 mutants have indicated that these viruses express an E8^E2C protein which negatively regulates genome replication. E8^E2C shares the DNA-binding and dimerization domain (E2C) with the essential viral replication activator E2 and the E8 domain replaces the replication/transcription activation domain of E2. The HR-HPV E8 domain is required for inhibiting viral transcription and the replication of the viral origin mediated by viral E1 and E2 proteins. We show now that E8^E2C also limits replication of HPV1, a mu-PV and HPV8, a beta-PV, in normal human keratinocytes. Proteomic analyses identified all NCoR/SMRT corepressor complex components (HDAC3, GPS2, NCoR, SMRT, TBL1 and TBLR1) as co-precipitating host cell proteins for HPV16 and 31 E8^E2C proteins. Co-immunoprecipitation and co-localization experiments revealed that NCoR/SMRT components interact with HPV1, 8, 16 and 31 E8^E2C proteins in an E8-dependent manner. SiRNA knock-down experiments confirm that NCoR/SMRT components are critical for both the inhibition of transcription and HPV origin replication by E8^E2C proteins. Furthermore, a dominant-negative NCoR fragment activates transcription and replication only from HPV16 and 31 wt but not from mutant genomes encoding NCoR/SMRT-binding deficient E8^E2C proteins. In summary, our data suggest that the repressive function of E8^E2C is highly conserved among HPV and that it is mediated by an E8-dependent interaction with NCoR/SMRT complexes. Our data also indicate for the first time that NCoR/SMRT complexes not only are involved in inhibiting cellular and viral transcription but also in controlling the replication of HPV origins.

  1. Both viral E2 protein and the cellular factor PEBP2 regulate transcription via E2 consensus sites within the bovine papillomavirus type 4 long control region.

    OpenAIRE

    Jackson, M E; Campo, M S

    1995-01-01

    The bovine papillomavirus type 4 (BPV4) long control region (LCR) contains three consensus binding sites, E2(1), E2(2), and E2(3) (ACCN6GGT), for the viral E2 transcription factor and a fourth degenerate site, dE2 (ATCN6GGT), which lies 3 bp upstream of E2(3). The E2(2) site was found to bind the cellular transcription factor PEBP2, and mutations at this site reduced basal promoter activity by as much as 60%, indicating an important role for PEBP2 in LCR function. Mutation of the E2(3) or dE2...

  2. B(E1) Strengths from Coulomb Excitation of 11Be

    CERN Document Server

    Summers, N C; Ashwood, N I; Bouchat, V; Catford, W N; Clarke, N M; Curtis, N; Freer, M; Fulton, B R; Hanappe, F; Labiche, M; Lecouey, J L; Lemmon, R C; Mahboub, D; Ninane, A; Normand, G; Nunes, F M; Orr, N A; Pain, S D; Soic, N; Stuttgé, L; Thompson, I J; Timis, C N; Winfield, J S; Ziman, V

    2007-01-01

    The $B$(E1;$1/2^+\\to1/2^-$) strength for $^{11}$Be has been extracted from intermediate energy Coulomb excitation measurements, over a range of beam energies using a new reaction model, the extended continuum discretized coupled channels (XCDCC) method. In addition, a measurement of the excitation cross section for $^{11}$Be+$^{208}$Pb at 38.6 MeV/nucleon is reported. The $B$(E1) strength of 0.105(12) e$^2$fm$^2$ derived from this measurement is consistent with those made previously at 60 and 64 MeV/nucleon, i n contrast to an anomalously low result obtained at 43 MeV/nucleon. By coupling a multi-configuration description of the projectile structure with realistic reaction theory, the XCDCC model provides for the first time a fully quantum mechanical description of Coulomb excitation. The XCDCC calculations reveal that the excitation process involves significant contributions from nuclear, continuum, and higher-order effects. An analysis of the present and two earlier intermediate energy measurements yields a...

  3. Selective inhibition of cytochrome P450 2D6 by Sarpogrelate and its active metabolite, M-1, in human liver microsomes.

    Science.gov (United States)

    Cho, Doo-Yeoun; Bae, Soo Hyeon; Lee, Joeng Kee; Kim, Yang Weon; Kim, Bom-Taeck; Bae, Soo Kyung

    2014-01-01

    The present study was performed to evaluate the in vitro inhibitory potential of sarpogrelate and its active metabolite, M-1, on the activities of nine human cytochrome (CYP) isoforms. Using a cocktail assay, the effects of sarpogrelate on nine CYP isoforms and M-1 were measured by specific marker reactions in human liver microsomes. Sarpogrelate potently and selectively inhibited CYP2D6-mediated dextromethorphan O-demethylation with an IC50 (Ki) value of 3.05 μM (1.24 μM), in a competitive manner. M-1 also markedly inhibited CYP2D6 activity; its inhibitory effect with an IC50 (Ki) value of 0.201 μM (0.120 μM) was more potent than that of sarpogrelate, and was similarly potent as quinidine (Ki, 0.129 μM), a well-known typical CYP2D6 inhibitor. In addition, sarpogrelate and M-1 strongly inhibited both CYP2D6-catalyzed bufuralol 1'-hydroxylation and metoprolol α-hydroxylation activities. However, sarpogrelate and M-1 showed no apparent inhibition of the other following eight CYPs: CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2E1, or CYP3A4/5. Upon 30-minute preincubation of human liver microsomes with sarpogrelate or M-1 in the presence of NADPH, no obvious shift in IC50 was observed in terms of inhibition of the nine CYP activities, suggesting that sarpogrelate and M-1 are not time-dependent inactivators. Sarpogrelate strongly inhibited the activity of CYP2D6 at clinically relevant concentrations in human liver microsomes. These observations suggest that sarpogrelate could have an effect on the metabolic clearance of drugs possessing CYP2D6-catalyzed metabolism as a major clearance pathway, thereby eliciting pharmacokinetic drug-drug interactions.

  4. Large scale genotype comparison of human papillomavirus E2-host interaction networks provides new insights for e2 molecular functions.

    Directory of Open Access Journals (Sweden)

    Mandy Muller

    Full Text Available Human Papillomaviruses (HPV cause widespread infections in humans, resulting in latent infections or diseases ranging from benign hyperplasia to cancers. HPV-induced pathologies result from complex interplays between viral proteins and the host proteome. Given the major public health concern due to HPV-associated cancers, most studies have focused on the early proteins expressed by HPV genotypes with high oncogenic potential (designated high-risk HPV or HR-HPV. To advance the global understanding of HPV pathogenesis, we mapped the virus/host interaction networks of the E2 regulatory protein from 12 genotypes representative of the range of HPV pathogenicity. Large-scale identification of E2-interaction partners was performed by yeast two-hybrid screenings of a HaCaT cDNA library. Based on a high-confidence scoring scheme, a subset of these partners was then validated for pair-wise interaction in mammalian cells with the whole range of the 12 E2 proteins, allowing a comparative interaction analysis. Hierarchical clustering of E2-host interaction profiles mostly recapitulated HPV phylogeny and provides clues to the involvement of E2 in HPV infection. A set of cellular proteins could thus be identified discriminating, among the mucosal HPV, E2 proteins of HR-HPV 16 or 18 from the non-oncogenic genital HPV. The study of the interaction networks revealed a preferential hijacking of highly connected cellular proteins and the targeting of several functional families. These include transcription regulation, regulation of apoptosis, RNA processing, ubiquitination and intracellular trafficking. The present work provides an overview of E2 biological functions across multiple HPV genotypes.

  5. Association between CYP1A1m1 gene polymorphism and primary open-angle glaucoma.

    Science.gov (United States)

    Costa, N B; Silva, C T X; Frare, A B; Silva, R E; Moura, K K V O

    2014-12-04

    The CYP1A1 gene is related to the generation of secondary metabolites that are capable of inducing DNA damage. The CYP1A1m1 polymorphism has been examined in many studies, and is located in a region near loci that have been linked to glaucoma, including the locus GLC1I. As a result, this polymorphism has been related to several diseases that are influenced by exposure to xenobiotic as well as primary open-angle glaucoma. We compared the prevalence of the CYP1A1m1 polymorphism in 152 Brazilian patients, 100 patients with primary open-angle glaucoma, and 52 normal controls using restriction fragment length polymorphism analysis. The frequency of the homozygous wild-type (w1/w1) CYP1A1 gene among patients with primary open-angle glaucoma (N = 100) was 16%, for genotype w1/m1, the frequency was 77%, and for m1/m1 it was 7%. Among the control group (N = 52), the frequency of the homozygous wild-type (w1/w1) CYP1A1 gene was 54%, the frequency of w1/m1 was 46%, and the frequency of m1/m1 was 0%. The presence of the CYP1A1m1 polymorphism may interfere with xenobiotic metabolism and exacerbate direct or indirect damage to the optic nerve. These CYP1A1m1 polymorphisms may be risk factors for primary open-angle glaucoma.

  6. Extra-amniotic prostaglandin E2 and the unfavourable cervix.

    Science.gov (United States)

    Shepherd, J; Sims, C; Craft, I

    1976-10-02

    A small dose of prostaglandin E2 suspended in a viscous medium was instilled as a single application into the extra-amniotic space of patients with unfavourable induction features the day before planned induction in an attempt to improve the condition of the cervix. Two groups of 15 patients were studied, one receiving prostaglandin E2 250 mug suspended in methyl ethyl cellulose ('Tylose') 6% solution, and the other tylose alone. Cervical status did not change in those receiving tylose alone, whereas a significant improvement occurred in 14 out of 15 patients receiving the prostaglandin. Labour began before formal induction in 1 patient receiving tylose and in 8 receiving prostaglandin.

  7. MECP2e1 isoform mutation affects the form and function of neurons derived from Rett syndrome patient iPS cells.

    Science.gov (United States)

    Djuric, Ugljesa; Cheung, Aaron Y L; Zhang, Wenbo; Mok, Rebecca S; Lai, Wesley; Piekna, Alina; Hendry, Jason A; Ross, P Joel; Pasceri, Peter; Kim, Dae-Sung; Salter, Michael W; Ellis, James

    2015-04-01

    MECP2 mutations cause the X-linked neurodevelopmental disorder Rett Syndrome (RTT) by consistently altering the protein encoded by the MECP2e1 alternative transcript. While mutations that simultaneously affect both MECP2e1 and MECP2e2 isoforms have been widely studied, the consequence of MECP2e1 deficiency on human neurons remains unknown. Here we report the first isoform-specific patient induced pluripotent stem cell (iPSC) model of RTT. RTTe1 patient iPS cell-derived neurons retain an inactive X-chromosome and express only the mutant allele. Single-cell mRNA analysis demonstrated they have a molecular signature of cortical neurons. Mutant neurons exhibited a decrease in soma size, reduced dendritic complexity and decreased cell capacitance, consistent with impaired neuronal maturation. The soma size phenotype was rescued cell-autonomously by MECP2e1 transduction in a level-dependent manner but not by MECP2e2 gene transfer. Importantly, MECP2e1 mutant neurons showed a dysfunction in action potential generation, voltage-gated Na(+) currents, and miniature excitatory synaptic current frequency and amplitude. We conclude that MECP2e1 mutation affects soma size, information encoding properties and synaptic connectivity in human neurons that are defective in RTT.

  8. SAR studies on carboxylic acid series M(1) selective positive allosteric modulators (PAMs).

    Science.gov (United States)

    Kuduk, Scott D; Beshore, Douglas C

    2014-01-01

    There is mounting evidence from preclinical and early proof-of-concept studies suggesting that selective modulation of the M1 muscarinic receptor is efficacious in cognitive models of Alzheimer's disease (AD). A number of nonselective M1 muscarinic agonists have previously shown positive effects on cognitive function in AD patients, but were limited due to cholinergic adverse events thought to be mediated by pan activation of the M2 to M5 sub-types. Thus, there is a need to identify selective activators of the M1 receptor to evaluate their potential in cognitive disorders. One strategy to confer selectivity for M1 is the identification of allosteric agonists or positive allosteric modulators, which would target an allosteric site on the M1 receptor rather than the highly conserved orthosteric acetylcholine binding site. BQCA has been identified as a highly selective carboxylic acid M1 PAM and this review focuses on an extensive lead optimization campaign undertaken on this compound.

  9. M1 Protein Allows Group A Streptococcal Survival in Phagocyte Extracellular Traps through Cathelicidin Inhibition

    OpenAIRE

    Lauth, Xavier; von Köckritz-Blickwede, Maren; McNamara, Case W; Myskowski, Sandra; Zinkernagel, Annelies S.; Beall, Bernard; Ghosh, Partho; Richard L Gallo; Nizet, Victor

    2009-01-01

    M1 protein contributes to Group A Streptococcus (GAS) systemic virulence by interfering with phagocytosis and through proinflammatory activities when released from the cell surface. Here we identify a novel role of M1 protein in the stimulation of neutrophil and mast cell extracellular trap formation, yet also subsequent survival of the pathogen within these DNA-based innate defense structures. Targeted mutagenesis and heterologous expression studies demonstrate M1 protein promotes resistance...

  10. Non-viral FoxM1 gene delivery to hepatocytes enhances liver repopulation.

    Science.gov (United States)

    Xiang, D; Liu, C-C; Wang, M-J; Li, J-X; Chen, F; Yao, H; Yu, B; Lu, L; Borjigin, U; Chen, Y-X; Zhong, L; Wangensteen, K J; He, Z-Y; Wang, X; Hu, Y-P

    2014-05-22

    Hepatocyte transplantation as a substitute strategy of orthotopic liver transplantation is being studied for treating end-stage liver diseases. Several technical hurdles must be overcome in order to achieve the therapeutic liver repopulation, such as the problem of insufficient expansion of the transplanted hepatocytes in recipient livers. In this study, we analyzed the application of FoxM1, a cell-cycle regulator, to enhance the proliferation capacity of hepatocytes. The non-viral sleeping beauty (SB) transposon vector carrying FoxM1 gene was constructed for delivering FoxM1 into the hepatocytes. The proliferation capacities of hepatocytes with FoxM1 expression were examined both in vivo and in vitro. Results indicated that the hepatocytes with FoxM1 expression had a higher proliferation rate than wild-type (WT) hepatocytes in vitro. In comparison with WT hepatocytes, the hepatocytes with FoxM1 expression had an enhanced level of liver repopulation in the recipient livers at both sub-acute injury (fumaryl acetoacetate hydrolase (Fah)(-/-) mice model) and acute injury (2/3 partial hepatectomy mice model). Importantly, there was no increased risk of tumorigenicity with FoxM1 expression in recipients even after serial transplantation. In conclusion, expression of FoxM1 in hepatocytes enhanced the capacity of liver repopulation without inducing tumorigenesis. FoxM1 gene delivered by non-viral SB vector into hepatocytes may be a viable approach to promote therapeutic repopulation after hepatocyte transplantation.

  11. Monocyte Differentiation towards Protumor Activity Does Not Correlate with M1 or M2 Phenotypes

    Directory of Open Access Journals (Sweden)

    G. Karina Chimal-Ramírez

    2016-01-01

    Full Text Available Macrophages facilitate breast cancer progression. Macrophages were initially classified as M1 or M2 based on their distinct metabolic programs and then expanded to include antitumoral (M1 and protumoral (M2 activities. However, it is still uncertain what markers define the pro- and antitumoral phenotypes and what conditions lead to their formation. In this study, monocytic cell lines and primary monocytes were subjected to commonly reported protocols of M1/M2 polarization and conditions known to engage monocytes into protumoral functions. The results showed that only IDO enzyme and CD86 M1 markers were upregulated correlating with M1 polarization. TNF-α, CCR7, IL-10, arginase I, CD36, and CD163 were expressed indistinguishably from M1 or M2 polarization. Similarly, protumoral engaging resulted in upregulation of both M1 and M2 markers, with conditioned media from the most aggressive breast cancer cell line promoting the greatest changes. In spite of the mixed phenotype, M1-polarized macrophages exhibited the highest expression/secretion of inflammatory mediators, many of which have previously been associated with breast cancer aggressiveness. These data argue that although the existence of protumoral macrophages is unquestionable, their associated phenotypes and the precise conditions driving their formation are still unclear, and those conditions may need both M1 and M2 stimuli.

  12. Monocyte Differentiation towards Protumor Activity Does Not Correlate with M1 or M2 Phenotypes

    Science.gov (United States)

    Chimal-Ramírez, G. Karina; Espinoza-Sánchez, Nancy Adriana; Chávez-Sánchez, Luis; Arriaga-Pizano, Lourdes

    2016-01-01

    Macrophages facilitate breast cancer progression. Macrophages were initially classified as M1 or M2 based on their distinct metabolic programs and then expanded to include antitumoral (M1) and protumoral (M2) activities. However, it is still uncertain what markers define the pro- and antitumoral phenotypes and what conditions lead to their formation. In this study, monocytic cell lines and primary monocytes were subjected to commonly reported protocols of M1/M2 polarization and conditions known to engage monocytes into protumoral functions. The results showed that only IDO enzyme and CD86 M1 markers were upregulated correlating with M1 polarization. TNF-α, CCR7, IL-10, arginase I, CD36, and CD163 were expressed indistinguishably from M1 or M2 polarization. Similarly, protumoral engaging resulted in upregulation of both M1 and M2 markers, with conditioned media from the most aggressive breast cancer cell line promoting the greatest changes. In spite of the mixed phenotype, M1-polarized macrophages exhibited the highest expression/secretion of inflammatory mediators, many of which have previously been associated with breast cancer aggressiveness. These data argue that although the existence of protumoral macrophages is unquestionable, their associated phenotypes and the precise conditions driving their formation are still unclear, and those conditions may need both M1 and M2 stimuli. PMID:27376091

  13. E2F target genes: unraveling the biology

    DEFF Research Database (Denmark)

    Bracken, Adrian P; Ciro, Marco; Cocito, Andrea

    2004-01-01

    The E2F transcription factors are downstream effectors of the retinoblastoma protein (pRB) pathway and are required for the timely regulation of numerous genes essential for DNA replication and cell cycle progression. Several laboratories have used genome-wide approaches to discover novel target...

  14. E2F target genes: unraveling the biology

    DEFF Research Database (Denmark)

    Bracken, Adrian P; Ciro, Marco; Cocito, Andrea

    2004-01-01

    The E2F transcription factors are downstream effectors of the retinoblastoma protein (pRB) pathway and are required for the timely regulation of numerous genes essential for DNA replication and cell cycle progression. Several laboratories have used genome-wide approaches to discover novel target ...... transcription and cellular homeostasis....

  15. Coexistence and B(E2)'s in 98Sr

    Science.gov (United States)

    Fortune, H. T.

    2017-01-01

    I have used a simple two-state model to fit E2 strengths connecting the first two 0+ states to the first two 2+ states in 98Sr. Results for mixing parameters are in excellent agreement with those from a recent analysis. Perhaps surprisingly, they are also in remarkable agreement with results from 1980, despite the wide variation reported in the intervening years.

  16. E-2C Loads Calibration in DFRC Flight Loads Lab

    Science.gov (United States)

    Schuster, Lawrence S.

    2008-01-01

    Objectives: a) Safely and efficiently perform structural load tests on NAVAIR E-2C aircraft to calibrate strain gage instrumentation installed by NAVAIR; b) Collect load test data and derive loads equations for use in NAVAIR flight tests; and c) Assist flight test team with use of loads equations measurements at PAX River.

  17. Prostaglandin E2(PGE2) induces headache in healthy subjects

    DEFF Research Database (Denmark)

    Wienecke, T; Olesen, Jes; Oturai, P S;

    2009-01-01

    The role of prostanoids in nociception is well established. The headache-eliciting effects of prostaglandin E(2) (PGE(2)) and its possible mechanisms have previously not been systematically studied in man. We hypothesized that infusion of PGE(2) might induce headache and vasodilation of cranial v...

  18. HPV16 E2 could act as down-regulator in cellular genes implicated in apoptosis, proliferation and cell differentiation

    Directory of Open Access Journals (Sweden)

    Valencia-Hernández Armando

    2011-05-01

    Full Text Available Abstract Background Human Papillomavirus (HPV E2 plays several important roles in the viral cycle, including the transcriptional regulation of the oncogenes E6 and E7, the regulation of the viral genome replication by its association with E1 helicase and participates in the viral genome segregation during mitosis by its association with the cellular protein Brd4. It has been shown that E2 protein can regulate negative or positively the activity of several cellular promoters, although the precise mechanism of this regulation is uncertain. In this work we constructed a recombinant adenoviral vector to overexpress HPV16 E2 and evaluated the global pattern of biological processes regulated by E2 using microarrays expression analysis. Results The gene expression profile was strongly modified in cells expressing HPV16 E2, finding 1048 down-regulated genes, and 581 up-regulated. The main cellular pathway modified was WNT since we found 28 genes down-regulated and 15 up-regulated. Interestingly, this pathway is a convergence point for regulating the expression of genes involved in several cellular processes, including apoptosis, proliferation and cell differentiation; MYCN, JAG1 and MAPK13 genes were selected to validate by RT-qPCR the microarray data as these genes in an altered level of expression, modify very important cellular processes. Additionally, we found that a large number of genes from pathways such as PDGF, angiogenesis and cytokines and chemokines mediated inflammation, were also modified in their expression. Conclusions Our results demonstrate that HPV16 E2 has regulatory effects on cellular gene expression in HPV negative cells, independent of the other HPV proteins, and the gene profile observed indicates that these effects could be mediated by interactions with cellular proteins. The cellular processes affected suggest that E2 expression leads to the cells in to a convenient environment for a replicative cycle of the virus.

  19. Phenomenology of heavy quarkonium radiative E1 transitions

    Energy Technology Data Exchange (ETDEWEB)

    Martinez, Hector E. [Physik-Department, Technische Universität München, James-Franck-Str. 1, 85748 Garching (Germany)

    2016-01-22

    We present preliminary results of the evaluation of the next-to-leading-order (NLO) relativistic corrections to the heavy quarkonium electric dipole transition (E1) rate. In our evaluation we use the quark-antiquark potential up to 1/m{sup 2} corrections that includes the effective string theory expression for the long range, a review on the method to construct this potential is given. Our results compare favorable with the experiments and may provide predictions for the rates for which no experimental data is yet available.

  20. The chang’E-1 topographic atlas of the Moon

    CERN Document Server

    Li, Chunlai; Mu, Lingli; Ren, Xin; Zuo, Wei

    2016-01-01

    This atlas is based on the lunar global Digital Elevation Models (DEM) of Chang'E-1 (CE-1), and presents CCD stereo image data with digital photogrammetry. The spatial resolution of the DEM in this atlas is 500m, with horizontal accuracy of 192m and vertical accuracy of 120m. Color-shaded relief maps with contour lines are used to show the lunar topographical characteristics. The topographical data gathered by CE-1 can provide fundamental information for the study of lunar topographical, morphological and geological structures, as well as for lunar evolution research.

  1. The role of cyclin E1 in hepatocellular carcinoma

    OpenAIRE

    Chan, Yan-yan; 陳茵茵

    2014-01-01

    Hepatocellular carcinoma (HCC) accounts for 70-85% of liver cancer, which is the sixth most common cancer in the world. Prognosis of HCC is dismal with little chance of complete recovery after diagnosis. It is of essence to discover the key molecules involved in the tumor progression. This could help earlier detection of HCC and establish targeted molecular therapies. Cyclin E1 (CCNE1) is a cyclin molecule responsible for the transition from G1 to S phase of the cell cycle and is often dysreg...

  2. Detection of vibrationally excited methyl formate in W51 e2

    Science.gov (United States)

    Demyk, K.; Wlodarczak, G.; Carvajal, M.

    2008-10-01

    Context: Hot cores in molecular clouds, such as Orion KL, Sgr B2, W51 e1/e2, are characterized by the presence of molecules at sufficiently high temperatures to populate their low-frequency vibrationally excited states significantly. Complex organic molecules, such as methyl formate, ethyl cyanide or dimethyl ether, are characterized by a dense spectrum both in the ground state and in the excited states and lines from vibrationally excited states certainly participate to the spectral confusion. Aims: Following a laboratory study of the first torsional excited mode of methyl formate, we search for methyl formate, HCOOCH3, in its first torsionally excited state (\\upsilon_t=1) in the molecular cloud W51 e2. Methods: We performed observations of the molecular cloud W51 e2 in different spectral regions at 1.3, 2, and 3 mm with the IRAM 30 m single dish antenna. Results: Methyl formate in its first torsionally excited state (\\upsilon_t=1 at 131 cm-1) is detected for the first time toward W51 e2. We detect 82 transitions among which 46 are unblended with other species. For a total of 16 A-E pairs in the observed spectrum, 9 are unblended; these 9 pairs are all detected. All transitions from excited methyl formate within the observed spectral range are detected and no strong lines are missing. The column density of the excited state is comparable to that of the ground state. For a source size of 7´´, we find that {T_rot} = 104 ± 14 K and N = 9.4+4.0-2.8 × 1016 cm-2 for the excited state and {T_rot} = 176 ± 24 K and N = 1.7+.2-.2 × 1017 cm-2 for the ground state. Lines from ethyl cyanide in its two first excited states (\\upsilon_t=1, torsion mode at 212 cm-1) and (\\upsilon_b=1, CCN in-plane bending mode at 206 cm-1) are also present in the observed spectrum. Blending problems prevent a precise estimate of its abundance, although as for methyl formate, it should be comparable to the value derived for the ground state for which we find {T_rot} = 103 ± 9 K and N = 3

  3. Coactivator-associated arginine methyltransferase 1 (CARM1) is a positive regulator of the Cyclin E1 gene

    OpenAIRE

    El Messaoudi, Selma; Fabbrizio, Eric; Rodriguez, Carmen; Chuchana, Paul; Fauquier, Lucas; Cheng, Donghang; Theillet, Charles; Vandel, Laurence; Bedford, Mark T.; Sardet, Claude

    2006-01-01

    The Cyclin E1 gene (CCNE1) is an ideal model to explore the mechanisms that control the transcription of cell cycle-regulated genes whose expression rises transiently before entry into S phase. E2F-dependent regulation of the CCNE1 promoter was shown to correlate with changes in the level of H3-K9 acetylation/methylation of nucleosomal histones positioned at the transcriptional start site region. Here we show that, upon growth stimulation, the same region is subject to variations of H3-R17 an...

  4. Detection of ethylene glycol - toward W51/e2 and G34.3+0.02

    Science.gov (United States)

    Lykke, Julie M.; Favre, Cécile

    2014-07-01

    Ethylene glycol (HOCH2CH2OH), also commenly known as antifreeze, is the reduced alcohol version of glycolaldehyde (CH2OHCHO). Glycoladehyde - the simplest possible aldehyde sugar (Marstokk and Møllendal 1973) - is the first intermediate step in the path toward forming more complex and biologically relevant molecules through the the formose reaction, which begins with formaldehyde (H2CO) and ends with the formation of sugars and ultimately ribose, the backbone of RNA (e.g., Larralde et al. 1995). The presence of glycolaldehyde is therefore an important indication that processes leading to biologically relevant molecules are taking place. It is however, still unclear as to how glycolaldehyde and ethylene glycol are formed in the ISM. It has been proposed that they share a common formation pathway through UV-irradiation of methanol (CH3OH) ices mixed with CO (Öberg et al. 2009). So far, ethylene glycol, in its lower energy con-former (g’Ga(CH2OH)2), has been detected toward SgrB2 (N) by Hollis et al. (2002), tentatively toward IRAS 16293-2422 (Jørgensen et al. 2012) and marginally by Kalenskii and Johansson (2010) toward W51 e1/e2. Here we present a firm detection of ethylene glycol toward W51/e2 as well as a first detection toward G34.3+0.02 at 1mm and 3mm using the IRAM 30m telescope.

  5. Crossover Analysis of CHANG'E-1 Laser Altimeter Data

    Science.gov (United States)

    Hu, W.; Yue, Z.; Di, K.

    2011-08-01

    This paper presents a preliminary result of crossover analysis and adjustment of Chang'E-1(CE-1) Laser Altimeter (LAM) data of the Moon for global and regional mapping applications. During the operation of Chang'E-1 from November 28, 2007 to December 4, 2008, the laser altimeter acquired 1400 orbital profiles with about 9.12 million altimetric points. In our experiment, we derived more than 1.38 million crossovers from 1395 ground tracks covering the entire lunar surface after eliminating outliers of orbits and altimetric points. A method of least-squares crossover adjustment with a series of basis functions of time (trigonometric functions and polynomials) is developed to reconcile the LAM data by minimizing the crossover residuals globally. The normal equations are very large but sparse; therefore they are stored and solved using sparse matrix technique. In a test area (0°N~60°N, 50°W~0°W), the crossover residuals are reduced from 62.1m to 32.8m, and the quality of the DEM generated from the adjusted LAM data is improved accordingly. We will optimize the method for the global adjustment to generate a high precision consistent global DEM, which can be used as absolute control for lunar mapping with orbital images.

  6. Experimental Conditions: SE37_S19_M1_D1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available opes SE37_S19 PSEUDO: Unlabeled and labeled Medicago samples for flavonoid annotation using ShiftedIonsFinde...03_M1) and for a blank sample (S16_M1 to S16_M3) are used. Import file name is unlabeling SE37_DS5 Flavonoid like peak search by ShiftedIonsFinder ...

  7. Radioiodinated ganglioside G/sub M1/: A potential tracer for neurological studies

    Energy Technology Data Exchange (ETDEWEB)

    Zalutsky, M.R.; Gallagher, P.; Magistretti, P.L.; Ghidoni, R.

    1985-05-01

    Ganglioside G/sub M1/ is a glycosphingolipid which appears to be involved in the regeneration of damaged neuronal tissue. In addition, it is being investigated clinically in the treatment of various neuropathies. If labeled with the appropriate isotope, G/sub M1/ might be useful as a probe of these processes, particularly if it accumulates preferentially in cerebral infarcts. The G/sub M1/ -tyr derivative was labeled with I-125 in 75% yield using the Iodogen method and at micellar concentration was isolated using gel chromatography. Binding of I-125 (G/sub M1/ -tyr) to rat neuronal membranes was measured at concentrations of 5,50, and 500 nM. The amount bound (8,26, and 158 pmol/gm membrane) was similar to that reported for H-3(G/sub M1/). The biodistribution of I-125(G/sub M1/ -tyr) in mice at both micellar and monomeric concentrations was also similar to that of H-3(G/sub M1/). However, at monomeric concentrations, thyroid uptake of I-125 was about 10 times higher than at micellar concentrations, suggesting differential dehalogenation of the two forms. Initial studies in the gerbil stroke model suggest that the uptake of I-125(G/sub M1/ -tyr) in damaged brain is twice that in normal tissue.

  8. CONDITIONAL INVOLVEMENT OF MUSCARINIC M(1) RECEPTORS IN VAGALLY MEDIATED CONTRACTION OF GUINEA-PIG BRONCHI

    NARCIS (Netherlands)

    TENBERGE, REJ; ROFFEL, AF; ZAAGSMA, J

    The involvement of ganglionic muscarinic M(1) receptors in vagally induced bronchoconstriction in guinea-pig airways is controversial. Therefore, we studied the effects of the M(1)-selective muscarinic receptor antagonist pirenzepine on vagus nerve (VNS, preganglionic) and electrical field

  9. A note on predicting recessions in the euro area using real M1

    OpenAIRE

    Jens Boysen-Hogrefe

    2012-01-01

    Real M1 is a renowned leading indicator used to forecast real economic activity. This note provides evidence that real M1 is also a suitable recession indicator that gave a clear and early signal for the Great Recession as long as changes in money demand are controlled for.

  10. Analytical Method (M): SE37_S18_M1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available SE37_S18_M1 This is a pseudo metadata prepared for integrated analyses of multiple ...datasets. The raw data obtained from LC-Orbitarp MS analyses for Medicago samples and a blank sample (S17_M1

  11. 12 CFR Appendix M1 to Part 226 - Generic Repayment Estimates

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Generic Repayment Estimates M1 Appendix M1 to Part 226 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE... rounded down to the nearest whole year if the estimate contains a fractional year less than 0.5,...

  12. Experimental Conditions: SE19_S2_M1_D1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available SE19_S2_M1_D1 SE19 Grobal triacylglycerol analysis in mouse liver and white adipose... tissue (WAT) by high resolution LC/ESI-QTOF MS/MS SE19_S2 Mouse white adipose tissue (WAT) SE19_S2_M1 20 ug

  13. FoxM1 is required for execution of the mitotic programme and chromosome stability

    NARCIS (Netherlands)

    Laoukili, J.; Kooistra, M.R.H.; Brás, A.; Kauw, J.; Kerkhoven, R.M.; Morrison, A.; Clevers, H.C.; Medema, R.H.

    2005-01-01

    Transcriptional induction of cell-cycle regulatory proteins ensures proper timing of subsequent cell-cycle events. Here we show that the Forkhead transcription factor FoxM1 regulates expression of many G2-specific genes and is essential for chromosome stability. Loss of FoxM1 leads to pleiotropic ce

  14. FoxM1 is required for execution of the mitotic programme and chromosome stability.

    NARCIS (Netherlands)

    Laoukili, J.; Kooistra, M.R.H.; Bras, A.; Kauw, J.; Kerkhoven, R.M.; Morrison, A.; Clevers, J.C.; Medema, R.H.

    2005-01-01

    Transcriptional induction of cell-cycle regulatory proteins ensures proper timing of subsequent cell-cycle events. Here we show that the Forkhead transcription factor FoxM1 regulates expression of many G2-specific genes and is essential for chromosome stability. Loss of FoxM1 leads to pleiotropic ce

  15. Nanometre-accurate form measurement machine for E-ELT M1 segments

    NARCIS (Netherlands)

    Bos, A.; Henselmans, R.; Rosielle, P.C.J.N.; Steinbuch, M.

    2015-01-01

    To enable important scientific discoveries, ESO has defined a new ground-based telescope: the European Extremely Large Telescope (E-ELT). The baseline design features a telescope with a 39-m-class primary mirror (M1), making it the largest and most powerful telescope in the world. The M1 consists of

  16. Regional distribution of M1, M2 and non-M1, non-M2 subtypes of muscarinic binding sites in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Ehlert, F.J.; Tran, L.P. (Univ. of California, Irvine (USA))

    1990-12-01

    The distribution of subtypes of the muscarinic receptor in homogenates of the rat brain was investigated by measuring the competitive inhibition of the binding (3H)N-methylscopolamine by pirenzepine and AF-DX 116 (11((2-((diethylamino)methyl)-1-piperidinyl)acetyl)-5, 11-dihydro-6H-pyrido(2,3-b)(1,4)benzodiazepine-6-one). In most brain regions, the competitive binding curves for AF-DX 116 and pirenzepine were consistent with a two-site model. The dissociation constant of pirenzepine for its high-affinity site (M1 receptor) was approximately 10(-8) M, whereas the dissociation constant of AF-DX 116 for its high affinity site (M2 receptor) was approximately 10(-7) M. In many regions, particularly those in the forebrain, the sum of the densities of the M1 and M2 binding sites was substantially less than 100% of the total sites, indicating the existence of a third population of sites lacking high affinity for both pirenzepine and AF-DX 116. We have designated these latter sites as non-M1, non-M2 muscarinic receptors. In general, the densities of the M1 and non-M1, non-M2 binding sites were highest in cerebral cortex, corpus striatum and hippocampus, intermediate in thalamus and hypothalamus, and lowest in midbrain, medulla-pons and cerebellum, whereas the M2 binding site had a relatively low, uniform density throughout the brain. The binding capacity of (3H)N-methylquinuclidinyl benzilate was estimated to be 20 to 30% lower than that of (3H)quinuclidinyl benzilate in various regions of the forebrain, but not in more caudal regions of the brain where the two radioligands had approximately the same binding capacities.

  17. The luminosity function of cluster galaxies relations among M$_{1}$, M* and the morphological type

    CERN Document Server

    Trevese, D; Appodia, B

    1996-01-01

    A study of the luminosity function of 36 Abell clusters of galaxies has been carried out using photographic plates obtained with the Palomar 1.2 m Schmidt telescope. The relation between the magnitude M_1 of the brightest cluster member and the Schechter function parameter M* has been analyzed. A positive correlation between M* and M_1 is found. However clusters appear segregated in the M_1-M* plane according to their Rood & Sastry class in such a way that on average M_1 becomes brighter while M* becomes fainter going from late to early Rood & Sastry and also Bautz & Morgan classes. Also a partial correlation analysis involving the magnitude M_10 of the 10th brightest galaxy, shows a negative intrinsic correlation between M_1 and M*. These results agree with the cannibalism model for the formation of brightest cluster members, and provide new constraints for theories of cluster formation and evolution.

  18. Effects of Lactobacillus kefiranofaciens M1 isolated from kefir grains on germ-free mice.

    Directory of Open Access Journals (Sweden)

    Yen-Po Chen

    Full Text Available Lactobacillus kefiranofaciens M1 is a novel probiotic strain that was isolated from kefir grains. Previously, we have demonstrated the immunoregulatory, anti-allergic, anti-asthmatic and anti-colitis abilities of L. kefiranofaciens M1 in a number of in-vitro and in-vivo experiments. However, whether the effects of L. kefiranofaciens M1 are elicited directly on the host or act by regulating the host's microbiota remains unknown. A number of studies have used germ-free or gnotobiotic animals to investigate the relationship between probiotics and colitis; therefore the aim of this study was to investigate the effects of L. kefiranofaciens M1 on germ-free mice. Such an approach should help in determining the direct effects of L. kefiranofaciens M1 on the host itself. Four-week-old female germ-free mice were inoculated intragastrically with 2×10(8 CFU/mouse L. kefiranofaciens M1 once or at 2-day intervals for 14 days. Bacterial colonization, the Th1/Th2 cytokine profile of the mice's splenocytes and the anti-colitis effect of L. kefiranofaciens M1 were investigated. The strongest response in terms of splenic Th1 cytokine IFN-γ and IL-12 production upon TLR activation was detected in the continuous treatment group when comparing to the single inoculation group and the germ-free control. In addition, continuous inoculation with L. kefiranofaciens M1 was found to ameliorate the symptoms of DSS-induced colitis in germ-free mice. However, L. kefiranofaciens M1 failed to colonize the host. Thus it would seem that L. kefiranofaciens M1 is likely to act directly on the host and not be involved in microbiota regulation.

  19. Chang'e-2 spacecraft observations of asteroid 4179 Toutatis

    Science.gov (United States)

    Ji, Jianghui; Jiang, Yun; Zhao, Yuhui; Wang, Su; Yu, Liangliang

    2016-01-01

    On 13 December 2012, Chang'e-2 completed a successful flyby of the near-Earth asteroid 4179 Toutatis at a closest distance of 770 meters from the asteroid's surface. The observations show that Toutatis has an irregular surface and its shape resembles a ginger-root of a smaller lobe (head) and a larger lobe (body). Such bilobate shape is indicative of a contact binary origin for Toutatis. In addition, the high-resolution images better than 3 meters provide a number of new discoveries about this asteroid, such as an 800-meter depression at the end of the large lobe, a sharply perpendicular silhouette near the neck region, boulders, indicating that Toutatis is probably a rubble-pile asteroid. Chang'e-2 observations have significantly revealed new insights into the geological features and the formation and evolution of this asteroid. In final, we brief the future Chinese asteroid mission concept.

  20. Chang'e-2 spacecraft observations of asteroid 4179 Toutatis

    CERN Document Server

    Ji, Jianghui; Zhao, Yuhui; Wang, Su; Yu, Liangliang

    2015-01-01

    On 13 December 2012, Chang'e-2 completed a successful flyby of the near-Earth asteroid 4179 Toutatis at a closest distance of 770 meters from the asteroid's surface. The observations show that Toutatis has an irregular surface and its shape resembles a ginger-root of a smaller lobe (head) and a larger lobe (body). Such bilobate shape is indicative of a contact binary origin for Toutatis. In addition, the high-resolution images better than 3 meters provide a number of new discoveries about this asteroid, such as an 800-meter depression at the end of the large lobe, a sharply perpendicular silhouette near the neck region, boulders, indicating that Toutatis is probably a rubble-pile asteroid. Chang'e-2 observations have significantly revealed new insights into the geological features and the formation and evolution of this asteroid. In final, we brief the future Chinese asteroid mission concept.

  1. Generalized seniority and E 2 transitions in the tin isotopes

    Science.gov (United States)

    Morales, Irving O.; Van Isacker, P.; Talmi, I.

    2011-09-01

    Recently, a shallow minimum was discovered in B(E2) values in even Sn isotopes around the middle of the neutron major shell. A peak in that region was expected according to calculations using generalized seniority. In a model calculation we show that the observed shape is consistent with generalized seniority. It seems to be due to the order of filling of j-orbits.

  2. Low Cost Network Emulator with Ethernet and E1 Interfaces

    Directory of Open Access Journals (Sweden)

    Zbynek Kocur

    2010-01-01

    Full Text Available Contemporary Next Generation Networks (NGN are mainly built on the Internet Protocol (IP and Ethernet. Major challenge for emerging types of wired and wireless IP-based networks is to provide an adequate Quality of Service (QoS for different services. The quality of evaluation requires a detailed knowledge of the performance requirements for particular services and applications. The paper is primarily oriented to the end-to-end testing for the Ethernet-based terminal equipment. The low cost Ethernet network emulator was developed on the Department of Telecommunication Technology of the Faculty of Electrical Engineering of the Czech Technical University in Prague. The extension for emulation network with the E1 interfaces and TDM over IP transmission can be used with external converters.

  3. Poster 14: Explorer of Enceladus and Titan (E2T)

    Science.gov (United States)

    Mitri, Giuseppe; Tobie, Gabriel; Postberg, Frank; Soderblom, Jason M.; Wurz, Peter; Barnes, Jason W.; Berga, Marco; Coustenis, Athena; D'Ottavio, Andrea Hayes, Alexander G.; Hayne, Paul O.; Lebreton, Jean-Pierre; Lorenz, Ralph D.; Martelli, Andrea; Petropoulos, Anastassios E.; Yen, Chen-wan L.; Reh, Kim R.; Sotin, Christophe; Srama, Ralf; Tortora, Paolo

    2016-06-01

    The NASA-ESA Cassini-Huygens mission has revealed Titan and Enceladus to be two of the most enigmatic worlds in the Solar System. Titan, with its organically rich and dynamic atmosphere and geology, and Enceladus, with its active plume, both harboring subsurface oceans, are prime environments in which to investigate the conditions for the emergence of life and the habitability of Ocean Worlds. Explorer of Enceladus and Titan (E2T) is dedicated to investigating the evolution and habitability of these Saturnian satellites and will be proposed as a medium-class mission led by ESA in collaboration with NASA in response to ESA's M5 Call. E2T has a focused payload that will provide in-situ sampling and high-resolution imaging during multiple flybys of Enceladus and Titan using a solar-electric powered spacecraft in orbit around Saturn. The E2T mission will provide high-resolution mass spectroscopy of the plume emanating from Enceladus' south polar terrain (SPT) and of Titan's upper atmosphere as well as high-resolution IR imaging of the plume and the source fractures on Enceladus' SPT, and it will detail Titan's geomorphology at 50-100 m resolution. The E2T mission has three scientific goals: 1) Investigate the origin and evolution of volatile-rich icy worlds by examining both Enceladus and Titan, 2) Investigate the habitability and potential for life in ocean worlds on both Enceladus and Titan and 3) Investigate Titan as an Earth-like world with an evolving climate and landscape. These investigations will be accomplished by measuring the nature, abundance and isotopic properties of solid- and vapor-phase species in Enceladus' plume and Titan's upper atmosphere. E2T's high-resolution time-of-flight mass spectrometers will enable us to untangle the ambiguities left by Cassini regarding the identification of low-mass organic species, identify high-mass organic species for the first time, further constrain trace species such as the noble gases, and clarify the evolution of

  4. Some novel insights on HPV16 related cervical cancer pathogenesis based on analyses of LCR methylation, viral load, E7 and E2/E4 expressions.

    Directory of Open Access Journals (Sweden)

    Damayanti Das Ghosh

    Full Text Available This study was undertaken to decipher the interdependent roles of (i methylation within E2 binding site I and II (E2BS-I/II and replication origin (nt 7862 in the long control region (LCR, (ii expression of viral oncogene E7, (iii expression of the transcript (E7-E1/E4 that encodes E2 repressor protein and (iv viral load, in human papillomavirus 16 (HPV16 related cervical cancer (CaCx pathogenesis. The results revealed over-representation (p<0.001 of methylation at nucleotide 58 of E2BS-I among E2-intact CaCx cases compared to E2-disrupted cases. Bisulphite sequencing of LCR revealed overrepresentation of methylation at nucleotide 58 or other CpGs in E2BS-I/II, among E2-intact cases than E2-disrupted cases and lack of methylation at replication origin in case of both. The viral transcript (E7-E1/E4 that produces the repressor E2 was analyzed by APOT (amplification of papillomavirus oncogenic transcript-coupled-quantitative-RT-PCR (of E7 and E4 genes to distinguish episomal (pure or concomitant with integrated from purely integrated viral genomes based on the ratio, E7 C(T/E4 C(T. Relative quantification based on comparative C(T (threshold cycle method revealed 75.087 folds higher E7 mRNA expression in episomal cases over purely integrated cases. Viral load and E2 gene copy numbers were negatively correlated with E7 C(T (p = 0.007 and E2 C(T (p<0.0001, respectively, each normalized with ACTB C(T, among episomal cases only. The k-means clustering analysis considering E7 C(T from APOT-coupled-quantitative-RT-PCR assay, in conjunction with viral load, revealed immense heterogeneity among the HPV16 positive CaCx cases portraying integrated viral genomes. The findings provide novel insights into HPV16 related CaCx pathogenesis and highlight that CaCx cases that harbour episomal HPV16 genomes with intact E2 are likely to be distinct biologically, from the purely integrated viral genomes in terms of host genes and/or pathways involved in cervical

  5. Exploration of FoxM1 and downstream related target molecule expression in cervical cancer tissue

    Institute of Scientific and Technical Information of China (English)

    Yi-Chong Yuan; QiongYang

    2016-01-01

    Objective:To study the expression of FoxM1 and downstream related target molecules in cervical cancer tissue.Methods:Cervical cancer tissue and normal cervical tissue were collected to detect the expression of FoxM1, proliferation-related genes (CDK6 and CDK8) and angiogenesis-related genes (VEGFA, VEGFB and VEGFC); Hela cells were cultured and transfected with FoxM1 siRNA, and then expression of CDK6, CDK8, VEGFA, VEGFB and VEGFC were detected.Results:mRNA contents of FoxM1, CDK6, CDK8, VEGFA, VEGFB and VEGFC in cervical cancer tissue were significantly higher than those in normal cervical tissue; mRNA content of FoxM1 was positively correlated with mRNA contents of CDK6, CDK8, VEGFA, VEGFB and VEGFC; mRNA contents of CDK6, CDK8, VEGFA, VEGFB and VEGFC of FoxM1-siRNA group were significantly lower than those of negative control-siRNA group.Conclusion:FoxM1 expression abnormally increases in cervical cancer tissue, and its downstream target genes include CDK6, CDK8, VEGFA, VEGFB and VEGFC.

  6. Emergence and oscillation of cosmic space by joining M1-branes

    CERN Document Server

    Sepehri, Alireza; Capozziello, Salvatore; Ali, Ahmed Farag; Pradhan, Anirudh

    2016-01-01

    Recently, it has been proposed by Padmanabhan that the difference between the number of degrees of freedom on the boundary surface and the number of degrees of freedom in a bulk region leads to the expansion of the universe. Now, a natural question arises, how this model could explain the oscillation of universe between contraction and expansion branches? We try to address this issue in the framework of BIonic system. In this model, $M0$-branes join to each other and give rise to a pair of $M1$-anti-$M1$-branes. The fields which live on these branes play the roles of massive gravitons that cause the emergence of a wormhole between them and formation of a BIon system. This wormhole dissolves into M1-branes and causes a divergence between the number of degrees of freedom on the boundary surface of $M1$ and the bulk leading to an expansion of $M1$-branes. When $M1$-branes become close to each other, the square energy of their system becomes negative and some tachyonic states emerge. To removes these states, $M1$...

  7. Expression of Hepatitis C Virus E2 Ectodomain in E.coli and Its Application in the Detection of Anti-E2 Antibodies in Human Sera

    Institute of Scientific and Technical Information of China (English)

    JingLIU; Xin-XinZHANG; Shen-YingZHANG; MinLU; Yu-YingKONG; YuanWANG; Guang-DiLI

    2004-01-01

    The second envelope glycoprotein (E2) of hepatitis C virus has been shown to bind human target cells and has become a major target for the development of anti-HCV vaccines. Anti-E2 antibodies have been suggested to be of clinical significance in diagnosis, treatment and prognosis of hepatitis C. However,large-scale expression and purification of E2 proteins in mammalian cells is difficult. As an alternative, E2 fragment (aa 385-730) with a four-amino-acid mutation (aa 568-571 PCNI to RVTS) was expressed as hexa-histidine-tagged full length protein [E2N730(m)] in E.coli and purified to over 85% purity. Purified E2N730(m) was specifically recognized by homologous hepatitis C patient serum in Western blot, suggesting that it displayed E2-specific antigenicity. Rabbit antiserum raised against E2N730(m) recognized E2 glycoproteins expressed in mammalian cells in Western blot. Purified E2N730(m) was ttsed to detect anti-E2 antibodies in human sera and showed better specificity and sensitivity than previously reported C-terminally truncated E2 fragment (aa 385-565). Association between anti-E2 antibodies in patient sera and HCV RNA status was also demonstrated using this E.coli-derived protein. E2N730(m) might serve as an inexpensive alternative to mammalian cell-expressed E2 proteins in clinical and research applications.

  8. Expression of Hepatitis C Virus E2 Ectodomain in E.coli and Its Application in the Detection of Anti-E2 Antibodies in Human Sera

    Institute of Scientific and Technical Information of China (English)

    Jing LIU; Xin-Xin ZHANG; Shen-Ying ZHANG; Min LU; Yu-Ying KONG; Yuan WANG; Guang-Di LI

    2004-01-01

    The second envelope glycoprotein (E2) of hepatitis C virus has been shown to bind human target cells and has become a major target for the development of anti-HCV vaccines. Anti-E2 antibodies have been suggested to be of clinical significance in diagnosis, treatment and prognosis of hepatitis C. However,large-scale expression and purification of E2 proteins in mammalian cells is difficult. As an alternative, E2 fragment (aa 385-730) with a four-amino-acid mutation (aa 568-571 PCNI to RVTS) was expressed as hexa-histidine-tagged full length protein [E2N730(m)] in E. Coli and purified to over 85% purity. Purified E2N730(m) was specifically recognized by homologous hepatitis C patient serum in Western blot, suggesting that it displayed E2-specific antigenicity. Rabbit antiserum raised against E2N730(m) recognized E2 glycoproteins expressed in mammalian cells in Western blot. Purified E2N730(m) was used to detect anti-E2 antibodies in human sera and showed better specificity and sensitivity than previously reported C-terminally truncated E2 fragment (aa 385-565). Association between anti-E2 antibodies in patient sera and HCV RNA status was also demonstrated using this E. Coli-derived protein. E2N730(m) might serve as an inexpensive alternative to mammalian cell-expressed E2 proteins in clinical and research applications.

  9. Subcellular Localization of Rat CYP2E1 Impacts Metabolic Efficiency toward Common Substrates

    OpenAIRE

    2015-01-01

    Cytochrome P450 2E1 (CYP2E1) detoxifies or bioactivates many low molecular-weight compounds. Most knowledge about CYP2E1 activity relies on studies of the enzyme localized to endoplasmic reticulum (erCYP2E1); however, CYP2E1 undergoes transport to mitochondria (mtCYP2E1) and becomes metabolically active. We report the first comparison of in vitro steady-state kinetic profiles for erCYP2E1 and mtCYP2E1 oxidation of probe substrate 4-nitrophenol and pollutants styrene and aniline using subcellu...

  10. Data of evolutionary structure change: 1E1QA-2HLDT [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1E1QA-2HLDT 1E1Q 2HLD A T DLEETGRVLSIGDGIARVHGLRNVQAEEMVEFSSGLKGM...VDALVPIGRGQRELIIGDRQTGKTAVALDTILNQKRWNNGSDESKKLYCVYVAVGQKRSTVAQLVQTLEQHDAMKYSIIVAATASEAAPLQYLAPFTAASIGEWFRDN...bID> T 2HLDT ALKQVAGS

  11. Data of evolutionary structure change: 1E1RC-2HLDT [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1E1RC-2HLDT 1E1R 2HLD C T ADTSVDLEETGRVLSIGDGIARVHGLRNVQAEEMVEFSS...VQTGLKAVDALVPIGRGQRELIIGDRQTGKTAVALDTILNQKRWNNGSDESKKLYCVYVAVGQKRSTVAQLVQTLEQHDAMKYSIIVAATASEAAPLQYLAPFTAASI... 2HLD T 2HLDT AAFAQ--

  12. Data of evolutionary structure change: 1E1RA-2HLDT [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1E1RA-2HLDT 1E1R 2HLD A T DLEETGRVLSIGDGIARVHGLRNVQAEEMVEFSSGLKGM...VDALVPIGRGQRELIIGDRQTGKTAVALDTILNQKRWNNGSDESKKLYCVYVAVGQKRSTVAQLVQTLEQHDAMKYSIIVAATASEAAPLQYLAPFTAASIGEWFRDN...bChain>T 2HLDT ALKQVAGSLKLFL

  13. Enzyme-linked immunosorbent assay for determination of aflatoxin M1 based on magnetic nanoparticles

    Science.gov (United States)

    Atanasova, M. K.; Ivanova, N. V.; Godjevargova, T. I.

    2017-02-01

    A sensitive enzyme immunoassay with magnetic nanoparticles (Method A) for the quantitative determination of aflatoxin M1 in milk was developed. This immunoassay was based on the immobilization of monoclonal antibody (mAb) on the modified magnetic nanoparticles (MNPs-NH2). It was observed that for each mg of the MNPs, 25 µg of antibody was immobilized. Both aflatoxin M1 in the sample and aflatoxin M1-BSA-peroxidase conjugate competed for the immobilized antibody. The proposed Method A was compared with other method (B). The Method B was based on the immobilization of aflatoxin M1-BSA conjugate on the MNPs-NH2, which competed with the aflatoxin M1 in the sample for binding to the added mAb. The binding of mAb to the aflatoxin M1-BSA-MNPs-NH2 was detected using a target secondary IgG-peroxidase antibody. The analytical characteristics of the two methods were compared. Real milk samples were investigated for present of aflatoxin M1. Two methods were based on the use of MNPs as a solid support for covalently immunoreagents immobilization. A comfortable separation of bound and free fraction of the tracer can be performed only through a simple collection of the MNPs by a permanent magnet. The application of MNPs helps to eliminate non-specific binding and to retain higher activity of bound biomolecules. The development of a MNPs-based ELISA for determination of aflatoxin M1 has a great potential to supersede the traditional ELISA for aflatoxin M1 diagnosis.

  14. A Very Fast Pulsed Electron Gun for (e, 2e) and (e, 3e) Studies

    Institute of Scientific and Technical Information of China (English)

    CaoShiping; MaXinwen; ShaShan; ZhuXiaolong; LiuHuipin

    2003-01-01

    Reaction microscope is a powerful tool for studying ion-atom/molecule dynamics, it can also be employed to investigate electron impact ionization processes. Traditionally these processes are studied by using the (e, 2e) or (e, 3e) techniques, most data are collected for single ionization and for very small scattering angles, i.e. (e, 2e), experimental data of double ionization (e, 3e)[1] and multiple ionization are scarce, because in most cases the efficiencies (mainly determined by solid angles) are extremely small for (e, 3e) processes, about 10-7~10-9. On the other hand, the new technique-reaction microscope can detect mutli-fragments in one collision with very

  15. Bounds on Subspace Codes Based on Subspaces of Type (m,1 in Singular Linear Space

    Directory of Open Access Journals (Sweden)

    You Gao

    2014-01-01

    Full Text Available The Sphere-packing bound, Singleton bound, Wang-Xing-Safavi-Naini bound, Johnson bound, and Gilbert-Varshamov bound on the subspace codes n+l,M,d,(m,1q based on subspaces of type (m,1 in singular linear space Fq(n+l over finite fields Fq are presented. Then, we prove that codes based on subspaces of type (m,1 in singular linear space attain the Wang-Xing-Safavi-Naini bound if and only if they are certain Steiner structures in Fq(n+l.

  16. The ancient function of RB-E2F Pathway: insights from its evolutionary history

    Directory of Open Access Journals (Sweden)

    Yang Xianmei

    2010-09-01

    Full Text Available Abstract Background The RB-E2F pathway is conserved in most eukaryotic lineages, including animals and plants. E2F and RB family proteins perform crucial functions in cycle controlling, differentiation, development and apoptosis. However, there are two kinds of E2Fs (repressive E2Fs and active E2Fs and three RB family members in human. Till now, the detail evolutionary history of these protein families and how RB-E2F pathway evolved in different organisms remain poorly explored. Results We performed a comprehensive evolutionary analysis of E2F, RB and DP (dimerization partners of E2Fs protein family in representative eukaryotic organisms. Several interesting facts were revealed. First, orthologues of RB, E2F, and DP family are present in several representative unicellular organisms and all multicellular organisms we checked. Second, ancestral E2F, RB genes duplicated before placozoans and bilaterians diverged, thus E2F family was divided into E2F4/5 subgroup (including repressive E2Fs: E2F4 and E2F5 and E2F1/2/3 subgroup (including active E2Fs: E2F1, E2F2 and E2F3, RB family was divided into RB1 subgroup (including RB1 and RBL subgroup (including RBL1 and RBL2. Third, E2F4 and E2F5 share more sequence similarity with the predicted E2F ancestral sequence than E2F1, E2F2 and E2F3; E2F4 and E2F5 also possess lower evolutionary rates and higher purification selection pressures than E2F1, E2F2 and E2F3. Fourth, for RB family, the RBL subgroup proteins possess lower evolutionary rates and higher purification selection pressures compared with RB subgroup proteins in vertebrates, Conclusions Protein evolutionary rates and purification selection pressures are usually linked with protein functions. We speculated that function conducted by E2F4/5 subgroup and RBL subgroup proteins might mainly represent the ancient function of RB-E2F pathway, and the E2F1/2/3 subgroup proteins and RB1 protein might contribute more to functional diversification in RB-E2F

  17. The ancient function of RB-E2F pathway: insights from its evolutionary history.

    Science.gov (United States)

    Cao, Lihuan; Peng, Bo; Yao, Lei; Zhang, Xinming; Sun, Kuan; Yang, Xianmei; Yu, Long

    2010-09-20

    The RB-E2F pathway is conserved in most eukaryotic lineages, including animals and plants. E2F and RB family proteins perform crucial functions in cycle controlling, differentiation, development and apoptosis. However, there are two kinds of E2Fs (repressive E2Fs and active E2Fs) and three RB family members in human. Till now, the detail evolutionary history of these protein families and how RB-E2F pathway evolved in different organisms remain poorly explored. We performed a comprehensive evolutionary analysis of E2F, RB and DP (dimerization partners of E2Fs) protein family in representative eukaryotic organisms. Several interesting facts were revealed. First, orthologues of RB, E2F, and DP family are present in several representative unicellular organisms and all multicellular organisms we checked. Second, ancestral E2F, RB genes duplicated before placozoans and bilaterians diverged, thus E2F family was divided into E2F4/5 subgroup (including repressive E2Fs: E2F4 and E2F5) and E2F1/2/3 subgroup (including active E2Fs: E2F1, E2F2 and E2F3), RB family was divided into RB1 subgroup (including RB1) and RBL subgroup (including RBL1 and RBL2). Third, E2F4 and E2F5 share more sequence similarity with the predicted E2F ancestral sequence than E2F1, E2F2 and E2F3; E2F4 and E2F5 also possess lower evolutionary rates and higher purification selection pressures than E2F1, E2F2 and E2F3. Fourth, for RB family, the RBL subgroup proteins possess lower evolutionary rates and higher purification selection pressures compared with RB subgroup proteins in vertebrates, Protein evolutionary rates and purification selection pressures are usually linked with protein functions. We speculated that function conducted by E2F4/5 subgroup and RBL subgroup proteins might mainly represent the ancient function of RB-E2F pathway, and the E2F1/2/3 subgroup proteins and RB1 protein might contribute more to functional diversification in RB-E2F pathway. Our results will enhance the current

  18. Locations of All Shotpoints, USGS Cruise M1-98-GM (GOM98SHTALLG.SHP)

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — All shotpoint locations from multichannel seismics survey, USGS cruise M1-98-GM. During June 1998 and April 1999, the U.S. Geological Survey (USGS) conducted two...

  19. Aflatoxin M1 levels in raw milk, pasteurized milk and infant formula

    National Research Council Canada - National Science Library

    Omar, Sharaf Shareef

    2016-01-01

    The incidence of contamination of aflatoxin M1 (AFM1) in milk samples collected from the Jordanian market was investigated by using the competitive enzyme linked immunosorbent assay (ELISA) technique...

  20. Experimental Conditions: SE24_S1_M1_D1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available rometry with 13C‑Labeling for Chemical Assignment of Sulfur-Containing Metabolites ...SE24_S1_M1_D1 SE24 Combination of Liquid Chromatography-Fourier Transform Ion Cyclotron Resonance-Mass Spect

  1. Towards Revised Step IV MICE Optics in the Absence of M1 SSD

    Energy Technology Data Exchange (ETDEWEB)

    Bayes, R. [Univ. of Glasgow, Scotland (United Kingdom); Berg, J. S. [Brookhaven National Lab. (BNL), Upton, NY (United States); Blackmore, V. [Imperial College, London (United Kingdom); Hunt, C. [Imperial College, London (United Kingdom); Liu, A. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Pasternak, J. [Imperial College, London (United Kingdom); Rogers, C. T. [Science and Technology Facilities Council (STFC), Oxford (United Kingdom). Rutherford Appleton Lab. (RAL)

    2015-10-01

    During magnet commissioning in September 2015, the leads on coil M1 of the downstream spectrometer solenoid failed. The coil will not be operational for MICE Step IV. Revised optics settings for the Step IV data taking are reviewed.

  2. Coiled-Coil Irregularities and Instabilities in Group A Streptococcus M1 Are Required for Virulence

    Energy Technology Data Exchange (ETDEWEB)

    McNamara, Case; Zinkernagel, Annelies S.; Macheboeuf, Pauline; Cunningham, Madeleine W.; Nizet, Victor; Ghosh, Partho (UO-HSC); (UCSD)

    2008-07-21

    Antigenically variable M proteins are major virulence factors and immunogens of the human pathogen group A Streptococcus (GAS). Here, we report the -3 angstrom resolution structure of a GAS M1 fragment containing the regions responsible for eliciting type-specific, protective immunity and for binding fibrinogen, which promotes M1 proinflammatory and antiphagocytic functions. The structure revealed substantial irregularities and instabilities throughout the coiled coil of the M1 fragment. Similar structural irregularities occur in myosin and tropomyosin, explaining the patterns of cross-reactivity seen in autoimmune sequelae of GAS infection. Sequence idealization of a large segment of the M1 coiled coil enhanced stability but diminished fibrinogen binding, proinflammatory effects, and antibody cross-reactivity, whereas it left protective immunogenicity undiminished. Idealized M proteins appear to have promise as vaccine immunogens.

  3. Presence of Aflatoxin M1 in Raw Milk for Human Consumption in Palestinian

    Directory of Open Access Journals (Sweden)

    Ibrahim Mahmoud AL ZUHEIR

    2012-09-01

    Full Text Available The absences or insufficient food control program result in the occurrence of mycotoxin in milk and milk products, which poses a serious risk for humans and can be a public health concern. This study was conducted to highlight the occurrence of aflatoxin M1 in Palestine raw milk collected at farms from Tulkarm, Nablus and Jenin. Aflatoxin M1 was determined by direct competitive ELISA technique. 85 % (34 of 40 of the total examined raw milk samples tested were positive. The aflatoxin M1 contamination levels were between 3 - 80 ppt with a mean of 29.57 ppt. There was a high incidence rate with 92 % (11 of 12 and the highest means of contaminated with aflatoxin M1 in the samples tested in Tulkarm city (P ≤ 0.05. 20 % of the analyzed samples (8 of 40 exceeded the maximum permissible limit (50 ppt in European Codex, with a range of 2 - 80 ppt.

  4. FoxM1 mediated resistance to gefitinib in non-small-cell lung cancer cells

    Institute of Scientific and Technical Information of China (English)

    Nuo XU; Xin ZHANG; Xun WANG; Hai-yan GE; Xiao-ying WANG; David GARFIELD; Ping YANG; Yuan-lin SONG; Chun-xue BAI

    2012-01-01

    Gefitinib is effective in only approximately 20% of patients with non-small-cell lung cancer (NSCLC),and the underlying mechanism remains unclear.FoxM1 is upregulated in NSCLC and associated with a poor prognosis in NSCLC patients.In this study,we examined the possible role of FoxM1 in gefitinib resistance and the related mechanisms.Methods:Gefitinib resistant human lung adenocarcinoma cell line SPC-A-1 and gefitinib-sensitive human lung mucoepidermoid carcinoma cell line NCI-H292 were used.mRNA and protein expression of FoxM1 and other factors were tested with quantitative RT PCR and Western blot analysis.RNA interference was performed to suppress FoxM1 expression in SPC-A-1 cells,and lentiviral infection was used to overexpress FoxM1 in H292 cells.MTT assay and flow cytometry were used to examine the proliferation and apoptosis of the cells.Results:Treatment of SPC-A-1 cells with gefitinib (1 and 10 μmol/L) upregulated the expression of FoxM1 in time- and concentrationdependent manners,while gefrtinib (1 μmol/L) downregulated in H292 cells.In SPC-A-1 cells treated with gefitinib (1 μmol/L),the expression of several downstream targets of FoxM1,including survivin,cyclin B1,SKP2,PLK1,Aurora B kinase and CDC25B,were significantly upregulated.Overexpression of FoxM1 increased the resistance in H292 cells,while attenuated FoxM1 expression restored the sensitivity to gefitinib in SPC-A-1 cells by inhibiting proliferation and inducing apoptosis.Conclusion:The results suggest that FoxM1 plays an important role in the resistance of NSCLC cells to gefitinib in vitro.FoxM1 could be used as a therapeutic target to overcome the resistance to gefitinib.

  5. Scattering properties of the 2 e-2 e+ polyelectronic system

    Science.gov (United States)

    Daily, K. M.; von Stecher, Javier; Greene, Chris H.

    2015-01-01

    We study the 2 e-2 e+ equal-mass charge-neutral four-body system in the adiabatic hyperspherical framework. The lowest few adiabatic potentials are calculated for zero orbital angular momentum, positive parity, and charge conjugation symmetries. Propagating the R matrix, the low-energy s -wave scattering lengths of the singlet-singlet and triplet-triplet spin configurations are calculated. Last, we calculate the S matrix for energies above the ionic threshold to estimate the transition rates between the single ionic fragmentation channel and the lowest few dimer-dimer fragmentation channels.

  6. Scattering properties of the $2e^-2e^+$ polyelectronic system

    CERN Document Server

    Daily, K M; Greene, Chris H

    2014-01-01

    We study the $2e^-2e^+$ equal-mass charge-neutral four-body system in the adiabatic hyperspherical framework. The lowest few adiabatic potentials are calculated for zero orbital angular momentum, positive parity, and charge conjugation symmetries. Propagating the R-matrix, the low-energy $s$-wave scattering lengths of the singlet-singlet and triplet-triplet spin configurations are calculated. Lastly, we calculate the S-matrix for energies above the ionic threshold to estimate the transition rates between the single ionic fragmentation channel and the lowest few dimer-dimer fragmentation channels.

  7. E-2-benzylidenebenzocyclanones. II. IR and mass spectrometric investigations

    Science.gov (United States)

    Tarczay, Gy; Vékey, K.; Ludányi, K.; Perjési, P.; Sohár, P.

    2000-03-01

    A series of E-2-benzylideneindanones (a) -tetralones (b) and -benzosuberones (c) with OCH 3 ( 2- 4), NO 2 ( 5- 7) and F ( 8- 10) substituents in ortho, meta or para position was studied by IR and mass spectrometry. The most important IR bands were assigned and stated correlations between some frequencies and the stereostructure or conjugation feature of the molecules investigated. IR spectra were also analyzed in order to find frequencies characteristic of the size of the alkanone ring. The mass spectrometric investigation aimed at determining fragmentation pathways and finding correlations between them and the ring size of the alkanone ring or the position of the substituents.

  8. q-differential operator representation of the quantum superalgebra Uq(sl(M+1|N+1))

    CERN Document Server

    Kimura, K

    1996-01-01

    A representation of the quantum superalgebra Uq(sl(M+1|N+1)) is constructed based on the q-differential operators acting on the coherent states parameterized by coordinates. These coordinates correspond to the local ones of the flag manifold. This realization provides us with a guide to construct the free field realization for the quantum affine superalgebra Uq^(sl(M+1|N+1)) at arbitrary level.

  9. Aflatoxin M1 Contamination in Milk and Milk Products in Iran: A Review

    Directory of Open Access Journals (Sweden)

    R. Kazemi Darsanaki

    2013-11-01

    Full Text Available Mycotoxins are secondary metabolites of molds and have adverse effects on humans, animals, and crops. Those can cause illnesses and economic losses. Aflatoxin M1 (AFM1 is one of the mycotoxins produced from the hydroxylated metabolite of aflatoxin B1 (AFB1. It can be found in milk or milk products obtained from livestock that have ingested contaminated feed. In this paper, recent studies were reviewed in aflatoxin M1 contamination in milk and milk products in Iran.

  10. Aflatoxin M1 Contamination in Milk and Milk Products in Iran: A Review

    Directory of Open Access Journals (Sweden)

    R. Kazemi Darsanaki

    2014-05-01

    Full Text Available Mycotoxins are secondary metabolites of molds and have adverse effects on humans, animals, and crops. Those can cause illnesses and economic losses. Aflatoxin M1 (AFM1 is one of the mycotoxins produced from the hydroxylated metabolite of aflatoxin B1 (AFB1. It can be found in milk or milk products obtained from livestock that have ingested contaminated feed. In this paper, recent studies were reviewed in aflatoxin M1 contamination in milk and milk products in Iran.

  11. The Evaluation of Aflatoxin M1 Level in Collected Raw Milk for Pasteurized Dairy

    Directory of Open Access Journals (Sweden)

    Ehsan Sadeghi

    2013-03-01

    Full Text Available Background: Aflatoxins are fungal toxins that have carcinogenic, cellular mutations and malformation effects. Aflatoxin M1 resists pasteurization, autoclave and the other methods that make foodstuff healthy. This study aims to determine the contents of aflatoxin M1 in raw milk of milk factories in Kermanshah province.Materials and Methods: This research is carried out through the descriptive-cross sectional method. Among the raw milk received by four pasteurized milk factories in Kermanshah, coded by (A, B, C, D labels, six samples, totally 320 samples (80 samples from each factory, were taken within four seasons. The concentration of aflatoxin M1 was examined by Enzyme-Linked Immunosorbent Assay (ELISA. The mean difference was analyzed statistically through t-test using SPSS software. Results: The content of aflatoxin was higher than Codex standard (0.5 µg/l in 295 samples. The total mean was 1.21, which exceeds two times the Codex standard. The highest and lowest contents of aflatoxin M1 were observed in “Factory D” in spring and in “Factory A” in autumn, respectively. There was a significant difference between contamination of aflatoxin M1 and different seasons (p< 0.05.Conclusion: High content of aflatoxin M1 in raw milk is worrying. Measuring the content of aflatoxin M1 is essential to reduce the toxin entering the daily food of animals and the other related factors. The considerable difference of aflatoxin M1 content between Factory D and Factory A can be attributed to the amount of the local milk and the industrial milk received by the factories.

  12. Emergence and oscillation of cosmic space by joining M1-branes

    Energy Technology Data Exchange (ETDEWEB)

    Sepehri, Alireza [Shahid Bahonar University, Faculty of Physics, Kerman (Iran, Islamic Republic of); Research Institute for Astronomy and Astrophysics of Maragha (RIAAM), Maragha (Iran, Islamic Republic of); Rahaman, Farook [Jadavpur University, Department of Mathematics, Kolkata, West Bengal (India); Capozziello, Salvatore [Universita di Napoli Federico II, Dipartimento di Fisica ' ' E. Pancini' ' , Naples (Italy); Gran Sasso Science Institute (INFN), L' Aquila (Italy); Tomsk State Pedagogical University, Tomsk (Russian Federation); INFN Sezione di Napoli, Naples (Italy); Ali, Ahmed Farag [Benha University, Department of Physics, Faculty of Science, Benha (Egypt); Pradhan, Anirudh [G L A University, Department of Mathematics, Institute of Applied Sciences and Humanities, Mathura, Uttar Pradesh (India)

    2016-05-15

    Recently, it has been proposed by Padmanabhan that the difference between the number of degrees of freedom on the boundary surface and the number of degrees of freedom in a bulk region leads to the expansion of the universe. Now, a natural question arises; how could this model explain the oscillation of the universe between contraction and expansion branches? We try to address this issue in the framework of a BIonic system. In this model, M0-branes join to each other and give rise to a pair of M1-anti-M1-branes. The fields which live on these branes play the roles of massive gravitons that cause the emergence of a wormhole between them and formation of a BIon system. This wormhole dissolves into M1-branes and causes a divergence between the number of degrees of freedom on the boundary surface of M1 and the bulk leading to an expansion of M1-branes. When M1-branes become close to each other, the square energy of their system becomes negative and some tachyonic states emerge. To remove these states, M1-branes become compact, the sign of compacted gravity changes, causing anti-gravity to arise: in this case, branes get away from each other. By articulating M1-BIons, an M3-brane and an anti-M3-brane are created and connected by three wormholes forming an M3-BIon. This new system behaves like the initial system and by closing branes to each other, they become compact and, by getting away from each other, they open. Our universe is located on one of these M3-branes and, by compactifying the M3-brane, it contracts and, by opening it, it expands. (orig.)

  13. Emergence and oscillation of cosmic space by joining M1-branes

    Science.gov (United States)

    Sepehri, Alireza; Rahaman, Farook; Capozziello, Salvatore; Ali, Ahmed Farag; Pradhan, Anirudh

    2016-05-01

    Recently, it has been proposed by Padmanabhan that the difference between the number of degrees of freedom on the boundary surface and the number of degrees of freedom in a bulk region leads to the expansion of the universe. Now, a natural question arises; how could this model explain the oscillation of the universe between contraction and expansion branches? We try to address this issue in the framework of a BIonic system. In this model, M0-branes join to each other and give rise to a pair of M1-anti- M1-branes. The fields which live on these branes play the roles of massive gravitons that cause the emergence of a wormhole between them and formation of a BIon system. This wormhole dissolves into M1-branes and causes a divergence between the number of degrees of freedom on the boundary surface of M1 and the bulk leading to an expansion of M1-branes. When M1-branes become close to each other, the square energy of their system becomes negative and some tachyonic states emerge. To remove these states, M1-branes become compact, the sign of compacted gravity changes, causing anti-gravity to arise: in this case, branes get away from each other. By articulating M1-BIons, an M3-brane and an anti- M3-brane are created and connected by three wormholes forming an M3-BIon. This new system behaves like the initial system and by closing branes to each other, they become compact and, by getting away from each other, they open. Our universe is located on one of these M3-branes and, by compactifying the M3-brane, it contracts and, by opening it, it expands.

  14. Enhanced M1/M2 macrophage ratio promotes orthodontic root resorption.

    Science.gov (United States)

    He, D; Kou, X; Luo, Q; Yang, R; Liu, D; Wang, X; Song, Y; Cao, H; Zeng, M; Gan, Y; Zhou, Y

    2015-01-01

    Mechanical force-induced orthodontic root resorption is a major clinical challenge in orthodontic treatment. Macrophages play an important role in orthodontic root resorption, but the underlying mechanism remains unclear. In this study, we examined the mechanism by which the ratio of M1 to M2 macrophage polarization affects root resorption during orthodontic tooth movement. Root resorption occurred when nickel-titanium coil springs were applied on the upper first molars of rats for 3 to 14 d. Positively stained odontoclasts or osteoclasts with tartrate-resistant acid phosphatase were found in resorption areas. Meanwhile, M1-like macrophages positive for CD68 and inducible nitric oxide synthase (iNOS) persistently accumulated on the compression side of periodontal tissues. In addition, the expressions of the M1 activator interferon-γ and the M1-associated pro-inflammatory cytokine tumor necrosis factor (TNF)-α were upregulated on the compression side of periodontal tissues. When the coil springs were removed at the 14th day after orthodontic force application, root resorption was partially rescued. The number of CD68(+)CD163(+) M2-like macrophages gradually increased on the compression side of periodontal tissues. The levels of M2 activator interleukin (IL)-4 and the M2-associated anti-inflammatory cytokine IL-10 also increased. Systemic injection of the TNF-α inhibitor etanercept or IL-4 attenuated the severity of root resorption and decreased the ratio of M1 to M2 macrophages. These data imply that the balance between M1 and M2 macrophages affects orthodontic root resorption. Root resorption was aggravated by an enhanced M1/M2 ratio but was partially rescued by a reduced M1/M2 ratio.

  15. Optical illusion alters M1 excitability after mirror therapy: a TMS study.

    Science.gov (United States)

    Läppchen, C H; Ringer, T; Blessin, J; Seidel, G; Grieshammer, S; Lange, R; Hamzei, F

    2012-11-01

    The contralesional primary motor cortex (M1) has been suggested to be involved in the motor recovery after mirror therapy, but whether the ipsilesional M1 is influenced by the contralesional M1 via transcallosal interhemispheric inhibition (IHI) is still unclear. The present study investigated the change of IHI as well as the intracortical inhibition and intracortical facilitation of both M1 induced by training in a mirror with the use of transcranial magnetic stimulation (TMS). In this 2 × 2 factorial design (time × group), healthy subjects exercised standardized motor skills with their right hand on four consecutive days. Either a mirror (mirror group) or a board (control group) was positioned between their hands. Before and after training TMS was applied along with training tests of both hands. Tests were the same motor skills exercised daily by both groups. Tests of the untrained left hand improved significantly more in the mirror group than in the control group after training (P = 0.02) and showed a close correlation with an increase of intracortical inhibition of M1(left). IHI did not show any difference between investigation time points and groups. The present study confirms the previous suggestion of the involvement of the "contralesional" left-side (ipsilateral to the hand behind the mirror) M1 after mirror therapy, which is not mediated by IHI. Even with the same motor skill training (both groups performed same motor skills) but with different visual information, different networks are involved in training-induced plasticity.

  16. Differential Roles of M1 and M2 Microglia in Neurodegenerative Diseases.

    Science.gov (United States)

    Tang, Yu; Le, Weidong

    2016-03-01

    One of the most striking hallmarks shared by various neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease (AD), and amyotrophic lateral sclerosis, is microglia-mediated neuroinflammation. Increasing evidence indicates that microglial activation in the central nervous system is heterogeneous, which can be categorized into two opposite types: M1 phenotype and M2 phenotype. Depending on the phenotypes activated, microglia can produce either cytotoxic or neuroprotective effects. In this review, we focus on the potential role of M1 and M2 microglia and the dynamic changes of M1/M2 phenotypes that are critically associated with the neurodegenerative diseases. Generally, M1 microglia predominate at the injury site at the end stage of disease, when the immunoresolution and repair process of M2 microglia are dampened. This phenotype transformation is very complicated in AD due to the phagocytosis of regionally distributed β-amyloid (Aβ) plaque and tangles that are released into the extracellular space. The endogenous stimuli including aggregated α-synuclein, mutated superoxide dismutase, Aβ, and tau oligomers exist in the milieu that may persistently activate M1 pro-inflammatory responses and finally lead to irreversible neuron loss. The changes of microglial phenotypes depend on the disease stages and severity; mastering the stage-specific switching of M1/M2 phenotypes within appropriate time windows may provide better therapeutic benefit.

  17. CDC25A phosphatase is a target of E2F and is required for efficient E2F-induced S phase

    DEFF Research Database (Denmark)

    Vigo, E; Müller, H; Prosperini, E

    1999-01-01

    in the absence of protein synthesis. Furthermore, CDC25A is defined as a novel E2F target whose expression can be directly regulated by E2F-1. Data showing that CDC25A is an essential target for E2F-1, since its activity is required for efficient induction of S phase by E2F-1, are provided. Finally, our results...... show that expression of two E2F target genes, namely CDC25A and cyclin E, is sufficient to induce entry into S phase in quiescent fibroblasts. Taken together, our results provide an important step in defining how E2F activity leads to deregulated proliferation....

  18. Estrogen sulfotransferase/SULT1E1 promotes human adipogenesis.

    Science.gov (United States)

    Ihunnah, Chibueze A; Wada, Taira; Philips, Brian J; Ravuri, Sudheer K; Gibbs, Robert B; Kirisci, Levent; Rubin, J Peter; Marra, Kacey G; Xie, Wen

    2014-05-01

    Estrogen sulfotransferase (EST/SULT1E1) is known to catalyze the sulfoconjugation and deactivation of estrogens. The goal of this study is to determine whether and how EST plays a role in human adipogenesis. By using human primary adipose-derived stem cells (ASCs) and whole-fat tissues from the abdominal subcutaneous fat of obese and nonobese subjects, we showed that the expression of EST was low in preadipocytes but increased upon differentiation. Overexpression and knockdown of EST in ASCs promoted and inhibited differentiation, respectively. The proadipogenic activity of EST in humans was opposite to the antiadipogenic effect of the same enzyme in rodents. Mechanistically, EST promoted adipogenesis by deactivating estrogens. The proadipogenic effect of EST can be recapitulated by using an estrogen receptor (ER) antagonist or ERα knockdown. In contrast, activation of ER in ASCs inhibited adipogenesis by decreasing the recruitment of the adipogenic peroxisome proliferator-activated receptor γ (PPARγ) onto its target gene promoters, whereas ER antagonism increased the recruitment of PPARγ to its target gene promoters. Linear regression analysis revealed a positive correlation between the expression of EST and body mass index (BMI), as well as a negative correlation between ERα expression and BMI. We conclude that EST is a proadipogenic factor which may serve as a druggable target to inhibit the turnover and accumulation of adipocytes in obese patients.

  19. Data of evolutionary structure change: 1E1QC-2HLDA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1E1QC-2HLDA 1E1Q 2HLD C A ADTSVDLEETGRVLSIGDGIARVHGLRNVQAEEMVEFSS...ELFYKGIRPAINVGLSVSRVGSAAQTRAMKQVAGTMKLELAQYREVAAFAQFGSDLDAATQQLLSRGVRLTELLKQGQYSPMAIEEQVAVIYAGVRGYLDKLEPSKIT...RPAINVGLSVSRVGSAAQVKALKQVAGSLKLFLAQYREVAAFAQS--DLDASTKQTLVRGERLTQLLKQNQYSPLATEEQV...> 0 2HLD A 2HLDA AFAQS--DLDA...ain> 1E1Q C 1E1QC AFAQFGSDLDA

  20. E2F-1 binding affinity for pRb is not the only determinant of the E2F-1 activity.

    Science.gov (United States)

    Sahin, Fikret; Sladek, Todd L

    2010-07-04

    E2F-1 is the major cellular target of pRB and is regulated by pRB during cell proliferation. Interaction between pRB and E2F-1 is dependent on the phosphorylation status of pRB. Despite the fact that E2F-1 and pRB have antagonistic activities when they are overexpressed, the role of the E2F-1-pRB interaction in cell growth largely remains unknown. Ideally, it would be better to study the properties of a pRB mutant that fails to bind to E2F, but retains all other activities. To date, no pRB mutation has been characterized in sufficient detail to show that it specifically eliminates E2F binding but leaves other interactions intact. An alternative approach to this issue is to ask whether mutations that change E2F proteins binding affinity to pRB are sufficient to change cell growth in aspect of cell cycle and tumor formation. Therefore, we used the E2F-1 mutants including E2F-1/S332-7A, E2F-1/S375A, E2F-1/S403A, E2F-1/Y411A and E2F-1/L132Q that have different binding affinities for pRB to better understand the roles of the E2F-1 phosphorylation and E2F-1-pRB interaction in the cell cycle, as well as in transformation and gene expression. Data presented in this study suggests that in vivo phosphorylation at amino acids 332-337, 375 and 403 is important for the E2F-1 and pRB interaction in vivo. However, although E2F-1 mutants 332-7, 375 and 403 showed similar binding affinity to pRB, they showed different characteristics in transformation efficiency, G(0) accumulation, and target gene experiments.

  1. The Plasmodium falciparum malaria M1 alanyl aminopeptidase (PfA-M1: insights of catalytic mechanism and function from MD simulations.

    Directory of Open Access Journals (Sweden)

    Peter M Jones

    Full Text Available Malaria caused by several species of Plasmodium is major parasitic disease of humans, causing 1-3 million deaths worldwide annually. The widespread resistance of the human parasite to current drug therapies is of major concern making the identification of new drug targets urgent. While the parasite grows and multiplies inside the host erythrocyte it degrades the host cell hemoglobin and utilizes the released amino acids to synthesize its own proteins. The P. falciparum malarial M1 alanyl-aminopeptidase (PfA-M1 is an enzyme involved in the terminal stages of hemoglobin digestion and the generation of an amino acid pool within the parasite. The enzyme has been validated as a potential drug target since inhibitors of the enzyme block parasite growth in vitro and in vivo. In order to gain further understanding of this enzyme, molecular dynamics simulations using data from a recent crystal structure of PfA-M1 were performed. The results elucidate the pentahedral coordination of the catalytic Zn in these metallo-proteases and provide new insights into the roles of this cation and important active site residues in ligand binding and in the hydrolysis of the peptide bond. Based on the data, we propose a two-step catalytic mechanism, in which the conformation of the active site is altered between the Michaelis complex and the transition state. In addition, the simulations identify global changes in the protein in which conformational transitions in the catalytic domain are transmitted at the opening of the N-terminal 8 Å-long channel and at the opening of the 30 Å-long C-terminal internal chamber that facilitates entry of peptides to the active site and exit of released amino acids. The possible implications of these global changes with regard to enzyme function are discussed.

  2. M1 contributes to the intrinsic but not the extrinsic components of motor-skills.

    Science.gov (United States)

    Romei, Vincenzo; Thut, Gregor; Ramos-Estebanez, Ciro; Pascual-Leone, Alvaro

    2009-10-01

    Procedural skills consist of several components that can be simultaneously acquired. During a motor-learning task we can distinguish between how a "movement" is performed (intrinsic component) and the spatial-related (extrinsic) component of this movement. The intrinsic movement component is thought to be supported by motor loops, including primary motor cortex (M1) as assessed with neuroimaging studies. Here we want to test further whether M1 makes a critical contribution to the movement rather than spatial-related component of skill-learning. To this purpose, we used repetitive Transcranial Magnetic Stimulation (rTMS) and the serial reaction time (SRT) task. Twenty right-handed participants performed the SRT-task starting with their left or right hand. After this learning session, participants switched to the untrained hand by performing original (spatial-related) and mirror-ordered (movement-based) sequences. rTMS was applied to M1 ipsi- or contralateral to the transfer-hand and both sequences were retested. Results revealed rTMS-interference with motor-skill transfer of mirror-ordered but not original sequences, showing that M1 is critically involved in the retrieval/transformation of the intrinsic but not the extrinsic movement coordinates. rTMS-interference in the mirror-condition consisted of both (i) disruption and (ii) release of motor-skill transfer depending on the stimulated hemisphere and on transfer-hand. The pattern of results suggests (i) contralateral (right) M1 involvement in retrieval/transformation of motor information during left-hand reproduction of previously acquired right-hand motor-skills; and (ii) modulatory interactions of inhibitory nature from the dominant (left) to the non-dominant (right) M1 in the same transfer-condition. These results provide further evidence that M1 is essential to intrinsic movement-based skill-learning and novel insight on models of motor-learning and hemispheric specialization, suggesting the involvement of

  3. Neoglycolipid analogues of ganglioside G sub M1 as functional receptors of cholera toxin

    Energy Technology Data Exchange (ETDEWEB)

    Pacuszka, T.; Bradley, R.M.; Fishman, P.H. (National Inst. of Health, Bethesda, MD (United States))

    1991-03-12

    The authors synthesized several lipid analogues of ganglioside G{sub M1} by attaching its oligosaccharide moiety (G{sub M1}OS) to aminophospholipids, aliphatic amines, and cholesteryl hemisuccinate. They incubated G{sub M1}-deficient rat glioma C6 cells with each of the derivatives as well as native G{sub M1} and assayed the cells for their ability to bind and respond to cholera toxin. On the basis of the observed increase in binding of {sup 125}I-labeled cholera toxin, it was apparent that the cells took up and initially incorporated most of the derivatives into the plasma membrane. In the case of the aliphatic amine derivatives, the ability to generate new toxin binding sites was dependent on chain length; whereas the C{sub 10} derivative was ineffective, C{sub 12} and higher analogues were effective. Increased binding was dependent on both the concentration of the neoglycolipid in the medium and the time of exposure. Cells pretreated with the various derivatives accumulated cyclic AMP in response to cholera toxin, but there were differences in their effectiveness. The cholesterol and long-chain aliphatic amine derivatives were more effective than native G{sub M1}, whereas the phospholipid derivatives were less effective. The distance between G{sub M1}OS and the phospholipid also appeared to influence its functional activity. The results indicate that although G{sub M1}OS provides the recognition site for the binding of cholera toxin, the nature of the lipid moiety plays an important role in the action of the toxin.

  4. Curcumin retunes cholesterol transport homeostasis and inflammation response in M1 macrophage to prevent atherosclerosis.

    Science.gov (United States)

    Chen, Fang-Yuan; Zhou, Juan; Guo, Ning; Ma, Wang-Ge; Huang, Xin; Wang, Huan; Yuan, Zu-Yi

    2015-11-27

    Lipoprotein cholesterol metabolism dysfunction in the arterial wall is a major contributor to atherosclerosis, and excessive lipid intake and failed cholesterol homeostasis may accelerate the atherogenic process. Curcumin exerts multiple effects by alleviating inflammation, hyperlipidemia, and atherosclerosis; however, its role in cholesterol transport homeostasis and its underlying impact on inflammatory M1 macrophages are poorly understood. This work aimed to investigate the effect of curcumin on cholesterol transport, the inflammatory response and cell apoptosis in M1 macrophages. RAW264.7 macrophages (M0) were induced with LPS plus IFN-γ for 12 h to develop a M1 subtype and were then incubated with curcumin at different concentrations (6.25 and 12.5 μmol/L) in the presence or absence of oxLDL. Then, cholesterol influx/efflux and foam cell formation as well as inflammation and apoptosis were evaluated. It was found that curcumin increased cholesterol uptake measured by the Dil-oxLDL binding assay, and simultaneously increased cholesterol efflux carried out by Apo-A1 and HDL in M1 cells. Curcumin further reinforced ox-LDL-induced cholesterol esterification and foam cell formation as determined by Oil Red O and BODIPY staining. Moreover, curcumin dramatically reduced ox-LDL-induced cytokine production such as IL-1β, IL-6 as well as TNF-α and M1 cell apoptosis. We also found that curcumin upregulated CD36 and ABCA1 in M1 macrophages. Curcumin increased PPARγ expression, which in turn promoted CD36 and ABCA1 expression. In conclusion, curcumin may increase the ability of M1 macrophages to handle harmful lipids, thus promoting lipid processing, disposal and removal, which may support cholesterol homeostasis and exert an anti-atherosclerotic effect.

  5. Electrical dipole polarizability and spin M1 strength from {sup 48}Ca(p,p') data under 0; Elektrische Dipol-Polarisierbarkeit und Spin-M1-Staerke aus {sup 48}Ca(p,p')-Daten unter 0

    Energy Technology Data Exchange (ETDEWEB)

    Birkhan, Jonny Hubertus

    2016-07-01

    In this thesis, proton scattering data on the nucleus {sup 48}Ca at very forward angles had been analysed. The data stem from a measurement campaign which was launched at the Research Centre of Nuclear Physics at Osaka, Japan, in the past. One of the two objectives of this analysis was to extract a value for the static electric dipole polarisability from the isovector giant dipole resonance (IVGDR). The second objective was to extract the total electromagnetic M1 strength B(M1) of the spin-flip transition which excites the prominent 1{sup +} state at an excitation energy of E{sub x}=10.22 MeV. The polarisability was calculated from the distribution of photo-absorption cross sections within an energy range from E{sub x}=11 MeV to E{sub x}=26 MeV. The photo-absorption cross sections had been deduced from the distribution of E1 cross sections by the method of virtual photons. For this purpose the experimental cross sections had been deconvoluted by a multipole deconvolution into an E1 part and a background part. Then, the best estimate of the polarisability is given by α{sub D}=(1.36±0.14) fm{sup 3}. If a E3 model was included into the multipole decomposition of the (p,p') data the result increased up to α{sub D}=(1.50±0.09) fm{sup 3}. The deviation between these two results is mainly due to the fact that the multipole decomposition is very sensitive on the background function. Assuming that the the IVGDR of the nuclei {sup 48}Ca and {sup 40}Ca have approximately the same structure, estimates for the polarisability of the nucleus {sup 48}Ca could be drawn from {sup 40}Ca(γ,abs) data. Additionally, data from a {sup 48}Ca(e,e'n) measurement were used to estimate the polarisability of the nucleus {sup 48}Ca. Its polarisability seems to fall within the range of α{sub D}=(1.50±0.09) fm{sup 3} and α{sub D}=(1.69±0.03) fm{sup 3}. Beside this, it could be shown by the {sup 40}Ca data that a significant contribution to the polarisability has to be expected

  6. Electrical dipole polarizability and spin M1 strength from {sup 48}Ca(p,p') data under 0; Elektrische Dipol-Polarisierbarkeit und Spin-M1-Staerke aus {sup 48}Ca(p,p')-Daten unter 0

    Energy Technology Data Exchange (ETDEWEB)

    Birkhan, Jonny Hubertus

    2016-07-01

    In this thesis, proton scattering data on the nucleus {sup 48}Ca at very forward angles had been analysed. The data stem from a measurement campaign which was launched at the Research Centre of Nuclear Physics at Osaka, Japan, in the past. One of the two objectives of this analysis was to extract a value for the static electric dipole polarisability from the isovector giant dipole resonance (IVGDR). The second objective was to extract the total electromagnetic M1 strength B(M1) of the spin-flip transition which excites the prominent 1{sup +} state at an excitation energy of E{sub x}=10.22 MeV. The polarisability was calculated from the distribution of photo-absorption cross sections within an energy range from E{sub x}=11 MeV to E{sub x}=26 MeV. The photo-absorption cross sections had been deduced from the distribution of E1 cross sections by the method of virtual photons. For this purpose the experimental cross sections had been deconvoluted by a multipole deconvolution into an E1 part and a background part. Then, the best estimate of the polarisability is given by α{sub D}=(1.36±0.14) fm{sup 3}. If a E3 model was included into the multipole decomposition of the (p,p') data the result increased up to α{sub D}=(1.50±0.09) fm{sup 3}. The deviation between these two results is mainly due to the fact that the multipole decomposition is very sensitive on the background function. Assuming that the the IVGDR of the nuclei {sup 48}Ca and {sup 40}Ca have approximately the same structure, estimates for the polarisability of the nucleus {sup 48}Ca could be drawn from {sup 40}Ca(γ,abs) data. Additionally, data from a {sup 48}Ca(e,e'n) measurement were used to estimate the polarisability of the nucleus {sup 48}Ca. Its polarisability seems to fall within the range of α{sub D}=(1.50±0.09) fm{sup 3} and α{sub D}=(1.69±0.03) fm{sup 3}. Beside this, it could be shown by the {sup 40}Ca data that a significant contribution to the polarisability has to be expected

  7. Construction of a mouse Aos1-Uba2 chimeric SUMO-E1 enzyme, mAU, and its expression in baculovirus-insect cells

    Science.gov (United States)

    Nakayama, Tomofumi; Yuasa, Eri; Kanemaru, Ayumi; Saito, Masayuki; Saitoh, Hisato

    2014-01-01

    Small ubiquitin-related modifier (SUMO) is a highly conserved protein that is covalently attached to target proteins. This posttranslational modification, designated SUMOylation, is a major protein-conjugation-driven strategy designed to regulate structure and function of cellular proteins. SUMOylation consists of an enzymatic cascade involving the E1-activating enzyme and the E2-conjugating enzyme. The SUMO-E1 enzyme consists of two subunits, a heterodimer of activation of Smt3p 1 (Aos1) and ubiquitin activating enzyme 2 (Uba2), which resembles the N- and C-terminal halves of ubiquitin E1 (Uba1). Herein, we describe the rational design of a single polypeptide version of SUMO-E1, a chimera of mouse Aos1 and Uba2 subunits, termed mAU, in which the functional domains appear to be arranged in a fashion similar to Uba1. We also describe the construction of a mAU plasmid for expression in a baculovirus-insect cell system and present an in situ SUMOylation assay using the recombinant mAU. Our results showed that mAU has SUMO-E1 activity, thereby indicating that mAU can be expressed in baculovirus-insect cells and represents a suitable source of SUMO-E1. PMID:24637489

  8. Peroxiredoxin II promotes hepatic tumorigenesis through cooperation with Ras/Forkhead box M1 signaling pathway.

    Science.gov (United States)

    Park, Y-H; Kim, S-U; Kwon, T-H; Kim, J-M; Song, I-S; Shin, H-J; Lee, B-K; Bang, D-H; Lee, S-J; Lee, D-S; Chang, K-T; Kim, B-Y; Yu, D-Y

    2016-07-07

    The current study was carried out to define the involvement of Peroxiredoxin (Prx) II in progression of hepatocellular carcinoma (HCC) and the underlying molecular mechanism(s). Expression and function of Prx II in HCC was determined using H-ras(G12V)-transformed HCC cells (H-ras(G12V)-HCC cells) and the tumor livers from H-ras(G12V)-transgenic (Tg) mice and HCC patients. Prx II was upregulated in H-ras(G12V)-HCC cells and H-ras(G12V)-Tg mouse tumor livers, the expression pattern of which highly similar to that of forkhead Box M1 (FoxM1). Moreover, either knockdown of FoxM1 or site-directed mutagenesis of FoxM1-binding site of Prx II promoter significantly reduced Prx II levels in H-ras(G12V)-HCC cells, indicating FoxM1 as a direct transcription factor of Prx II in HCC. Interestingly, the null mutation of Prx II markedly decreased the number and size of tumors in H-ras(G12V)-Tg livers. Consistent with this, knockdown of Prx II in H-ras(G12V)-HCC cells reduced the expression of cyclin D1, cell proliferation, anchorage-independent growth and tumor formation in athymic nude mice, whereas overexpression of Prx II increased or aggravated the tumor phenotypes. Importantly, the expression of Prx II was correlated with that of FoxM1 in HCC patients. The activation of extracellular signal-related kinase (ERK) pathway and the expression of FoxM1 and cyclin D1 were highly dependent on Prx II in H-ras(G12V)-HCC cells and H-ras(G12V)-Tg livers. Prx II is FoxM1-dependently-expressed antioxidant in HCC and function as an enhancer of Ras(G12V) oncogenic potential in hepatic tumorigenesis through activation of ERK/FoxM1/cyclin D1 cascade.

  9. Reassessing embryogenesis in the Ctenophora: the inductive role of e1 micromeres in organizing ctene row formation in the 'mosaic' embryo, Mnemiopsis leidyi.

    Science.gov (United States)

    Martindale, M Q; Henry, J Q

    1997-05-01

    Ctenophores are a phylum of diploblastic marine animals displaying biradial symmetry organized along an oral-aboral axis. One of the apomorphic sets of adult structures in ctenophores are the eight external comb rows, which run along the oral-aboral axis. Comb rows consist of serial arrays of individual comb plates of cilia, which beat in a coordinated fashion for locomotory behavior. Classical cell lineage experiments using chalk particles indicated that comb rows are derived exclusively from the four e1 micromeres at the 16-cell stage. This conclusion was also supported by the fact that no ctene rows (or their underlying endodermal canals) form when all four e1 micromeres were deleted. We have used intracellular diI cell lineage tracing to determine that, in addition to e1 micromeres, the four m1 micromeres also make significant contributions to the ctene rows. Thus, e1 micromere derivatives not only generate comb plates but are required for ctene row formation by m1 derivatives. These results demonstrate that inductive interactions are an important component of early development in ctenophores and indicate that e1 micromeres influence the development of adjacent cell lineages (both m1 and endodermal lineages) during ctenophore embryogenesis. In addition, intracellular labeling has revealed that there are subtle variations in the composition of clones derived from identified embryonic blastomeres. Together these findings reveal a picture of ctenophore embryogenesis, which is in marked contrast to the former rigid 'mosaic' reputation of ctenophore development, and invite speculation as to the role of the cleavage program in embryonic patterning in the lower Metazoa.

  10. Mice Lacking M1 and M3 Muscarinic Acetylcholine Receptors Have Impaired Odor Discrimination and Learning

    Science.gov (United States)

    Chan, Wilson; Singh, Sanmeet; Keshav, Taj; Dewan, Ramita; Eberly, Christian; Maurer, Robert; Nunez-Parra, Alexia; Araneda, Ricardo C.

    2017-01-01

    The cholinergic system has extensive projections to the olfactory bulb (OB) where it produces a state-dependent regulation of sensory gating. Previous work has shown a prominent role of muscarinic acetylcholine (ACh) receptors (mAChRs) in regulating the excitability of OB neurons, in particular the M1 receptor. Here, we examined the contribution of M1 and M3 mAChR subtypes to olfactory processing using mice with a genetic deletion of these receptors, the M1−/− and the M1/M3−/− knockout (KO) mice. Genetic ablation of the M1 and M3 mAChRs resulted in a significant deficit in odor discrimination of closely related molecules, including stereoisomers. However, the discrimination of dissimilar molecules, social odors (e.g., urine) and novel object recognition was not affected. In addition the KO mice showed impaired learning in an associative odor-learning task, learning to discriminate odors at a slower rate, indicating that both short and long-term memory is disrupted by mAChR dysfunction. Interestingly, the KO mice exhibited decreased olfactory neurogenesis at younger ages, a deficit that was not maintained in older animals. In older animals, the olfactory deficit could be restored by increasing the number of new born neurons integrated into the OB after exposing them to an olfactory enriched environment, suggesting that muscarinic modulation and adult neurogenesis could be two different mechanism used by the olfactory system to improve olfactory processing. PMID:28210219

  11. Dynamic Changes of Microglia/Macrophage M1 and M2 Polarization in Theiler's Murine Encephalomyelitis.

    Science.gov (United States)

    Herder, Vanessa; Iskandar, Cut Dahlia; Kegler, Kristel; Hansmann, Florian; Elmarabet, Suliman Ahmed; Khan, Muhammad Akram; Kalkuhl, Arno; Deschl, Ulrich; Baumgärtner, Wolfgang; Ulrich, Reiner; Beineke, Andreas

    2015-11-01

    Microglia and macrophages play a central role for demyelination in Theiler's murine encephalomyelitis (TME) virus infection, a commonly used infectious model for chronic-progressive multiple sclerosis. In order to determine the dynamic changes of microglia/macrophage polarization in TME, the spinal cord of Swiss Jim Lambert (SJL) mice was investigated by gene expression profiling and immunofluorescence. Virus persistence and demyelinating leukomyelitis were confirmed by immunohistochemistry and histology. Electron microscopy revealed continuous myelin loss together with abortive myelin repair during the late chronic infection phase indicative of incomplete remyelination. A total of 59 genes out of 151 M1- and M2-related genes were differentially expressed in TME virus-infected mice over the study period. The onset of virus-induced demyelination was associated with a dominating M1 polarization, while mounting M2 polarization of macrophages/microglia together with sustained prominent M1-related gene expression was present during the chronic-progressive phase. Molecular results were confirmed by immunofluorescence, showing an increased spinal cord accumulation of CD16/32(+) M1-, arginase-1(+) M2- and Ym1(+) M2-type cells associated with progressive demyelination. The present study provides a comprehensive database of M1-/M2-related gene expression involved in the initiation and progression of demyelination supporting the hypothesis that perpetuating interaction between virus and macrophages/microglia induces a vicious circle with persistent inflammation and impaired myelin repair in TME.

  12. Reverse phase liquid chromatographic determination and confirmation of aflatoxin M1 in cheese.

    Science.gov (United States)

    Hisada, K; Terada, H; Yamamoto, K; Tsubouchi, H; Sakabe, Y

    1984-01-01

    A systematic method is proposed for determination and confirmation of aflatoxin M1 in cheese by liquid chromatography (LC). A sample of cheese is extracted with chloroform, cleaned up on 2 silica gel columns followed by a Sep-Pak C18 cartridge, and chromatographed on a 5 microns octadecyl silica column with fluorometric detection. The sample extract or standard is treated with n-hexane-trifluoroacetic acid (TFA) (4 + 1) for 30 min at 40 degrees C. Analysis by LC with TFA-treatment of the extract provides quantitative data. Multiple assays of 5 samples of Gouda cheese spiked with aflatoxin M1 at levels of 0.5, 0.1, and 0.05 ng/g showed average recoveries of 93.2, 91.6, and 92.4%, with coefficients of variation of 2.63, 3.97, and 4.52%, respectively. Assay of 5 naturally contaminated cheeses resulted in 0.051-0.448 ng/g of aflatoxin M1. Limit of quantitation is about 0.01 ng/g. The identity of aflatoxin M1 is confirmed by treating aflatoxin M1 or the M2a derivative with TFA-methanol (or ethanol) (3 + 1). The TFA-methanol reaction products of M2a could be detected quantitatively.

  13. Crystal structure of (E-2-hydroxy-4′-methoxyazastilbene

    Directory of Open Access Journals (Sweden)

    Suchada Chantrapromma

    2015-06-01

    Full Text Available The title azastilbene derivative, C14H13NO2 {systematic name: (E-2-[(4-methoxybenzylideneamino]phenol}, is a product of the condensation reaction between 4-methoxybenzaldehyde and 2-aminophenol. The molecule adopts an E conformation with respect to the azomethine C=N bond and is almost planar, the dihedral angle between the two substituted benzene rings being 3.29 (4°. The methoxy group is coplanar with the benzene ring to which it is attached, the Cmethyl—O—C—C torsion angle being −1.14 (12°. There is an intramolecular O—H...N hydrogen bond generating an S(5 ring motif. In the crystal, molecules are linked via C—H...O hydrogen bonds, forming zigzag chains along [10-1]. The chains are linked via C—H...π interactions, forming a three-dimensional structure.

  14. Spectrin’s chimeric E2/E3 enzymatic activity

    Science.gov (United States)

    Goodman, Steven R; Petrofes Chapa, Rachel

    2015-01-01

    In this minireview, we cover the discovery of the human erythrocyte α spectrin E2/E3 ubiquitin conjugating/ligating enzymatic activity and the specific cysteines involved. We then discuss the consequences when this activity is partially inhibited in sickle cell disease and the possibility that the same attenuation is occurring in multiple organ dysfunction syndrome. We finish by discussing the reasons for believing that nonerythroid α spectrin isoforms (I and II) also have this activity and the importance of testing this hypothesis. If correct, this would suggest that the nonerythroid spectrin isoforms play a major role in protein ubiquitination in all cell types. This would open new fields in experimental biology focused on uncovering the impact that this enzymatic activity has upon protein–protein interactions, protein turnover, cellular signaling, and many other functions impacted by spectrin, including DNA repair. PMID:26283706

  15. Triply differential (e,2e) studies of phenol

    Energy Technology Data Exchange (ETDEWEB)

    Silva, G. B. da [School of Chemical and Physical Sciences, Flinders University, GPO Box 2100, Adelaide, South Australia 5001 (Australia); Universidade Federal de Mato Grosso, Barra do Garças, MT 78600-000 (Brazil); Neves, R. F. C. [School of Chemical and Physical Sciences, Flinders University, GPO Box 2100, Adelaide, South Australia 5001 (Australia); Instituto Federal do Sul de Minas Gerais, Câmpus Poços de Caldas, MG (Brazil); Departamento de Física, UFJF, Juiz de Fora, 36036-330, MG (Brazil); Chiari, L.; Jones, D. B. [School of Chemical and Physical Sciences, Flinders University, GPO Box 2100, Adelaide, South Australia 5001 (Australia); Ali, E.; Madison, D. H. [Department of Physics, Missouri University of Science and Technology, Rolla, Missouri 65409 (United States); Ning, C. G. [Department of Physics, State Key Laboratory of Low-Dimensional Quantum Physics, Tsinghua University, Beijing 100084 (China); Nixon, K. L.; Lopes, M. C. A. [Departamento de Física, UFJF, Juiz de Fora, 36036-330, MG (Brazil); Brunger, M. J., E-mail: Michael.Brunger@flinders.edu.au [School of Chemical and Physical Sciences, Flinders University, GPO Box 2100, Adelaide, South Australia 5001 (Australia); Institute of Mathematical Sciences, University of Malaya, 50603 Kuala Lumpur (Malaysia)

    2014-09-28

    We have measured (e,2e) triple differential cross sections (TDCS) for the electron-impact ionisation of phenol with coplanar asymmetrical kinematics for an incident electron energy of 250 eV. Experimental measurements of the angular distribution of the slow outgoing electrons at 20 eV are obtained when the incident electron scatters through angles of −5°, −10°, and −15°, respectively. The TDCS data are compared with calculations performed within the molecular 3-body distorted wave model. In this case, a mixed level of agreement, that was dependent on the kinematical condition being probed, was observed between the theoretical and experimental results in the binary peak region. The experimental intensity of the recoil features under all kinematical conditions was relatively small, but was still largely underestimated by the theoretical calculations.

  16. The Search For The Cp-violating Emission Of An E1 Photon From The Kaon Long Decays To Positive Pion Negative Pion Gamma

    CERN Document Server

    Shields, J M

    2005-01-01

    A search for the CP-violating electric dipole (E1) direct emission contribution to the KL → π+π −γ decay is performed using data from the 1997 KTeV/E832 experiment. Because the KL → π +π−γ decay mode is massively dominated by the CP-violating inner bremsstrahlung (IB) and the CP-conserving magnetic dipole (M1) direct emission processes, previous analyses have neglected the E1 contribution. Therefore, this measurement is the first attempt to directly quantify the size of the E1 decay process. This E1 transition is one of the very few CP-violating processes that is accessible to experiment and, in principle, will produce new insights into the structure of the neutral kaon. The result of this analysis is that the E1 contribution is below the threshold of sensitivity, and therefore an upper bound of |g E1| < 0.14 (90% CL) is reported. In the process of obtaining this upper limit, high resolution measurements of fit parame...

  17. M1 muscarinic acetylcholine receptor agonism alters sleep without affecting memory consolidation.

    Science.gov (United States)

    Nissen, Christoph; Power, Ann E; Nofzinger, Eric A; Feige, Bernd; Voderholzer, Ulrich; Kloepfer, Corinna; Waldheim, Bernhard; Radosa, Marc-Philipp; Berger, Mathias; Riemann, Dieter

    2006-11-01

    Preclinical studies have implicated cholinergic neurotransmission, specifically M1 muscarinic acetylcholine receptor (mAChR) activation, in sleep-associated memory consolidation. In the present study, we investigated the effects of administering the direct M1 mAChR agonist RS-86 on pre-post sleep memory consolidation. Twenty healthy human participants were tested in a declarative word-list task and a procedural mirror-tracing task. RS-86 significantly reduced rapid eye movement (REM) sleep latency and slow wave sleep (SWS) duration in comparison with placebo. Presleep acquisition and postsleep recall rates were within the expected ranges. However, recall rates in both tasks were almost identical for the RS-86 and placebo conditions. These results indicate that selective M1 mAChR activation in healthy humans has no clinically relevant effect on pre-post sleep consolidation of declarative or procedural memories at a dose that reduces REM sleep latency and SWS duration.

  18. Attenuation of cocaine's reinforcing and discriminative stimulus effects via muscarinic M1 acetylcholine receptor stimulation

    DEFF Research Database (Denmark)

    Thomsen, Morgane; Conn, P Jeffrey; Lindsley, Craig

    2010-01-01

    Muscarinic cholinergic receptors modulate dopaminergic function in brain pathways thought to mediate cocaine's abuse-related effects. Here, we sought to confirm and extend in the mouse species findings that nonselective muscarinic receptor antagonists can enhance cocaine's discriminative stimulus....... More importantly, we tested the hypothesis that muscarinic receptor agonists with varied receptor subtype selectivity can blunt cocaine's discriminative stimulus and reinforcing effects; we hypothesized a critical role for the M(1) and/or M(4) receptor subtypes in this modulation. Mice were trained...... to discriminate cocaine from saline, or to self-administer intravenous cocaine chronically. The nonselective muscarinic antagonists scopolamine and methylscopolamine, the nonselective muscarinic agonists oxotremorine and pilocarpine, the M(1)/M(4)-preferring agonist xanomeline, the putative M(1)-selective agonist...

  19. Nonlinear {omega}*-stabilization of the m = 1 mode in tokamaks

    Energy Technology Data Exchange (ETDEWEB)

    Rogers, B. [Univ. of Maryland, College Park, MD (United States). Inst. for Plasma Research; Zakharov, L. [Princeton Univ., NJ (United States). Plasma Physics Lab.

    1995-08-01

    Earlier studies of sawtooth oscillations in Tokamak Fusion Test Reactor supershots (Levinton et al, Phys. Rev. Lett. 72, 2895 (1994); Zakharov, et al, Plasma Phys. and Contr. Nucl. Fus. Res., Proc. 15th Int. Conf., Seville 1994, Vienna) have found an apparent contradiction between conventional linear theory and experiment: even in sawtooth-free discharges, the theory typically predicts instability due to a nearly ideal m = 1 mode. Here, the nonlinear evolution of such mode is analyzed using numerical simulations of a two-fluid magnetohydrodynamic (MHD) model. We find the mode saturates nonlinearly at a small amplitude provided the ion and electron drift-frequencies {omega}*{sub i,e} are somewhat above the linear stability threshold of the collisionless m = 1 reconnecting mode. The comparison of the simulation results to m = 1 mode activity in TFTR suggests additional, stabilizing effects outside the present model are also important.

  20. Prostaglandin E2-induced colonic secretion in patients with and without colorectal neoplasia

    Directory of Open Access Journals (Sweden)

    Poulsen Steen S

    2010-01-01

    Full Text Available Abstract Background The pathogenesis for colorectal cancer remains unresolved. A growing body of evidence suggests a direct correlation between cyclooxygenase enzyme expression, prostaglandin E2 metabolism and neoplastic development. Thus further understanding of the regulation of epithelial functions by prostaglandin E2 is needed. We hypothesized that patients with colonic neoplasia have altered colonic epithelial ion transport and express functionally different prostanoid receptor levels in this respect. Methods Patients referred for colonoscopy were included and grouped into patients with and without colorectal neoplasia. Patients without endoscopic findings of neoplasia served as controls. Biopsy specimens were obtained from normally appearing mucosa in the sigmoid part of colon. Biopsies were mounted in miniaturized modified Ussing air-suction chambers. Indomethacin (10 μM, various stimulators and inhibitors of prostanoid receptors and ion transport were subsequently added to the chamber solutions. Electrogenic ion transport parameters (short circuit current and slope conductance were recorded. Tissue pathology and tissue damage before and after experiments was assessed by histology. Results Baseline short circuit current and slope conductance did not differ between the two groups. Patients with neoplasia were significantly more sensitive to indomethacin with a decrease in short circuit current of 15.1 ± 2.6 μA·cm-2 compared to controls, who showed a decrease of 10.5 ± 2.1 μA·cm-2 (p = 0.027. Stimulation or inhibition with theophylline, ouabain, bumetanide, forskolin or the EP receptor agonists prostaglandin E2, butaprost, sulprostone and prostaglandin E1 (OH did not differ significantly between the two groups. Histology was with normal findings in both groups. Conclusions Epithelial electrogenic transport is more sensitive to indomethacin in normal colonic mucosa from patients with previous or present colorectal neoplasia compared

  1. M1 AFLATOXIN, TOTAL BACTERIAL COUNT AND SOMATIC CELL COUNT IN ORGANIC AND CONVENTIONAL MILK

    Directory of Open Access Journals (Sweden)

    M. Trevisani

    2009-09-01

    Full Text Available Comparative quality evaluation of organic and conventional milk produced in similar environmental condition was performed. Bulk-tank milk was sampled once a week during 30 weeks from 10 organic and 10 conventional dairy farms where aflatoxin M1 level was previous tested during 11 months on bulk-tank milk from tanker at the processing plant. Somatic Cells and Total Microbial Counts did not show differences that can be related to the organic production system, suggesting an effect induced by farm size and technical factors. Higher level of Aflatoxin M1 was found in organic than conventional milk.

  2. E2 GLYCOPROTEIN OF GENOTYPE Ⅲ CHINESE ISOLATES OF HEPATITIS C VIRUS EXPRESSED IN MAMMALIAN CELL AS ANTIGEN FOR ANTI-E2 ANTIBODY DETECTION

    Institute of Scientific and Technical Information of China (English)

    吴朝栋; 陶其敏

    1998-01-01

    Expression vector inserted with E2/NS1 gane derived from ganotype Ⅲ Chinese isolates of HCV was transfected into mammalian cells to express E2 glycoprotein. Expressed protein was used as antigen for anti-E2 antibody detection in 19 cases of hepatitis C patients by Western blot. It was first to express E2 glycoprotein of genotype Ⅲ Chinese hepatitis C virus isolates. For anti-E2 detection, 14 cases of patients were positive of antibodies against E2(73.7%). These results indicated that E2 glycoprotein expressed in mammalian cells had good immunoganicity and cross reactivity to serum infected with genotype Ⅱ Chinese hepatitis C virus isolates.

  3. Fluorescent Protein-Tagged Sindbis Virus E2 Glycoprotein Allows Single Particle Analysis of Virus Budding from Live Cells.

    Science.gov (United States)

    Jose, Joyce; Tang, Jinghua; Taylor, Aaron B; Baker, Timothy S; Kuhn, Richard J

    2015-12-01

    Sindbis virus (SINV) is an enveloped, mosquito-borne alphavirus. Here we generated and characterized a fluorescent protein-tagged (FP-tagged) SINV and found that the presence of the FP-tag (mCherry) affected glycoprotein transport to the plasma membrane whereas the specific infectivity of the virus was not affected. We examined the virions by transmission electron cryo-microscopy and determined the arrangement of the FP-tag on the surface of the virion. The fluorescent proteins are arranged icosahedrally on the virus surface in a stable manner that did not adversely affect receptor binding or fusion functions of E2 and E1, respectively. The delay in surface expression of the viral glycoproteins, as demonstrated by flow cytometry analysis, contributed to a 10-fold reduction in mCherry-E2 virus titer. There is a 1:1 ratio of mCherry to E2 incorporated into the virion, which leads to a strong fluorescence signal and thus facilitates single-particle tracking experiments. We used the FP-tagged virus for high-resolution live-cell imaging to study the spatial and temporal aspects of alphavirus assembly and budding from mammalian cells. These processes were further analyzed by thin section microscopy. The results demonstrate that SINV buds from the plasma membrane of infected cells and is dispersed into the surrounding media or spread to neighboring cells facilitated by its close association with filopodial extensions.

  4. Fluorescent Protein-Tagged Sindbis Virus E2 Glycoprotein Allows Single Particle Analysis of Virus Budding from Live Cells

    Directory of Open Access Journals (Sweden)

    Joyce Jose

    2015-11-01

    Full Text Available Sindbis virus (SINV is an enveloped, mosquito-borne alphavirus. Here we generated and characterized a fluorescent protein-tagged (FP-tagged SINV and found that the presence of the FP-tag (mCherry affected glycoprotein transport to the plasma membrane whereas the specific infectivity of the virus was not affected. We examined the virions by transmission electron cryo-microscopy and determined the arrangement of the FP-tag on the surface of the virion. The fluorescent proteins are arranged icosahedrally on the virus surface in a stable manner that did not adversely affect receptor binding or fusion functions of E2 and E1, respectively. The delay in surface expression of the viral glycoproteins, as demonstrated by flow cytometry analysis, contributed to a 10-fold reduction in mCherry-E2 virus titer. There is a 1:1 ratio of mCherry to E2 incorporated into the virion, which leads to a strong fluorescence signal and thus facilitates single-particle tracking experiments. We used the FP-tagged virus for high-resolution live-cell imaging to study the spatial and temporal aspects of alphavirus assembly and budding from mammalian cells. These processes were further analyzed by thin section microscopy. The results demonstrate that SINV buds from the plasma membrane of infected cells and is dispersed into the surrounding media or spread to neighboring cells facilitated by its close association with filopodial extensions.

  5. EBV Nuclear Antigen 3C Mediates Regulation of E2F6 to Inhibit E2F1 Transcription and Promote Cell Proliferation.

    Science.gov (United States)

    Pei, Yonggang; Banerjee, Shuvomoy; Sun, Zhiguo; Jha, Hem Chandra; Saha, Abhik; Robertson, Erle S

    2016-08-01

    Epstein-Barr virus (EBV) is considered a ubiquitous herpesvirus with the ability to cause latent infection in humans worldwide. EBV-association is evidently linked to different types of human malignancies, mainly of epithelial and lymphoid origin. Of interest is the EBV nuclear antigen 3C (EBNA3C) which is critical for EBV-mediated immortalization. Recently, EBNA3C was shown to bind the E2F1 transcription regulator. The E2F transcription factors have crucial roles in various cellular functions, including cell cycle, DNA replication, DNA repair, cell mitosis, and cell fate. Specifically, E2F6, one of the unique E2F family members, is known to be a pRb-independent transcription repressor of E2F-target genes. In our current study, we explore the role of EBNA3C in regulating E2F6 activities. We observed that EBNA3C plays an important role in inducing E2F6 expression in LCLs. Our study also shows that EBNA3C physically interacts with E2F6 at its amino and carboxy terminal domains and they form a protein complex in human cells. In addition, EBNA3C stabilizes the E2F6 protein and is co-localized in the nucleus. We also demonstrated that both EBNA3C and E2F6 contribute to reduction in E2F1 transcriptional activity. Moreover, E2F1 forms a protein complex with EBNA3C and E2F6, and EBNA3C competes with E2F1 for E2F6 binding. E2F6 is also recruited by EBNA3C to the E2F1 promoter, which is critical for EBNA3C-mediated cell proliferation. These results demonstrate a critical role for E2F family members in EBV-induced malignancies, and provide new insights for targeting E2F transcription factors in EBV-associated cancers as potential therapeutic intervention strategies.

  6. The Role of the E2F Transcription Factor Family in UV-Induced Apoptosis

    Directory of Open Access Journals (Sweden)

    Orla Gannon

    2011-12-01

    Full Text Available The E2F transcription factor family is traditionally associated with cell cycle control. However, recent data has shown that activating E2Fs (E2F1-3a are potent activators of apoptosis. In contrast, the recently cloned inhibitory E2Fs (E2F7 and 8 appear to antagonize E2F-induced cell death. In this review we will discuss (i the potential role of E2Fs in UV-induced cell death and (ii the implications of this to the development of UV-induced cutaneous malignancies.

  7. Effect of specific amino acid substitutions in the putative fusion peptide of structural glycoprotein E2 on Classical Swine Fever Virus replication

    Energy Technology Data Exchange (ETDEWEB)

    Fernández-Sainz, I.J. [Plum Island Animal Disease Center, ARS, USDA (United States); Largo, E. [Biophysics Unit (CSIC-UPV/EHU), Department of Biochemistry and Molecular Biology, University of the Basque Country (UPV/EHU), P.O. Box 644, 48080 Bilbao (Spain); Gladue, D.P.; Fletcher, P. [Plum Island Animal Disease Center, ARS, USDA (United States); O’Donnell, V. [Plum Island Animal Disease Center, ARS, USDA (United States); Plum Island Animal Disease Center, DHS, Greenport, NY 11944 (United States); Holinka, L.G. [Plum Island Animal Disease Center, ARS, USDA (United States); Carey, L.B. [Department of Experimental and Health Sciences, Universitat Pompeu Fabra (UPF), E-08003 Barcelona (Spain); Lu, X. [Plum Island Animal Disease Center, DHS, Greenport, NY 11944 (United States); Nieva, J.L. [Biophysics Unit (CSIC-UPV/EHU), Department of Biochemistry and Molecular Biology, University of the Basque Country (UPV/EHU), P.O. Box 644, 48080 Bilbao (Spain); Borca, M.V., E-mail: manuel.borca@ars.usda.gov [Plum Island Animal Disease Center, ARS, USDA (United States)

    2014-05-15

    E2, along with E{sup rns} and E1, is an envelope glycoprotein of Classical Swine Fever Virus (CSFV). E2 is involved in several virus functions: cell attachment, host range susceptibility and virulence in natural hosts. Here we evaluate the role of a specific E2 region, {sup 818}CPIGWTGVIEC{sup 828}, containing a putative fusion peptide (FP) sequence. Reverse genetics utilizing a full-length infectious clone of the highly virulent CSFV strain Brescia (BICv) was used to evaluate how individual amino acid substitutions within this region of E2 may affect replication of BICv. A synthetic peptide representing the complete E2 FP amino acid sequence adopted a β-type extended conformation in membrane mimetics, penetrated into model membranes, and perturbed lipid bilayer integrity in vitro. Similar peptides harboring amino acid substitutions adopted comparable conformations but exhibited different membrane activities. Therefore, a preliminary characterization of the putative FP {sup 818}CPIGWTGVIEC{sup 828} indicates a membrane fusion activity and a critical role in virus replication. - Highlights: • A putative fusion peptide (FP) region in CSFV E2 protein was shown to be critical for virus growth. • Synthetic FPs were shown to efficiently penetrate into lipid membranes using an in vitro model. • Individual residues in the FP affecting virus replication were identified by reverse genetics. • The same FP residues are also responsible for mediating membrane fusion.

  8. Recent Development of QCD Factorization for B-> M1 M2

    CERN Document Server

    Yang, Deshan

    2010-01-01

    After briefly introducing the framework of QCD factorization for B-> M1 M2 in the language of the Soft-Collinear Effective Theory, we firstly address the recent efforts on higher-order radiative corrections in QCD factorization. Then we discuss some phenomenologies in B-> V V within the framework of QCD factorization.

  9. 26 CFR 31.3306(m)-1 - American vessel and aircraft.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false American vessel and aircraft. 31.3306(m)-1... vessel and aircraft. (a) The term “American vessel” means any vessel which is documented (that is....) (b) The term “American aircraft” means any aircraft registered under the laws of the United States...

  10. M1 corticospinal mirror neurons and their role in movement suppression during action observation.

    Science.gov (United States)

    Vigneswaran, Ganesh; Philipp, Roland; Lemon, Roger N; Kraskov, Alexander

    2013-02-04

    Evidence is accumulating that neurons in primary motor cortex (M1) respond during action observation, a property first shown for mirror neurons in monkey premotor cortex. We now show for the first time that the discharge of a major class of M1 output neuron, the pyramidal tract neuron (PTN), is modulated during observation of precision grip by a human experimenter. We recorded 132 PTNs in the hand area of two adult macaques, of which 65 (49%) showed mirror-like activity. Many (38 of 65) increased their discharge during observation (facilitation-type mirror neuron), but a substantial number (27 of 65) exhibited reduced discharge or stopped firing (suppression-type). Simultaneous recordings from arm, hand, and digit muscles confirmed the complete absence of detectable muscle activity during observation. We compared the discharge of the same population of neurons during active grasp by the monkeys. We found that facilitation neurons were only half as active for action observation as for action execution, and that suppression neurons reversed their activity pattern and were actually facilitated during execution. Thus, although many M1 output neurons are active during action observation, M1 direct input to spinal circuitry is either reduced or abolished and may not be sufficient to produce overt muscle activity. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. A fluorescence anisotropy assay for the muscarinic M1 G-protein-coupled receptor.

    Science.gov (United States)

    Huwiler, Kristin G; De Rosier, Therese; Hanson, Bonnie; Vogel, Kurt W

    2010-06-01

    In the search for new chemical entities that interact with G-proteincoupled receptors (GPCRs), assays that quantify efficacy and affinity are employed. Traditional methods for measuring affinity involve radiolabeled ligands. To address the need for homogeneous biochemical fluorescent assays to characterize orthosteric ligand affinity and dissociation rates, we have developed a fluorescence anisotropy (FA) assay for the muscarinic M1 receptor that can be conducted in a 384-well plate. We used membranes from a muscarinic M1 cell line optimized for high-throughput functional assays and the previously characterized fluorescent antagonist BODIPY FL pirenzepine. The affinities of reference compounds were determined in the competitive FA assay and compared with those obtained with a competitive filter-based radioligand-binding assay using [(3)H] N-methylscopolamine. The IC(50) values produced from the FA assay were well-correlated with the radioligand-binding K(i) values (R(2) = 0.98). The dissociation of the BODIPY FL pirenzepine was readily monitored in real time using the FA assay and was sensitive to the presence of the allosteric modulator gallamine. This M1 FA assay offers advantages over traditional radioligandbinding assays as it eliminates radioactivity while allowing investigation of orthosteric or allosteric muscarinic M1 ligands in a homogeneous format.

  12. Stereospecific reduction of virginiamycin M1 as the virginiamycin resistance pathway in Streptomyces virginiae.

    Science.gov (United States)

    Lee, C K; Minami, M; Sakuda, S; Nihira, T; Yamada, Y

    1996-03-01

    In a cell extract of Streptomyces virginiae, virginiamycin M1 was inactivated in the presence of NADPH, while virginiamycin S remained intact. The inactivated product of virginiamycin M1 was isolated, and structure analysis revealed that the inactivation involves reduction of a C-16 carbonyl group leading to the formation of 16-dihydrovirginiamycin M1. Acetonide and benzylidene acetal derivatives were synthesized from the two hydroxyl groups on C-14 and C-16, and the C-16 stereochemistry was determined by 13C nuclear magnetic resonance spectroscopy. Two methyl groups of the acetonide derivative gave 13C signals of 20.1 and 30.1 ppm, indicating that the relative stereochemistry of the C-14 and C-16 hydroxy groups is syn. Furthermore, irradiation of the benzylidene methine proton gave clear nuclear Overhauser effect enhancement of the C-14 or C-16 methine protons, indicating that H-14 and H-16 were in an axial configuration. From the (14S) absolute configuration of natural virginiamycin M1 and the syn relative configuration for the C-14 and C-16 hydroxyl groups of the inactivated product, the C-16 absolute configuration of the inactivated product was thus identified as R.

  13. Multiple outflows in the bipolar planetary nebula M1-16: A molecular line study

    NARCIS (Netherlands)

    Sahai, Raghvendra; Wootten, Alwyn; Schwarz, Hugo E.; Wild, W.

    1994-01-01

    Extensive observations of the molecular gas in the young, compact planetary nebula M1-16 have been made, using the Swedish-ESO-Submillimeter Telescope. A map of the CO J = 2-1 emission shows that the molecular envelope contains both a slow and a fast outflow with expansion velocities of 19 km/s and

  14. Molecular mechanisms that regulate the macrophage M1/M2 polarization balance

    Directory of Open Access Journals (Sweden)

    Nan eWang

    2014-11-01

    Full Text Available As an essential component of innate immunity, macrophages have multiple functions in both inhibiting or promoting cell proliferation and tissue repair. Diversity and plasticity are hallmarks of macrophages. Classical M1 and alternative M2 activation of macrophages, mirroring the Th1–Th2 polarization of T cells, represent two extremes of a dynamic changing state of macrophage activation. M1-type macrophages release cytokines that inhibit the proliferation of surrounding cells and damage contiguous tissue, and M2-type macrophages release cytokines that promote the proliferation of contiguous cells and tissue repair. M1-M2 polarization of macrophage is a tightly controlled process entailing a set of signaling pathways, transcriptional and posttranscriptional regulatory networks. An imbalance of macrophage M1-M2 polarization is often associated with various diseases or inflammatory conditions. Therefore identification of the molecules associated with the dynamic changes of macrophage polarization and understanding their interactions is crucial for elucidating the molecular basis of disease progression and designing novel macrophage-mediated therapeutic strategies.

  15. A Busy period analysis for the state dependent M/M/1/K queue

    NARCIS (Netherlands)

    Al Hanbali, Ahmad; Boxma, Onno

    2010-01-01

    In this paper, we study the transient behavior of a state dependent M/M/1/K queue during the busy period. We derive in closed-form the joint transform of the length of the busy period, the number of customers served during the busy period, and the number of losses during the busy period. For two

  16. Aflatoxin M1 in raw milk and binding of aflatoxin by lactic acid bacteria

    Directory of Open Access Journals (Sweden)

    Aflatoxin M1 in raw milk and binding of aflatoxin by lactic acid bacteria

    2010-12-01

    Full Text Available Aflatoxin M1 (AFM1 is potential human carcinogen. Its presence in milk and dairy products represents risk for human health. Therefore, this study was carried out in order to determine thedegree of microbiological contamination by mold, and the potential presence of aflatoxin M1 in 60 raw milk samples, randomly taken from individual producers from different regions of the continental Croatia. The most common genera isolated fungi were Geotrichum (78.3 %, Aspergillus (32.4 % and Penicillium (27.0 %. From total of 60 studied milk samples, 86.66 % were positive for the presence of aflatoxin M1, and 6.66 % of samples were above the prescribed limits. Lactic acid bacteria used in fermented dairy products as a starter culture may play a role in reduction of aflatoxin in foods and nutrients. In this paper the ability of lactic acid bacteria: Lactobacillus rhamnosus GG (ATCC 53103, Lactobacillus delbrueckii S1 and Lactobacillus plantarum A1 to bind aflatoxin M1 was investigated. Standard strain L. rhamnosus GG (ATCC 53103 and L. delbrueckii S1 can significantly (P50 % compared to L. plantarum A1, which binds AFM1 between 18.7 to 28.7 %.

  17. Chlorogenic acid inhibits glioblastoma growth through repolarizating macrophage from M2 to M1 phenotype

    Science.gov (United States)

    Xue, Nina; Zhou, Qin; Ji, Ming; Jin, Jing; Lai, Fangfang; Chen, Ju; Zhang, Mengtian; Jia, Jing; Yang, Huarong; Zhang, Jie; Li, Wenbin; Jiang, Jiandong; Chen, Xiaoguang

    2017-01-01

    Glioblastoma is an aggressive tumor that is associated with distinctive infiltrating microglia/macrophages populations. Previous studies demonstrated that chlorogenic acid (5-caffeoylquinic acid, CHA), a phenolic compound with low molecular weight, has an anti-tumor effect in multiple malignant tumors. In the present study, we focused on the macrophage polarization to investigate the molecular mechanisms behind the anti-glioma response of CHA in vitro and in vivo. We found that CHA treatment increased the expression of M1 markers induced by LPS/IFNγ, including iNOS, MHC II (I-A/I-E subregions) and CD11c, and reduced the expression of M2 markers Arg and CD206 induced by IL-4, resulting in promoting the production of apoptotic-like cancer cells and inhibiting the growth of tumor cells by co-culture experiments. The activations of STAT1 and STAT6, which are two crucial signaling events in M1 and M2-polarization, were significantly promoted and suppressed by CHA in macrophages, respectively. Furthermore, In G422 xenograft mice, CHA increased the proportion of CD11c-positive M1 macrophages and decreased the distribution of CD206-positive M2 macrophages in tumor tissue, consistent with the reduction of tumor weight observed in CHA-treated mice. Overall these findings indicated CHA as a potential therapeutic approach to reduce glioma growth through promoting M1-polarized macrophage and inhibiting M2 phenotypic macrophage. PMID:28045028

  18. Tim-3 promotes intestinal homeostasis in DSS colitis by inhibiting M1 polarization of macrophages.

    Science.gov (United States)

    Jiang, Xingwei; Yu, Jiahui; Shi, Qingzhu; Xiao, Yan; Wang, Wei; Chen, Guojiang; Zhao, Zhi; Wang, Renxi; Xiao, He; Hou, Chunmei; Feng, Jiannan; Ma, Yuanfang; Shen, Beifen; Wang, Lili; Li, Yan; Han, Gencheng

    2015-10-01

    Tim-3 is involved in the physiopathology of inflammatory bowel disease (IBD), but the underlying mechanism is unknown. Here, we demonstrated that, in mouse with DSS colitis, Tim-3 inhibited the polarization of pathogenic pro-inflammatory M1 macrophages, while Tim-3 downregulation or blockade resulted in an increased M1 response. Adoptive transfer of Tim-3-silenced macrophages worsened DSS colitis and enhanced inflammation, while Tim-3 overexpression attenuated DSS colitis by decreasing the M1 macrophage response. Co-culture of Tim-3-overexpressing macrophages with intestinal lymphocytes decreased the pro-inflammatory response. Tim-3 shaped intestinal macrophage polarization may be TLR-4 dependent since Tim-3 blockade failed to exacerbate colitis or increase M1 macrophage response in the TLR-4 KO model. Finally, Tim-3 signaling inhibited phosphorylation of IRF3, a TLR-4 downstream transcriptional factor regulating macrophage polarization. A better understanding of this pathway may shed new light on colitis pathogenesis and result in a new therapeutic strategy.

  19. Experimental Conditions: SE18_S1_M1_D1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available liver and brain by Orbitrap MS and automated search engine Lipid Search SE18_S1 Mouse liver SE18_S1_M1 34.1...phy. SE18_MS1 Preparation of lipid extract and ESI negative detection by LC-MS analysis SE18_DS1 Identification of phospholipids with Lipid Search default ...

  20. Experimental Conditions: SE18_S2_M1_D1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available liver and brain by Orbitrap MS and automated search engine Lipid Search SE18_S2 Mouse brain SE18_S2_M1 10.8...phy. SE18_MS1 Preparation of lipid extract and ESI negative detection by LC-MS analysis SE18_DS1 Identification of phospholipids with Lipid Search default ...

  1. Design of an E-ELT M1 segment measurement machine with nanometer accuracy

    NARCIS (Netherlands)

    Bos, A.; Henselmans, R.; Rosielle, P.C.J.N.; Steinbuch, M.; Voert, M.J.A. te

    2014-01-01

    The baseline design of the European Extremely Large Telescope features a telescope with a 39-meter-class primary mirror (M1), consisting of 798 hexagonal segments. A measurement machine design is presented based on a non-contact single-point scanning technique, capable of measuring the form error of

  2. Experimental Conditions: SE37_S16_M1_D1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available opes SE37_S16 Blank (80% methanol) SE37_S16_M1 0mg [MassBase ID] MDLC1_43484 SE37_MS1 Metabolites extraction... with 80% methanol and analysis by LC-Orbitrap-MS SE37_DS1 Peak extraction for unlabeled data 6|ITMS 2 ...

  3. Multiple outflows in the bipolar planetary nebula M1-16: A molecular line study

    NARCIS (Netherlands)

    Sahai, Raghvendra; Wootten, Alwyn; Schwarz, Hugo E.; Wild, W.

    1994-01-01

    Extensive observations of the molecular gas in the young, compact planetary nebula M1-16 have been made, using the Swedish-ESO-Submillimeter Telescope. A map of the CO J = 2-1 emission shows that the molecular envelope contains both a slow and a fast outflow with expansion velocities of 19 km/s and

  4. Aflatoxin M1 in white cheese and butter consumed in Istanbul, Turkey.

    Science.gov (United States)

    Aycicek, Hasan; Yarsan, Ender; Sarimehmetoglu, Belgin; Cakmak, Omer

    2002-10-01

    We studied the occurrence of Aflatoxin M1 (AFM1) in 183 sample of white cheese and butter in Istanbul, Turkey in 2001. The incidence of AFM1 in white cheese and butter samples was as high as 65 and 81, respectively. The particularly high AFM,concentrations imply that more importance should be given to routine analysis of these dairy products.

  5. Effects on Variations in M1 Generation of Durum Wheat (T. durum Thell by Induced Mutagen

    Directory of Open Access Journals (Sweden)

    O. Bilgin

    2005-01-01

    Full Text Available In this research conducted ın Department of Field Crops, Tekirdağ Agricultural Faculty, TrakyaUniversity, the effect of six different gamma ray doses on plant growth in M1 generations derived from twodurum wheat cultivars was investigated.In the experiment, 10 plants in each pot (17 x 40 cm containing 5 kgsoil were grown with three replicates. Total 30 plants for each treatment were used. In M1 generation, numberof leaves, number of roots, seedling height, seedling weight, leaf weight and germination rate were determined.Application of 100-200 gray gamma ray doses did not have any inhibitory effect on investigated characters inseedling growth of M1 generation. On the other hand, 400-500 gray doses significantly inhibited the plantgrowth. 100-200 gray doses did not affect the seed germination rate whereas germination rate decreased with400-500 gray gamma ray applications. At 600 gray dose, only one seed remained viably, rest of them could notsurvive. It was generally observed the highest variations at 300-400 gray gamma doses in M1 plants.

  6. Metabolic inactivation of resolvin E1 and stabilization of its anti-inflammatory actions.

    Science.gov (United States)

    Arita, Makoto; Oh, Sungwhan F; Chonan, Tomomichi; Hong, Song; Elangovan, Siva; Sun, Yee-Ping; Uddin, Jasim; Petasis, Nicos A; Serhan, Charles N

    2006-08-11

    The resolvins (Rv) are lipid mediators derived from omega-3 polyunsaturated fatty acids that act within a local inflammatory milieu to stop leukocyte recruitment and promote resolution. Resolvin E1 (RvE1; (5S,12R,18R)-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid) is an oxygenase product derived from omega-3 eicosapentaenoic acid that displays potent anti-inflammation/pro-resolution actions in vivo. Here, we determined whether oxidoreductase enzymes catalyze the conversion of RvE1 and assessed the biological activity of the RvE1 metabolite. With NAD+ as a cofactor, recombinant 15-hydroxyprostaglandin dehydrogenase acted as an 18-hydroxyl dehydrogenase to form 18-oxo-RvE1. In the murine lung, dehydrogenation of the hydroxyl group at carbon 18 position to form 18-oxo-RvE1 represented the major initial metabolic route for RvE1. At a concentration where RvE1 potently reduced polymorphonuclear leukocyte (PMN) recruitment in zymosan-induced peritonitis, 18-oxo-RvE1 was devoid of activity. In human neutrophils, carbon 20 hydroxylation of RvE1 was the main route of conversion. An RvE1 analog, i.e. 19-(p-fluorophenoxy)-RvE1, was synthesized that resisted rapid metabolic inactivation and proved to retain biological activity reducing PMN infiltration and pro-inflammatory cytokine/chemokine production in vivo. These results established the structure of a novel RvE1 initial metabolite, indicating that conversion of RvE1 to the oxo product represents a mode of RvE1 inactivation. Moreover, the designed RvE1 analog, which resisted further metabolism/inactivation, could be a useful tool to evaluate the actions of RvE1 in complex disease models.

  7. STS-70 Launch - Nikon E-2 Digital Image

    Science.gov (United States)

    1995-01-01

    This test images was taken with a Nikon E-2 Digital Imaging System camera and are provided courtesy of Nikon (GIF 450x450 JPEG 1280x1000): The second Shuttle launch in 16 days hurtles off the pad into a sweltering summer sky. The unstable weather typical to Florida in the summertime didn't have a chance to coalesce and impact this morning's launch window, and the Space Shuttle Discovery began its planned seven-day, 22-hour flight on Mission STS-70 from Launch Pad 39B at 9:41:55.078 a.m. EDT, just seconds off schedule. On board for Discovery's 21st spaceflight are a crew of five: Commander Terence 'Tom' Henricks; Pilot Kevin R. Kregel; and Mission Specialists Nancy Jane Currie, Donald A. Thomas and Mary Ellen Weber. The crew's primary objective during the 70th Shuttle flight is to deploy the Tracking and Data Relay Satellite (TDRS-G), which will join a constellation of other TDRS spacecraft already on orbit. TDRS-G is destined to become an on- orbit, fully operational 'ready reserve' satellite, available along with one other ready reserve TDRS spacecraft to back up the two primary TDRS satellites positions, TDRS East over the Atlantic Ocean and TDRS West over the Pacific. Assured capability of the TDRS communications network is essential for linking Earth-orbiting spacecraft such as the Shuttle and the Hubble Space Telescope with the ground.

  8. Prostaglandin E2-induced inflammation: Relevance of prostaglandin E receptors.

    Science.gov (United States)

    Kawahara, Kohichi; Hohjoh, Hirofumi; Inazumi, Tomoaki; Tsuchiya, Soken; Sugimoto, Yukihiko

    2015-04-01

    Prostaglandin E2 (PGE2) is one of the most typical lipid mediators produced from arachidonic acid (AA) by cyclooxygenase (COX) as the rate-limiting enzyme, and acts on four kinds of receptor subtypes (EP1-EP4) to elicit its diverse actions including pyrexia, pain sensation, and inflammation. Recently, the molecular mechanisms underlying the PGE2 actions mediated by each EP subtype have been elucidated by studies using mice deficient in each EP subtype as well as several compounds highly selective to each EP subtype, and their findings now enable us to discuss how PGE2 initiates and exacerbates inflammation at the molecular level. Here, we review the recent advances in PGE2 receptor research by focusing on the activation of mast cells via the EP3 receptor and the control of helper T cells via the EP2/4 receptor, which are the molecular mechanisms involved in PGE2-induced inflammation that had been unknown for many years. We also discuss the roles of PGE2 in acute inflammation and inflammatory disorders, and the usefulness of anti-inflammatory therapies that target EP receptors. This article is part of a Special Issue entitled "Oxygenated metabolism of PUFA: analysis and biological relevance". Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Prostaglandin E2 As a Modulator of Viral Infections

    Science.gov (United States)

    Sander, Willem J.; O'Neill, Hester G.; Pohl, Carolina H.

    2017-01-01

    Viral infections are a major cause of infectious diseases worldwide. Inflammation and the immune system are the major host defenses against these viral infection. Prostaglandin E2 (PGE2), an eicosanoid generated by cyclooxygenases, has been shown to modulate inflammation and the immune system by regulating the expression/concentration of cytokines. The effect of PGE2 on viral infection and replication is cell type- and virus-family-dependent. The host immune system can be modulated by PGE2, with regards to immunosuppression, inhibition of nitrogen oxide (NO) production, inhibition of interferon (IFN) and apoptotic pathways, and inhibition of viral receptor expression. Furthermore, PGE2 can play a role in viral infection directly by increasing the production and release of virions, inhibiting viral binding and replication, and/or stimulating viral gene expression. PGE2 may also have a regulatory role in the induction of autoimmunity and in signaling via Toll-like receptors. In this review the known effects of PGE2 on the pathogenesis of various infections caused by herpes simplex virus, rotavirus, influenza A virus and human immunodeficiency virus as well the therapeutic potential of PGE2 are discussed. PMID:28261111

  10. Intravirion cohesion of matrix protein M1 with ribonucleocapsid is a prerequisite of influenza virus infectivity.

    Science.gov (United States)

    Zhirnov, O P; Manykin, A A; Rossman, J S; Klenk, H D

    2016-05-01

    Influenza virus has two major structural modules, an external lipid envelope and an internal ribonucleocapsid containing the genomic RNA in the form of the ribonucleoprotein (RNP) complex, both of which are interlinked by the matrix protein M1. Here we studied M1-RNP cohesion within virus exposed to acidic pH in vitro. The effect of acidification was dependent on the cleavage of the surface glycoprotein HA. Acidic pH caused a loss of intravirion RNP-M1 cohesion and activated RNP polymerase activity in virus with cleaved HA (HA1/2) but not in the uncleaved (HA0) virus. The in vitro acidified HA1/2 virus rapidly lost infectivity whereas the HA0 one retained infectivity, following activation by trypsin, suggesting that premature activation and release of the RNP is detrimental to viral infectivity. Rimantadine, an inhibitor of the M2 ion channel, was found to protect the HA1/2 virus interior against acidic disintegration, confirming that M2-dependent proton translocation is essential for the intravirion RNP release and suggesting that the M2 ion channel is only active in virions with cleaved HA. Acidic treatment of both HA0 and HA1/2 influenza viruses induces formation of spikeless bleb-like protrusion of ~ 25 nm in diameter on the surface of the virion, though only the HA1/2 virus was permeable to protons and permitted RNP release. It is likely that this bleb corresponds to the M2-enriched and M1-depleted focus arising from pinching off of the virus during the completion of budding. Cooperatively, the data suggest that the influenza virus has an asymmetric structure where the M1-mediated organization of the RNP inside the virion is a prerequisite for infectious entry into target cell. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Increased SMA-M1 coherence in Parkinson's disease - Pathophysiology or compensation?

    Science.gov (United States)

    Pollok, Bettina; Kamp, Daniel; Butz, Markus; Wojtecki, Lars; Timmermann, Lars; Südmeyer, Martin; Krause, Vanessa; Schnitzler, Alfons

    2013-09-01

    Parkinson's disease (PD) is a common neurodegenerative disorder owing to loss of dopaminergic cells. Akinesia - one of the core symptoms of PD - is associated with exaggerated oscillations at beta frequency (13-30 Hz) within the subthalamic nucleus (STN). Thus, enhanced oscillations below 30 Hz are assumed to represent a pathophysiological marker of PD. However, recent data suggest that OFF medication exaggerated beta oscillations within basal ganglia (BG) cortical networks may serve for the compensation of BG dysfunctions. The STN is functionally connected to mesial prefrontal areas like the supplementary motor area (SMA). But, it is still not fully understood how enhanced beta oscillations within the BG exert dominance over the primary motor cortex (M1) thereby yielding motor impairment. The present study, therefore, investigates the effect of dopaminergic state on SMA-M1 functional connectivity using Magnetoencephalography (MEG). MEG data were recorded in 7 patients suffering from PD with preponderance of akinesia during isometric contraction of the right forearm and during rest. Coherence as a measure of functional connectivity between M1 and SMA was calculated OFF and ON medication and correlated with the motor part of the Unified Parkinson's Disease Rating Scale (UPDRS III) and with disease duration. During rest a significant positive correlation between disease duration and SMA-M1 coherence was found ON but not OFF medication. Conversely, during isometric contraction SMA-M1 coherence and UPDRS III were inversely correlated OFF but not ON medication explaining more than 80% of variance. The results favor the hypothesis that OFF medication exaggerated cortical coherence at beta frequency represents a compensatory mechanism rather than a pathophysiological marker per se. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Balancing the excitability of M1 circuitry during movement observation without overt replication

    Directory of Open Access Journals (Sweden)

    Pablo eArias

    2014-09-01

    Full Text Available Although observation of a movement increases the excitability of the motor system of the observer, it does not induce a motor replica. What is the mechanism for replica suppression? We performed a series of experiments, involving a total of 66 healthy humans, to explore the excitability of different M1 circuits and the spinal cord during observation of simple movements. Several strategies were used. In the first and second experimental blocks, we used several delay times from movement onset to evaluate the time-course modulation of the cortico-spinal excitability (CSE, and its potential dependency on the duration of the movement observed; in order to do this single pulse transcranial magnetic stimulation (TMS over M1 was used. In subsequent experiments, at selected delay times from movement-onset, we probed the excitability of the cortico-spinal circuits using three different approaches: i electric cervicomedullary stimulation, to test spinal excitability, ii paired-pulse TMS over M1, to evaluate the cortical inhibitory-excitatory balance (short intracortical inhibition SICI and intracortical facilitation ICF and iii continuous theta-burst stimulation (cTBS, to modulate the excitability of M1cortical circuits. We observed a stereotyped response in the modulation of CSE. At 500ms after movement-onset the ICF was increased; although the most clear-cut effect was a decrease of CSE. The compensatory mechanism was not explained by changes in SICI, but by M1-intracortical circuits targeted by cTBS. Meanwhile, the spinal cord maintained the elevated level of excitability induced when expecting to observe movements, potentially useful to facilitate any required response to the movement observed.

  13. Investigating the consequences of eIF4E2 (4EHP interaction with 4E-transporter on its cellular distribution in HeLa cells.

    Directory of Open Access Journals (Sweden)

    Dorota Kubacka

    Full Text Available In addition to the canonical eIF4E cap-binding protein, eukaryotes have evolved sequence-related variants with distinct features, some of which have been shown to negatively regulate translation of particular mRNAs, but which remain poorly characterised. Mammalian eIF4E proteins have been divided into three classes, with class I representing the canonical cap-binding protein eIF4E1. eIF4E1 binds eIF4G to initiate translation, and other eIF4E-binding proteins such as 4E-BPs and 4E-T prevent this interaction by binding eIF4E1 with the same consensus sequence YX 4Lϕ. We investigate here the interaction of human eIF4E2 (4EHP, a class II eIF4E protein, which binds the cap weakly, with eIF4E-transporter protein, 4E-T. We first show that ratios of eIF4E1:4E-T range from 50:1 to 15:1 in HeLa and HEK293 cells respectively, while those of eIF4E2:4E-T vary from 6:1 to 3:1. We next provide evidence that eIF4E2 binds 4E-T in the yeast two hybrid assay, as well as in pull-down assays and by recruitment to P-bodies in mammalian cells. We also show that while both eIF4E1 and eIF4E2 bind 4E-T via the canonical YX 4Lϕ sequence, nearby downstream sequences also influence eIF4E:4E-T interactions. Indirect immunofluorescence was used to demonstrate that eIF4E2, normally homogeneously localised in the cytoplasm, does not redistribute to stress granules in arsenite-treated cells, nor to P-bodies in Actinomycin D-treated cells, in contrast to eIF4E1. Moreover, eIF4E2 shuttles through nuclei in a Crm1-dependent manner, but in an 4E-T-independent manner, also unlike eIF4E1. Altogether we conclude that while both cap-binding proteins interact with 4E-T, and can be recruited by 4E-T to P-bodies, eIF4E2 functions are likely to be distinct from those of eIF4E1, both in the cytoplasm and nucleus, further extending our understanding of mammalian class I and II cap-binding proteins.

  14. Data of evolutionary structure change: 1E1QC-2HLDT [Confc[Archive

    Lifescience Database Archive (English)

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  15. Data of evolutionary structure change: 1E1QB-2HLDT [Confc[Archive

    Lifescience Database Archive (English)

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  16. Data of evolutionary structure change: 1E1RB-2HLDT [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1E1RB-2HLDT 1E1R 2HLD B T DLEETGRVLSIGDGIARVHGLRNVQAEEMVEFSSGLKGM...SDRLVKEGELVKRTGNIVDVPVGPGLLGRVVDALGNPIDGKGPIDAAGRSRAQVKAPGILPRRSVHEPVQTGLKAVDALVPIGRGQRELIIGDRQTGKTAVALDT...T 2HLDT ALKQVAGSLKLFL2HLD T 2HLDT VAAFAQDLDAST

  17. A note on inextensible flows of partially and pseudo null curves in E_1^4

    OpenAIRE

    Yuzbasi, Zuhal Kucukarslan; Bektas, Mehmet

    2013-01-01

    In this paper, we study inextensible flows of partially null and pseudo null curves in E_1^4. We give neccessary and sufficent conditions for inextensible flows of partially null and pseudo null curves in E_1^4

  18. Data of evolutionary structure change: 1E1RC-2HLDA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1E1RC-2HLDA 1E1R 2HLD C A ADTSVDLEETGRVLSIGDGIARVHGLRNVQAEEMVEFSS...ELFYKGIRPAINVGLSVSRVGSAAQTRAMKQVAGTMKLELAQYREVAAFAQFGSDLDAATQQLLSRGVRLTELLKQGQYSPMAIEEQVAVIYAGVRGYLDKLEPSKIT...RPAINVGLSVSRVGSAAQVKALKQVAGSLKLFLAQYREVAAFAQS--DLDASTKQTLVRGERLTQLLKQNQYSPLATEEQV...fEVID> 0 2HLD A 2HLDA AFAQS--DLDAS GGG -- HH

  19. Cell-based analysis of Chikungunya virus E1 protein in membrane fusion

    Directory of Open Access Journals (Sweden)

    Kuo Szu-Cheng

    2012-04-01

    Full Text Available Abstract Background Chikungunya fever is a pandemic disease caused by the mosquito-borne Chikungunya virus (CHIKV. E1 glycoprotein mediation of viral membrane fusion during CHIKV infection is a crucial step in the release of viral genome into the host cytoplasm for replication. How the E1 structure determines membrane fusion and whether other CHIKV structural proteins participate in E1 fusion activity remain largely unexplored. Methods A bicistronic baculovirus expression system to produce recombinant baculoviruses for cell-based assay was used. Sf21 insect cells infected by recombinant baculoviruses bearing wild type or single-amino-acid substitution of CHIKV E1 and EGFP (enhanced green fluorescence protein were employed to investigate the roles of four E1 amino acid residues (G91, V178, A226, and H230 in membrane fusion activity. Results Western blot analysis revealed that the E1 expression level and surface features in wild type and mutant substituted cells were similar. However, cell fusion assay found that those cells infected by CHIKV E1-H230A mutant baculovirus showed little fusion activity, and those bearing CHIKV E1-G91D mutant completely lost the ability to induce cell-cell fusion. Cells infected by recombinant baculoviruses of CHIKV E1-A226V and E1-V178A mutants exhibited the same membrane fusion capability as wild type. Although the E1 expression level of cells bearing monomeric-E1-based constructs (expressing E1 only was greater than that of cells bearing 26S-based constructs (expressing all structural proteins, the sizes of syncytial cells induced by infection of baculoviruses containing 26S-based constructs were larger than those from infections having monomeric-E1 constructs, suggesting that other viral structure proteins participate or regulate E1 fusion activity. Furthermore, membrane fusion in cells infected by baculovirus bearing the A226V mutation constructs exhibited increased cholesterol-dependences and lower pH thresholds

  20. Immunohistochemical localisation of cholinergic muscarinic receptor subtype 1 (M1r) in the guinea pig and human enteric nervous system.

    Science.gov (United States)

    Harrington, A M; Hutson, J M; Southwell, B R

    2007-07-01

    Little is known regarding the location of cholinergic muscarinic receptor 1 (M1r) in the ENS, even though physiological data suggest that M1rs are central to cholinergic neurotransmission. This study localised M1rs in the ENS of the guinea pig ileum and human colon using fluorescence immunohistochemistry and RT-PCR in human colon. Double labelling using antibodies against neurochemical markers was used to identify neuron subytpes bearing M1r. M1r immunoreactivity (IR) was present on neurons in the myenteric and submucosal ganglia. The two antibodies gave similar M1r-IR patterns and M1r-IR was abolished upon antibody preabsorption. M1r-IR was present on cholinergic and nNOS-IR nerve cell bodies in both guinea pig and human myenteric neurons. Presynaptic M1r-IR was present on NOS-IR and VAChT-IR nerve fibres in the circular muscle in the human colon. In the submucosal ganglia, M1r-IR was present on a population of neurons that contained cChAT-IR, but did not contain NPY-IR or calretinin-IR. M1r-IR was present on endothelial cells of blood vessels in the submucosal plexus. The localisation of M1r-IR in the guinea pig and human ENS shown in this study agrees with physiological studies. M1r-IR in cholinergic and nitrergic neurons and nerve fibres indicate that M1rs have a role in both cholinergic and nitrergic transmission. M1r-IR present in submucosal neurons suggests a role in mediating acetylcholine's effect on submucosal sensory and secretomotor/vasodilator neurons. M1r-IR present on blood vessel endothelial cells suggests that M1rs may also mediate acetylcholine's direct effect on vasoactivation.

  1. The Reaction Dynamics of the Reactions Ba+CmH2m+1Br(m=1,2,3,4,5)

    Institute of Scientific and Technical Information of China (English)

    韩克利; 郑锡光; 张瑞勤; 孙本繁; 何国钟; 楼南泉

    1994-01-01

    The internal energy distributions of the nascent BaBr products formed in the reactions ofBa+BrR(R=CH3,C2H5,C3H7,C4H9,C5H11) under the single collision condition have been first studied bylaser-induced fluorescence method.With computer simulations of the experimental spectra,we obtained thevibrational distributions of the BaBr products,and found that the vibrational excitation and reaction cross-section increase with the number of the carbon atoms in the alkyl radical R.The quasitriatomic LEPS poten-tial of the Ba+CH3 reaction has been deduced reversely from the experimental results.The dynamics of thereactions Ba+BrR have been studied by the classical trajectory calculations based on the model LEPS poten-tials.It is concluded that the mass factor and the C-Br bond strength are the major factors affecting the rela-tionship between vibrational excitation and reaction cross-section with the number of the carbon atoms in thealkyl radical R.Furthermore,we obtained all the LEPS potentials of the reactive systems Ba+CmH2m+1 andconfirmed its reliability with ab initio calculations.

  2. Tropical Cyclones in the GISS ModelE2

    Science.gov (United States)

    Camargo, Suzana J.; Sobel, Adam H.; Del Genio, Anthony; Jonas, Jeffrey A.; Kelley, Maxwell; Lu, Yun; Shaevitz, Daniel; Henderson, Naomi

    2016-01-01

    The authors describe the characteristics of tropical cyclone (TC) activity in the GISS general circulation ModelE2 with a horizontal resolution 1deg x 1deg. Four model simulations are analyzed. In the first, the model is forced with sea surface temperature (SST) from the recent historical climatology. The other three have different idealized climate change simulations, namely (1) a uniform increase of SST by 2 deg., (2) doubling of the CO2 concentration and (3) a combination of the two. These simulations were performed as part of the US Climate Variability and Predictability Program Hurricane Working Group. Diagnostics of standard measures of TC activity are computed from the recent historical climatological SST simulation and compared with the same measures computed from observations. The changes in TC activity in the three idealized climate change simulations, by comparison with that in the historical climatological SST simulation, are also described. Similar to previous results in the literature, the changes in TC frequency in the simulation with a doubling CO2 and an increase in SST are approximately the linear sum of the TC frequency in the other two simulations. However, in contrast with previous results, in these simulations the effects of CO2 and SST on TC frequency oppose each other. Large-scale environmental variables associated with TC activity are then analyzed for the present and future simulations. Model biases in the large-scale fields are identified through a comparison with ERA-Interim reanalysis. Changes in the environmental fields in the future climate simulations are shown and their association with changes in TC activity discussed.

  3. Prostaglandin E2 Reduces Cardiac Contractility via EP3 Receptor.

    Science.gov (United States)

    Gu, Xiaosong; Xu, Jiang; Zhu, Liping; Bryson, Timothy; Yang, Xiao-Ping; Peterson, Edward; Harding, Pamela

    2016-08-01

    Prostaglandin E2 (PGE2) EP receptors EP3 and EP4 signal via decreased and increased cAMP production, respectively. Previously, we reported that cardiomyocyte-specific EP4 knockout mice develop dilated cardiomyopathy with reduced ejection fraction. Thus, we hypothesized that PGE2 increases contractility via EP4 but decreases contractility via EP3. The effects of PGE2 and the EP1/EP3 agonist sulprostone on contractility were examined in the mouse Langendorff preparation and in adult mouse cardiomyocytes. Isolated hearts of adult male C57Bl/6 mice were perfused with PGE2 (10(-6) M) or sulprostone (10(-6) M) and compared with vehicle. Both PGE2 and sulprostone decreased +dp/dt (PEP3 antagonist. In contrast, the EP4 agonist had the opposite effect. Adult mouse cardiomyocytes contractility was also reduced after treatment with either PGE2 or sulprostone for 10 minutes. We then examined the acute effects of PGE2, sulprostone, and the EP4 agonist on expression of phosphorylated phospholamban and sarcoendoplasmic reticulum Ca(2+)-ATPase 2a in adult mouse cardiomyocytes using Western blot. Treatment with either PGE2 or sulprostone decreased expression of phosphorylated phospholamban corrected to total phospholamban, whereas treatment with the EP4 agonist had the opposite effect. Sarcoendoplasmic reticulum Ca(2+)-ATPase 2a expression was unaffected. Finally, we examined the effect of these compounds in vivo using pressure-volume loops. Both PGE2 and sulprostone decreased +dp/dt, whereas the EP4 agonist increased +dp/dt. Contractility is reduced via the EP3 receptor but increased via EP4. These effects may be mediated through changes in phospholamban phosphorylation and has relevance to detrimental effects of inflammation. © 2016 American Heart Association, Inc.

  4. Tropical Cyclones in the GISS ModelE2

    Science.gov (United States)

    Camargo, Suzana J.; Sobel, Adam H.; Del Genio, Anthony; Jonas, Jeffrey A.; Kelley, Maxwell; Lu, Yun; Shaevitz, Daniel; Henderson, Naomi

    2016-01-01

    The authors describe the characteristics of tropical cyclone (TC) activity in the GISS general circulation ModelE2 with a horizontal resolution 1deg x 1deg. Four model simulations are analyzed. In the first, the model is forced with sea surface temperature (SST) from the recent historical climatology. The other three have different idealized climate change simulations, namely (1) a uniform increase of SST by 2 deg., (2) doubling of the CO2 concentration and (3) a combination of the two. These simulations were performed as part of the US Climate Variability and Predictability Program Hurricane Working Group. Diagnostics of standard measures of TC activity are computed from the recent historical climatological SST simulation and compared with the same measures computed from observations. The changes in TC activity in the three idealized climate change simulations, by comparison with that in the historical climatological SST simulation, are also described. Similar to previous results in the literature, the changes in TC frequency in the simulation with a doubling CO2 and an increase in SST are approximately the linear sum of the TC frequency in the other two simulations. However, in contrast with previous results, in these simulations the effects of CO2 and SST on TC frequency oppose each other. Large-scale environmental variables associated with TC activity are then analyzed for the present and future simulations. Model biases in the large-scale fields are identified through a comparison with ERA-Interim reanalysis. Changes in the environmental fields in the future climate simulations are shown and their association with changes in TC activity discussed.

  5. Tropical cyclones in the GISS ModelE2

    Directory of Open Access Journals (Sweden)

    Suzana J. Camargo

    2016-07-01

    Full Text Available The authors describe the characteristics of tropical cyclone (TC activity in the GISS general circulation ModelE2 with a horizontal resolution 1°×1°. Four model simulations are analysed. In the first, the model is forced with sea surface temperature (SST from the recent historical climatology. The other three have different idealised climate change simulations, namely (1 a uniform increase of SST by 2 degrees, (2 doubling of the CO2 concentration and (3 a combination of the two. These simulations were performed as part of the US Climate Variability and Predictability Program Hurricane Working Group. Diagnostics of standard measures of TC activity are computed from the recent historical climatological SST simulation and compared with the same measures computed from observations. The changes in TC activity in the three idealised climate change simulations, by comparison with that in the historical climatological SST simulation, are also described. Similar to previous results in the literature, the changes in TC frequency in the simulation with a doubling CO2 and an increase in SST are approximately the linear sum of the TC frequency in the other two simulations. However, in contrast with previous results, in these simulations the effects of CO2 and SST on TC frequency oppose each other. Large-scale environmental variables associated with TC activity are then analysed for the present and future simulations. Model biases in the large-scale fields are identified through a comparison with ERA-Interim reanalysis. Changes in the environmental fields in the future climate simulations are shown and their association with changes in TC activity discussed.

  6. E2F-1 binding affinity for pRb is not the only determinant of the E2F-1 activity

    Directory of Open Access Journals (Sweden)

    Fikret Sahin, Todd L. Sladek

    2010-01-01

    Full Text Available E2F-1 is the major cellular target of pRB and is regulated by pRB during cell proliferation. Interaction between pRB and E2F-1 is dependent on the phosphorylation status of pRB. Despite the fact that E2F-1 and pRB have antagonistic activities when they are overexpressed, the role of the E2F-1-pRB interaction in cell growth largely remains unknown. Ideally, it would be better to study the properties of a pRB mutant that fails to bind to E2F, but retains all other activities. To date, no pRB mutation has been characterized in sufficient detail to show that it specifically eliminates E2F binding but leaves other interactions intact. An alternative approach to this issue is to ask whether mutations that change E2F proteins binding affinity to pRB are sufficient to change cell growth in aspect of cell cycle and tumor formation. Therefore, we used the E2F-1 mutants including E2F-1/S332-7A, E2F-1/S375A, E2F-1/S403A, E2F-1/Y411A and E2F-1/L132Q that have different binding affinities for pRB to better understand the roles of the E2F-1 phosphorylation and E2F-1-pRB interaction in the cell cycle, as well as in transformation and gene expression. Data presented in this study suggests that in vivo phosphorylation at amino acids 332-337, 375 and 403 is important for the E2F-1 and pRB interaction in vivo. However, although E2F-1 mutants 332-7, 375 and 403 showed similar binding affinity to pRB, they showed different characteristics in transformation efficiency, G0 accumulation, and target gene experiments.

  7. Absence of NR2E1 mutations in patients with aniridia

    DEFF Research Database (Denmark)

    Corso-Díaz, Ximena; Borrie, Adrienne E; Bonaguro, Russell;

    2012-01-01

    Nuclear receptor 2E1 (NR2E1) is a transcription factor with many roles during eye development and thus may be responsible for the occurrence of certain congenital eye disorders in humans. To test this hypothesis, we screened NR2E1 for candidate mutations in patients with aniridia and other congen...

  8. Intravirion cohesion of matrix protein M1 with ribonucleocapsid is a prerequisite of influenza virus infectivity

    Energy Technology Data Exchange (ETDEWEB)

    Zhirnov, O.P., E-mail: zhirnov@inbox.ru [D.I. Ivanovsky Institute of Virology, Moscow 123098 (Russian Federation); Manykin, A.A. [D.I. Ivanovsky Institute of Virology, Moscow 123098 (Russian Federation); Rossman, J.S. [School of Biosciences, University of Kent, Canterbury CT27NJ (United Kingdom); Klenk, H.D. [Institute of Virology, Philipps University, Marburg 35037 (Germany)

    2016-05-15

    Influenza virus has two major structural modules, an external lipid envelope and an internal ribonucleocapsid containing the genomic RNA in the form of the ribonucleoprotein (RNP) complex, both of which are interlinked by the matrix protein M1. Here we studied M1-RNP cohesion within virus exposed to acidic pH in vitro. The effect of acidification was dependent on the cleavage of the surface glycoprotein HA. Acidic pH caused a loss of intravirion RNP-M1 cohesion and activated RNP polymerase activity in virus with cleaved HA (HA1/2) but not in the uncleaved (HA0) virus. The in vitro acidified HA1/2 virus rapidly lost infectivity whereas the HA0 one retained infectivity, following activation by trypsin, suggesting that premature activation and release of the RNP is detrimental to viral infectivity. Rimantadine, an inhibitor of the M2 ion channel, was found to protect the HA1/2 virus interior against acidic disintegration, confirming that M2-dependent proton translocation is essential for the intravirion RNP release and suggesting that the M2 ion channel is only active in virions with cleaved HA. Acidic treatment of both HA0 and HA1/2 influenza viruses induces formation of spikeless bleb-like protrusion of ~25 nm in diameter on the surface of the virion, though only the HA1/2 virus was permeable to protons and permitted RNP release. It is likely that this bleb corresponds to the M2-enriched and M1-depleted focus arising from pinching off of the virus during the completion of budding. Cooperatively, the data suggest that the influenza virus has an asymmetric structure where the M1-mediated organization of the RNP inside the virion is a prerequisite for infectious entry into target cell. - Highlights: • The influenza A virus has a novel asymmetric internal structure. • The structure is largely maintained by M1-RNP cohesion within the virion. • This asymmetry plays an important role during viral entry, facilitating virus uncoating and the initiation of a productive

  9. FRET-Based Detection of M1 Muscarinic Acetylcholine Receptor Activation by Orthosteric and Allosteric Agonists

    Science.gov (United States)

    Markovic, Danijela; Holdich, Jonathan; Al-Sabah, Suleiman; Mistry, Rajendra; Krasel, Cornelius; Mahaut-Smith, Martyn P.; Challiss, R. A. John

    2012-01-01

    Background and Objective Muscarinic acetylcholine receptors (mAChRs) are 7-transmembrane, G protein-coupled receptors that regulate a variety of physiological processes and represent potentially important targets for therapeutic intervention. mAChRs can be stimulated by full and partial orthosteric and allosteric agonists, however the relative abilities of such ligands to induce conformational changes in the receptor remain unclear. To gain further insight into the actions of mAChR agonists, we have developed a fluorescently tagged M1 mAChR that reports ligand-induced conformational changes in real-time by changes in Förster resonance energy transfer (FRET). Methods Variants of CFP and YFP were inserted into the third intracellular loop and at the end of the C-terminus of the mouse M1 mAChR, respectively. The optimized FRET receptor construct (M1-cam5) was expressed stably in HEK293 cells. Results The variant CFP/YFP-receptor chimera expressed predominantly at the plasma membrane of HEK293 cells and displayed ligand-binding affinities comparable with those of the wild-type receptor. It also retained an ability to interact with Gαq/11 proteins and to stimulate phosphoinositide turnover, ERK1/2 phosphorylation and undergo agonist-dependent internalization. Addition of the full agonist methacholine caused a reversible decrease in M1 FRET (FEYFP/FECFP) that was prevented by atropine pre-addition and showed concentration-dependent amplitude and kinetics. Partial orthosteric agonists, arecoline and pilocarpine, as well as allosteric agonists, AC-42 and 77-LH-28-1, also caused atropine-sensitive decreases in the FRET signal, which were smaller in amplitude and significantly slower in onset compared to those evoked by methacholine. Conclusion The M1 FRET-based receptor chimera reports that allosteric and orthosteric agonists induce similar conformational changes in the third intracellular loop and/or C-terminus, and should prove to be a valuable molecular reagent for

  10. FRET-based detection of M1 muscarinic acetylcholine receptor activation by orthosteric and allosteric agonists.

    Directory of Open Access Journals (Sweden)

    Danijela Markovic

    Full Text Available BACKGROUND AND OBJECTIVE: Muscarinic acetylcholine receptors (mAChRs are 7-transmembrane, G protein-coupled receptors that regulate a variety of physiological processes and represent potentially important targets for therapeutic intervention. mAChRs can be stimulated by full and partial orthosteric and allosteric agonists, however the relative abilities of such ligands to induce conformational changes in the receptor remain unclear. To gain further insight into the actions of mAChR agonists, we have developed a fluorescently tagged M(1 mAChR that reports ligand-induced conformational changes in real-time by changes in Förster resonance energy transfer (FRET. METHODS: Variants of CFP and YFP were inserted into the third intracellular loop and at the end of the C-terminus of the mouse M(1 mAChR, respectively. The optimized FRET receptor construct (M(1-cam5 was expressed stably in HEK293 cells. RESULTS: The variant CFP/YFP-receptor chimera expressed predominantly at the plasma membrane of HEK293 cells and displayed ligand-binding affinities comparable with those of the wild-type receptor. It also retained an ability to interact with Gα(q/11 proteins and to stimulate phosphoinositide turnover, ERK1/2 phosphorylation and undergo agonist-dependent internalization. Addition of the full agonist methacholine caused a reversible decrease in M(1 FRET (F(EYFP/F(ECFP that was prevented by atropine pre-addition and showed concentration-dependent amplitude and kinetics. Partial orthosteric agonists, arecoline and pilocarpine, as well as allosteric agonists, AC-42 and 77-LH-28-1, also caused atropine-sensitive decreases in the FRET signal, which were smaller in amplitude and significantly slower in onset compared to those evoked by methacholine. CONCLUSION: The M(1 FRET-based receptor chimera reports that allosteric and orthosteric agonists induce similar conformational changes in the third intracellular loop and/or C-terminus, and should prove to be a

  11. A neutralizing monoclonal antibody targeting the acid-sensitive region in chikungunya virus E2 protects from disease.

    Directory of Open Access Journals (Sweden)

    Suganya Selvarajah

    Full Text Available The mosquito-borne alphavirus, chikungunya virus (CHIKV, has recently reemerged, producing the largest epidemic ever recorded for this virus, with up to 6.5 million cases of acute and chronic rheumatic disease. There are currently no licensed vaccines for CHIKV and current anti-inflammatory drug treatment is often inadequate. Here we describe the isolation and characterization of two human monoclonal antibodies, C9 and E8, from CHIKV infected and recovered individuals. C9 was determined to be a potent virus neutralizing antibody and a biosensor antibody binding study demonstrated it recognized residues on intact CHIKV VLPs. Shotgun mutagenesis alanine scanning of 98 percent of the residues in the E1 and E2 glycoproteins of CHIKV envelope showed that the epitope bound by C9 included amino-acid 162 in the acid-sensitive region (ASR of the CHIKV E2 glycoprotein. The ASR is critical for the rearrangement of CHIKV E2 during fusion and viral entry into host cells, and we predict that C9 prevents these events from occurring. When used prophylactically in a CHIKV mouse model, C9 completely protected against CHIKV viremia and arthritis. We also observed that when administered therapeutically at 8 or 18 hours post-CHIKV challenge, C9 gave 100% protection in a pathogenic mouse model. Given that targeting this novel neutralizing epitope in E2 can potently protect both in vitro and in vivo, it is likely to be an important region both for future antibody and vaccine-based interventions against CHIKV.

  12. E2F-4, a new member of the E2F gene family, has oncogenic activity and associates with p107 in vivo

    NARCIS (Netherlands)

    Beijersbergen, R.L.; Kerkhoven, R.M.; Zhu, L.; Carlée, L.; Voorhoeve, P.M.; Bernards, R.A.

    1994-01-01

    The E2F family of transcription factors controls the expression of genes that are involved in cell cycle regulation. E2F DNA-binding activity is found in complex with the retinoblastoma protein, pRb, and with the pRb-related p107 and p130. To date, cDNAs for three members of the E2F gene family have

  13. Design and optimization of selective azaindole amide M1 positive allosteric modulators.

    Science.gov (United States)

    Davoren, Jennifer E; O'Neil, Steven V; Anderson, Dennis P; Brodney, Michael A; Chenard, Lois; Dlugolenski, Keith; Edgerton, Jeremy R; Green, Michael; Garnsey, Michelle; Grimwood, Sarah; Harris, Anthony R; Kauffman, Gregory W; LaChapelle, Erik; Lazzaro, John T; Lee, Che-Wah; Lotarski, Susan M; Nason, Deane M; Obach, R Scott; Reinhart, Veronica; Salomon-Ferrer, Romelia; Steyn, Stefanus J; Webb, Damien; Yan, Jiangli; Zhang, Lei

    2016-01-15

    Selective activation of the M1 receptor via a positive allosteric modulator (PAM) is a new approach for the treatment of the cognitive impairments associated with schizophrenia and Alzheimer's disease. A novel series of azaindole amides and their key pharmacophore elements are described. The nitrogen of the azaindole core is a key design element as it forms an intramolecular hydrogen bond with the amide N-H thus reinforcing the bioactive conformation predicted by published SAR and our homology model. Representative compound 25 is a potent and selective M1 PAM that has well aligned physicochemical properties, adequate brain penetration and pharmacokinetic (PK) properties, and is active in vivo. These favorable properties indicate that this series possesses suitable qualities for further development and studies.

  14. IKKα Promotes Intestinal Tumorigenesis by Limiting Recruitment of M1-like Polarized Myeloid Cells

    Directory of Open Access Journals (Sweden)

    Serkan I. Göktuna

    2014-06-01

    Full Text Available The recruitment of immune cells into solid tumors is an essential prerequisite of tumor development. Depending on the prevailing polarization profile of these infiltrating leucocytes, tumorigenesis is either promoted or blocked. Here, we identify IκB kinase α (IKKα as a central regulator of a tumoricidal microenvironment during intestinal carcinogenesis. Mice deficient in IKKα kinase activity are largely protected from intestinal tumor development that is dependent on the enhanced recruitment of interferon γ (IFNγ-expressing M1-like myeloid cells. In IKKα mutant mice, M1-like polarization is not controlled in a cell-autonomous manner but, rather, depends on the interplay of both IKKα mutant tumor epithelia and immune cells. Because therapies aiming at the tumor microenvironment rather than directly at the mutated cancer cell may circumvent resistance development, we suggest IKKα as a promising target for colorectal cancer (CRC therapy.

  15. Extended M1 sum rule for excited symmetric and mixed-symmetry states in nuclei

    CERN Document Server

    Smirnova, N A; Leviatan, A; Ginocchio, J N; Fransen, C

    2002-01-01

    A generalized M1 sum rule for orbital magnetic dipole strength from excited symmetric states to mixed-symmetry states is considered within the proton-neutron interacting boson model of even-even nuclei. Analytic expressions for the dominant terms in the B(M1) transition rates from the first and second $2^+$ states are derived in the U(5) and SO(6) dynamic symmetry limits of the model, and the applicability of a sum rule approach is examined at and in-between these limits. Lastly, the sum rule is applied to the new data on mixed-symmetry states of 94Mo and a quadrupole d-boson ratio $nd(0^+_1)/nd(2^+_2) \\approx 0.6$ is obtained in a largely parameter-independent way

  16. M=1 and 2 gravitational instabilities in gaseous disks; 1, diffuse gas

    CERN Document Server

    Junqueira, S

    1996-01-01

    We report the results of self-gravitating simulations of spiral galaxies, modeled by stellar and gaseous components, developed to investigate in particular the role of dissipation in the evolution of galaxy disks. The gas disk is simulated by the Beam-Scheme method, where it is considered as a self-gravitating fluid. The results suggest that the gravitational coupling between the stars and gas plays a fundamental role in the formation and dissolution of stellar bars, depending on the gaseous mass concentration and on the degree of dissipation. In addition we remark that initially concentrated gas disks can be unstable to the one-armed (m=1) spiral perturbations, which may explain the lopsided features observed in the gas distribution of the late-type isolated galaxies. The development of the m=1 feature slows down the radial gas flows towards the center, since the large-scale gravity torques are then much weaker.

  17. Cholinergic impact on neuroplasticity drives muscarinic M1 receptor mediated differentiation into neurons.

    Science.gov (United States)

    Benninghoff, Jens; Rauh, Werner; Brantl, Victor; Schloesser, Robert J; Moessner, Rainald; Möller, Hans-Jürgen; Rujescu, Dan

    2013-04-01

    Increasing evidence indicates that canonical neurotransmitters act as regulatory signals during neuroplasticity. Here, we report that muscarinic cholinergic neurotransmission stimulates differentiation of adult neural stem cells in vitro. Adult neural stem cells (ANSC) dissociated from the adult mouse hippocampus were expanded in culture with basic fibroblast growth factor (BFGF) and epidermal growth factor (EGF). Carbachol (CCh), an analog of acetylcholine (ACh) significantly enhanced de novo differentiation into neurons on bFGF- and EGF-deprived stem cells as shown by the percentage of TUJ1 positive cells. By contrast, pirenzepine (PIR), a muscarinic M1 receptor antagonist, reduced the generation of neurons. Activation of cholinergic signaling drives the de novo differentiation of uncommitted stem cells into neurons. These effects appear to be predominantly mediated via the muscarinic M1 receptor subtype.

  18. Commercial scale demonstration enhanced oil recovery by miceller-polymer flooding. M-1 project: facilities report

    Energy Technology Data Exchange (ETDEWEB)

    Knight, B.L. (ed.)

    1977-04-01

    ERDA and Marathon Oil Company contracted together for a commercial scale demonstration of enhanced oil recovery by the Maraflood (TM) oil recovery process. This M-1 Project is located within Sections 15, 16, 21 and 22, T6N, R13W, Crawford County, Illinois, encompassing approximately 407 acres of Robinson Sand reservoir developed in the first decade of the century. The area covers portions of several waterfloods developed on 10-acre spacing in the 1950's that were approaching their economic limit. This report describes all M-1 Project facilities, how they were prepared or constructed, their purpose and how they operate: (1) wells (drilling and completion); (2) production facility; (3) injection facility; and (4) various service systems required during project development and/or operation. (48 fig, 7 tables) (DLC).

  19. Data on sulforaphane treatment mediated suppression of autoreactive, inflammatory M1 macrophages

    Directory of Open Access Journals (Sweden)

    Sanjima Pal

    2016-06-01

    Full Text Available Any chronic, inflammatory, autoimmune disease (e.g. arthritis associated pathogenesis directs uncontrolled accumulation of both soluble forms of collagens in the synovial fluids and M1 macrophages around inflamed tissues. Despite of few studies demonstrating efficiency of Sulforaphane (SFN in suppressing arthritis associated collagen restricted T cells or fibroblasts, its effects on macrophage polarity and plasticity are less understood. Recently, we reported regulation of phenotypic and functional switching by SFN in induced and spontaneously differentiating human monocytes [1]. Here, flow cytometry, western blot and ELISA derived data demonstrated that SFN inhibited in vitro inflammatory responses developed by soluble human collagens (I–IV induced auto-reactive M1 type monocyte/macrophage model.

  20. THE BULK INPUT M[X]/M/1 QUEUE WITH WORKING VACATIONS

    Institute of Scientific and Technical Information of China (English)

    Xiuli XU; Mingxin LIU; Xiaohua ZHAO

    2009-01-01

    In this paper, we analyze a bulk input M[X]/M/1 queue with multiple working vacations. A quasi upper triangle transition probability matrix of two-dimensional Markov chain in this model is obtained, and with the matrix analysis method, highly complicated probability generating function(PGF) of the stationary queue length is firstly derived, from which we got the stochastic decomposition result for the stationary queue length which indicates the evident relationship with that of the classical M[X]/M/1 queue without vacation. It is important that we find the upper and the lower bounds of the stationary waiting time in the Laplace transform order using the properties of the conditional Erlang distribution. Furthermore, we gain the mean queue length and the upper and the lower bounds of the mean waiting time.

  1. Formation of Polyhydroxyalkanoate Blends by Pseudomonas pseudoalcaligenes M1-2 from Various Carbon Sources

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Pseudomonas pseudoalcaligenes strain M1-2 isolated from oil-contaminated soil collected from an oilfield in northern China was found to be able to synthesize a blend of polyhydroxyalkanoates (PHAs) containing monomers of 3-hydroxybutyrate (C4), 3-hydroxyvalerate (C5), 3-hydroxyheptanoate (C7), 3-hydroxyoctanoate (C8), 3-hydroxynonanoate (C9), 3-hydroxydecanoate (C10) and 3-hydroxydodecanoate (C12) from various carbon sources.The hydroxyalkanoate (HA) monomer composition varied both quantitatively and qualitatively, depending on the carbon sources used.The presence of octanoate in substrates of myristic acid or tridecanoate promoted the synthesis of HB monomer in the blend.Concentration of octanoate was also found to significantly affect the PHB content in the blend.A PHA biosynthesis pathway in Pseudomonas pseudoalcaligens M1-2 was proposed.

  2. Infection with E1B-mutant adenovirus stabilizes p53 but blocks p53 acetylation and activity through E1A

    DEFF Research Database (Denmark)

    Savelyeva, I.; Dobbelstein, M.

    2011-01-01

    Wild-type adenovirus type 5 eliminates p53 through the E1B-55 kDa and E4-34 kDa gene products. Deletion or mutation of E1B-55 kDa has long been thought to confer p53-selective replication of oncolytic viruses. We show here that infection with E1B-defective adenovirus mutants induces massive...... accumulation of p53, without obvious defects in p53 localization, phosphorylation, conformation and oligomerization. Nonetheless, p53 completely failed to induce its target genes in this scenario, for example, p21/CDKN1A, Mdm2 and PUMA. Two regions of the E1A gene products independently contributed...... acetylation in infected cells. Mutating either of these E1A regions, in addition to E1B, partially restored p21 mRNA levels. Our findings argue that adenovirus attenuates p53-mediated p21 induction, through at least two E1B-independent mechanisms. Other virus species and cancer cells may employ analogous...

  3. Modulating activity of M1 receptor to the reaction of ileal smooth muscle.

    Science.gov (United States)

    Glaza, Izabela; Szadujkis-Szadurski, Leszek; Szadujkis-Szadurski, Rafał; Gajdus, Marta; Olkowska, Joanna

    2011-08-03

    The subject of the study was determination of the effect of drugs on ileal smooth muscle contraction induced by activation of M(1) type muscarinic receptors. Drugs that have an effect on muscarinic receptors are divided to agonists, with close ties to the receptor and high internal activity and antagonists, with no internal activity. Conducted experiments tested interactions between a broad-spectrum agonist of muscarinic receptors, carbachol and a selective muscarinic receptor antagonist of M(1) type, pirenzepine. Testing was conducted on tissues isolated from rat's intestine. Male Wistar rats with weight between 220 g and 360 g were anesthetized by intraperitoneal injection of urethane (120 mg/kg). Concentration-effect curves were determined with the use of cumulated concentration method, in accordance with the van Rossum method (1963) in Kenakin modification (2006). The purpose of the study was determination of concentration-effect curves for carbachol. This curve was compared with the curve of receptor occupation depending on concentration of this drug. Based on concentration-effect curves, the average value of EC(50) was calculated for carbachol, amounting to 2.44×10(-6) [M/l]. The results confirmed that atropine is effective in stopping contractions caused by carbachol, meeting the conditions of competitive antagonists. Atropine caused the shift of curves for carbachol to the right. Pirenzepine, selectively blocking muscarinic receptors of M(1) type gave similar results. It was proved that in the preparation of gastric fundus smooth muscle, M(1) type receptors occur not only presynaptically, but also postsynaptically.

  4. Modulating activity of M1 receptor to the reaction of ileal smooth muscle

    Directory of Open Access Journals (Sweden)

    Izabela Glaza

    2011-08-01

    Full Text Available Background:The subject of the study was determination of the effect of drugs on ileal smooth muscle contraction induced by activation of M1 type muscarinic receptors. Drugs that have an effect on muscarinic receptors are divided to agonists, with close ties to the receptor and high internal activity and antagonists, with no internal activity. Conducted experiments tested interactions between a broad-spectrum agonist of muscarinic receptors, carbachol and a selective muscarinic receptor antagonist of M1 type, pirenzepine.Material/Methods:Testing was conducted on tissues isolated from rat’s intestine. Male Wistar rats with weight between 220 g and 360 g were anesthetized by intraperitoneal injection of urethane (120 mg/kg. Concentration-effect curves were determined with the use of cumulated concentration method, in accordance with the van Rossum method (1963 in Kenakin modification (2006.Results:The purpose of the study was determination of concentration-effect curves for carbachol. This curve was compared with the curve of receptor occupation depending on concentration of this drug. Based on concentration-effect curves, the average value of EC50 was calculated for carbachol, amounting to 2.44×10–6 [M/l].Conclusions:The results confirmed that atropine is effective in stopping contractions caused by carbachol, meeting the conditions of competitive antagonists. Atropine caused the shift of curves for carbachol to the right. Pirenzepine, selectively blocking muscarinic receptors of M1 type gave similar results. It was proved that in the preparation of gastric fundus smooth muscle, M1 type receptors occur not only presynaptically, but also postsynaptically.

  5. Role of M1 receptor in regulation of gastric fundus smooth muscle contraction

    Directory of Open Access Journals (Sweden)

    Marta Gajdus

    2011-09-01

    Full Text Available Background:The subject of this study is determination of the influence of drugs on gastric fundus smooth muscle contraction induced by activation of muscarinic receptors M1. Experiments tested interactions between a receptor agonist, carbachol and muscarinic receptor antagonists, atropine and pirenzepine.Material/Methods:Testing was conducted on tissues isolated from rat’s stomach. Male Wistar rats with weight between 220 g and 360 g were anesthetized by intraperitoneal injection of urethane (120 mg/kg. The stomach was dissected, and later the gastric fundus was isolated. Tissue was placed in a dish for insulated organs with 20 ml in capacity, filled with Krebs fluid. Results contained in the study are average values ± SE. In order to determine statistical significance, the principles of receptor theory were used (Kenakin modification.Results:According to tests, carbachol, in concentrations ranging between 10–8 M to 10–4 M, in a dosage-dependent way induces gastric fundus smooth muscle contraction. Presented results indicate that carbachol meets the conditions posed to full agonists. On the other hand, atropine, a non-selective muscarinic receptor antagonist, causes a concentration-dependent shift of concentration-effect curve (for carbachol to the right, maintaining maximum reaction. According to analysis of the curve determined, we can deduce that atropine meets the conditions posed to competitive antagonists. The use of pirenzepine, a competitive receptor agonist M1, causes shift of concentration-effect curve (for carbachol to the right, maintaining maximum reaction.Conclusions:From the testing conducted on the preparation of the gastric fundus we can deduce that atropine causes shift of concentration-effect curves for carbachol to the right. A similar effect is released by pirenzepine, selectively blocking muscarinic receptors of M1 type. The results indicate that in the preparation of the gastric fundus smooth muscle, M1 type

  6. Role of M1 receptor in regulation of gastric fundus smooth muscle contraction.

    Science.gov (United States)

    Gajdus, Marta; Szadujkis-Szadurska, Katarzyna; Szadujkis-Szadurski, Leszek; Glaza, Izabela; Szadujkis-Szadurski, Rafał; Olkowska, Joanna

    2011-09-14

    The subject of this study is determination of the influence of drugs on gastric fundus smooth muscle contraction induced by activation of muscarinic receptors M1. Experiments tested interactions between a receptor agonist, carbachol and muscarinic receptor antagonists, atropine and pirenzepine. Testing was conducted on tissues isolated from rat's stomach. Male Wistar rats with weight between 220 g and 360 g were anesthetized by intraperitoneal injection of urethane (120 mg/kg). The stomach was dissected, and later the gastric fundus was isolated. Tissue was placed in a dish for insulated organs with 20 ml in capacity, filled with Krebs fluid. Results contained in the study are average values ± SE. In order to determine statistical significance, the principles of receptor theory were used (Kenakin modification). According to tests, carbachol, in concentrations ranging between 10(-8) M to 10(-4) M, in a dosage-dependent way induces gastric fundus smooth muscle contraction. Presented results indicate that carbachol meets the conditions posed to full agonists. On the other hand, atropine, a non-selective muscarinic receptor antagonist, causes a concentration-dependent shift of concentration-effect curve (for carbachol) to the right, maintaining maximum reaction. According to analysis of the curve determined, we can deduce that atropine meets the conditions posed to competitive antagonists. The use of pirenzepine, a competitive receptor agonist M1, causes shift of concentration-effect curve (for carbachol) to the right, maintaining maximum reaction. From the testing conducted on the preparation of the gastric fundus we can deduce that atropine causes shift of concentration-effect curves for carbachol to the right. A similar effect is released by pirenzepine, selectively blocking muscarinic receptors of M1 type. The results indicate that in the preparation of the gastric fundus smooth muscle, M1 type receptors occur also postsynaptically.

  7. "5M1E"法在生产管理中的运用

    Institute of Scientific and Technical Information of China (English)

    刘秋香

    2010-01-01

    人(man)、机械(machine)、材料(material)、方法(method)、环境(enviroment)、管理(manage)这几个主要环节实行全面质量管理,称为"5M1E"法.在生产管理中应用该法,可以达到提升人品质、提升产品品质,提高员工士气.

  8. Radiationless transitions to atomic M 1,2,3 shells - Results of relativistic theory

    Science.gov (United States)

    Chen, M. H.; Crasemann, B.; Mark, H.

    1983-01-01

    Radiationless transitions filling vacancies in atomic M1, M2, and M3 subshells have been calculated relativistically with Dirac-Hartree-Slater wave functions for ten elements with atomic numbers 67-95. Results are compared with those of nonrelativistic calculations and experiment. Relativistic effects are found to be significant. Limitations of an independent-particle model for the calculation of Coster-Kronig rates are noted.

  9. Study of Mutagenic Effects of M1 Generation of Maize Seeds Irradiated by Heavy Ions

    Institute of Scientific and Technical Information of China (English)

    LUOHong-bing; ZHAOKui; GUOJi-yu; SUILi; NIMei-nan; MEIJun-ping; LUXiu-qin; ZHOUPing; KONGFu-quan; ZHANGGen-fa

    2003-01-01

    In order to study M1 biological effects induced by heavy ion irradiation on maize seeds, the embryos of dry maize seeds are irradiated with 7Li and 12C ions. The experiment is performed at the heavy ion scanning tube of the HI-13 tandem accelerator. The beam goes through a thickness of 25μm. Then the maize seeds are irradiated in the air uniformly.

  10. Cellular stress response in human Müller cells (MIO-M1) after bevacizumab treatment.

    Science.gov (United States)

    Matsuda, Monique; Krempel, Paloma Gava; Marquezini, Mônica Valeria; Sholl-Franco, Alfred; Lameu, Amanda; Monteiro, Mário Luiz R; Miguel, Nádia Campos de Oliveira

    2017-07-01

    Bevacizumab, an anti-vascular endothelial growth factor (VEGF) agent, is widely used in the treatment of retinal vascular diseases. However, due to the essential role Müller cell derived-VEGF plays in the maintenance of retinal neurons and glial cells, cell viability is likely to be affected by VEGF inhibition. We therefore evaluated the effect of bevacizumab-induced VEGF inhibition on Müller cells (MIO-M1) in vitro. MIO-M1 cells were cultured for 12 or 24 h in media containing bevacizumab at 0.25 or 0.5 mg/mL. Controls were cultured in medium only. Cell viability was determined with the trypan blue exclusion test and MTT assay. Caspase-3, beclin-1, glial fibrillary acidic protein (GFAP) and vimentin content were quantified by immunohistochemistry. Gene expression was evaluated by real-time quantitative PCR. Treatment with bevacizumab did not reduce MIO-M1 cell viability, but increased metabolic activity at 24 h (0.5 mg/mL) and induced apoptosis and autophagy, as shown by the increased caspase-3 levels at 12 h (0.25 and 0.5 mg/mL) and the increased beclin levels at 24 h (0.5 mg/mL). Caspase-3 mRNA was upregulated at 12 h and downregulated at 24 h in cells treated with bevacizumab at 0.25 mg/mL. Bevacizumab treatment was also associated with structural protein abnormalities, with decreased GFAP and vimentin content and upregulated GFAP and vimentin mRNA expression. Although bevacizumab did not significantly affect MIO-M1 cell viability, it led to metabolic and molecular changes (apoptosis, autophagy and structural abnormalities) suggestive of significant cellular toxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Feedback regulation between atypical E2Fs and APC/CCdh1 coordinates cell cycle progression.

    Science.gov (United States)

    Boekhout, Michiel; Yuan, Ruixue; Wondergem, Annelotte P; Segeren, Hendrika A; van Liere, Elsbeth A; Awol, Nesibu; Jansen, Imke; Wolthuis, Rob M F; de Bruin, Alain; Westendorp, Bart

    2016-03-01

    E2F transcription factors control the oscillating expression pattern of multiple target genes during the cell cycle. Activator E2Fs, E2F1-3, induce an upswing of E2F targets, which is essential for the G1-to-S phase transition, whereas atypical E2Fs, E2F7 and E2F8, mediate a downswing of the same targets during late S, G2, and M phases. Expression of atypical E2Fs is induced by E2F1-3, but it is unknown how atypical E2Fs are inactivated in a timely manner. Here, we demonstrate that E2F7 and E2F8 are substrates of the anaphase-promoting complex/cyclosome (APC/C). Removal of CDH1, or mutating the CDH1-interacting KEN boxes, stabilized E2F7/8 from anaphase onwards and during G1. Expressing KEN mutant E2F7 during G1 impairs S phase entry and eventually results in cell death. Furthermore, we show that E2F8, but not E2F7, interacts also with APC/C(C) (dc20). Importantly, atypical E2Fs can activate APC/C(C) (dh1) by repressing its inhibitors cyclin A, cyclin E, and Emi1. In conclusion, we discovered a feedback loop between atypical E2Fs and APC/C(C) (dh1), which ensures balanced expression of cell cycle genes and normal cell cycle progression.

  12. Fingerprinting the substrate specificity of M1 and M17 aminopeptidases of human malaria, Plasmodium falciparum.

    Directory of Open Access Journals (Sweden)

    Marcin Poreba

    Full Text Available BACKGROUND: Plasmodium falciparum, the causative agent of human malaria, expresses two aminopeptidases, PfM1AAP and PfM17LAP, critical to generating a free amino acid pool used by the intraerythrocytic stage of the parasite for proteins synthesis, growth and development. These exopeptidases are potential targets for the development of a new class of anti-malaria drugs. METHODOLOGY/PRINCIPAL FINDINGS: To define the substrate specificity of recombinant forms of these two malaria aminopeptidases we used a new library consisting of 61 fluorogenic substrates derived both from natural and unnatural amino acids. We obtained a detailed substrate fingerprint for recombinant forms of the enzymes revealing that PfM1AAP exhibits a very broad substrate tolerance, capable of efficiently hydrolyzing neutral and basic amino acids, while PfM17LAP has narrower substrate specificity and preferentially cleaves bulky, hydrophobic amino acids. The substrate library was also exploited to profile the activity of the native aminopeptidases in soluble cell lysates of P. falciparum malaria. CONCLUSIONS/SIGNIFICANCE: This data showed that PfM1AAP and PfM17LAP are responsible for majority of the aminopeptidase activity in these extracts. These studies provide specific substrate and mechanistic information important for understanding the function of these aminopeptidases and could be exploited in the design of new inhibitors to specifically target these for anti-malaria treatment.

  13. Fingerprinting the Substrate Specificity of M1 and M17 Aminopeptidases of Human Malaria, Plasmodium falciparum

    Science.gov (United States)

    Poreba, Marcin; McGowan, Sheena; Skinner-Adams, Tina S.; Trenholme, Katharine R.; Gardiner, Donald L.; Whisstock, James C.; To, Joyce; Salvesen, Guy S.; Dalton, John P.; Drag, Marcin

    2012-01-01

    Background Plasmodium falciparum, the causative agent of human malaria, expresses two aminopeptidases, PfM1AAP and PfM17LAP, critical to generating a free amino acid pool used by the intraerythrocytic stage of the parasite for proteins synthesis, growth and development. These exopeptidases are potential targets for the development of a new class of anti-malaria drugs. Methodology/Principal Findings To define the substrate specificity of recombinant forms of these two malaria aminopeptidases we used a new library consisting of 61 fluorogenic substrates derived both from natural and unnatural amino acids. We obtained a detailed substrate fingerprint for recombinant forms of the enzymes revealing that PfM1AAP exhibits a very broad substrate tolerance, capable of efficiently hydrolyzing neutral and basic amino acids, while PfM17LAP has narrower substrate specificity and preferentially cleaves bulky, hydrophobic amino acids. The substrate library was also exploited to profile the activity of the native aminopeptidases in soluble cell lysates of P. falciparum malaria. Conclusions/Significance This data showed that PfM1AAP and PfM17LAP are responsible for majority of the aminopeptidase activity in these extracts. These studies provide specific substrate and mechanistic information important for understanding the function of these aminopeptidases and could be exploited in the design of new inhibitors to specifically target these for anti-malaria treatment. PMID:22359643

  14. A novel strain of Bacteroides fragilis enhances phagocytosis and polarises M1 macrophages

    Science.gov (United States)

    Deng, Huimin; Li, Zhengchao; Tan, Yafang; Guo, Zhaobiao; Liu, Yangyang; Wang, Ye; Yuan, Yuan; Yang, Ruifu; Bi, Yujing; Bai, Yang; Zhi, Fachao

    2016-01-01

    Commensal Bacteroides fragilis possesses immune-regulatory characteristics. Consequently, it has been proposed as a potential novel probiotic because of its therapeutic effects on immune imbalance, mental disorders and inflammatory diseases. Macrophages play a central role in the immune response, developing either a classical-M1 or an alternative-M2 phenotype after stimulation with various signals. The interactions between macrophages and B. fragilis, however, remain to be defined. Here, a new isolate of B. fragilis, ZY-312, was shown to possess admirable properties, including tolerance to simulated gastric fluid, intestinal fluid and ox bile, and good safety (MOI = 100, 200) and adherent ability (MOI = 100) to LoVo cells. Isolate ZY-312 cell lysate promoted phagocytosis of fluorescent microspheres and pathogenic bacteria in bone marrow-derived macrophage (BMDM) cells. Gene expression of IL-12, iNOS and IL-1β in BMDM cells was increased after treatment with ZY-312, indicating the induction of M1 macrophages, consistent with enhanced secretion of NO. Cell surface expression of CD80 and CD86 was also increased. This study is the first to demonstrate that B. fragilis enhances the phagocytic functions of macrophages, polarising them to an M1 phenotype. Our findings provide insight into the close relationship between B. fragilis and the innate immune system. PMID:27381366

  15. Tramadol differentially regulates M1 and M2 macrophages from human umbilical cord blood.

    Science.gov (United States)

    Zhang, Jun; Chen, Liang; Sun, Yunyun; Li, Yuanhai

    2017-03-17

    Tramadol is an analgesic drug and relieves pain through activating μ-opioid receptors and inhibiting serotonin and noradrenaline reuptake. Emerging evidence shows that it also stimulates immune cells, including NK cells, splenocytes, and lymphocytes, and elevates IL-2 production. However, it remains unknown whether and how tramadol directly affects macrophages. To answer these questions, we collected human umbilical cord blood, isolated macrophages, and examined their responses to tramadol. Although tramadol did not alter resting macrophages and the antigen-presenting function in lipopolysaccharide-activated macrophages, it regulated M1 and M2 macrophages, which are, respectively, transformed by IFN-γ and IL-4. Interestingly, tramadol inhibits production and secretion of cytokines in M1 macrophages, but facilitates the production of inflammation-responding molecules, synthesized in M2 macrophages. We also found that STAT6 cascade pathway in M2 macrophages was significantly enhanced by tramadol. Therefore, this study reveals that tramadol regulates inflammation by inhibiting M1 macrophages (killing process), but promoting the function of M2 macrophages (healing process).

  16. Muscarinic M1 receptors regulate propofol modulation of GABAergic transmission in rat ventrolateral preoptic neurons.

    Science.gov (United States)

    Zhang, Yu; Yu, Tian; Liu, Yang; Qian, Kun; Yu, Bu-Wei

    2015-04-01

    GABAergic neurons within the ventrolateral preoptic area (VLPO) play an important role in sleep-wakefulness regulation. Propofol, a widely used systemic anesthetic, has lately been reported to excite noradrenaline (NA)-inhibited type of VLPO neurons. Present study tested if acetylcholine system takes part in the propofol modulation of GABAergic spontaneous miniature inhibitory postsynaptic currents (mIPSCs) in mechanically dissociated rat VLPO neurons using a conventional whole-cell patch clamp technique. Propofol reversibly decreased mIPSC frequency without affecting the current amplitude, indicating that propofol acts presynaptically to decrease the probability of spontaneous GABA release. The propofol action on GABAergic mIPSC frequency was completely blocked by atropine, a nonselective muscarinic acetylcholine (mACh) receptor antagonist, and pirenzepine, a selective M1 receptor antagonist. These results suggest that propofol acts on M1 receptors on GABAergic nerve terminals projecting to VLPO neurons to inhibit spontaneous GABA release. The M1 receptor-mediated modulation of GABAergic transmission onto VLPO neurons may contribute to the regulation of loss of consciousness induced by propofol.

  17. Chronic treatment with simvastatin upregulates muscarinic M1/4 receptor binding in the rat brain.

    Science.gov (United States)

    Wang, Q; Zengin, A; Ying, W; Newell, K A; Wang, P; Yeo, W; Wong, P T-H; Yenari, M A; Huang, X-F

    2008-06-26

    Statins are increasingly being used for the treatment of a variety of conditions beyond their original indication for cholesterol lowering. We previously reported that simvastatin affected the dopaminergic system in the rat brain. This study aims to investigate regional changes of muscarinic M1/4 receptors in the rat brain after 4-week administration of simvastatin (1 or 10 mg/kg/day). M1/4 receptor distribution and alterations in the post-mortem rat brain were detected by [(3)H]pirenzepine binding autoradiography. Simvastatin (1 mg/kg/day) increased [(3)H]pirenzepine binding, predominantly in the prefrontal cortex (171%, Ppirenzepine binding were observed in the examined regions following simvastatin (10 mg/kg/day) treatment. Our results also provide strong evidence that chronic simvastatin administration, especially at a low dosage, up-regulates M1/4 receptor binding, which is likely to be independent of its muscarinic agonist-like effect. Alterations in [(3)H]pirenzepine binding in the examined brain areas may represent the specific regions that mediate the clinical effects of simvastatin treatment on cognition and memory via the muscarinic cholinergic system. These findings contribute to a better understanding of the critical roles of simvastatin in treating neurodegenerative disorders, via muscarinic receptors.

  18. The mechanism of the anticancer function of M1 macrophages and their use in the clinic

    Institute of Scientific and Technical Information of China (English)

    Xing-Qing Pan

    2012-01-01

    M1-type macrophages are capable of inducing lysis in various types of cancer cells,but the mechanism of action is unclear.It has been noted that an "unknown protein" produced together with protease by activated macrophages is responsible for this action.Activated M1 macrophages have been recently reported to produce family 18 chitinases,all of which have been named chitotriosidase.Our experiments have demonstrated that family 18 chitinases work together with proteases and can damage various cancer cells both in vitro and in vivo.Thus,in this article,we suggest that the 50-kDa chitotriosidase is the reported "unknown protein".In addition,we discuss how to properly stimulate activated M1 macrophages to produce 50-kDa chitotriosidases and proteases for destroying cancer cells.Because family 19 chitinase has recently been reported to kill cancer cells,we also discuss the possibility of directly using human family 18 chitotriosidase and the humanized plant family 19 chitinase for cancer treatment.

  19. The detection of C60 in the well-characterized planetary nebula M1-11

    CERN Document Server

    Otsuka, Masaaki; Hyung, S; Sargent, B A; Meixner, M; Tajitsu, A; Yanagisawa, K

    2013-01-01

    We performed multiwavelength observations of the young planetary nebula (PN) M1-11 and obtained its elemental abundances, dust mass, and the evolutionary status of the central star. The AKARI/IRC, VLT/VISIR, and Spitzer/IRS spectra show features due to carbon-rich dust, such as the 3.3, 8.6, and 11.3 um features due to polycyclic aromatic hydrocarbons (PAHs), a smooth continuum attributable to amorphous carbon, and the broad 11.5 and 30 um features often ascribed to SiC and MgS, respectively. We also report the presence of an unidentified broad feature at 16-22 um, similar to the feature found in Magellanic Cloud PNe with either C-rich or O-rich gas-phase compositions. We identify for the first time in M1-11 spectral lines at 8.5 (blended with PAH), 17.3, and 18.9 um that we attribute to the C60 fullerene. This identification is strengthened by the fact that other Galactic PNe in which fullerenes are detected, have similar central stars, similar gas-phase abundances, and a similar dust composition to M1-11. T...

  20. Surface Termination of M1 Phase and Rational Design of Propane Ammoxidation Catalysts

    Energy Technology Data Exchange (ETDEWEB)

    Guliants, Vadim

    2015-02-16

    This final report describes major accomplishments in this research project which has demonstrated that the M1 phase is the only crystalline phase required for propane ammoxidation to acrylonitrile and that a surface monolayer terminating the ab planes of the M1 phase is responsible for their activity and selectivity in this reaction. Fundamental studies of the topmost surface chemistry and mechanism of propane ammoxidation over the Mo-V-(Te,Sb)-(Nb,Ta)-O M1 and M2 phases resulted in the development of quantitative understanding of the surface molecular structure – reactivity relationships for this unique catalytic system. These oxides possess unique catalytic properties among mixed metal oxides, because they selectively catalyze three alkane transformation reactions, namely propane ammoxidation to acrylonitrile, propane oxidation to acrylic acid and ethane oxidative dehydrogenation, all of considerable economic significance. Therefore, the larger goal of this research was to expand this catalysis to other alkanes of commercial interest, and more broadly, demonstrate successful approaches to rational design of improved catalysts that can be applied to other selective (amm)oxidation processes.

  1. Aflatoxin M1 in raw milk in Qazvin Province, Iran: a seasonal study.

    Science.gov (United States)

    Fallah, Aziz A; Barani, Afshin; Nasiri, Zeinab

    2015-01-01

    Occurrence of aflatoxin M1 (AFM1) was determined in 254 samples of raw milk obtained from dairy cow farms of Qazvin Province, Iran. Aflatoxin M1 analysis was carried out by using the competitive enzyme-linked immunosorbent assay technique for screening and high-performance liquid chromatography with fluorescence detection for confirmatory purposes. The limit of detection and quantification of the confirmatory method were 0.003 and 0.01 µg/l, respectively. Aflatoxin M1 was detected in 204 analysed samples (80.3%), ranging from 0.011 to 0.321 μg/l, and 144 samples (56.7%) had levels above the Iranian national standard limit of 0.050 μg/l. Considering the seasonal variability, the occurrence and levels of AFM1 in samples obtained in winter were significantly higher (P < 0.05) than those obtained in summer. The results of this survey indicate the usefulness of a monitoring programme to supervise food safety for consumers.

  2. Enhanced Macrophage M1 Polarization and Resistance to Apoptosis Enable Resistance to Plague.

    Science.gov (United States)

    Pachulec, Emilia; Abdelwahed Bagga, Rym Ben; Chevallier, Lucie; O'Donnell, Hope; Guillas, Chloé; Jaubert, Jean; Montagutelli, Xavier; Carniel, Elisabeth; Demeure, Christian E

    2017-09-15

    Susceptibility to infection is in part genetically driven, and C57BL/6 mice resist various pathogens through the proinflammatory response of their M1 macrophages (MPs). However, they are susceptible to plague. It has been reported elsewhere that Mus spretus SEG mice resist plague and develop an immune response characterized by a strong recruitment of MPs. The responses of C57BL/6 and SEG MPs exposed to Yersinia pestis in vitro were examined. SEG MPs exhibit a stronger bactericidal activity with higher nitric oxide production, a more proinflammatory polarized cytokine response, and a higher resistance to Y. pestis-induced apoptosis. This response was not specific to Y. pestis and involved a reduced sensitivity to M2 polarization/signal transducer and activator of transcription 6 activation and inhibition of caspase 8. The enhanced M1 profile was inducible in C57BL/6 MPs in vitro, and when transferred to susceptible C57BL/6 mice, these MPs significantly increased survival of bubonic plague. MPs can develop an enhanced functional profile beyond the prototypic M1, characterized by an even more potent proinflammatory response coordinated with resistance to killing. This programming plays a key role in the plague-resistance phenotype and may be similarly significant in other highly lethal infections, suggesting that orienting the MP response may represent a new therapeutic approach.

  3. Characterization of competing distortions in YF e2O4

    Science.gov (United States)

    Blasco, J.; Lafuerza, S.; García, J.; Subías, G.; Cuartero, V.; García-Muñoz, J. L.; Popescu, C.; Peral, I.

    2016-05-01

    We report the structural changes of three YF e2O4 -δ (δ cell at room temperature (space group R 3 ¯m ). This cell becomes unstable for the three samples on cooling, and the oxygen-poor specimen (δ ˜0.1 ) shows a single transition at 240 K. The nearly stoichiometric (δ ≤0.03 ) compounds exhibit two structural transitions with decreasing temperature at about 240 and 200 K. Each transition is revealed by an anomaly in the heat capacity measurements and a jump in the electric resistivity. Below 240 K, a strong splitting of some diffraction peaks is accompanied by the occurrence of superstructure peaks that follow the propagation vector k =(1 /7 ,-2 /7 ,9 /7 ) . The cell symmetry is then triclinic, and the structural transition is characterized by an expansion of the c axis coupled to a contraction of the other two lattice parameters. There are 49 nonequivalent sites for Fe atoms with a maximum charge disproportionation of ˜0.5 e- . Upon cooling at 200 K, the previous superstructure peaks begin to vanish, and finally they are replaced by a new set of superstructure peaks following the propagation vector k =(1 /4 ,1 /2 ,1 /4 ) with respect to the rhombohedral cell. The transition is also reflected in sudden changes in the lattice parameters that seem to smooth the changes observed in the previous transition. The new cell is also triclinic, and there are 48 nonequivalent Fe sites with a maximum charge disproportionation of ˜0.7 e- . Both phases coexist in a wide temperature range because this second transition is not completed at 80 K. A symmetry mode analysis indicates a complicated pattern for the charge distribution in the Fe sublattice of both distorted structures but clearly discard any bimodal distribution of only two types of Fe cations. Therefore, the sharp jumps in the electric resistivity at the phase transitions are clearly correlated with two different structural changes. Finally, the oxygen stoichiometry seems to be a key factor in the stabilization

  4. Prostaglandin E2 and patent ductus arteriosus in premature infants

    Directory of Open Access Journals (Sweden)

    Mochammading,

    2016-01-01

    Full Text Available Background Patent ductus arteriosus (PDA is a congenital heart disease most commonly occurring in premature infants. Spontaneous ductus arteriosus (DA closure in premature infants has been suggested to be associated with duct lumen maturity and the DA sensitivity to prostaglandin E2 (PGE2. Objective To assess for a possible correlation between serum PGE2 levels and PDA size in premature infants. Methods This observational study using repeated measurements on premature infants with PDA detected at days 2-3 of life was undertaken in Cipto Mangunkusumo Hospital and Fatmawati Hospital, Jakarta, from April to May 2014. The PDA was diagnosed using 2-D echocardiography and PGE2 levels were measured by immunoassay. Pearson’s correlation test was used to evaluate a possible correlation between PGE2 level and DA diameter. Results Thirty-three premature infants of median gestational age 31 (range 28-32 weeks and median birth weight 1,360 (range 1,000-1,500 grams were enrolled. Almost two-thirds of the subjects were male. Almost all (30/33 subjects had spontaneous DA closure before the age of 10 days. Subjects’ mean DA diameter was 2.9 (SD 0.5 mm with maximum flow velocity of 0.2 (SD 0.06 cm/sec, and left atrial-to-aortic root ratio (LA/Ao of 1.5 (SD 0.2. Their mean PGE2 levels at the ages of 2-3, 5-7, and after 10 days were 5,238.6 (SD 1,225.2, 4,178.2 (SD 1,534.5, and 915.2 (SD 151.6 pg/mL, respectively. The PGE2 level at days 2-3 was significantly correlated with DA diameter (r = 0.667; P < 0.001, but not at days 5-7 (r = 0.292; P = 0.105 or at day 10 (r = 0.041; P = 0.941. Conclusion There is a strong, positive correlation between the PGE2 level and DA diameter in preterm infants at 2-3 days of age. However, there is no significant correlation between PGE2 level and persistence of PDA.

  5. E2 protein cage as a multifunctional nanoplatform

    Science.gov (United States)

    Dalmau Mallorqui, Merce

    Caged protein systems such as viral capsids, heat shock proteins, and ferritin are spherical structures that occur naturally in living organisms and are a growing class of biomimetic templates used to create new materials in nanotechnology. Such systems have been proposed as general drug carriers since they form highly symmetric nanoscale architectures that offer the potential to be tailored according to the desired application. Within this framework, this dissertation focuses on the design and development of a new drug delivery nanoplatform based on the E2 subunit of the pyruvate dehydrogenase protein from Bacillus stearothermophilus. This scaffold forms a 25-nm nanocapsule structure with a hollow cavity. We produced a variant of this protein consisting only of the structural core, and found the thermostability of this self-assembled scaffold to be unusually high, with an onset unfolding temperature of 81.1 +/- 0.9°C and an apparent midpoint unfolding temperature of 91.4 +/- 1.4°C. To evaluate the potential of this scaffold for encapsulation of guest molecules in the internal cavity, we made variants which altered the physicochemical properties of the hollow internal surface. These mutants, yielding up to 240 mutations within this cavity, assembled into correct architectures and exhibited high thermostability that was also comparable to the wild-type scaffold. To show the applicability of this scaffold we coupled two drug-like small molecules to the internal cavity. We also developed a new strategy for encapsulation of small hydrophobic drug molecules. This method is based on hydrophobic differences between the interior cavity and the external buffer to nucleate drug-like agents inside the protein cage. We demonstrate that internal mutations can introduce non-native functionality and enable molecular encapsulation within the cavity while still retaining the dodecahedral structure. Another surface amenable to modifications is the interface between subunits. Such

  6. Forkhead transcription factor FoxM1 regulates mitotic entry and prevents spindle defects in cerebellar granule neuron precursors

    NARCIS (Netherlands)

    Schueller, Ulrich; Zhao, Qing; Godinho, Susana A.; Heine, Vivi M.; Medema, Rene H.; Pellman, David; Rowitch, David H.

    2007-01-01

    The forkhead transcription factor FoxM1 has been reported to regulate, variously, proliferation and/or spindle formation during the G(2)/M transition of the cell cycle. Here we define specific functions of FoxM1 during brain development by the investigation of FoxM1 loss-of-function mutations in the

  7. Macrophage polarisation: an immunohistochemical approach for identifying M1 and M2 macrophages.

    Directory of Open Access Journals (Sweden)

    Mário Henrique M Barros

    Full Text Available Macrophage polarization is increasingly recognised as an important pathogenetic factor in inflammatory and neoplastic diseases. Proinflammatory M1 macrophages promote T helper (Th 1 responses and show tumoricidal activity. M2 macrophages contribute to tissue repair and promote Th2 responses. CD68 and CD163 are used to identify macrophages in tissue sections. However, characterisation of polarised macrophages in situ has remained difficult. Macrophage polarisation is regulated by transcription factors, pSTAT1 and RBP-J for M1, and CMAF for M2. We reasoned that double-labelling immunohistochemistry for the detection of macrophage markers together with transcription factors may be suitable to characterise macrophage polarisation in situ. To test this hypothesis, we have studied conditions associated with Th1- and Th2-predominant immune responses: infectious mononucleosis and Crohn's disease for Th1 and allergic nasal polyps, oxyuriasis, wound healing and foreign body granulomas for predominant Th2 response. In all situations, CD163+ cells usually outnumbered CD68+ cells. Moreover, CD163+ cells, usually considered as M2 macrophages, co-expressing pSTAT1 and RBP-J were found in all conditions examined. The numbers of putative M1 macrophages were higher in Th1- than in Th2-associated diseases, while more M2 macrophages were seen in Th2- than in Th1 related disorders. In most Th1-related diseases, the balance of M1 over M2 cells was shifted towards M1 cells, while the reverse was observed for Th2-related conditions. Hierarchical cluster analysis revealed two distinct clusters: cluster I included Th1 diseases together with cases with high numbers of CD163+pSTAT1+, CD68+pSTAT1+, CD163+RBP-J+ and CD68+RBP-J+ macrophages; cluster II comprised Th2 conditions together with cases displaying high numbers of CD163+CMAF+ and CD68+CMAF+ macrophages. These results suggest that the detection of pSTAT1, RBP-J, and CMAF in the context of CD68 or CD163 expression is a

  8. Stereospecific preparation of (Z)- and (E)-2,3-difluoro-3-stannylacrylic ester synthons and a new, efficient stereospecific route to (Z)- and (E)-2,3-difluoroacrylic esters.

    Science.gov (United States)

    Wang, Yi; Lu, Long; Burton, Donald J

    2005-12-23

    [reaction: see text] The (Z)-2,3-difluoro-3-stannylacrylic ester is readily prepared from (Z)-1,2-difluorovinyltriethylsilane via stereospecific stannyl/silyl exchange with KF/(Bu3Sn)2O or Bu3SnCl in DMF at 70 degrees C. The corresponding (E)-2,3-difluoro-3-stannylacrylate is prepared by stereospecific carbonylation of (E)-1,2-difluorovinyl iodide followed by low temperature/in situ stannylation of the resultant (Z)-2,3-difluoroacrylic ester. With Cu(I) iodide and Pd(PPh3)4 catalysis, the (Z)- and (E)-stannylacrylate esters readily couple with aryl iodides and vinyl bromides, as well as 2-iodothiophene, at room temperature to stereospecifically produce the respective (E)- and (Z)-2,3-difluoro-3-aryl substituted acrylic esters or conjugated dienes in high yields.

  9. A potential oncogenic role of the commonly observed E2F5 overexpression in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Yuzhu Jiang; Seon-Hee Yim; Hai-Dong Xu; Seung-Hyun Jung; So Young Yang; Hae-Jin Hu; Chan-Kwon Jung; Yeun-Jun Chung

    2011-01-01

    AIM: To explore the expression pattern of E2F5 in primary hepatocellular carcinomas (HCCs) and elucidate the roles of E2F5 in hepatocarcinogenesis. METHODS: E2F5 expression was analyzed in 120 primary HCCs and 29 normal liver tissues by immunohistochemistry analysis. E2F5-small interfering RNA was transfected into HepG2, an E2F5-overexpressed HCC cell line. After E2F5 knockdown, cell growth capacity and migrating potential were examined. RESULTS: E2F5 was significantly overexpressed in primary HCCs compared with normal liver tissues (P = 0.008). The E2F5-silenced cells showed significantly reduced proliferation (P = 0.004). On the colony formation and soft agar assays, the number of colonies was significantly reduced in E2F5-silenced cells (P = 0.004 and P = 0.009, respectively). E2F5 knockdown resulted in the accumulation of G0/G1 phase cells and a reduction of S phase cells. The number of migrating/invading cells was also reduced after E2F5 knockdown (P = 0.021). CONCLUSION: To our knowledge, this is the first evidence that E2F5 is commonly overexpressed in primary HCC and that E2F5 knockdown significantly repressed the growth of HCC cells.

  10. Production of a monoclonal antibody against aflatoxin M1 and its application for detection of aflatoxin M1 in fortified milk

    Directory of Open Access Journals (Sweden)

    Umarphorn Chadseesuwan

    2016-10-01

    Full Text Available Aflatoxin M1 (AFM1 is a toxic metabolite of the fungal product aflatoxin found in milk. For food safety concern, maximum residual limits of AFM1 in milk and dairy products have been differently enforced in many countries. A suitable detection method is required to screen a large number of product samples for the AFM1 contamination. In this study, monoclonal antibodies (MAbs against AFM1 were generated using a conventional somatic cell fusion technique. After screening, five MAbs (AFM1-1, AFM1-3, AFM1-9, AFM1-11, and AFM1-17 were obtained that showed cross-reactivity with aflatoxin B1 (AFB1 and aflatoxin G1 (AFG1 but with no other tested compounds. An indirect competitive enzyme-linked immunosorbent assay (ELISA using a partially purified MAb and antigen-coated plates yielded the best sensitivity with the 50% inhibition concentration (IC50 and the limit of detection (LOD values of 0.13 ng/mL and 0.04 ng/mL, respectively. This indirect competitive ELISA was used to quantify the amount of fortified AFM1 in raw milk. The precision and accuracy in terms of % coefficient of variation (CV and % recovery of the detection was investigated for both intra- (n = 6 and inter- (n = 12 variation assays. The % CV was found in the range of 3.50–15.8% and 1.32–7.98%, respectively, while the % recovery was in the range of 92–104% and 100–103%, respectively. In addition, the indirect ELISA was also used to detect AFM1 fortified in processed milk samples. The % CV and % recovery values were in the ranges of 0.1–33.0% and 91–109%, respectively. Comparison analysis between the indirect ELISA and high performance liquid chromatography was also performed and showed a good correlation with the R2 of 0.992 for the concentration of 0.2–5.0 ng/mL. These results indicated that the developed MAb and ELISA could be used for detection of AFM1 in milk samples.

  11. Inhibition of the entomopathogenic fungus Metarhizium anisopliae in vitro by the bed bug defensive secretions (E)-2-hexenal and (E)-2-octenal

    Science.gov (United States)

    The two major aldehydes (E)-2-hexenal and (E)-2-octenal emitted as defensive secretions by bed bugs Cimex lectularius L. (Hemiptera: Cimicidae), inhibit the in vitro growth of Metarhizium anisopliae (Metsch.) Sokorin (Hypocreales: Clavicipitaceae). These chemicals inhibit fungal growth by direct con...

  12. Ability of the bed bug (Hemiptera: Cimicidae) defensive secretions (E)-2-hexenal and (E)-2-octenal to attract adult bed bugs

    Science.gov (United States)

    Accurate and timely surveillance of bed bug infestations is critical for development of effective control strategies. While the bed bug produced volatiles (E)-2-hexenal and (E)-2-octenal are considered defensive secretions, through use of EthoVision® video-tracking software we demonstrate that low ...

  13. Regulation of cell proliferation by the E2F transcription factors

    DEFF Research Database (Denmark)

    Helin, K

    1998-01-01

    demonstrated that individual members of the E2F transcription factor family are likely to have distinct roles in mammalian development and homeostasis. Additional mechanisms regulating the activity of the E2F transcription factors have been reported, including subcellular localization and proteolysis of the E2......Experimental data generated in the past year have further emphasized the essential role for the E2F transcription factors in the regulation of cell proliferation. Genetic studies have shown that E2F activity is required for normal development in fruitflies, and the generation of E2F-1(-/-) mice has......Fs in the proteasomes. Novel target genes for the E2F transcription factors have been identified that link the E2Fs directly to the initiation of DNA replication....

  14. Misoprostol inhibits gastric mucosal release of endogenous prostaglandin E2 and thromboxane B2 in healthy volunteers

    DEFF Research Database (Denmark)

    Mertz-Nielsen, A; Eskerod, O; Bukhave, K

    1995-01-01

    Prostaglandin analogues of the E-series theoretically offer the ideal antiulcer drugs. Peptic ulcer healing with prostaglandin analogues is, however, no better than would be predicted from their ability to inhibit gastric acid secretion and they are less effective than histamine H2 receptor...... antagonists in preventing ulcer relapse. It could be that prostaglandin analogues inhibit gastric mucosal synthesis or release of endogenous eicosanoids, thereby abrogating their own effects. This study, therefore, examined how a single therapeutic dose (200 micrograms) of misoprostol, a synthetic analogue...... of prostaglandin E1, influences gastric mucosal release of endogenous prostaglandin E2 (PGE2), thromboxane B2 (TXB2), and chemotactic leukotriene B4 (LTB4) during basal conditions and in response to gastric luminal acidification (0.1 M HCl; 5 ml/min for 10 minutes). Nine healthy volunteers were studied in a single...

  15. The Search for the Emission of a CP-Violating E1 Photon in the KL → π+π-γ Decay

    Energy Technology Data Exchange (ETDEWEB)

    Shields, John Michael [Univ. of Virginia, Charlottesville, VA (United States)

    2005-08-01

    A search for the CP-violating electric dipole (E1) direct emission contribution to the KL → π+π-γ decay is performed using data from the 1997 KTeV/E832 experiment. Because the KL → π+π-γ decay mode is massively dominated by the CP-violating inner bremsstrahlung (IB) and the CP-conserving magnetic dipole (M1) direct emission processes, previous analyses have neglected the E1 contribution. Therefore, this measurement is the first attempt to directly quantify the size of the E1 decay process. This E1 transition is one of the very few CP-violating processes that is accessible to experiment and, in principle, will produce new insights into the structure of the neutral kaon. The result of this analysis is that the E1 contribution is below the threshold of sensitivity, and therefore an upper bound of |gE1| < 0.14 (90% CL) is reported. In the process of obtaining this upper limit, high resolution measurements of fit parameters (~gM1 and a1/a2) associated with the size and shape of the M1 direct emission peak are also extracted. The fit results for these parameters: ~gM1 = 1.229 ± 0.035 (stat) ± 0.087 (syst); a1/a2 = -0.733 ± 0.007 (stat) ± 0.014 (syst) are in strong agreement with previous measurements.

  16. Differential expression of members of the E2F family of transcription factors in rodent testes

    Directory of Open Access Journals (Sweden)

    Toppari Jorma

    2006-12-01

    Full Text Available Abstract Background The E2F family of transcription factors is required for the activation or repression of differentially expressed gene programs during the cell cycle in normal and abnormal development of tissues. We previously determined that members of the retinoblastoma protein family that interacts with the E2F family are differentially expressed and localized in almost all the different cell types and tissues of the testis and in response to known endocrine disruptors. In this study, the cell-specific and stage-specific expression of members of the E2F proteins has been elucidated. Methods We used immunohistochemical (IHC analysis of tissue sections and Western blot analysis of proteins, from whole testis and microdissected stages of seminiferous tubules to study the differential expression of the E2F proteins. Results For most of the five E2F family members studied, the localizations appear conserved in the two most commonly studied rodent models, mice and rats, with some notable differences. Comparisons between wild type and E2F-1 knockout mice revealed that the level of E2F-1 protein is stage-specific and most abundant in leptotene to early pachytene spermatocytes of stages IX to XI of mouse while strong staining of E2F-1 in some cells close to the basal lamina of rat tubules suggest that it may also be expressed in undifferentiated spermatogonia. The age-dependent development of a Sertoli-cell-only phenotype in seminiferous tubules of E2F-1 knockout males corroborates this, and indicates that E2F-1 is required for spermatogonial stem cell renewal. Interestingly, E2F-3 appears in both terminally differentiated Sertoli cells, as well as spermatogonial cells in the differentiative pathway, while the remaining member of the activating E2Fs, E2F-2 is most concentrated in spermatocytes of mid to late prophase of meiosis. Comparisons between wildtype and E2F-4 knockout mice demonstrated that the level of E2F-4 protein displays a distinct

  17. Modulation of the E2F1-driven cancer cell fate by the DNA damage response machinery and potential novel E2F1 targets in osteosarcomas

    DEFF Research Database (Denmark)

    Liontos, Michalis; Niforou, Katerina; Velimezi, Georgia

    2009-01-01

    Osteosarcoma is the most common primary bone cancer. Mutations of the RB gene represent the most frequent molecular defect in this malignancy. A major consequence of this alteration is that the activity of the key cell cycle regulator E2F1 is unleashed from the inhibitory effects of pRb. Studies...... in animal models and in human cancers have shown that deregulated E2F1 overexpression possesses either "oncogenic" or "oncosuppressor" properties, depending on the cellular context. To address this issue in osteosarcomas, we examined the status of E2F1 relative to cell proliferation and apoptosis...... in a clinical setting of human primary osteosarcomas and in E2F1-inducible osteosarcoma cell line models that are wild-type and deficient for p53. Collectively, our data demonstrated that high E2F1 levels exerted a growth-suppressing effect that relied on the integrity of the DNA damage response network...

  18. [Induction of rat hepatic CYP2E1 expression by arecoline in vivo].

    Science.gov (United States)

    Huang, Xiang-tao; Xiao, Run-mei; Wang, Ming-feng; Wang, Jun-jun; Chen, Yong

    2016-01-01

    The regulation mechanism of arecoline on rat hepatic CYP2E1 was studied in vivo. After oral administration of arecoline hydrobromide (AH; 4, 20 and 100 mg x kg(-1) x d(-1)) to rats for one week, the hepatic CYP2E1 mRNA level remained unchanged, but the hepatic CYP2E1 protein content was dose-dependently increased. Additionally, although the hepatic CYP2E1 activity was induced by AH treatment, the induction was attenuated with the increase in dosage. The results indicate that the effect of arecoline on rat hepaticdoes not involve transcriptional activation of the gene, but largely involves the stabilization of CYP2E1 protein against degradation or increased efficiency of CYP2E1 mRNA translation, and additionally involve the post- ranslational modification of CYP2E1 protein. Furthermore, the CYP2E1 response is fairly equal among the different species, the induction of rat hepatic CYP2E1 by arecoline suggests that there is a risk of metabolic interaction among the substrate drugs of CYP2E1 in betel-quid use human.

  19. Improved Plant-based Production of E1 endoglucanase Using Potato: Expression Optimization and Tissue Targeting

    Energy Technology Data Exchange (ETDEWEB)

    Dai, Ziyu [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Hooker, Brian S. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Anderson, Daniel B. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Thomas, Steven R. [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2000-06-01

    Optimization of Acidothermus cellulolyticus endoglucanase (E1) gene expression in transgenic potato (Solanum tuberosum L.) was examined in this study, where the E1 coding sequence was transcribed under control of a leaf specific promoter (tomato RbcS-3C) or the Mac promoter (a hybrid promoter of mannopine synthase promoter and cauliflower mosaic virus 35S promoter enhancer region). Average E1 activity in leaf extracts of potato transformants, in which E1 protein was targeted by a chloroplast signal peptide and an apoplast signal peptide were much higher than those by an E1 native signal peptide and a vacuole signal peptide. E1 protein accumulated up to 2.6% of total leaf soluble protein, where E1 gene was under control of the RbcS-3C promoter, alfalfa mosaic virus 5-untranslated leader, and RbcS-2A signal peptide. E1 protein production, based on average E1 activity and E1 protein accumulation in leaf extracts, is higher in potato than those measured previously in transgenic tobacco bearing the same transgene constructs. Comparisons of E1 activity, protein accumulation, and relative mRNA levels showed that E1 expression under control of tomato RbcS-3C promoter was specifically localized in leaf tissues, while E1 gene was expressed in both leaf and tuber tissues under control of Mac promoter. This suggests dual-crop applications in which potato vines serve as enzyme production `bioreactors' while tubers are preserved for culinary applications.

  20. Ethics control of vertebrate animals experiments in biosatellite BION-M1 project

    Science.gov (United States)

    Ilyin, Eugene

    During April 19-May 19, 2013 it was realized 30-days flight of Russian biosatellite Bion-M1. The main goal of this flight was to study effects of microgravity upon behavior and structural-functional state of different physiological systems of vertebrates. The folloving species were accommodated aboard of biosatellite: 45 mice C57bl/6, 8 Mongolian gerbils Meriones unguiculatus, 15 lizards, i.e. geckos Chondrodctylus turneri Gray, and fish Oreochromis mossambicus. The selection and traing of mice for the flight and ground-based control experiments was carried out at the Research Institute of Mitoengineering by Moscow State University. The protocols for animals care and reserch were revised and adopted by Bioethics Commission of above mentioned institute (decision on November 01, 2013, N35). The final version of Bion-M1 Scientific Reseach Program and protocols for separate experiments were discussed and adopted by Biomedical Ethics Commission of Institute of Biomedical Problems (decision on April 4, 2014, N317). The IMBP Commission has a status of Physiological Section of Russian Bioethics Committee by Russian Commision for UNESCO affairs and follows the Russian Bioethical Guidelines for Experiments in Aerospace and Naval Medicine and other national and international rules including COSPAR International Policy and Guidelines for Animal Care and Use in Space-born Research. Because US-scientists were the main partners in mice investigations the decision of IMBP Biomedical Commission related to Bion-M1 project was sended for information to Institutional Animal Care and Use Committee of NASA Ames Research Center. Postflight estimation of mice was done by Russian veterinary with the participation of NASA Chief veterinary.

  1. Effect of pirenzepine, a muscarinic M1 receptor antagonist, on amygdala kindling in rat.

    Science.gov (United States)

    Eşkazan, E; Aker, R; Onat, F; Köseoğlu, S; Gören, M Z; Hasanoğlu, A

    1999-11-01

    Kindling, an animal model of complex partial seizures with secondary generalization, is performed by daily application of low-intensity electrical brain stimulation. The purpose of this study was to investigate the role of muscarinic M1 receptors on amygdala kindling in the rat. Bipolar nichrome stimulation and recording electrodes were stereotaxically implanted into the right and left basolateral amygdala. Extradural recording electrodes were also placed bilaterally in the skull over the cortex. Amygdala stimulation was applied twice daily at the current intensity of afterdischarge threshold. Seizure intensity was graded by using Racine's standard five-stage scale. In the first group of experiments, saline or pirenzepine (10, 25, 50 and 100 nmol), a muscarinic M1 receptor antagonist, was injected intracerebroventricularly 1 h before the electrical stimulation. In the second group of experiments, rats were kindled to full stage 5 seizures. After a recovery period, 50 nmol of pirenzepine was administered intracerebroventricularly to kindled animals. In the first group of experiments, none of the animals pretreated with the doses of 50 and 100 nmol of pirenzepine reached a stage 5 seizure. Pirenzepine significantly retarded kindling seizure development and increased the total number of stimulations required to reach the first stage 5 seizure. Afterdischarge duration was also reduced in the pirenzepine 10 nmol group as compared with that in the saline-pretreated group. In the second group, seizure stage and afterdischarge duration were not affected by pirenzepine in fully-kindled animals. The findings of this study suggest that muscarinic M1 receptors may have a critical role in the development of kindling epileptic activity, but not in already kindled seizures.

  2. Spatio-kinematics of the optical nebula M1-92 with HST/STIS

    Science.gov (United States)

    Ramos-Medina, J.; Sánchez-Contreras, C.; Sahai, R.; Bujarrabal, V.; Castro-Carrizo, A.; Morris, M.

    2014-04-01

    We report optical long-slit spectroscopy with HST/STIS of the well known pre-Planetary Nebula (pPN) M1-92 (a.k.a. Minkowski's footprint). Complementary long-slit echelle spectra obtained with Keck II+ESI have been also used. We have used our high-angular (~0.1arcsec) resolution spectra to characterize the spatio-kinematic structure of the optical nebula of this object. From the analysis of the Halpha two-dimensional profile we identify several distinct nebular components at different spatial scales. The blue-shifted absorption component of the broad 'P cygni'-like profile of the Halpha emission is spatially and spectrally resolved and is found to be composed of not one but two different features centered at Vlsr~-600 and -200 km/s. To assist in the interpretation of the data, we have used a simple spatio-kinematic model which has allowed us to describe the main properties of the fast, bipolar winds (expanding with velocities of up to ~700 km/s) running inside the reflection lobes of M1-92 and that produce the absorptions. At the nebula center, we also discover an equatorially extended H-alpha emitting region that is expanding at moderate velocity (~300 km/s) in the direction perpendicular to the lobes. We have estimated the column density of the inner post-AGB winds and other physical parameters that have helped improving our understanding of the evolutionary history of M1-92.

  3. Relationship between pattern of ischemic manifestation and hemodynamics in symptomatic M1 stenosis

    Energy Technology Data Exchange (ETDEWEB)

    Tokumitsu, Naoki; Sako, Kazuhiro; Aizawa, Shizuka; Shirai, Wakako [Nayoro City Hospital, Hokkaido (Japan)

    2002-07-01

    The mechanism through which ischemic manifestations develop in patients with middle cerebral artery (MCA) stenosis is still uncertain. It may cause ischemic symptoms through both embolic and hemodynamic mechanisms. In this study, we compared the findings from cerebral angiograms with single photon emission computed tomography (SPECT) in patients with M1 stenosis to determine the pathogenesis of ischema. At our hospital from 1994 to 2000, 14 patients (12 males and 2 females; mean age, 60.9; range, 31 to 85 years) with angiographically demonstrated symptomatic M1 stenosis were enrolled in this study. In 10, their stenotic lesion was located at the proximal site of the perforating arteries and for the other 4, stenosis was found at the distal site. Nine presented with transient ischemic attack (TIA) and 5 with completed stroke for an initial episode. The discrepancy in regional cerebral blood flow (rCBF) was evaluated in relation to the site and degree of stenosis, type of ischemic presentation, and frequency of ischemic events. There was no significant difference in CBF between the patients with stenosis involving the proximal site and those with distal stenosis; but the cortical CBF decreased significantly in those with severe stenosis compared with moderate stenosis. The cortical CBF of those who had a complete stroke is similar to that of the patients with TIA; but CBF of BGA decreased significantly in those with a complete stroke. The single ischemic event group showed a significant decrease in cortical CBF. On the other hand, the group with multiple ischemic events exhibited normal hemodynamics. We concluded that multiple ischemic events that occurred in M1 stenosis are caused by an embolic mechanism. (author)

  4. E2 multimeric scaffold for vaccine formulation: immune response by intranasal delivery and transcriptome profile of E2-pulsed dendritic cells.

    Science.gov (United States)

    Trovato, Maria; Maurano, Francesco; D'Apice, Luciana; Costa, Valerio; Sartorius, Rossella; Cuccaro, Fausta; McBurney, Sean P; Krebs, Shelly J; Prisco, Antonella; Ciccodicola, Alfredo; Rossi, Mauro; Haigwood, Nancy L; De Berardinis, Piergiuseppe

    2016-07-16

    The E2 multimeric scaffold represents a powerful delivery system able to elicit robust humoral and cellular immune responses upon systemic administrations. Here recombinant E2 scaffold displaying the third variable loop of HIV-1 Envelope gp120 glycoprotein was administered via mucosa, and the mucosal and systemic immune responses were analysed. To gain further insights into the molecular mechanisms that orchestrate the immune response upon E2 vaccination, we analysed the transcriptome profile of dendritic cells (DCs) exposed to the E2 scaffold with the aim to define a specific gene expression signature for E2-primed immune responses. The in vivo immunogenicity and the potential of E2 scaffold as a mucosal vaccine candidate were investigated in BALB/c mice vaccinated via the intranasal route. Fecal and systemic antigen-specific IgA antibodies, cytokine-producing CD4(+) and CD8(+) cells were induced assessing the immunogenicity of E2 particles via intranasal administration. The cytokine analysis identified a mixed T-helper cell response, while the systemic antibody response showed a prevalence of IgG1 isotype indicative of a polarized Th2-type immune response. RNA-Sequencing analysis revealed that E2 scaffold up-regulates in DCs transcriptional regulators of the Th2-polarizing cell response, defining a type 2 DC transcriptomic signature. The current study provides experimental evidence to the possible application of E2 scaffold as antigen delivery system for mucosal immunization and taking advantages of genome-wide approach dissects the type of response induced by E2 particles.

  5. ISSR Analysis of M_1 Generation of Gladiolus hybridus Hort Treated by EMS

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Gladiolus hybridus Hort is one of famous cutting flowers,being famous of big size,bright color,various shapes and long bloom period.New species should be cultivated in order to meet consumers' needs.Mutagenic breeding is a shortcut to cultivate new species of flowers.In this study,corm bud of G.hybridus Hort was treated with different concentrations of EMS.Then M 1 generation was analyzed by ISSR.Results showed that EMS was a very effective mutagenic agent for the corm bud of G.hybridus Hort.With the increa...

  6. Aflatoxin M1 level in pasteurized and sterilized milk of Babol city

    Directory of Open Access Journals (Sweden)

    Hashemi S J

    2007-11-01

    Full Text Available Background: Aflatoxins are severe toxic secondary metabolites found in most plant products. When animals consume contaminated feed stuff to Aflatoxin B1 (AFB1, the toxin is metabolized by liver and is excreted as Aflatoxin M1 (AFM1 via milk. Aflatoxins are acute toxic compounds, immunosuppressive, mutagen, tratogen and carcinogen."nMethods: During the winter of 2006, pasteurized and sterilized (ultra high temperature (UHT milk packages were collected from supermarkets in Babol city. 78 pasteurized and 33 sterilized milk, totally 111 samples were tested for AFM1 by competitive Enzyme Linked Immunosorbent Assay (ELISA. Solid phase in plastic micro wells coated whit anti-Aflatoxin M1 antibodies. We added 100 microliter skimmed milk and Aflatoxin M1 standard solutions in each well. In each plate, we appointed seven wells for standards. Plates were incubated at 20-25 centigrade for 45 min. Each well was washed four times by washing buffer 20X concentration. Then 100 micro liter conjugated solution (100X was added to each well, and the plate was incubated at 20-25 centigrade for 15 min. After that, the wells were washed. After adding the substrates to wells, we incubated the plate at 20-25 centigrade in a dark place for 15 min. The reaction was stopped by stop solution. After one hour, light absorption was read at 450 nm by ELISA reader."nResults: AFM1 were detected in 100% of all samples. 100% of samples were above of European community regulations (50ng/l. AFM1 contamination mean levels pasteurized and sterilized milk were 230.5 and 221.66 respectively. Therefore more than four fold levels European community. There is not a significant relationship between AFM1 contamina-tion level and different months of winter applying statistical test."nConclusion: The results showed the need for introducing safety limits for AFM1 levels in child milk under Food Legislative liable of Iran. Aflatoxin M1 contamination is a serious problem for public health

  7. Daniel Hertz SA M1落地式音箱

    Institute of Scientific and Technical Information of China (English)

    许成文

    2011-01-01

    Daniel Hertz SA M1落地式音箱在箱体结构上取经典造型。毫无疑问,Daniel Hertz的SAM1落地式音箱甫一亮相干市场,便已经奠定了它作为一代经典作品的基础——这不仅使其采用最经典的前障板布局和单元配置,在更大的程度上还包括它的综合技术内涵。

  8. THE DETECTION OF C60 IN THE WELL-CHARACTERIZED PLANETARY NEBULA M1-11

    Energy Technology Data Exchange (ETDEWEB)

    Otsuka, Masaaki; Kemper, F. [Institute of Astronomy and Astrophysics, Academia Sinica, P.O. Box 23-141, Taipei 10617, Taiwan (China); Hyung, S. [School of Science Education (Astronomy), Chungbuk National University, CheongJu, Chungbuk 361-763 (Korea, Republic of); Sargent, B. A.; Meixner, M. [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD 21218 (United States); Tajitsu, A. [Subaru Telescope, NAOJ, 650 North A' ohoku Place, Hilo, HI 96720 (United States); Yanagisawa, K., E-mail: otsuka@asiaa.sinica.edu.tw [Okayama Astrophysical Observatory (OAO), NAOJ, Kamogata, Okayama 719-0232 (Japan)

    2013-02-10

    We performed multiwavelength observations of the young planetary nebula (PN) M1-11 and obtained its elemental abundances, dust mass, and the evolutionary status of the central star. The AKARI/IRC, VLT/VISIR, and Spitzer/IRS spectra show features due to carbon-rich dust, such as the 3.3, 8.6, and 11.3 {mu}m features due to polycyclic aromatic hydrocarbons (PAHs), a smooth continuum attributable to amorphous carbon, and the broad 11.5 and 30 {mu}m features often ascribed to SiC and MgS, respectively. We also report the presence of an unidentified broad feature at 16-22 {mu}m, similar to the feature found in Magellanic Cloud PNe with either C-rich or O-rich gas-phase compositions. We identify for the first time in M1-11 spectral lines at 8.5 (blended with PAH), 17.3, and 18.9 {mu}m that we attribute to the C{sub 60} fullerene. This identification is strengthened by the fact that other Galactic PNe in which fullerenes are detected have similar central stars, similar gas-phase abundances, and a similar dust composition to M1-11. The weak radiation field due to the relatively cool central stars in these PNe may provide favorable conditions for fullerenes to survive in the circumstellar medium. Using the photoionization code CLOUDY, combined with a modified blackbody, we have fitted the {approx}0.1-90 {mu}m spectral energy distribution (SED) and determined the dust mass in the nebula to be {approx}3.5 Multiplication-Sign 10{sup -4} M {sub Sun }. Our chemical abundance analysis and SED model suggest that M1-11 is perhaps a C-rich PN with C/O ratio in the gas phase of +0.19 dex, and that it evolved from a 1-1.5 M {sub Sun} star.

  9. Scaled-energy spectroscopy of helium \\|M\\|=1 Rydberg atoms in a static electric field

    Science.gov (United States)

    Kips, Annemieke; Vassen, Wim; Hogervorst, Wim; Dando, Paul A.

    1998-10-01

    We present scaled-energy spectra on helium Rydberg atoms in a static electric field. \\|M\\|=1 states were studied in excitation from the 2 1S0 metastable state. Spectra were recorded for ɛ=-2.940(4), ɛ=-2.350(4), both below the saddle point, and ɛ=-1.760(4), above the saddle point. Closed-orbit theory was applied to interpret the spectra. A recent extension to closed-orbit theory, incorporating core effects, was used. This significantly improved agreement between experiment and theory.

  10. Enhancement of M1 Transition Rates at High Spin in 90Mo

    Institute of Scientific and Technical Information of China (English)

    WU Xiao-Guang; YANG Chun-Xiang; LI Guang-Sheng; PENG Zhao-Hua; WEN Shu-Xian; HAN Guang-Bing; LI Cheng-Po; LU Shao-Jun; WU Shao-Yong; YUAN Guan-Jun

    2001-01-01

    High spin states in 90Mo have been populated through the 59Co (35C1,2p2n) 90Mo reaction at a beam energy of116 Me V. Level lifetimes of the positive-parity decay sequence are measured by using the Doppler shift attenuationmethod. It is observed that the M1 transition strengths show a substantial enhancement at high spin. Thisbehaviour may be related to occupation of high Ω orbitals by a pair of g9/2 protons. A deformed, oblate, shapeis suggested above the 13+ state.

  11. Asymmetric Mach-Zehnder Interferometer Based Biosensors for Aflatoxin M1 Detection.

    Science.gov (United States)

    Chalyan, Tatevik; Guider, Romain; Pasquardini, Laura; Zanetti, Manuela; Falke, Floris; Schreuder, Erik; Heideman, Rene G; Pederzolli, Cecilia; Pavesi, Lorenzo

    2016-01-06

    In this work, we present a study of Aflatoxin M1 detection by photonic biosensors based on Si₃N₄ Asymmetric Mach-Zehnder Interferometer (aMZI) functionalized with antibodies fragments (Fab'). We measured a best volumetric sensitivity of 10⁴ rad/RIU, leading to a Limit of Detection below 5 × 10(-7) RIU. On sensors functionalized with Fab', we performed specific and non-specific sensing measurements at various toxin concentrations. Reproducibility of the measurements and re-usability of the sensor were also investigated.

  12. AN M/M/1/N FEEDBACK QUEUING SYSTEM WITH REVERSE BALKING

    Directory of Open Access Journals (Sweden)

    Rakesh Kumar

    2015-06-01

    Full Text Available In this paper we develop an M/M/1/N feedback queuing system with reverse balking. Reverse balking is a type of customer behavior according to which an arriving customer joins a system with high probability if he encounters large system size and vice-versa. This behavior of a customer can be observed in many businesses such as investment. Feedback customer in queuing literature refers to a customer who is unsatisfied with incomplete, partial or unsatisfactory service. We derive the steady-state solution of the model and obtain some important measures of performance. Sensitivity analysis of the model is also performed with respect to the parameters involved.

  13. STS-34 crewmembers sit in M1-13 APC during emergency egress training at KSC

    Science.gov (United States)

    1989-01-01

    STS-34 crewmembers sit in M1-13 Armored Personnel Carrier (APC) during emergency egress training at KSC's shuttle landing facility (SLF) prior to terminal countdown demonstration test (TCDT) activities. Wearing launch and entry suits (LESs), are (from left) Mission Specialist (MS) Ellen S. Baker, MS Shannon W. Lucid, Commander Donald E. Williams (right side, in back), MS Franklin R. Chang-Diaz, and Pilot Michael J. McCulley (holding headset). View provided by KSC with alternate number KSC-89PC-871.

  14. The M/M/1 queue with inventory, lost sale and general lead times

    DEFF Research Database (Denmark)

    Saffari, Mohammad; Asmussen, Søren; Haji, Rasoul

    We consider an M/M/1 queueing system with inventory under the (r,Q) policy and with lost sales, in which demands occur according to a Poisson process and service times are exponentially distributed. All arriving customers during stockout are lost. We derive the stationary distributions of the joi...... queue length (number of customers in the system) and on-hand inventory when lead times are random variables and can take various distributions. The derived stationary distributions are used to formulate long-run average performance measures and cost functions in some numerical examples....

  15. E2fl1 is a meiosis-specific transcription factor in the protist Tetrahymena thermophila.

    Science.gov (United States)

    Zhang, Jing; Tian, Miao; Yan, Guan-Xiong; Shodhan, Anura; Miao, Wei

    2017-01-02

    Members of the E2F family of transcription factors have been reported to regulate the expression of genes involved in cell cycle control, DNA replication, and DNA repair in multicellular eukaryotes. Here, E2FL1, a meiosis-specific E2F transcription factor gene, was identified in the model ciliate Tetrahymena thermophila. Loss of this gene resulted in meiotic arrest prior to anaphase I. The cytological experiments revealed that the meiotic homologous pairing was not affected in the absence of E2FL1, but the paired homologous chromosomes did not separate and assumed a peculiar tandem arrangement. This is the first time that an E2F family member has been shown to regulate meiotic events. Moreover, BrdU incorporation showed that DSB processing during meiosis was abnormal upon the deletion of E2FL1. Transcriptome sequencing analysis revealed that E2FL1 knockout decreased the expression of genes involved in DNA replication and DNA repair in T. thermophila, suggesting that the function of E2F is highly conserved in eukaryotes. In addition, E2FL1 deletion inhibited the expression of related homologous chromosome segregation genes in T. thermophila. The result may explain the meiotic arrest phenotype at anaphase I. Finally, by searching for E2F DNA-binding motifs in the entire T. thermophila genome, we identified 714 genes containing at least one E2F DNA-binding motif; of these, 235 downregulated represent putative E2FL1 target genes.

  16. 26 CFR 1.669(e)-2A - Illustration of the provisions of section 669.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Illustration of the provisions of section 669. 1.669(e)-2A Section 1.669(e)-2A Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... Taxable Years Beginning Before January 1, 1969 § 1.669(e)-2A Illustration of the provisions of section...

  17. E2F Transcription Factors Control the Roller Coaster Ride of Cell Cycle Gene Expression

    NARCIS (Netherlands)

    Thurlings, Ingrid; de Bruin, Alain

    2016-01-01

    Initially, the E2F transcription factor was discovered as a factor able to bind the adenovirus E2 promoter and activate viral genes. Afterwards it was shown that E2F also binds to promoters of nonviral genes such as C-MYC and DHFR, which were already known at that time to be important for cell growt

  18. The Role of CYP2E1 in the Drug Metabolism or Bioactivation in the Brain

    Science.gov (United States)

    García-Suástegui, W. A.; Ramos-Chávez, L. A.; Rubio-Osornio, M.; Calvillo-Velasco, M.; Atzin-Méndez, J. A.; Guevara, J.

    2017-01-01

    Organisms have metabolic pathways that are responsible for removing toxic agents. We always associate the liver as the major organ responsible for detoxification of the body; however this process occurs in many tissues. In the same way, as in the liver, the brain expresses metabolic pathways associated with the elimination of xenobiotics. Besides the detoxifying role of CYP2E1 for compounds such as electrophilic agents, reactive oxygen species, free radical products, and the bioactivation of xenobiotics, CYP2E1 is also related in several diseases and pathophysiological conditions. In this review, we describe the presence of phase I monooxygenase CYP2E1 in regions of the brain. We also explore the conditions where protein, mRNA, and the activity of CYP2E1 are induced. Finally, we describe the relation of CYP2E1 in brain disorders, including the behavioral relations for alcohol consumption via CYP2E1 metabolism. PMID:28163821

  19. The Role of CYP2E1 in the Drug Metabolism or Bioactivation in the Brain

    Directory of Open Access Journals (Sweden)

    W. A. García-Suástegui

    2017-01-01

    Full Text Available Organisms have metabolic pathways that are responsible for removing toxic agents. We always associate the liver as the major organ responsible for detoxification of the body; however this process occurs in many tissues. In the same way, as in the liver, the brain expresses metabolic pathways associated with the elimination of xenobiotics. Besides the detoxifying role of CYP2E1 for compounds such as electrophilic agents, reactive oxygen species, free radical products, and the bioactivation of xenobiotics, CYP2E1 is also related in several diseases and pathophysiological conditions. In this review, we describe the presence of phase I monooxygenase CYP2E1 in regions of the brain. We also explore the conditions where protein, mRNA, and the activity of CYP2E1 are induced. Finally, we describe the relation of CYP2E1 in brain disorders, including the behavioral relations for alcohol consumption via CYP2E1 metabolism.

  20. M1-46: A Case Study on Multiple-Shell Planetary Nebula Formation

    Science.gov (United States)

    Guerrero, M. A.; Manchado, A.; Stanghellini, L.; Herrero, A.

    1996-06-01

    We discuss in detail the evolutionary path of the multiple-shell planetary nebula M1-46, in the light of our new observations. The velocities of the halo and main nebula correspond to a dynamical time lap between the shells of about 6.8 x 104 yr. By means of a non-LTE analysis of the central star's spectrum, we derived a stellar temperature of Teff = 45,000 K, which, coupled to the visual magnitude and an appropriate bolometric correction, gives a stellar luminosity of 5370 Lsun. The mass of the central star has been evaluated to be 0.6 Msun, and its interpulse time on the asymptotic giant branch is 7.6 x 104 yr. The agreement between the observed intershell time lap and the evolutionary interpulse time lap points to the fact that the formation of this planetary nebula could be ascribed to the gasping mass loss associated with the thermal pulses at the thermally pulsating asymptotic giant branch. The high-resolution spatially resolved observations reveal the presence of different kinematical components in the main nebula which cannot be understood in a homogeneous expanding shell scenario. As regards the chemical abundances, M1-46 has the typical abundances of a type II planetary nebula. No definite abundance gradient between the shells is found.

  1. Structural basis for the inhibition of the essential Plasmodium falciparum M1 neutral aminopeptidase

    Science.gov (United States)

    McGowan, Sheena; Porter, Corrine J.; Lowther, Jonathan; Stack, Colin M.; Golding, Sarah J.; Skinner-Adams, Tina S.; Trenholme, Katharine R.; Teuscher, Franka; Donnelly, Sheila M.; Grembecka, Jolanta; Mucha, Artur; Kafarski, Pawel; DeGori, Ross; Buckle, Ashley M.; Gardiner, Donald L.; Whisstock, James C.; Dalton, John P.

    2009-01-01

    Plasmodium falciparum parasites are responsible for the major global disease malaria, which results in >2 million deaths each year. With the rise of drug-resistant malarial parasites, novel drug targets and lead compounds are urgently required for the development of new therapeutic strategies. Here, we address this important problem by targeting the malarial neutral aminopeptidases that are involved in the terminal stages of hemoglobin digestion and essential for the provision of amino acids used for parasite growth and development within the erythrocyte. We characterize the structure and substrate specificity of one such aminopeptidase, PfA-M1, a validated drug target. The X-ray crystal structure of PfA-M1 alone and in complex with the generic inhibitor, bestatin, and a phosphinate dipeptide analogue with potent in vitro and in vivo antimalarial activity, hPheP[CH2]Phe, reveals features within the protease active site that are critical to its function as an aminopeptidase and can be exploited for drug development. These results set the groundwork for the development of antimalarial therapeutics that target the neutral aminopeptidases of the parasite. PMID:19196988

  2. 新加坡M1与Vodafone达成漫游协议

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    为了让经常旅游的客户能够更方便有效地使用数据业务。新加坡M1用户推出了数据漫游业务。用户在Vodafone的网络上进行数据漫游时,将只需支付本地数据资费,从而节省了60%的数据使用费。这一优惠目前可以在8个有Vodafone网络运营的国家实现,今年早些时候将有超过30个国家可以享受到这项服务,包括一些很流行的漫游目的地,如香港、法国、英国、澳大利亚和德国。随着数据漫游资费的推出,M1成为新加坡第一个提供在Vodafone网络上的单一数据漫游资费的移动运营商。

  3. Structural basis for the inhibition of the essential Plasmodium falciparum M1 neutral aminopeptidase.

    Science.gov (United States)

    McGowan, Sheena; Porter, Corrine J; Lowther, Jonathan; Stack, Colin M; Golding, Sarah J; Skinner-Adams, Tina S; Trenholme, Katharine R; Teuscher, Franka; Donnelly, Sheila M; Grembecka, Jolanta; Mucha, Artur; Kafarski, Pawel; Degori, Ross; Buckle, Ashley M; Gardiner, Donald L; Whisstock, James C; Dalton, John P

    2009-02-24

    Plasmodium falciparum parasites are responsible for the major global disease malaria, which results in >2 million deaths each year. With the rise of drug-resistant malarial parasites, novel drug targets and lead compounds are urgently required for the development of new therapeutic strategies. Here, we address this important problem by targeting the malarial neutral aminopeptidases that are involved in the terminal stages of hemoglobin digestion and essential for the provision of amino acids used for parasite growth and development within the erythrocyte. We characterize the structure and substrate specificity of one such aminopeptidase, PfA-M1, a validated drug target. The X-ray crystal structure of PfA-M1 alone and in complex with the generic inhibitor, bestatin, and a phosphinate dipeptide analogue with potent in vitro and in vivo antimalarial activity, hPheP[CH(2)]Phe, reveals features within the protease active site that are critical to its function as an aminopeptidase and can be exploited for drug development. These results set the groundwork for the development of antimalarial therapeutics that target the neutral aminopeptidases of the parasite.

  4. Determination of aflatoxin M1 levels in Iranian white and cream cheese.

    Science.gov (United States)

    Fallah, Aziz A; Jafari, Tina; Fallah, Ali; Rahnama, Mohammad

    2009-08-01

    A screening survey on the occurrence of aflatoxin M1 (AFM1) was accomplished on 210 cheese samples composed of white cheese (116 samples) and cream cheese (94 samples) purchased from popular markets in central part of Iran (Esfahan and Yazd provinces). The quantitative analysis of AFM1 levels in the samples was performed by using the competitive enzyme-linked immunosorbent assay (ELISA) technique. Aflatoxin M1 at measurable level (50 ng/kg) was detected in 161 (76.6%) samples, consisting of 93 (80.1%) white and 68 (72.3%) cream cheese samples. The concentration of AFM1 in the samples ranged from 52.1 to 785.4 ng/kg. Comparing to legal regulation (250 ng/kg) accepted by some of the countries, 24.2% of the samples exceeded the accepted limit. Among these, the AFM1 levels in 28.4% of white and 19.1% of cream cheese samples were not in accordance with the safety limit. The results indicated that contamination of the samples with AFM1 in such a level appear to be a potential hazard for public health. This paper represents the data of the first survey on the occurrence of AFM1 in cheeses consumed in central part of Iran.

  5. Pirenzepine Promotes the Dimerization of Muscarinic M1 Receptors through a Three-step Binding Process*

    Science.gov (United States)

    Ilien, Brigitte; Glasser, Nicole; Clamme, Jean-Pierre; Didier, Pascal; Piemont, Etienne; Chinnappan, Raja; Daval, Sandrine B.; Galzi, Jean-Luc; Mely, Yves

    2009-01-01

    Ligand binding to G protein-coupled receptors is a complex process that involves sequential receptor conformational changes, ligand translocation, and possibly ligand-induced receptor oligomerization. Binding events at muscarinic acetylcholine receptors are usually interpreted from radioligand binding studies in terms of two-step ligand-induced receptor isomerization. We report here, using a combination of fluorescence approaches, on the molecular mechanisms for Bodipy-pirenzepine binding to enhanced green fluorescent protein (EGFP)-fused muscarinic M1 receptors in living cells. Real time monitoring, under steady-state conditions, of the strong fluorescence energy transfer signal elicited by this interaction permitted a fine kinetic description of the binding process. Time-resolved fluorescence measurements allowed us to identify discrete EGFP lifetime species and to follow their redistribution upon ligand binding. Fluorescence correlation spectroscopy, with EGFP brightness analysis, showed that EGFP-fused muscarinic M1 receptors predominate as monomers in the absence of ligand and dimerize upon pirenzepine binding. Finally, all these experimental data could be quantitatively reconciled into a three-step mechanism, with four identified receptor conformational states. Fast ligand binding to a peripheral receptor site initiates a sequence of conformational changes that allows the ligand to access to inner regions of the protein and drives ligand-receptor complexes toward a high affinity dimeric state. PMID:19451648

  6. Fluorescent pirenzepine derivatives as potential bitopic ligands of the human M1 muscarinic receptor.

    Science.gov (United States)

    Tahtaoui, Chouaib; Parrot, Isabelle; Klotz, Philippe; Guillier, Fabrice; Galzi, Jean-Luc; Hibert, Marcel; Ilien, Brigitte

    2004-08-12

    Following a recent description of fluorescence resonance energy transfer between enhanced green fluorescent protein (EGFP)-fused human muscarinic M1 receptors and Bodipy-labeled pirenzepine, we synthesized seven fluorescent derivatives of this antagonist in order to further characterize ligand-receptor interactions. These compounds carry Bodipy [558/568], Rhodamine Red-X [560/580], or Fluorolink Cy3 [550/570] fluorophores connected to pirenzepine through various linkers. All molecules reversibly bind with high affinity to M1 receptors (radioligand and energy transfer binding experiments) provided that the linker contains more than six atoms. The energy transfer efficiency exhibits modest variations among ligands, indicating that the distance separating EGFP from the fluorophores remains almost constant. This also supports the notion that the fluorophores may bind to the receptor protein. Kinetic analyses reveal that the dissociation of two Bodipy derivatives (10 or 12 atom long linkers) is sensitive to the presence of the allosteric modulator brucine, while that of all other molecules (15-24 atom long linkers) is not. The data favor the idea that these analogues might interact with both the acetylcholine and the brucine binding domains. Copyright 2004 American Chemical Society

  7. Pirenzepine promotes the dimerization of muscarinic M1 receptors through a three-step binding process.

    Science.gov (United States)

    Ilien, Brigitte; Glasser, Nicole; Clamme, Jean-Pierre; Didier, Pascal; Piemont, Etienne; Chinnappan, Raja; Daval, Sandrine B; Galzi, Jean-Luc; Mely, Yves

    2009-07-17

    Ligand binding to G protein-coupled receptors is a complex process that involves sequential receptor conformational changes, ligand translocation, and possibly ligand-induced receptor oligomerization. Binding events at muscarinic acetylcholine receptors are usually interpreted from radioligand binding studies in terms of two-step ligand-induced receptor isomerization. We report here, using a combination of fluorescence approaches, on the molecular mechanisms for Bodipy-pirenzepine binding to enhanced green fluorescent protein (EGFP)-fused muscarinic M1 receptors in living cells. Real time monitoring, under steady-state conditions, of the strong fluorescence energy transfer signal elicited by this interaction permitted a fine kinetic description of the binding process. Time-resolved fluorescence measurements allowed us to identify discrete EGFP lifetime species and to follow their redistribution upon ligand binding. Fluorescence correlation spectroscopy, with EGFP brightness analysis, showed that EGFP-fused muscarinic M1 receptors predominate as monomers in the absence of ligand and dimerize upon pirenzepine binding. Finally, all these experimental data could be quantitatively reconciled into a three-step mechanism, with four identified receptor conformational states. Fast ligand binding to a peripheral receptor site initiates a sequence of conformational changes that allows the ligand to access to inner regions of the protein and drives ligand-receptor complexes toward a high affinity dimeric state.

  8. Molecular Probes for Muscarinic Receptors: Derivatives of the M1-Antagonist Telenzepine

    Science.gov (United States)

    Karton, Yishai; Baumgold, Jesse; Handen, Jeffrey S.; Jacobson, Kenneth A.

    2012-01-01

    Functionalized congeners of the M1-selective muscarinic antagonist telenzepine (4,9-dihydro-3-methyl-4-[(4-methyl-1-piperazinyl)acetyl]-10H-thieno[3,4–b][1,5]benzodiazepin-10-one) were developed and found to bind to the receptor with affinities (Ki values) in approximately the nanomolar range. The derivatives contain a 10-aminodecyl group, which provides a nucleophilic functionality for further derivatization. The attachment of a spacer chain to the distal piperazinyl nitrogen was based on previous findings of enhanced affinity at muscarinic receptors in an analogous series of alkylamino derivatives of pirenzepine [J. Med. Chem. (1991) 34, 2133–2145]. The telenzepine derivatives contain prosthetic groups for radioiodination, protein cross-linking, photoaffinity labeling, and fluorescent labeling and biotin for avidin complexation. The affinity for muscarinic receptors in rat forebrain (mainly m1 subtype) was determined in competitive binding assays vs [3H]-N-methylscopolamine. A (p-aminophenyl)-acetyl derivative for photoaffinity labeling had a Ki value of 0.29 nM at forebrain muscarinic receptors (16-fold higher affinity than telenzepine). A biotin conjugate displayed a Ki value of 0.60 nM at m2-receptors and a 5-fold selectivity versus forebrain. The high affinity of these derivatives makes them suitable for the characterization of muscarinic receptors in pharmacological and spectroscopic studies, for peptide mapping, and for histochemical studies. PMID:1520727

  9. Process economics and safety considerations for the oxidative dehydrogenation of ethane using the M1 catalyst

    Energy Technology Data Exchange (ETDEWEB)

    Baroi, Chinmoy; Gaffney, Anne M.; Fushimi, Rebecca

    2017-05-01

    Olefins or unsaturated hydrocarbons play a vital role as feedstock for many industrially significant processes. Ethylene is the simplest olefin and a key raw material for consumer products. Oxidative Dehydrogenation (ODH) is one of the most promising new routes for ethylene production that can offer a significant advantage in energy efficiency over the conventional steam pyrolysis process. This study is focused on the ODH chemistry using the mixed metal oxide MoVTeNbOx catalysts, generally referred to as M1 for the key phase known to be active for dehydrogenation. Using performance results from the patent literature a series of process simulations were conducted to evaluate the effect of feed composition on operating costs, profitability and process safety. The key results of this study indicate that the ODH reaction can be made safer and more profitable without use of an inert diluent and furthermore by replacing O2 with CO2 as an oxidant. Modifications of the M1 catalyst composition in order to adopt these changes are discussed.

  10. Microscopic description of low-lying M1 excitations in odd-mass actinide nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Tabar, Emre, E-mail: etabar@sakarya.edu.tr [Physics Department, Sakarya University, 54187 Sakarya (Turkey); Biomedical, Magnetic and Semiconductor Materials Research Center (BIMAS-RC), Sakarya University, 54187 Sakarya (Turkey); Yakut, Hakan, E-mail: hyakut@sakarya.edu.tr [Physics Department, Sakarya University, 54187 Sakarya (Turkey); Biomedical, Magnetic and Semiconductor Materials Research Center (BIMAS-RC), Sakarya University, 54187 Sakarya (Turkey); Kuliev, Ali Akbar [Azerbaijan National Academy of Aviation, Baku (Azerbaijan)

    2017-01-15

    A restoration method of a broken symmetry which allows self-consistent determination of the separable effective restoration forces is now adapted to odd-mass nuclei in order to restore violated rotational invariance (RI-) of the Quasiparticle Phonon Nuclear Model (QPNM) Hamiltonian. Because of the self-consistency of the method, these effective forces contain no arbitrary parameters. Within RI-QPNM, the properties of the low-lying magnetic dipole excitations in odd-mass deformed {sup 229–233}Th and {sup 233–239}U nuclei have been investigated for the first time. It has been shown that computed fragmentation of the M1 strengths below 4 MeV in these nuclei is much stronger than that in neighboring doubly even {sup 228–232}Th and {sup 232–238}U nuclei. For {sup 235}U the summed M1 strength in the energy range 1.5–2.8 MeV is in agreement with the relevant experimental data where the missing strength was extracted by means of a fluctuation analysis.

  11. The Truth-Telling Motor Cortex: Response Competition in M1 Discloses Deceptive Behaviour

    Directory of Open Access Journals (Sweden)

    Aviad A. Hadar

    2011-05-01

    Full Text Available Recent studies have suggested that circuits associated with response conflict and response inhibition are strongly implicated in deception. Using single-pulse transcranial magnetic stimulation (TMS, we examined whether conflict between competing responses in primary motor cortex (M1 can be used for discriminating between intentionally false and true facial recognition. Participants used little finger and thumb key-presses to lie or tell the truth regarding their familiarity with a series of famous and nonfamous faces. Single-pulse TMS was administered to M1 at three intervals prior to response execution in order to evoke motor evoked potentials (MEPs in both Abductor Digiti Minimi (ADM and first dorsal interosseous (FDI of the right hand. As predicted, we found that the MEP of the nonresponding digit was greater than the MEP of the responding digit when participants prepared to engage in deception, while a mirror-reversed pattern was observed for truth telling. This effect did not interact with the stimulation interval suggesting consistent activation of the motor plan representing the truth throughout the response preparation process. We discuss these results with reference to models of response selection and procedures for the detection of deception.

  12. Microscopic description of low-lying M1 excitations in odd-mass actinide nuclei

    Science.gov (United States)

    Tabar, Emre; Yakut, Hakan; Kuliev, Ali Akbar

    2017-01-01

    A restoration method of a broken symmetry which allows self-consistent determination of the separable effective restoration forces is now adapted to odd-mass nuclei in order to restore violated rotational invariance (RI-) of the Quasiparticle Phonon Nuclear Model (QPNM) Hamiltonian. Because of the self-consistency of the method, these effective forces contain no arbitrary parameters. Within RI-QPNM, the properties of the low-lying magnetic dipole excitations in odd-mass deformed 229-233Th and 233-239U nuclei have been investigated for the first time. It has been shown that computed fragmentation of the M1 strengths below 4 MeV in these nuclei is much stronger than that in neighboring doubly even 228-232Th and 232-238U nuclei. For 235U the summed M1 strength in the energy range 1.5-2.8 MeV is in agreement with the relevant experimental data where the missing strength was extracted by means of a fluctuation analysis.

  13. The role of soil layers in preventing ground water pollution with 17ß-estradiol hormone (E 2

    Directory of Open Access Journals (Sweden)

    A’zam Golzari

    2016-03-01

    Full Text Available Background: Estrogens include estoril (E3, estradiol and estrone (E1. These chemicals are produced in human and animal bodies as well as in synthetic chemicals (drugs. Estrogens can enter water sources in different ways. When these chemicals enter the human body through water and wastewater, they have the ability to mimic or disrupt the normal estrogen activities in humans and animals. Estrogens in wastewater are able to pass soil layers and contaminate groundwater. Therefore, in this study, the removal of the hormone 17ß-estradiol (E2 as a representative of estrogens in three types of soils was studied. The selection was chosen in respect to the importance of entering the hormone into groundwater through the soil. Methods: This study was an experimental study in which the removal of the hormone E2 from different depths of three types of soils was experimented. The soils were consisted of two different textures, the silty sandy clay and the silty sand with gravel. The hormone E2 was diluted and injected into the drilled holes. Soils were characterized in the soil mechanics laboratory. Hormone extraction from the soils was performed using a centrifuge and analyzed with the Elecsys device. The results were analyzed using the IBM SPSS version 22 software. Results: The results showed that the removal rates of hormone E2 in the three types of soils were higher than 99.5%, and the removal rate in the silty sand was more than the others. In all three soil samples, the removal rates in the first layer were high. The average injected hormone in the soil decreased from 3500 to 3112 ng/l. The results showed that the adhesion and plasticity of the soil had also affected the removal rates. Conclusion: Results showed that the soil plays a significant role in the removal of E2 hormone and this hormone was reduced or eliminated in the first layers of the soils. Thus, the risk of groundwater contamination is low.

  14. Carboxyl- and amino-functionalized polystyrene nanoparticles differentially affect the polarization profile of M1 and M2 macrophage subsets.

    Science.gov (United States)

    Fuchs, Ann-Kathrin; Syrovets, Tatiana; Haas, Karina A; Loos, Cornelia; Musyanovych, Anna; Mailänder, Volker; Landfester, Katharina; Simmet, Thomas

    2016-04-01

    Macrophages are key regulators of innate and adaptive immune responses. Exposure to microenvironmental stimuli determines their polarization into proinflammatory M1 and anti-inflammatory M2 macrophages. M1 exhibit high expression of proinflammatory TNF-α and IL-1β, and M2 promote tissue repair, but likewise support tumor growth and cause immune suppression by expressing IL-10. Thus, the M1/M2 balance critically determines tissue homeostasis. By using carboxyl- (PS-COOH) and amino-functionalized (PS-NH2) polystyrene nanoparticles, the effects of surface decoration on the polarization of human macrophages were investigated. The nanoparticles did not compromise macrophage viability nor did they affect the expression of the M1 markers CD86, NOS2, TNF-α, and IL-1β. By contrast, in M2, both nanoparticles impaired expression of scavenger receptor CD163 and CD200R, and the release of IL-10. PS-NH2 also inhibited phagocytosis of Escherichia coli by both, M1 and M2. PS-COOH did not impair phagocytosis by M2, but increased protein mass in M1 and M2, TGF-β1 release by M1, and ATP levels in M2. Thus, nanoparticles skew the M2 macrophage polarization without affecting M1 markers. Given the critical role of the M1 and M2 polarization for the immunological balance in patients with cancer or chronic inflammation, functionalized nanoparticles might serve as tools for reprogramming the M1/M2 polarization.

  15. Inhibitory Potency of 4-Carbon Alkanes and Alkenes toward CYP2E1 Activity

    OpenAIRE

    2014-01-01

    CYP2E1 has been implicated in the bioactivation of many small molecules into reactive metabolites which form adducts with proteins and DNA, and thus a better understanding of the molecular determinants of its selectivity are critical for accurate toxicological predictions. In this study, we determined the potency of inhibition of human CYP2E1 for various 4-carbon alkanes, alkenes and alcohols. In addition, known CYP2E1 substrates and inhibitors including 4-methylpyrazole, aniline, and dimethy...

  16. CYP2E1 mediated isoniazid-induced hepatotoxicity in rats

    Institute of Scientific and Technical Information of China (English)

    Jiang YUE; Ren-xiu PENG; Jing YANG; Rui KONG; Juan LIU

    2004-01-01

    AIM: To investigate the role of CYP2E1 in isoniazid (INH)-induced hepatotoxicity and the influence of rifampicin (RFP) on INH-induced liver injury. METHODS: Rats were treated with INH alone (100 mg/kg, ip) or co-administered with RFP (100 mg/kg, ig) for 10 d and 21 d. Hepatotoxicity was assayed by plasma enzymes (sALT, sAST) and histopathological examinations. Hepatic CYP2E1 activity was measured by aniline hydroxylase (ANH), and CYP2E1 mRNA expression was determined by RT-PCR. Plasma hydrazine concentration was determined by RP-HPLC.RESULTS: For a 10 d INH-treatment, hepatic CYP2E1 level was increased to 3.7-fold over the control; liver impairment appeared after 21 d treatment, while CYP2E1 and plasma hydrazine were, respectively, increased to 4.6-fold and 1.7-fold. However, in INH-RFP group for 10 d, CYP2E1 and plasma hydrazine were, respectively,decreased by 13 % and 18 % over INH group; similarly, hepatic injury is equal to INH group appeared after 21 d,and CYP2E1 was further decreased by 26 %. Correlation analysis showed that sALT had a positive correlation with plasma hydrazine and with CYP2E1 activity; CYP2E1 activity was also markedly correlated with plasma hydrazine.And compared with control, there is no difference in changes of CYP2E1 mRNA expression in INH and INH-RFP treatment for 21 d. CONCLUSION: The metabolite of INH, hydrazine, plays an important role in INH-induced hepatotoxicity in rats. The induction of CYP2E1 by hydrazine is involved in the hepatotoxicity of INH. RFP does not exacerbate INH-induced hepatotoxicity in short term, which relates to down-regulation of CYP2E1.

  17. 26 CFR 1.1059(e)-1 - Non-pro rata redemptions.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 11 2010-04-01 2010-04-01 true Non-pro rata redemptions. 1.1059(e)-1 Section 1... (CONTINUED) INCOME TAXES Special Rules § 1.1059(e)-1 Non-pro rata redemptions. (a) In general. Section 1059(d... 1059(e)(1). For example, if a redemption of stock is not pro rata as to all shareholders, any...

  18. Absence of NR2E1 mutations in patients with aniridia

    DEFF Research Database (Denmark)

    Corso-Díaz, Ximena; Borrie, Adrienne E; Bonaguro, Russell;

    2012-01-01

    Nuclear receptor 2E1 (NR2E1) is a transcription factor with many roles during eye development and thus may be responsible for the occurrence of certain congenital eye disorders in humans. To test this hypothesis, we screened NR2E1 for candidate mutations in patients with aniridia and other congen...... congenital ocular malformations (anterior segment dysgenesis, congenital optic nerve malformation, and microphthalmia)....

  19. Differentiation-associated microRNAs antagonize the Rb–E2F pathway to restrict proliferation

    Science.gov (United States)

    Marzi, Matteo J.; Puggioni, Eleonora M. R.; Dall'Olio, Valentina; Bucci, Gabriele; Bernard, Loris; Bianchi, Fabrizio; Crescenzi, Marco

    2012-01-01

    The cancer-associated loss of microRNA (miRNA) expression leads to a proliferative advantage and aggressive behavior through largely unknown mechanisms. Here, we exploit a model system that recapitulates physiological terminal differentiation and its reversal upon oncogene expression to analyze coordinated mRNA/miRNA responses. The cell cycle reentry of myotubes, forced by the E1A oncogene, was associated with a pattern of mRNA/miRNA modulation that was largely reciprocal to that induced during the differentiation of myoblasts into myotubes. The E1A-induced mRNA response was preponderantly Retinoblastoma protein (Rb)-dependent. Conversely, the miRNA response was mostly Rb-independent and exerted through tissue-specific factors and Myc. A subset of these miRNAs (miR-1, miR-34, miR-22, miR-365, miR-29, miR-145, and Let-7) was shown to coordinately target Rb-dependent cell cycle and DNA replication mRNAs. Thus, a dual level of regulation—transcriptional regulation via Rb–E2F and posttranscriptional regulation via miRNAs—confers robustness to cell cycle control and provides a molecular basis to understand the role of miRNA subversion in cancer. PMID:23027903

  20. Involvement of an Arginine Triplet in M1 Matrix Protein Interaction with Membranes and in M1 Recruitment into Virus-Like Particles of the Influenza A(H1N1)pdm09 Virus

    Science.gov (United States)

    Moncorgé, Olivier; Panthu, Baptiste; Prchal, Jan; Décimo, Didier; Ohlmann, Théophile; Lina, Bruno; Favard, Cyril; Decroly, Etienne; Ottmann, Michèle; Roingeard, Philippe; Muriaux, Delphine

    2016-01-01

    The influenza A(H1N1)pdm09 virus caused the first influenza pandemic of the 21st century. In this study, we wanted to decipher the role of conserved basic residues of the viral M1 matrix protein in virus assembly and release. M1 plays many roles in the influenza virus replication cycle. Specifically, it participates in viral particle assembly, can associate with the viral ribonucleoprotein complexes and can bind to the cell plasma membrane and/or the cytoplasmic tail of viral transmembrane proteins. M1 contains an N-terminal domain of 164 amino acids with two basic domains: the nuclear localization signal on helix 6 and an arginine triplet (R76/77/78) on helix 5. To investigate the role of these two M1 basic domains in influenza A(H1N1)pdm09 virus molecular assembly, we analyzed M1 attachment to membranes, virus-like particle (VLP) production and virus infectivity. In vitro, M1 binding to large unilamellar vesicles (LUVs), which contain negatively charged lipids, decreased significantly when the M1 R76/77/78 motif was mutated. In cells, M1 alone was mainly observed in the nucleus (47%) and in the cytosol (42%). Conversely, when co-expressed with the viral proteins NS1/NEP and M2, M1 was relocated to the cell membranes (55%), as shown by subcellular fractionation experiments. This minimal system allowed the production of M1 containing-VLPs. However, M1 with mutations in the arginine triplet accumulated in intracellular clusters and its incorporation in VLPs was strongly diminished. M2 over-expression was essential for M1 membrane localization and VLP production, whereas the viral trans-membrane proteins HA and NA seemed dispensable. These results suggest that the M1 arginine triplet participates in M1 interaction with membranes. This R76/77/78 motif is essential for M1 incorporation in virus particles and the importance of this motif was confirmed by reverse genetic demonstrating that its mutation is lethal for the virus. These results highlight the molecular

  1. CYP2E1-dependent hepatotoxicity and oxidative damage after ethanol administration in human primary hepatocytes

    Institute of Scientific and Technical Information of China (English)

    Lie-Gang Liu; Hong Yan; Ping Yao; Wen Zhang; Li-Jun Zou; Fang-Fang Song; Ke Li; Xiu-Fa Sun

    2005-01-01

    AIM: To observe the relationship between ethanol-induced oxidative damage in human primary cultured hepatocytes and cytochrome P450 2E1 (CYP2E1) activity, in order to address if inhibition of CYP2E1 could attenuate ethanol-induced cellular damage.METHODS: The dose-dependent (25-100 mmol/L) and time-dependent (0-24 h) exposures of primary human cultured hepatocytes to ethanol were carried out. CYP2E1 activity and protein expression were detected by spectrophotometer and Western blot analysis respectively.Hepatotoxicity was investigated by determination of lactate dehydrogenase (LDH) and aspartate transaminase (AST) level in hepatocyte culture supernatants, as well as the intracellular formation of malondialdehyde (MDA).RESULTS: A dose-and time-dependent response between ethanol exposure and CYP2E1 activity in human hepatocytes was demonstrated. Moreover, there was a time-dependent increase of CYP2E1 protein after 100 mmol/L ethanol exposure. Meanwhile, ethanol exposure of hepatocytes caused a time-dependent increase of ceilular MDA level, LDH, and AST activities in supernatants.Furthermore, the inhibitor of CYP2E1, diallyl sulfide (DAS) could partly attenuate the increases of MDA, LDH, and AST in human hepatocytes.CONCLUSION: A positive relationship between ethanol-induced oxidative aamage in human primary cultured hepatocytes and CYP2E1 activity was exhibited, and the inhibition of CYP2E1 could partly attenuate ethanol-induced oxidative damage.

  2. Requirements for E1A dependent transcription in the yeast Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Mymryk Joe S

    2009-04-01

    Full Text Available Abstract Background The human adenovirus type 5 early region 1A (E1A gene encodes proteins that are potent regulators of transcription. E1A does not bind DNA directly, but is recruited to target promoters by the interaction with sequence specific DNA binding proteins. In mammalian systems, E1A has been shown to contain two regions that can independently induce transcription when fused to a heterologous DNA binding domain. When expressed in Saccharomyces cerevisiae, each of these regions of E1A also acts as a strong transcriptional activator. This allows yeast to be used as a model system to study mechanisms by which E1A stimulates transcription. Results Using 81 mutant yeast strains, we have evaluated the effect of deleting components of the ADA, COMPASS, CSR, INO80, ISW1, NuA3, NuA4, Mediator, PAF, RSC, SAGA, SAS, SLIK, SWI/SNF and SWR1 transcriptional regulatory complexes on E1A dependent transcription. In addition, we examined the role of histone H2B ubiquitylation by Rad6/Bre1 on transcriptional activation. Conclusion Our analysis indicates that the two activation domains of E1A function via distinct mechanisms, identify new factors regulating E1A dependent transcription and suggest that yeast can serve as a valid model system for at least some aspects of E1A function.

  3. Human CYP2E1 mediates the formation of glycidamide from acrylamide.

    Science.gov (United States)

    Settels, Eva; Bernauer, Ulrike; Palavinskas, Richard; Klaffke, Horst S; Gundert-Remy, Ursula; Appel, Klaus E

    2008-10-01

    Regarding the cancer risk assessment of acrylamide (AA) it is of basic interest to know, as to what amount of the absorbed AA is metabolized to glycidamide (GA) in humans, compared to what has been observed in laboratory animals. GA is suspected of being the ultimate carcinogenic metabolite of AA. From experiments with CYP2E1-deficient mice it can be concluded that AA is metabolized to GA primarily by CYP2E1. We therefore examined whether CYP2E1 is involved in GA formation in non-rodent species with the focus on humans by using human CYP2E1 supersomes, marmoset and human liver microsomes and in addition, genetically engineered V79 cells expressing human CYP2E1 (V79h2E1 cells). Special emphasis was placed on the analytical detection of GA, which was performed by gas chromatography/mass spectrometry. The results show that AA is metabolized to GA in human CYP2E1 supersomes, in marmoset and human liver microsomes as well as in V79h2E1 cells. The activity of GA formation is highest in supersomes; in human liver it is somewhat higher than in marmoset liver. A monoclonal CYP2E1 human selective antibody (MAB-2E1) and diethyldithiocarbamate (DDC) were used as specific inhibitors of CYP2E1. The generation of GA could be inhibited by MAB-2E1 to about 80% in V79h2E1 cells and to about 90% in human and marmoset liver microsomes. Also DDC led to an inhibition of about 95%. In conclusion, AA is metabolized to GA by human CYP2E1. Overall, the present work describes (1) the application and refinement of a sensitive methodology in order to determine low amounts of GA, (2) the applicability of genetically modified V79 cell lines in order to investigate specific questions concerning metabolism and (3) the involvement, for the first time, of human CYP2E1 in the formation of GA from AA. Further studies will compare the activities of GA formation in genetically engineered V79 cells expressing CYP2E1 from different species.

  4. Identification and characterization of multiple conserved nuclear localization signals within adenovirus E1A

    Energy Technology Data Exchange (ETDEWEB)

    Marshall, Kris S.; Cohen, Michael J.; Fonseca, Greg J.; Todorovic, Biljana; King, Cason R. [Department of Microbiology and Immunology, Western University, London Regional Cancer Program, London, ON, Canada N6A 4L6 (Canada); Yousef, Ahmed F. [Department of Chemical and Environmental Engineering, Masdar Institute, Abu Dhabi (United Arab Emirates); Zhang, Zhiying [College of Animal Science and Technologies, Northwest A and F University, Yangling, Shaanxi 712100 (China); Mymryk, Joe S., E-mail: jmymryk@uwo.ca [Department of Microbiology and Immunology, Western University, London Regional Cancer Program, London, ON, Canada N6A 4L6 (Canada); Department of Oncology, Western University, London Regional Cancer Program, London, ON, Canada N6A 4L6 (Canada)

    2014-04-15

    The human adenovirus 5 (HAdV-5) E1A protein has a well defined canonical nuclear localization signal (NLS) located at its C-terminus. We used a genetic assay in the yeast Saccharomyces cerevisiae to demonstrate that the canonical NLS is present and functional in the E1A proteins of each of the six HAdV species. This assay also detects a previously described non-canonical NLS within conserved region 3 and a novel active NLS within the N-terminal/conserved region 1 portion of HAdV-5 E1A. These activities were also present in the E1A proteins of each of the other five HAdV species. These results demonstrate that, despite substantial differences in primary sequence, HAdV E1A proteins are remarkably consistent in that they contain one canonical and two non-canonical NLSs. By utilizing independent mechanisms, these multiple NLSs ensure nuclear localization of E1A in the infected cell. - Highlights: • HAdV E1A uses multiple mechanisms for nuclear import. • We identified an additional non-canonical NLS in the N-terminal/CR1 portion of E1A. • The new NLS does not contact importin-alpha directly. • All NLSs are functionally conserved in the E1A proteins of all 6 HAdV species.

  5. Human CYP2E1 mediates the formation of glycidamide from acrylamide

    Energy Technology Data Exchange (ETDEWEB)

    Settels, Eva; Appel, Klaus E. [Federal Institute for Risk Assessment, Center for Experimental Toxicology, Berlin (Germany); Bernauer, Ulrike; Gundert-Remy, Ursula [Federal Institute for Risk Assessment, Department of Safety of Substances and Preparations, Berlin (Germany); Palavinskas, Richard; Klaffke, Horst S. [Federal Institute for Risk Assessment, Center for Analytical Chemistry, Berlin (Germany)

    2008-10-15

    Regarding the cancer risk assessment of acrylamide (AA) it is of basic interest to know, as to what amount of the absorbed AA is metabolized to glycidamide (GA) in humans, compared to what has been observed in laboratory animals. GA is suspected of being the ultimate carcinogenic metabolite of AA. From experiments with CYP2E1-deficient mice it can be concluded that AA is metabolized to GA primarily by CYP2E1. We therefore examined whether CYP2E1 is involved in GA formation in non-rodent species with the focus on humans by using human CYP2E1 supersomes trademark, marmoset and human liver microsomes and in addition, genetically engineered V79 cells expressing human CYP2E1 (V79h2E1 cells). Special emphasis was placed on the analytical detection of GA, which was performed by gas chromatography/mass spectrometry. The results show that AA is metabolized to GA in human CYP2E1 supersomes trademark, in marmoset and human liver microsomes as well as in V79h2E1 cells. The activity of GA formation is highest in supersomes trademark; in human liver it is somewhat higher than in marmoset liver. A monoclonal CYP2E1 human selective antibody (MAB-2E1) and diethyldithiocarbamate (DDC) were used as specific inhibitors of CYP2E1. The generation of GA could be inhibited by MAB-2E1 to about 80% in V79h2E1 cells and to about 90% in human and marmoset liver microsomes. Also DDC led to an inhibition of about 95%. In conclusion, AA is metabolized to GA by human CYP2E1. Overall, the present work describes (1) the application and refinement of a sensitive methodology in order to determine low amounts of GA, (2) the applicability of genetically modified V79 cell lines in order to investigate specific questions concerning metabolism and (3) the involvement, for the first time, of human CYP2E1 in the formation of GA from AA. Further studies will compare the activities of GA formation in genetically engineered V79 cells expressing CYP2E1 from different species. (orig.)

  6. Methodology to assay CYP2E1 mixed function oxidase catalytic activity and its induction

    Directory of Open Access Journals (Sweden)

    Arthur I. Cederbaum

    2014-01-01

    Full Text Available The cytochrome P450 mixed function oxidase enzymes are the major catalysts involved in drug metabolism. There are many forms of P450. CYP2E1 metabolizes many toxicologically important compounds including ethanol and is active in generating reactive oxygen species. Since several of the contributions in the common theme series “Role of CYP2E1 and Oxidative/Nitrosative Stress in the Hepatotoxic Actions of Alcohol” discuss CYP2E1, this methodology review describes assays on how CYP2E1 catalytic activity and its induction by ethanol and other inducers can be measured using substrate probes such as the oxidation of para-nitrophenol to para-nitrocatechol and the oxidation of ethanol to acetaldehyde. Approaches to validate that a particular reaction e.g. oxidation of a drug or toxin is catalyzed by CYP2E1 or that induction of that reaction is due to induction of CYP2E1 are important and specific examples using inhibitors of CYP2E1, anti-CYP2E1 IgG or CYP2E1 knockout and knockin mice will be discussed.

  7. The Human p73 Promoter: Characterization and Identification of Functional E2F Binding Sites

    Directory of Open Access Journals (Sweden)

    Ratnam S. Seelan

    2002-01-01

    Full Text Available p73, a member of the p53 family, is overexpressed in many cancers. To understand the mechanism(s underlying this overexpression, we have undertaken a detailed characterization of the human p73 promoter. The promoter is strongly activated in cells expressing exogenous E2F1 and suppressed by exogenous Rb. At least three functional E2F binding sites, located immediately upstream of exon 1 (at-284,-155 and-132 mediate this induction. 5' serially deleted promoter constructs and constructs harboring mutated E2F sites were analyzed for their response to exogenously expressed E2F1 or Rb to establish functionality of these sites. Authenticity of E2F sites was further confirmed by electrophoretic mobility shift assay (EMSA using E2F1 /DP1 heterodimers synthesized in vitro, followed by competition assays with unlabeled wild-type or mutant oligonucleotides and supershift analysis using anti-E2F1 antibodies. In vivo binding of E2F1 to the p73 promoter was demonstrated using nuclear extracts prepared from E2F1-inducible Saos2 cells. The region conferring the highest promoter activity was found to reside between-113 to-217 of the p73 gene. Two of the three functional E2F sites (at-155 and-132 reside within this region. Our results suggest that regulation of p73 expression is primarily mediated through binding of E2 F1 to target sites at-155 and-132.

  8. Regulation of human genome expression and RNA splicing by human papillomavirus 16 E2 protein.

    Science.gov (United States)

    Gauson, Elaine J; Windle, Brad; Donaldson, Mary M; Caffarel, Maria M; Dornan, Edward S; Coleman, Nicholas; Herzyk, Pawel; Henderson, Scott C; Wang, Xu; Morgan, Iain M

    2014-11-01

    Human papillomavirus 16 (HPV16) is causative in human cancer. The E2 protein regulates transcription from and replication of the viral genome; the role of E2 in regulating the host genome has been less well studied. We have expressed HPV16 E2 (E2) stably in U2OS cells; these cells tolerate E2 expression well and gene expression analysis identified 74 genes showing differential expression specific to E2. Analysis of published gene expression data sets during cervical cancer progression identified 20 of the genes as being altered in a similar direction as the E2 specific genes. In addition, E2 altered the splicing of many genes implicated in cancer and cell motility. The E2 expressing cells showed no alteration in cell growth but were altered in cell motility, consistent with the E2 induced altered splicing predicted to affect this cellular function. The results present a model system for investigating E2 regulation of the host genome.

  9. The human Müller cell line MIO-M1 expresses opsins.

    Science.gov (United States)

    Hollborn, Margrit; Ulbricht, Elke; Rillich, Katja; Dukic-Stefanovic, Sladjana; Wurm, Antje; Wagner, Lysann; Reichenbach, Andreas; Wiedemann, Peter; Limb, Gloria Astrid; Bringmann, Andreas; Kohen, Leon

    2011-01-01

    To determine whether the human Müller cell line Moorfields/Institute of Ophthalmology-Müller 1 (MIO-M1) expresses opsins. The gene expression of opsins was determined by reverse-transcription PCR (RT-PCR). The presence of opsin proteins was determined by western blotting and immunocytochemistry. The light sensitivity of the cells was examined with imaging experiments using the calcium-sensitive dye Fluo-4. MIO-M1 cells express glial (glutamine synthase [GLUL], vimentin [VIM], glial fibrillary acidic protein [GFAP], cellular retinaldehyde-binding protein [RLBP1], glial high-affinity glutamate transporter [SLCA1], aquaporin-4 [AQP4], inwardly rectifying potassium channel Kir4.1 [Kir4.1]), neuronal (Thy-1 cell surface antigen [THY1], heavy neurofilament polypeptide [NEFH], microtubule-associated protein 2 [MAP2], neurogenic differentiation 1 [NEUROD1], neuronal nuclei [NEUN]), and neural progenitor markers (Nestin [NES], paired-type homeobox transcription factor [PAX6], neurogenic locus notch homolog 1 [NOTCH1]). The cells contain mRNA for the following opsins: blue opsin (OPN1SW), rhodopsin (OPN2), panopsin (OPN3), melanopsin (OPN4), neuropsin (OPN5), and peropsin (RRH), as well as for the transducins (guanine nucleotide binding protein [GNAZ], alpha transducing activity polypeptide 1 [GNAT1], alpha transducing activity polypeptide 2 [GNAT2]). The presence of blue opsin and melanopsin was confirmed with immunocytochemistry and western blotting. The immunoreactivity and mRNA of red-green opsin were found in some but not all cultures, while the immunoreactivity for rhodopsin was absent in all cultures investigated. Repetitive stimulation with 480 nm light evoked slow and fast transient calcium responses in the majority of cells investigated, while irradiation with 600 nm light was ineffective. The human Müller cell line MIO-M1 expresses opsins. This suggests immortalized Müller cells could be used as a cellular source to produce human opsins for their potential

  10. State-dependent and timing-dependent bidirectional associative plasticity in the human SMA-M1 network.

    Science.gov (United States)

    Arai, Noritoshi; Müller-Dahlhaus, Florian; Murakami, Takenobu; Bliem, Barbara; Lu, Ming-Kuei; Ugawa, Yoshikazu; Ziemann, Ulf

    2011-10-26

    The supplementary motor area (SMA-proper) plays a key role in the preparation and execution of voluntary movements. Anatomically, SMA-proper is densely reciprocally connected to primary motor cortex (M1), but neuronal coordination within the SMA-M1 network and its modification by external perturbation are not well understood. Here we modulated the SMA-M1 network using MR-navigated multicoil associative transcranial magnetic stimulation in healthy subjects. Changes in corticospinal excitability were assessed by recording motor evoked potential (MEP) amplitude bilaterally in a hand muscle. We found timing-dependent bidirectional Hebbian-like MEP changes during and for at least 30 min after paired associative SMA-M1 stimulation. MEP amplitude increased if SMA stimulation preceded M1 stimulation by 6 ms, but decreased if SMA stimulation lagged M1 stimulation by 15 ms. This associative plasticity in the SMA-M1 network was highly topographically specific because paired associative stimulation of pre-SMA and M1 did not result in any significant MEP change. Furthermore, associative plasticity in the SMA-M1 network was strongly state-dependent because it required priming by near-simultaneous M1 stimulation to occur. We conclude that timing-dependent bidirectional associative plasticity is demonstrated for the first time at the systems level of a human corticocortical neuronal network. The properties of this form of plasticity are fully compatible with spike-timing-dependent plasticity as defined at the cellular level. The necessity of priming may reflect the strong interhemispheric connectivity of the SMA-M1 network. Findings are relevant for better understanding reorganization and potentially therapeutic modification of neuronal coordination in the SMA-M1 network after cerebral lesions such as stroke.

  11. Reduction of benzene metabolism and toxicity in mice that lack CYP2E1 expression.

    Science.gov (United States)

    Valentine, J L; Lee, S S; Seaton, M J; Asgharian, B; Farris, G; Corton, J C; Gonzalez, F J; Medinsky, M A

    1996-11-01

    Transgenic CYP2E1 knockout mice (cyp2e1-/-) were used to investigate the involvement of CYP2E1 in the in vivo metabolism of benzene and in the development of benzene-induced toxicity. After benzene exposure, absence of CYP2E1 protein was confirmed by Western blot analysis of mouse liver samples. For the metabolism studies, male cyp2e1-/- and wild-type control mice were exposed to 200 ppm benzene, along with a radiolabeled tracer dose of [14C]benzene (1.0 Ci/mol) by nose-only inhalation for 6 hr. Total urinary radioactivity and all radiolabeled individual metabolites were reduced in urine of cyp2e1-/- mice compared to wild-type controls during the 48-hr period after benzene exposure. In addition, a significantly greater percentage of total urinary radioactivity could be accounted for as phenylsulfate conjugates in cyp2e1-/- mice compared to wild-type mice, indicating the importance of CYP2E1 in oxidation of phenol following benzene exposure in normal mice. For the toxicity studies, male cyp2e1-/-, wild-type, and B6C3F1 mice were exposed by whole-body inhalation to 0 ppm (control) or 200 ppm benzene, 6 hr/day for 5 days. On Day 5, blood, bone marrow, thymus, and spleen were removed for evaluation of micronuclei frequencies and tissue cellularities. No benzene-induced cytotoxicity or genotoxicity was observed in cyp2e1-/- mice. In contrast, benzene exposure resulted in severe genotoxicity and cytotoxicity in both wild-type and B6C3F1 mice. These studies conclusively demonstrate that CYP2E1 is the major determinant of in vivo benzene metabolism and benzene-induced myelotoxicity in mice.

  12. Characteristics and Soft-Demodulation of Galileo E1 Signal%Galileo E1信号特征及其软件解调

    Institute of Scientific and Technical Information of China (English)

    易翔

    2009-01-01

    Galileo E1民用信号采用新的BOC(1,1)扩频调制方式.针对E1信号进行信号建模,并对其信号特征进行了详细研究,最后设计了Galileo软件解调器中的信号处理模块.通过仿真验证表明,软件解调器成功实现了对Galileo E1信号的捕获、跟踪、解扩、解调全过程处理,克服了BOC解调的错锁问题.

  13. Irreducible Modular Representations of the Reflection Group G(m,1,n

    Directory of Open Access Journals (Sweden)

    José O. Araujo

    2015-01-01

    Full Text Available In an article published in 1980, Farahat and Peel realized the irreducible modular representations of the symmetric group. One year later, Al-Aamily, Morris, and Peel constructed the irreducible modular representations for a Weyl group of type Bn. In both cases, combinatorial methods were used. Almost twenty years later, using a geometric construction based on the ideas of Macdonald, first Aguado and Araujo and then Araujo, Bigeón, and Gamondi also realized the irreducible modular representations for the Weyl groups of types An and Bn. In this paper, we extend the geometric construction based on the ideas of Macdonald to realize the irreducible modular representations of the complex reflection group of type G(m,1,n.

  14. Occurrence of aflatoxin M(1) in dairy products in southern Italy.

    Science.gov (United States)

    Montagna, Maria Teresa; Napoli, Christian; De Giglio, Osvalda; Iatta, Roberta; Barbuti, Giovanna

    2008-12-01

    A screening survey of the presence of aflatoxin M(1) (AFM(1)) was carried out on 265 samples of cheese made from cow, buffalo, goat, sheep, sheep-goat milk collected in the Apulia region (Southern Italy). Selected samples included unripened, medium and long-term ripened cheeses. AFM(1) was found in 16.6% of the analyzed samples. The highest positive incidence was for medium and long-term ripened cheeses, especially those made from sheep-goat milk, while buffalo cheeses tested consistently negative. Our results show that the level of contamination by AFM(1) in dairy products from Apulia Region are lower than in other Italian and European regions. Moreover, it is important to underline that a common European norm concerning the AFM(1) threshold limits for dairy products is still lacking.

  15. Excretion of Aflatoxin M1 in milk of goats fed diet contaminated by Aflatoxin B1

    Directory of Open Access Journals (Sweden)

    Gianni Battacone

    2010-01-01

    Full Text Available An experiment was carried out to study the excretion of aflatoxin M1(AFM1 in milk of three goats fed a single dose (0.8mg/head of pure aflatoxin B1 (AFB1. The values of AFM1 concentration excreted in milk was highly variable among goats, even if the pattern of excretion over time was very similar among the three animals. AFM1 was first detected at the milking performed 1h after the AFB1 administration. The highest values of AFM1 concentration in milk were reached 3 and 6h after the AFB1 intake. The trend of clearance of AFM1 in milk over time was expressed by a decreasing exponential equation. AFM1 concentration was below the EU maximum allowed level (50 ng/L in milk collected 36 h after the AFB1 administration.

  16. Robinson-Schensted-Knuth Correspondence and Weak Polynomial Identities of M1,1(E)

    Institute of Scientific and Technical Information of China (English)

    Onofrio Mario Di Vincenzo; Roberto La Scala

    2005-01-01

    In this paper, it is proved that the ideal Iω of the weak polynomial identities of the superalgebra M1,1(E) is generated by the p roper polynomials [x1,x2, x3] and [x2,x1][xa,x1][x4, x1]. This is proved for any infinite field F of characteristic different a basis and the dimension of any multihomogeneous component of the quotient algebra B/(B ∩ Iw). We also compute the Hilbert series of this algebra. One of the main tools of this paper is a variant we found of the Robinson-Schensted-Knuth correspondence defined for single semistandard tableaux of double shape.

  17. Solvent affects the conformation of virginiamycin M1 (pristinamycin IIA, streptogramin A).

    Science.gov (United States)

    Dang, Jason; Bergdahl, Mikael; Separovic, Frances; Brownlee, Robert T C; Metzger, Robert P

    2004-10-21

    The streptogramins are antibiotics which act by binding two different components at separate nearby sites on the bacterial 50S ribosome, inhibiting protein synthesis. The first component, a macrolactone, is common to many of the streptogramin antibiotics and, thus, is referred to by many names including virginiamycin M1(VM1), pristinamycin IIA, ostreogrycin A and streptogramin A. X-Ray crystallographic studies of VM1 bound to ribosomes and to a deactivating enzyme show a different conformation to that of VM1 in chloroform solution. We now report the results of high resolution 2D NMR experiments that show that the conformation of VM1 in dimethyl sulfoxide and methanol differs from both that in chloroform solution and in the bound form. The 3D structure and the 1H NMR and 13C NMR chemical shifts of VM1 in dimethyl sulfoxide and methanol are described.

  18. RAPD Analysis of M1 Generation of Gladiolus hybridus Hort Treated by EMS

    Institute of Scientific and Technical Information of China (English)

    WANG Jingang; GUO Ying; CHE Daidi; LIU Shenkui; YANG Chuanpin

    2009-01-01

    Gladiolus hybridus Hort is one of the world's famous cutting flowers. It is very popular because of the big size, bright color, various shape, and long period of bloom. New species should be cultivated in order to meet the consumers' need of asking for the new. Among the technologies of cultivating new species of flowers, mutagenic breeding is a shortcut. This study treated corm bud of G. hybridus Hort with EMS of different consistency. Then M1 after treated was analyzed by RAPD. The result showed that EMS was a very effective mutagenic agent for the corm bud of G. hybridus Hort. With the increase of consistency, the mutagenic range increased first, then decreased, among which 0.6% EMS treatment had the biggest influence. However, with the same EMS consistency, there was not close relevancy between the amount of mutagenic agent and the divergence of plant's genomes, which offered a molecular basis for selecting plants with good mutation.

  19. Occurrence of Aflatoxin M1 in Dairy Products in Southern Italy

    Directory of Open Access Journals (Sweden)

    Giovanna Barbuti

    2008-12-01

    Full Text Available A screening survey of the presence of aflatoxin M1 (AFM1 was carried out on 265 samples of cheese made from cow, buffalo, goat, sheep, sheep-goat milk collected in the Apulia region (Southern Italy. Selected samples included unripened, medium and long-term ripened cheeses. AFM1 was found in 16.6% of the analyzed samples. The highest positive incidence was for medium and long-term ripened cheeses, especially those made from sheep-goat milk, while buffalo cheeses tested consistently negative. Our results show that the level of contamination by AFM1 in dairy products from Apulia Region are lower than in other Italian and European regions. Moreover, it is important to underline that a common European norm concerning the AFM1 threshold limits for dairy products is still lacking.

  20. An Automatic Detection Method of Nanocomposite Film Element Based on GLCM and Adaboost M1

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    Hai Guo

    2015-01-01

    Full Text Available An automatic detection model adopting pattern recognition technology is proposed in this paper; it can realize the measurement to the element of nanocomposite film. The features of gray level cooccurrence matrix (GLCM can be extracted from different types of surface morphology images of film; after that, the dimension reduction of film can be handled by principal component analysis (PCA. So it is possible to identify the element of film according to the Adaboost M1 algorithm of a strong classifier with ten decision tree classifiers. The experimental result shows that this model is superior to the ones of SVM (support vector machine, NN and BayesNet. The method proposed can be widely applied to the automatic detection of not only nanocomposite film element but also other nanocomposite material elements.

  1. The M/M/1 Queue with Controlled Multiple Working Vacations

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hong-bo; FENG Ping-hua

    2013-01-01

    In this paper,we study an M/M/1 queue with multiple working vacations under following Bernoulli control policy:at the instants of the completion of a service in vacation,the server will interrupt the vacation and enter regular busy period with probabiiity1-p (if there are customers in the queue) or continue the vacation with probability p.For this model,we drive the analytic expression of the stationary queue length and demonstrate stochastic decomposition structures of the stationary queue length and waiting time,also we obtain the additional queue length and the additional delay of this model.The results we got agree with the corresponding results for working vacation model with or without vacation interruption if we set p =0 or p =1,respectively.

  2. Detection of Aflatoxin M1 in Milk from Qom (Aried and Semiaried Province of Iran

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    Mohammad Dakhili

    2016-06-01

    Full Text Available Background: Aflatoxins are secondary metabolites fungal When animals consume contaminated feed stuff to Aflatoxin B1 (AFB1, the toxin hydrolyzed and changed to the aflatoxin M1 and transmit to the milk consumers. Methods: seventy milk samples from different milk producers who were selling their milk to the dairy plant during two season in winter and summer and investigated by Enzyme Linked Immuno Sorbent Assay (ELISA. Results: AFM1 was found in 100% of the milk samples in winter. About 15% of the samples had AFM1 greater than the maximum tolerance limit (50ng/l accepted by European Union. Mean concentrations of AFM1 in Winter, Summer were 122, 53 ng/L, respectively. Mean concentrations of AFM1 in winter and Summer samples were significantly higher (P<0.05. Conclusion: these results show that the important of periodically monitoring the occurrence of AFM1 in raw milk and dairy products in Qom province.

  3. Fluid queues driven by an M/M/1/N queue

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    R. B. Lenin

    2000-01-01

    Full Text Available In this paper, we consider fluid queue models with infinite buffer capacity which receives and releases fluid at variable rates in such a way that the net input rate of fluid into the buffer (which is negative when fluid is flowing out of the buffer is uniquely determined by the number of customers in an M/M/1/N queu