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Sample records for fr e1 transition

  1. Octupole deformation in sup 221 Fr; E1 transition rates

    SciTech Connect

    Liang, C.F.; Peghaire, A. ); Sheline, R.K. )

    1990-07-10

    Experimental data following the alpha decay of{sup 225}Ac are interpreted in terms of a spectroscopy in {sup 221}Fr consistent with octupole deformation. However, the measured E1 transition probabilities suggest that the low lying bands in {sup 221}Fr are considerably more mixed than in nuclei with slightly higher mass number. It is suggested that this mixing of states in {sup 221}Fr is indicative of the partial collapse of Nilsson-like orbitals into more degenerate shell model orbitals.

  2. E1-forbidden transition rates in ions of astrophysical interest

    NASA Astrophysics Data System (ADS)

    Träbert, E.

    2014-11-01

    Transition rates in atomic systems may appear to be of little importance in steady-state plasmas that are observed at great distances from Earth. However, some of the transition rates compete with collision rates, and in these cases certain line intensity ratios are affected and can serve as remote indicators of density. In the low-density environments of stellar coronae and planetary nebulae, the transition rates of interest are mostly spin-forbidden E1 decays, higher-multipole order transitions (M1, E2, M2, M3), and hyperfine-induced transitions. On Earth, measurements of the long upper level lifetimes of these atomic systems require the use of ion traps. A fair number of test cases with lifetimes in the range from nanoseconds to many seconds have been treated successfully, and the evolution of calculations along with the experimental progress is notable. A new generation of cold ion traps is expected to extend the atomic lifetime measurements on multiply charged ions into the range of many minutes.

  3. Rates of E1, E2, M1, and M2 transitions in Ni II

    NASA Astrophysics Data System (ADS)

    Cassidy, C. M.; Hibbert, A.; Ramsbottom, C. A.

    2016-03-01

    Aims: We present rates for all E1, E2, M1, and M2 transitions among the 295 fine-structure levels of the configurations 3d9, 3d84s, 3d74s2, 3d84p, and 3d74s4p, determined through an extensive configuration interaction calculation. Methods: The CIV3 code developed by Hibbert and coworkers is used to determine for these levels configuration interaction wave functions with relativistic effects introduced through the Breit-Pauli approximation. Results: Two different sets of calculations have been undertaken with different 3d and 4d functions to ascertain the effect of such variation. The main body of the text includes a representative selection of data, chosen so that key points can be discussed. Some analysis to assess the accuracy of the present data has been undertaken, including comparison with earlier calculations and the more limited range of experimental determinations. The full set of transition data is given in the supplementary material as it is very extensive. Conclusions: We believe that the present transition data are the best currently available. Full Table 4 and Tables 5-8 are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/587/A107

  4. Calculation of energy levels, {ital E}1 transition amplitudes, and parity violation in francium

    SciTech Connect

    Dzuba, V.A.; Flambaum, V.V.; Sushkov, O.P.

    1995-05-01

    Many-body perturbation theory in the screened Coulomb interaction was used to calculate energy levels, {ital E}1 trransition amplitudes, and the parity-nonconserving (PNC) {ital E}1 amplitude of the 7{ital s}-8{ital s} transition in francium. The method takes into account the core-polarization effect, the second-order correlations, and the three dominating sequences of higher-order correlation diagrams: screening of the electron-electron interaction, particle-hole interaction, and the iterations of the self-energy operator. The result for the PNC amplitude for {sup 223}Fr is {ital E}1(7{ital s}-8{ital s})=(1.59{plus_minus}{similar_to}1%){times}10{sup {minus}10}{ital iea}{sub {ital B}}({minus}{ital Q}{sub {ital W}}/{ital N}), where {ital Q}{sub {ital W}} is the weak charge of the nucleus, {ital N}=136 is the number of neutrons, {ital e}={vert_bar}{ital e}{vert_bar} is the elementary charge, and {ital a}{sub {ital B}} is the Bohr radius. Our prediction for the position of the 8{ital s} energy level of Fr, which has not been measured yet, is 13 110 cm{sup {minus}1} below the limit of the continuous spectrum. The accuracy of the calculations was controlled by comparison with available experimental data and analogous calculations for cesium. It is estimated to be {similar_to}0.1% for the energy levels and {similar_to}1% for the transition amplitudes.

  5. Enhanced E1 transitions and {alpha}-clustering in {sup 212}Po

    SciTech Connect

    Suzuki, Y.; Ohkubo, S.

    2011-05-06

    An {alpha}+{sup 208}Pb(0{sup +},3{sup -}) cluster model explains the recently observed enhanced E1 transitions from the new negative-parity levels to the yrast states in {sup 212}Po. Heavy and light nuclei present good examples of surface clustering and well-localized clustering.

  6. Collective vector method for calculation of E1 moments in atomic transition arrays

    SciTech Connect

    Bloom, S.D.; Goldberg, A.

    1985-10-01

    The CV (collective vector) method for calculating E1 moments for a transition array is described and applied in two cases, herein denoted Z26A and Z26B, pertaining to two different configurations of iron VI. The basic idea of the method is to create a CV from each of the parent (''initial state'') state-vectors of the transition array by application of the E1 operator. The moments of each of these CV's, referred to the parent energy, are then the rigorous moments for that parent, requiring no state decomposition of the manifold of daughter state-vectors. Since, in cases of practical interest, the daughter manifold can be orders of magnitude larger in size than the parent manifold, this makes possible the calculation of many moments higher than the second in situations hitherto unattainable via standard methods. The combination of the moments of all the parents, with proper statistical weighting, then yields the transition array moments from which the transition strength distribution can be derived by various procedures. We describe two of these procedures: (1) The well-known GC (Gram-Charlier) expansion in terms of Hermite polynomials, (2) The Lanczos algorithm or Stieltjes imaging method, also called herein the delta expansion. Application is made in the cases of Z26A (50 lines) and Z26B (5523 lines) and the relative merits and shortcomings of the two procedures are discussed. 10 refs., 15 figs., 2 tabs.

  7. E1, E2 and M1 transition parameters for some levels over ionization limit of Ne III

    NASA Astrophysics Data System (ADS)

    Eser, Selda; Özdemir, Leyla

    2016-07-01

    We have reported the level energies and radiative transition ( E1 , E2 and M1 parameters, such as wavelengths, transition rates, oscillator strengths and line strengths for some levels over the ionization limit of Ne III (oxygen-like). The calculations have been performed using the general-purpose relativistic atomic structure package (GRASP) based on the fully relativistic multiconfiguration Dirac-Fock (MCDF) method. The results obtained have been compared with the available theoretical and experimental values in the literature.

  8. E1 and E2 transitions for Fe XVI, Co XVII and Ni XVIII

    NASA Astrophysics Data System (ADS)

    Çelik, G.; Ateş, Ş.

    2016-07-01

    Electric dipole and electric quadrupole transition data for sodium-like iron, cobalt and nickel have been calculated within the weakest bound electron potential model (WBEPM) theory using experimental energy levels and theoretical expectation values of orbital radii corresponding to those energy levels under the assumption of the {LS} coupling scheme. The results obtained from this study provide theoretical transition probability and oscillator strength data requested in many fields of researches, especially astrophysics. The calculated transition data results have been compared with available data in the literature. The present results are consistent with earlier calculations. Some new electric quadrupole transition probability values not existing in the data bases, especially for iron have been obtained using this method.

  9. Enhanced E1 transitions and {alpha}+{sup 208}Pb(3{sup -}) clustering in {sup 212}Po

    SciTech Connect

    Suzuki, Y.; Ohkubo, S.

    2010-10-15

    We formulate a model for {sup 212}Po, based on the coupled-channels of {alpha}+{sup 208}Pb(0{sup +}) and {alpha}+{sup 208}Pb(3{sup -}) in which the {alpha}-Pb interaction contains scalar, quadrupole, and octupole terms. The model reproduces the recently observed enhanced E1 transitions from the several new negative-parity levels to the yrast states. Because these data are hard to understand in the shell model, this success gives a strong support for a unique role of {alpha}+{sup 208}Pb(3{sup -}) clustering in {sup 212}Po.

  10. A shock-tube measurement of the SiO/E 1 Sigma + - X 1 Sigma +/ transition moment

    NASA Technical Reports Server (NTRS)

    Park, C.

    1978-01-01

    The sum of the squares of the electronic transition moments for the (E 1 Sigma +) - (X 1 Sigma +) band system of SiO has been determined from absorption measurements conducted in the reflected-shock region of a shock tube. The test gas produced by shock-heating a mixture of SiCl4, N2O, and Ar, and the spectra were recorded photographically in the 150-230-nm wavelength range. The values of the sum of the squares were determined by comparing the measured absorption spectra with those produced by a line-by-line synthetic spectrum calculation. The value so deduced at an r-centroid value of 3.0 bohr was 0.86 + or - 0.10 atomic unit.

  11. 78 FR 15597 - Special Conditions: GE Aviation CT7-2E1 Turboshaft Engine Model

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-12

    ... published on July 20, 2012 (77 FR 42677). We received six comments from European Aviation Safety Agency... the special conditions 33-002-SC, published on May 28, 1999 (64 FR 28900). We are therefore adopting...)(7), and 33.88(c). The 2.5 minute time duration for the rating would affect the structural...

  12. Energy levels, wavelengths, and transition rates of multipole transitions (E1, E2, M1, M2) in Au{sup 67+} and Au{sup 66+} ions

    SciTech Connect

    Hamasha, Safeia

    2013-11-15

    The fully relativistic configuration interaction method of the FAC code is used to calculate atomic data for multipole transitions in Mg-like Au (Au{sup 67+}) and Al-like Au (Au{sup 66+}) ions. Generated atomic data are important in the modeling of M-shell spectra for heavy Au ions and Au plasma diagnostics. Energy levels, oscillator strengths and transition rates are calculated for electric-dipole (E1), electric quadrupole (E2), magnetic dipole (M1), and magnetic quadrupole (M2) for transitions between excited and ground states 3l−nl{sup ′}, such that n=4,5,6,7. The local central potential is derived using the Dirac–Fock–Slater method. Correlation effects to all orders are considered by the configuration interaction expansion. All relativistic effects are included in the calculations. Calculated energy levels are compared against published values that were calculated using the multi-reference many body perturbation theory, which includes higher order QED effects. Favorable agreement was observed, with less than 0.15% difference.

  13. 77 FR 42677 - Special Conditions: General Electric CT7-2E1 Turboshaft Engine

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-20

    ... Privacy Act Statement can be found in the Federal Register published on April 11, 2000 (65 FR 19477-19478... structural and operational characteristics that are time dependent, such as the values for transients, time duration for stabilization to steady state, and part growth due to deformation. In addition, we...

  14. On the enhanced E1 transitions in the K = 3/2 parity doublet band in 223Ra

    NASA Astrophysics Data System (ADS)

    Mach, H.; Lindroth, A.; Ruchowska, E.; Kvasil, J.; Fogelberg, B.; Gulda, K.; Aas, A. J.; Borge, M. J. G.; Grant, I. S.; Hagebø, E.; Kurcewicz, W.; Martinez, T.; Rubio, B.; Smith, J. F.; Steffensen, K.; Tain, J. L.; Tengblad, O.; Thorsteinsen, T. F.

    2016-06-01

    We have applied the fast timing βγγ (t) technique to remeasure lifetimes of selected states in 223Ra populated in the β- decay of 223Fr. T_{1/2}=587(12) ps and 210(13)ps have been obtained for the 3/2- and 5/2- states at 50.1 and 79.7 keV, that are more accurate than the previous values of 630(70)ps and 166(55)ps, respectively. Our \\vert D0\\vert value of 0.155(10)e·fm obtained for the K=3/2 configuration together with the available values of \\vert D0\\vert for the K=1/2 and K=5/2 parity doublet bands establish the configuration dependence of \\vert D0\\vert at low spins in this nucleus. Results of theoretical calculations performed for 223Ra, using the quasiparticle-phonon model (QPM) with inclusion of the Coriolis coupling, reasonably well reproduce octupole correlations in this nucleus.

  15. Radiative rates for E1, E2, M1, and M2 transitions in F-like ions with 37 ≤ Z ≤ 53

    NASA Astrophysics Data System (ADS)

    Aggarwal, Kanti M.; Keenan, Francis P.

    2016-05-01

    Calculations of energy levels, radiative rates and lifetimes are reported for 17 F-like ions with 37≤Z≤53. For brevity, results are only presented among the lowest 113 levels of the 2s22p5, 2s2p6, 2s22p43 ℓ, 2s2p53 ℓ, and 2p63 ℓ configurations, although the calculations have been performed for up to 501 levels in each ion. The general-purpose relativistic atomic structure package (GRASP) has been adopted for the calculations, and radiative rates (along with oscillator strengths and line strengths) are listed for all E1, E2, M1, and M2 transitions of the ions. Comparisons are made with earlier available experimental and theoretical energies, although these are limited to only a few levels for most ions. Therefore for additional accuracy assessments, particularly for energy levels, analogous calculations have been performed with the Flexible Atomic Code (FAC), for up to 72 259 levels. Limited previous results are available for radiative rates for comparison purposes, and no large discrepancy is observed for any transition and/or ion.

  16. Radiative rates for E1, E2, M1, and M2 transitions in Br-like ions with 43 ≤ Z ≤ 50

    NASA Astrophysics Data System (ADS)

    Aggarwal, Kanti M.; Keenan, Francis P.

    2016-01-01

    Energies and lifetimes are reported for the eight Br-like ions with 43 ≤ Z ≤ 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 4s24p5, 4s24p44ℓ, 4s4p6,4s24p45ℓ, 4s24p34d2, 4s4p54ℓ, and 4s4p55ℓ configurations. Extensive configuration interaction among 39 configurations (generating 3990 levels) has been considered and the general-purpose relativistic atomic structure package (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 lifetimes, prior results are limited to those involving only 31 levels of the 4s24p5, 4s24p44d, and 4s4p6 configurations for the last four ions. Moreover, there are generally no discrepancies with our results, although the larger calculations reported here differ by up to two orders of magnitude for a few transitions.

  17. 75 FR 43197 - Public Housing Assessment System (PHAS): Asset Management Transition Year 2 Extension

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-23

    ... notice, Public Housing Assessment System (PHAS): Asset Management Transition Year 2 Information (75 FR... Register notice (FR-5227- N-01), ``Public Housing Assessment System (PHAS): Asset Management Transition Year Information and Uniform Financial Reporting Standards (UFRS) Information'' (73 FR 49588). In...

  18. 77 FR 48733 - Transitional Program for Covered Business Method Patents-Definitions of Covered Business Method...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-14

    ... Covered Business Method Patents, 77 FR 7080 (Feb. 10, 2012), to provide rules specific to the transitional... Method Patents, 77 FR 7080 (Feb. 10, 2012) and Transitional Program for Covered Business Method Patents... Covered Business Method Patents, 77 FR 7080 (Feb. 10, 2012) (notice of proposed rulemaking)...

  19. The E1 proteins

    SciTech Connect

    Bergvall, Monika; Melendy, Thomas; Archambault, Jacques

    2013-10-15

    E1, an ATP-dependent DNA helicase, is the only enzyme encoded by papillomaviruses (PVs). It is essential for replication and amplification of the viral episome in the nucleus of infected cells. To do so, E1 assembles into a double-hexamer at the viral origin, unwinds DNA at the origin and ahead of the replication fork and interacts with cellular DNA replication factors. Biochemical and structural studies have revealed the assembly pathway of E1 at the origin and how the enzyme unwinds DNA using a spiral escalator mechanism. E1 is tightly regulated in vivo, in particular by post-translational modifications that restrict its accumulation in the nucleus. Here we review how different functional domains of E1 orchestrate viral DNA replication, with an emphasis on their interactions with substrate DNA, host DNA replication factors and modifying enzymes. These studies have made E1 one of the best characterized helicases and provided unique insights on how PVs usurp different host-cell machineries to replicate and amplify their genome in a tightly controlled manner. - Highlights: • The papillomavirus E1 helicase orchestrates replication of the viral DNA genome. • E1 assembles into a double-hexamer at the viral origin with the help of E2. • E1 interacts with cellular DNA replication factors. • E1 unwinds DNA using a spiral escalator mechanism. • Nuclear accumulation of E1 is regulated by post-translational modifications.

  20. 77 FR 35199 - Swap Data Recordkeeping and Reporting Requirements: Pre-Enactment and Transition Swaps

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-12

    ... Reporting Pre-Enactment Swap Transactions (``Pre-Enactment Swaps IFR''), 75 FR 63080 (Oct. 14, 2010...-Enactment Swap Transactions (``Post-Enactment Swaps IFR'' or ``Transition Swaps IFR''), 75 FR 78892 (Dec. 17... to particular swaps. \\19\\ 77 FR 2136 (February 13, 2012). With respect to recordkeeping, part...

  1. 78 FR 30951 - SBIR/STTR Phase I to Phase II Transition Benchmarks

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-23

    ... INFORMATION: Section 4(a)(3)(iii) of the SBIR Policy Directive (77 FR 46806) and the STTR Policy Directive (77 FR 46855) require each agency to establish an SBA-approved Phase I-Phase II Transition Rate benchmark... benchmarks can take effect. As a result, on October 16, 2012, at 77 FR 63410, SBA published the...

  2. Multipole (E1, M1, E2, M2, E3, M3) transition wavelengths and rates between 3l-15l' excited and ground states in nickel-like ions

    SciTech Connect

    Safronova, U I; Safronova, A S; Beiersdorfer, P

    2006-05-04

    A relativistic many-body method is developed to calculate energy and transition rates for multipole transitions in many-electron ions. This method is based on relativistic many-body perturbation theory (RMBPT), agrees with MCDF calculations in lowest-order, includes all second-order correlation corrections and includes corrections from negative energy states. Reduced matrix elements, oscillator strengths, and transition rates are calculated for electric-multipole (dipole (E1), quadrupole (E2), and octupole (E3)) and magnetic-multipole (dipole (M1), quadrupole (M2), and octupole (M3)) transitions between 3l{sup -1}5l{prime} excited and ground states in Ni-like ions with nuclear charges ranging from Z = 30 to 100. The calculations start from a 1s{sup 2}s{sup 2}2p{sup 6}3s{sup 2}3p{sup 6}3d{sup 10} Dirac-Fock potential. First-order perturbation theory is used to obtain intermediate-coupling coefficients, and second-order RMBPT is used to determine the matrix elements. A detailed discussion of the various contributions to the dipole matrix elements and energy levels is given for nickel-like tungsten (Z = 74). The contributions from negative-energy states are included in the second order E1, M1, E2, M2, E3 and M3 matrix elements. The resulting transition energies and transition rates are compared with experimental values and with results from other recent calculations. These atomic data are important in modeling of M-shell radiation spectra of heavy ions generated in electron beam ion trap experiments and in M-shell diagnostics of plasmas.

  3. THE E1 PROTEINS

    PubMed Central

    Bergvall, Monika; Melendy, Thomas; Archambault, Jacques

    2013-01-01

    E1, an ATP-dependent DNA helicase, is the only enzyme encoded by papillomaviruses (PVs). It is essential for replication and amplification of the viral episome in the nucleus of infected cells. To do so, E1 assembles into a double-hexamer at the viral origin, unwinds DNA at the origin and ahead of the replication fork and interacts with cellular DNA replication factors. Biochemical and structural studies have revealed the assembly pathway of E1 at the origin and how the enzyme unwinds DNA using a spiral escalator mechanism. E1 is tightly regulated in vivo, in particular by post-translational modifications that restrict its accumulation in the nucleus. Here we review how different functional domains of E1 orchestrate viral DNA replication, with an emphasis on their interactions with substrate DNA, host DNA replication factors and modifying enzymes. These studies have made E1 one of the best characterized helicases and provided unique insights on how PVs usurp different host-cell machineries to replicate and amplify their genome in a tightly controlled manner. PMID:24029589

  4. A Large-scale Relativistic Configuration-interaction Approach: Application to the 4s2 - 4s4p Transition Energies and E1 Rates for Zn-like Ions

    SciTech Connect

    Chen, M H; Cheng, K T

    2009-08-28

    Relativistic configuration-interaction calculations of the 4s4p excitation energies and 4s{sup 2} - 4s4p E1 transitions for Zn-like ions from Z = 30 to 92 are shown. B-spline basis functions are used for these large-scale calculations. QED corrections to the excitation energies are also calculated. Results are in good agreement with other theories and with experiment, and demonstrate the utility of this method for high-precision atomic structure calculations not just for few-electron systems but also for large atomic systems such as Zn-like ions along the entire isoelectronic sequence.

  5. Translational regulation of Inhibin βA by TGFβ via the RNA-binding protein hnRNP E1 enhances the invasiveness of epithelial-to-mesenchymal transitioned cells

    PubMed Central

    Howley, Breege V; Hussey, George S; Link, Laura A; Howe, Philip H

    2015-01-01

    The epithelial-to-mesenchymal transition (EMT) is a cellular process that functions during embryonic development and tissue regeneration, thought to be aberrantly activated in epithelial-derived cancer and play an important role in the process of metastasis. The TGFβ signaling pathway is a key inducer of EMT and we have elucidated a post-transcriptional mechanism by which TGFβ modulates expression of select transcripts via the RNA binding protein hnRNP E1 during EMT. One such transcript inhibin βA is a member of the TGFβ superfamily. Here, we show by polysome profiling that inhibin βA is translationally regulated by TGFβ via hnRNP E1. TGFβ treatment or knockdown of hnRNP E1 relieves silencing of the inhibin βA transcript, resulting in increased protein expression and secreted levels of the inhibin βA homodimer, activin A. Our data indicates that the translational up-regulation of inhibin βA enhances the migration and invasion of cells that have undergone an EMT and promotes cancer progression in vivo. PMID:26096938

  6. 77 FR 63410 - SBIR/STTR Phase I to Phase II Transition Benchmarks

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    2012-10-16

    ... 4(a)(3)(iii) of the SBIR Policy Directive, which was published on August 6, 2012, at 77 FR 46806 and the STTR Policy Directive, which was published the same day at 77 FR 46855, requires each agency to... ADMINISTRATION SBIR/STTR Phase I to Phase II Transition Benchmarks AGENCY: U.S. Small Business...

  7. 77 FR 7095 - Transitional Program for Covered Business Method Patents-Definition of Technological Invention

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    2012-02-10

    ... Flexibility Analysis for Patent-Related Regulations, 71 FR 67109 (Nov. 20, 2006), 1313 Off. Gaz. Pat. Office..., 71 FR at 67112 (Nov 20, 2006), 1313 Off. Gaz. Pat. Office at 63 (Dec. 12, 2006). As discussed above... Patent and Trademark Office 37 CFR Part 42 RIN 0651-AC75 Transitional Program for Covered Business...

  8. 76 FR 30997 - National Transit Database: Amendments to Urbanized Area Annual Reporting Manual

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    2011-05-27

    ... Federal Register (73 FR 7361) inviting comments on proposed amendments to the 2011 Annual Manual. This... Federal Register (75 FR 192) inviting comments on proposed amendments to the 2011 Annual Manual. FTA... Manual AGENCY: Federal Transit Administration (FTA), DOT. ACTION: Notice of Amendments to 2011...

  9. Radiative rates for E1, E2, M1, and M2 transitions in S-like to F-like tungsten ions (W LIX to W LXVI)

    NASA Astrophysics Data System (ADS)

    Aggarwal, Kanti M.; Keenan, Francis P.

    2016-09-01

    Calculations of energy levels, radiative rates and lifetimes are reported for eight ions of tungsten, i.e. S-like (W LIX) to F-like (W LXVI). A large number of levels have been considered for each ion and extensive configuration interaction has been included among a range of configurations. For the calculations, the general-purpose relativistic atomic structure package (GRASP) has been adopted, and radiative rates (as well as oscillator strengths and line strengths) are listed for all E1, E2, M1, and M2 transitions of the ions. Comparisons have been made with earlier available experimental and theoretical energies, although these are limited to only a few levels for most ions. Therefore for additional accuracy assessments, particularly for energy levels, analogous calculations have been performed with the flexible atomic code (FAC).

  10. Radiative rates for E1, E2, M1, and M2 transitions in S-like to F-like tungsten ions (W LIX to W LXVI)

    NASA Astrophysics Data System (ADS)

    Aggarwal, Kanti M.; Keenan, Francis P.

    2016-09-01

    Calculations of energy levels, radiative rates and lifetimes are reported for eight ions of tungsten, i.e. S-like (W LIX) to F-like (W LXVI). A large number of levels have been considered for each ion and extensive configuration interaction has been included among a range of configurations. For the calculations, the general-purpose relativistic atomic structure package (GRASP) has been adopted, and radiative rates (as well as oscillator strengths and line strengths) are listed for all E1, E2, M1, and M2 transitions of the ions. Comparisons have been made with earlier available experimental and theoretical energies, although these are limited to only a few levels for most ions. Therefore for additional accuracy assessments, particularly for energy levels, analogous calculations have been performed with the flexible atomic code (FAC).

  11. The role of Domain:Domain Interactions Vs Domain:Water Interactions in the coarse-grained simulations of the E1P to E2P transitions in Ca-ATPase (SERCA)

    PubMed Central

    Andersen, Jens Peter; Woolf, Thomas B.

    2012-01-01

    SERCA is an important model system for understanding the molecular details of conformational change in membrane transport systems. This reflects the large number of solved x-ray structures and the equally large database of mutations that have been assayed. In this computational study we provide a molecular dynamics description of the conformational changes during the E1P -> E2P transitions. This set of states further changes with insertion mutants in the A-M3 linker region. These mutants were experimentally shown to lead to significant shifts in rates between the E1P -> E2P states. Using the population shift framework and dynamic importance sampling method along with coarse-grained representations of the protein, lipid and water, we suggest why these changes are found. The calculations sample on intermediates and suggest that changes in interactions, individual helix interactions and water behavior are key elements in the molecular compositions that underlie shifts in kinetics. In particular, as the insertion length grows, it attracts more water and disrupts domain interactions, creating changes as well at the sites of key helix interactions between the A-Domain and the P-Domain. This provides a conceptual picture that aids understanding of the experimental results. PMID:22422644

  12. 77 FR 77180 - Notice of Transportation Services' OMB Designation, timely return of excess transit benefits to...

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    2012-12-31

    ... Transportation Facilitation, 65 FR 19482 (April 11, 2000). III. Minimum Internal Controls To ensure that funds... return of excess transit benefits to the Treasury, and stakeholder notification of the minimum internal... of the Federal internal controls that now govern the Transit Benefit Program to prevent...

  13. 76 FR 18930 - Medicare Programs: Changes to the End-Stage Renal Disease Prospective Payment System Transition...

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    2011-04-06

    ... published a final rule (75 FR 49030 through 49214) in the Federal Register, entitled ``Medicare Program; End... the transition budget-neutrality adjustment. As described in the CY 2011 ESRD PPS final rule (75 FR... FR 49082), we explained that section 1881(b)(14)(E)(iii) of the Act requires that we make...

  14. Radiative rates for E1, E2, M1, and M2 transitions in the Br-like ions Sr IV, Y V, Zr VI, Nb VII, and Mo VIII

    SciTech Connect

    Aggarwal, Kanti M. Keenan, Francis P.

    2015-09-15

    Energies and lifetimes are reported for the lowest 375 levels of five Br-like ions, namely Sr IV, Y V, Zr VI, Nb VII, and Mo VIII, mostly belonging to the 4s{sup 2}4p{sup 5}, 4s{sup 2}4p{sup 4}4ℓ, 4s4p{sup 6}, 4s{sup 2}4p{sup 4}5ℓ, 4s{sup 2}4p{sup 3}4d{sup 2}, 4s4p{sup 5}4ℓ, and 4s4p{sup 5}5ℓ configurations. Extensive configuration interaction has been included and the general-purpose relativistic atomic structure package (GRASP) has been adopted for the calculations. Additionally, radiative rates are listed among these levels for all E1, E2, M1, and M2 transitions. From a comparison with the measurements, the majority of our energy levels are assessed to be accurate to better than 2%, although discrepancies between theory and experiment for a few are up to 6%. An accuracy assessment of the calculated radiative rates (and lifetimes) is more difficult, because no prior results exist for these ions.

  15. 78 FR 50396 - Common Format for Federal Entity Transition Plans

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    2013-08-19

    ..., 78 FR 5310 (Jan. 25, 2013) (to be codified at 47 CFR Part 301), available at http://go.usa.gov/jRHB... whether the revised plan is sufficient. See Technical Panel Rules at Sec. 301.120, 78 FR 5316-17. \\17\\ See... Technical Panel Rules at Sec. 301.10, 78 FR 5315 (cross-referencing Annex O). NTIA will provide the...

  16. Oscillator Strengths and Predissociation Rates for Rydberg Transitions in 12C16O, 13C16O, and 13C18O Involving the E 1Π, B 1Σ+, and W 1Π States

    NASA Astrophysics Data System (ADS)

    Eidelsberg, M.; Sheffer, Y.; Federman, S. R.; Lemaire, J. L.; Fillion, J. H.; Rostas, F.; Ruiz, J.

    2006-08-01

    One of the processes controlling the interstellar CO abundance and the ratio of its isotopologues is photodissociation. Accurate oscillator strengths and predissociation rates for Rydberg transitions are needed for modeling this process. We present results on absorption from the E 1Π-X 1Σ+ (1-0) and B 1Σ+-X 1Σ+ (6-0) bands at 1051 and 1002 Å, respectively, and the vibrational progression W 1Π-X 1Σ+ (v'-0) bands with v'=0-3 at 972, 956, 941, and 925 Å, respectively. The corresponding spectra were acquired at the high resolution (R~30,000) SU5 beam line at the Super ACO Synchrotron in Orsay, France. Spectra were obtained for the 12C16O, 13C 16O, and 13C18O isotopologues. These represent the most complete set of measurements available. Comparison is made with earlier results, both empirical and theoretical. While earlier determinations of oscillator strengths based on absorption from synchrotron radiation tend to be somewhat smaller than ours, the suite of measurements from a variety of techniques agree for the most part, considering the mutual uncertainties. For the bands studied here, their relative weakness, or their significant line widths arising from predissociation, minimizes potential problems from large optical depths at line center in absorption measurements. Predissociating line widths could generally be extracted from the spectra thanks to the profile simulations used in the analysis. In many cases, these simulations allowed us to consider e and f parity levels separately and to determine the dependence of the width on rotational quantum number, J. Our results are consistent with earlier determinations, especially the widths inferred from laser experiments.

  17. 77 FR 32174 - Innovative Transit Workforce Development Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-31

    ... Federal Transit Administration Innovative Transit Workforce Development Program AGENCY: Federal Transit Administration (FTA), DOT. ACTION: Notice of funding availability (NOFA) for innovative workforce development... (NOFA) for the Innovative Workforce Development Program. This NOFA seeks proposals that promote...

  18. 78 FR 50313 - Physical Protection of Irradiated Reactor Fuel in Transit

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-19

    ... safety. On May 20, 2013 (78 FR 29520), the NRC published the final rule for 10 CFR 73.37, ``Physical... 3150-AI64 Physical Protection of Irradiated Reactor Fuel in Transit AGENCY: Nuclear Regulatory... Transportation of Spent Nuclear Fuel Greater than 100 Grams,'' dated October 10, 2002, and subsequent...

  19. 77 FR 43903 - Intent To Prepare an Environmental Impact Statement for Proposed Transit Improvements to the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-26

    ... at http://www.gpo.gov/fdsys/pkg/FR-2011-01-03/pdf/2010-33065.pdf . FOR FURTHER INFORMATION CONTACT... Improvements to the North Red and Purple Lines, Cook County, IL AGENCY: Federal Transit Administration, U.S... Impact Statement (EIS) for the North Red and Purple Line Modernization (RPM) Project in Cook...

  20. 76 FR 71934 - Tobacco Transition Payment Program; Availability of Current Assessment Methods Determination...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-21

    ... addresses the rulemaking matter covered in a Federal Register document published March 22, 2011 (76 FR 15859... Farm Service Agency Tobacco Transition Payment Program; Availability of Current Assessment Methods... regarding two consolidated determinations with respect to the current methods used to calculate...

  1. 77 FR 28765 - Homeless Emergency Assistance and Rapid Transition to Housing: Emergency Solutions Grants Program...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-16

    ... (this is a toll-free number). SUPPLEMENTARY INFORMATION: On December 5, 2011, at 76 FR 75954, HUD... URBAN DEVELOPMENT 24 CFR Parts 91 and 576 RIN 2506-AC31 Homeless Emergency Assistance and Rapid Transition to Housing: Emergency Solutions Grants Program and Consolidated Plan Conforming...

  2. 76 FR 22833 - Swap Data Recordkeeping and Reporting Requirements: Pre-Enactment and Transition Swaps

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-25

    ... Final Rule for Reporting Pre-Enactment Swap Transactions (``Pre-Enactment Swaps IFR''), 75 FR 63080 (Oct... COMMISSION 17 CFR Part 46 Swap Data Recordkeeping and Reporting Requirements: Pre-Enactment and Transition... rules adopted by the Commission shall provide for the reporting of data relating to swaps entered...

  3. 76 FR 55501 - Commonwealth of the Northern Mariana Islands Transitional Worker Classification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-07

    ... labor force. Such workers outnumber U.S. citizens and other local residents in most industries central... classification (CW classification) intended to be effective for the duration of the transition period. See 74 FR... Federal Register reopening and extending the public comment period for an additional 30 days. See 74...

  4. 77 FR 38042 - TRICARE; Implementation of TRICARE Transitional Outpatient Payments

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-26

    ... Federal Register (73 FR 74945) on December 10, 2008, states Agency will adopt the hold harmless TOPs for... Management Activity (TMA), Medical Benefits and Reimbursement Branch, 16401 East Centretech Parkway,...

  5. 78 FR 1306 - Transition Period Under Section 716 of the Dodd-Frank Wall Street Reform and Consumer Protection Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-08

    ... dealers as swap dealers. \\4\\ Guidance on the Effective Date of Section 716, 77 FR 27465 (May 10, 2012... deems necessary and appropriate.\\12\\ \\11\\ See Further Definition of Swap Dealer, 77 FR 30595 (May 23... Office of the Comptroller of the Currency Transition Period Under Section 716 of the Dodd-Frank...

  6. sup 219 Fr, a transitional reflection asymmetric nucleus

    SciTech Connect

    Liang, C.F.; Paris, P. ); Kvasil, J.; Sheline, R.K. )

    1991-08-01

    Mass-separated sources of {sup 223}Ac (separated as AcF{sub 2}{sup +}) were used to study the level structure of {sup 219}Fr following alpha decay. The levels in {sup 219}Fr are interpreted in terms of {ital K}=1/2{sup {plus minus}}, 3/2{sup {plus minus}}, and 5/2{sup {plus minus}} parity doublet bands which have a natural theoretical explanation in terms of reflection asymmetric models. The 9/2{sup {minus}} ground-state member of the {ital K}=1/2{sup {minus}} band in {sup 219}Fr can be understood in terms of both reflection asymmetry and the collapse of the quadrupole-octupole Nilsson orbitals towards the {ital h}{sub 9/2} orbitals of spherical symmetry. Comparison of the {ital K}=1/2{sup {minus}} ground-state bands in {sup 219}Fr and {sup 221}Fr reveals the details of this transformation. Theoretical analysis of the microscopic structure of several of the positive-parity bands indicates the presence of important Nilsson configurations arising from the shell below.

  7. Influence of shear flow on the Fréedericksz transition in nematic liquid crystals.

    PubMed

    Makarov, D V; Zakhlevnykh, A N

    2006-10-01

    Within the framework of Ericksen-Leslie continuum theory we analyze the influence of shear flow on the magnetic-field-induced Fréedericksz transition in nematic liquid crystal with rodlike molecules. We consider three basic orientational configurations of a nematic planar layer in the uniform magnetic field. Conditions of rigid director coupling on the boundaries of the layer and constant shear flow gradient inside the layer are used. We exhibit some flow aligning effects for nematic liquid crystals with various ratio of rotary viscosities and investigate how unequal elastic constants (elastic anisotropy) alter the magnetic Fréedericksz transition in sheared nematics. Our calculations predict that surface boundary effects in nematic films and magnetic field action lead to existence of stationary flow regimes in the so-called nonflow aligning nematics, otherwise, surface and magnetic forces extend the range of viscous coefficient values corresponding to the flow aligning regimes. We show that imposing of shear flow on the Fréedericksz transition leads to a threshold behavior or to a "smoothing" of the transition. It depends on the orientation of the nematic layer in magnetic field and magnitudes of rotary viscous coefficients. PMID:17155081

  8. Jet-gas interactions and hotspots in FR I/II transition sources

    NASA Astrophysics Data System (ADS)

    Worrall, Diana; Birkinshaw, Mark

    2016-07-01

    Sources with intermediate FR I/II morphologies, and with powers in the decade straddling the FR I/II boundary, provide an opportunity to understand triggers responsible for the different workings of the two classes. Illustrated by deep Chandra observations of several sources, this presentation will show evidence that the physics changes within the transition range, and the work done in driving shocks can exceed that in evacuating the cavities common in FR I sources. Hotspots can be absent, seen only on one side (jet-side or counter-jet-side), or both, in which case X-ray/radio correspondence can be very different on the two sides. Evidence will be shown for radio-emitting plasma running along boundaries between gas of different temperature, apparently lubricating the gas flows and inhibiting heat transfer.

  9. 75 FR 45677 - Draft Regulatory Guide, DG-1216,”Plant-Specific Applicability of Transition Break Size Specified...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-03

    .... SUPPLEMENTARY INFORMATION: On June 28, 2010 (75 FR 36700), the NRC published a notice of issuance and... COMMISSION Draft Regulatory Guide, DG-1216,''Plant-Specific Applicability of Transition Break Size Specified... . The Draft Regulatory Guide, DG-1216, ``Plant- Specific Applicability of Transition Break...

  10. 78 FR 46905 - Tobacco Transition Program; Final Assessment Procedures

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-02

    ... information about the final quarterly assessments for the Tobacco Transition Program (TTP). Through the Tobacco Transition Payment Program (TTPP), which is part of the TTP, eligible former tobacco quota holders..., 2014. Also, as specified in the TTP regulations, the final two calendar quarterly payments are both...

  11. 77 FR 37346 - Export Control Reform Transition Plan

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-21

    ... will transition from the jurisdiction of the Department of State to the Department of Commerce. The... transition of items to the jurisdiction of the Department of Commerce. The revisions ] to this rule are part of the Department of State's retrospective plan under E.O. 13563 completed on August 17, 2011....

  12. 75 FR 27165 - Conservation Reserve Program; Transition Incentives Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-14

    ...The Commodity Credit Corporation (CCC) is amending the Conservation Reserve Program (CRP) regulations to add provisions for incentives to retired or retiring owners or operators to transition land enrolled in CRP to a beginning or socially disadvantaged farmer or rancher for production. The Transition Incentives Program involves new and mandatory provisions for CRP authorized by the Food,......

  13. 78 FR 16675 - First Technology Transitions; Policy Task Force Workshop

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-18

    ... COMMISSION First Technology Transitions; Policy Task Force Workshop AGENCY: Federal Communications Commission... Policy Task Force, at (202) 418-1438 or rebekah.goodheart@fcc.gov . SUPPLEMENTARY INFORMATION: The FCC... Policy Task Force, see Ex Parte Meetings with the Technology Transitions Policy Task Force, Public...

  14. 76 FR 27168 - Airmen Transition to Experimental or Unfamiliar Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-10

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF TRANSPORTATION Federal Aviation Administration Airmen Transition to Experimental or Unfamiliar Airplanes AGENCY: Federal... accomplish the test program using AC 90-89. This AC may also be useful in planning the transition to...

  15. A Two-Photon E1-M1 Optical Clock

    NASA Astrophysics Data System (ADS)

    Alden, Emily A.

    Innovations in precision frequency measurement advance popular technologies such as global positioning systems (GPS), permit the testing of fundamental physics constants, and have the potential to measure local variations in gravity. Driving optical transitions for frequency measurement using an E1-M1 excitation scheme in a hot mercury (Hg) vapor cell is viable and could be the basis of a portable optical frequency standard with comparable accuracy to the most precise atomic clocks in the world. This dissertation explores the fundamental physics of the new E1-M1 method of high-precision frequency measurement in an optical, atomic clock and describes the construction of a high-power E1-M1 clock laser. The value of this new scheme compared to existing optical frequency standards is the simplicity and portability of the experimental setup. Such an optical frequency standard would permit frequency measurement in far-flung locations on earth and in space. Analysis of both the E1-M1 optical transition and thermal properties of the candidate clock atoms are presented. These models allow a stability estimate of an E1-M1 optical clock and recommend experimental settings to optimize the standard. The experimental work that has been performed in pursuit of observing the E1-M1 clock transition in Hg is also discussed. An optical clock operates by making a precision frequency measurement of a laser that has been brought into resonance with a clock atom's oscillator: a high quality atomic level transition. Group II type atoms, such as Hg, have the 1S0-3P0 transition that is an ideal basis for a clock. The E1-M1 excitation is performed by driving the two-photon allowed transition 1S0-3P1-3P0. This is in contrast to the single-photon E1 transition used in other systems. Single-photon schemes must use ultracold atoms to reduce atomic motion to attain high levels of accuracy. Driving the clock transition with a pair of degenerate counter-propagating photons in an E1-M1 scheme

  16. Energy surface and minimum energy paths for Fréedericksz transitions in bistable cholesteric liquid crystals

    NASA Astrophysics Data System (ADS)

    Ivanov, A. V.; Bessarab, P. F.; Aksenova, E. V.; Romanov, V. P.; Uzdin, V. M.

    2016-04-01

    The multidimensional energy surface of a cholesteric liquid crystal in a planar cell is investigated as a function of spherical coordinates determining the director orientation. Minima on the energy surface correspond to the stable states with particular director distribution. External electric and magnetic fields deform the energy surface and positions of minima. It can lead to the transitions between states, known as the Fréedericksz effect. Transitions can be continuous or discontinuous depending on parameters of the liquid crystal which determine an energy surface. In a case of discontinuous transition when a barrier between stable states is comparable with the thermal energy, the activation transitions may occur, and it leads to the modification of characteristics of the Fréedericksz effect with temperature without explicit temperature dependencies of liquid crystal parameters. A minimum energy path between stable states on the energy surface for the Fréedericksz transition is found using the geodesic nudged elastic band method. Knowledge of this path, which has maximal statistical weight among all other paths, gives the information about a barrier between stable states and configuration of director orientation during the transition. It also allows one to estimate the stability of states with respect to the thermal fluctuations and their lifetime when the system is close to the Fréedericksz transition.

  17. Transitions.

    ERIC Educational Resources Information Center

    Nathanson, Jeanne H., Ed.

    1993-01-01

    This theme issue on transitions for individuals with disabilities contains nine papers discussing transition programs and issues. "Transition Issues for the 1990s," by Michael J. Ward and William D. Halloran, discusses self-determination, school responsibility for transition, continued educational engagement of at-risk students, and service…

  18. 75 FR 70966 - Transit Asset Management (TAM) Pilot Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-19

    ... Federal Transit Administration (FTA) is soliciting proposals from public transportation providers, state... be replicated to improve transportation asset management at the nation's rail and bus public transportation agencies. Public sector applicants may partner with asset management system suppliers; however...

  19. Transitions.

    ERIC Educational Resources Information Center

    Field, David; And Others

    1992-01-01

    Includes four articles: "Career Aspirations" (Field); "Making the Transition to a New Curriculum" (Baker, Householder); "How about a 'Work to School' Transition?" (Glasberg); and "Technological Improvisation: Bringing CNC to Woodworking" (Charles, McDuffie). (SK)

  20. 77 FR 38556 - Export Control Reform Transition Plan

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-28

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF STATE 22 CFR Parts 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, and 130 ] Export Control Reform Transition Plan Correction In proposed rule document 2012-15070 appearing on pages 37346-37349 in the issue of Thursday,...

  1. Transition.

    ERIC Educational Resources Information Center

    Thompson, Sandy, Ed.; And Others

    1990-01-01

    This "feature issue" focuses on transition from school to adult life for persons with disabilities. Included are "success stories," brief program descriptions, and a list of resources. Individual articles include the following titles and authors: "Transition: An Energizing Concept" (Paul Bates); "Transition Issues for the 1990s" (William Halloran…

  2. Energies and E1, M1, E2, M2 transition rates for states of the 2s{sup 2}2p, 2s2p{sup 2}, and 2p{sup 3} configurations in boron-like ions between N III and Zn XXVI

    SciTech Connect

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

    2012-07-15

    Energies, E1, M1, E2, M2 transition rates, line strengths, oscillator strengths, and lifetimes from relativistic configuration interaction calculations are reported for the states of the (1s{sup 2})2s{sup 2}2p, 2s2p{sup 2}, and 2p{sup 3} configurations in all boron-like ions between N III and Zn XXVI. Valence, core-valence, and core-core correlation effects were accounted for through single-double multireference (SD-MR) expansions to increasing sets of active orbitals.

  3. 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

    NASA Astrophysics Data System (ADS)

    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].

  4. 78 FR 31542 - FCC Technology Transitions Policy Task Force Seeks Comment on Potential Trials

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-24

    ...) or (2) by filing paper copies. See Electronic Filing of Documents in Rulemaking Proceedings, 63 FR... FR 78384, 76 FR 76623, 77 FR 26987, December 8, 2011, December 16, 2011, May 8, 2012. The... filing paper copies. See Electronic Filing of Documents in Rulemaking Proceedings, 63 FR 24121...

  5. 26 CFR 1.367(e)-1 - Distributions described in section 367(e)(1).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 4 2013-04-01 2013-04-01 false Distributions described in section 367(e)(1). 1.367(e)-1 Section 1.367(e)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Effects on Corporation § 1.367(e)-1 Distributions described in section 367(e)(1)....

  6. Gene coding for the E1 endoglucanase

    DOEpatents

    Thomas, Steven R.; Laymon, Robert A.; Himmel, Michael E.

    1996-01-01

    The gene encoding Acidothermus cellulolyticus E1 endoglucanase is cloned and expressed in heterologous microorganisms. A new modified E1 endoglucanase enzyme is produced along with variants of the gene and enzyme. The E1 endoglucanase is useful for hydrolyzing cellulose to sugars for simultaneous or later fermentation into alcohol.

  7. Gene coding for the E1 endoglucanase

    DOEpatents

    Thomas, S.R.; Laymon, R.A.; Himmel, M.E.

    1996-07-16

    The gene encoding Acidothermus cellulolyticus E1 endoglucanase is cloned and expressed in heterologous microorganisms. A new modified E1 endoglucanase enzyme is produced along with variants of the gene and enzyme. The E1 endoglucanase is useful for hydrolyzing cellulose to sugars for simultaneous or later fermentation into alcohol. 6 figs.

  8. A Conserved Regulatory Module at the C Terminus of the Papillomavirus E1 Helicase Domain Controls E1 Helicase Assembly

    PubMed Central

    Schuck, Stephen

    2014-01-01

    ABSTRACT Viruses frequently combine multiple activities into one polypeptide to conserve coding capacity. This strategy creates regulatory challenges to ascertain that the combined activities are compatible and do not interfere with each other. The papillomavirus E1 protein, as many other helicases, has the intrinsic ability to form hexamers and double hexamers (DH) that serve as the replicative DNA helicase. However, E1 also has the more unusual ability to generate local melting by forming a double trimer (DT) complex that can untwist the double-stranded origin of DNA replication (ori) DNA in preparation for DH formation. Here we describe a switching mechanism that allows the papillomavirus E1 protein to form these two different kinds of oligomers and to transition between them. We show that a conserved regulatory module attached to the E1 helicase domain blocks hexamer and DH formation and promotes DT formation. In the presence of the appropriate trigger, the inhibitory effect of the regulatory module is relieved and the transition to DH formation can occur. IMPORTANCE This study provides a mechanistic understanding into how a multifunctional viral polypeptide can provide different, seemingly incompatible activities. A conserved regulatory sequence module attached to the AAA+ helicase domain in the papillomavirus E1 protein allows the formation of different oligomers with different biochemical activities. PMID:25378487

  9. Energies and E1, M1, E2, and M2 transition rates for states of the 2s{sup 2}2p{sup 3}, 2s2p{sup 4}, and 2p{sup 5} configurations in nitrogen-like ions between F III and Kr XXX

    SciTech Connect

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

    2014-03-15

    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 (1s{sup 2})2s{sup 2}2p{sup 3},2s2p{sup 4}, and 2p{sup 5} 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{sup −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 and A 385 (2002) 716].

  10. 26 CFR 1.367(e)-1 - Distributions described in section 367(e)(1).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 4 2010-04-01 2010-04-01 false Distributions described in section 367(e)(1). 1.367(e)-1 Section 1.367(e)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Effects on Corporation § 1.367(e)-1 Distributions described in section 367(e)(1). (a) Purpose and...

  11. 75 FR 53521 - Procedures for the Handling of Retaliation Complaints Under the National Transit Systems Security...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-31

    ... (Secretary's Order 5-2007, 72 FR 31160 (June 5, 2007)). Hearings on determinations by the Assistant Secretary... decided by the ARB (Secretary's Order 1-2010 (Jan. 15, 2010), 75 FR 3924-01 (Jan. 25, 2010)). Subpart A.... 1142 and 49 U.S.C. 20109; Secretary of Labor's Order No. 5-2007, 72 FR 31160 (June 5, 2007);...

  12. 75 FR 1632 - Public Housing Assessment System (PHAS): Asset Management Transition Year 2 Information

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-12

    ..., 1998 (63 FR 46596). Prior to 1998, PHAs were evaluated by HUD under the Public Housing Management... remedial action. By final rule published on January 11, 2000 (65 FR 1712), HUD amended the PHAS regulations... Operating Fund Program are found at 24 CFR part 990, were published on September 19, 2005 (70 FR...

  13. 77 FR 71287 - CNMI-Only Transitional Worker Numerical Limitation for Fiscal Year 2013

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-30

    ... includes CW-1 for principal workers and CW-2 for spouses and minor children). See 76 FR 55502 (Sept. 7... economic conditions. See 76 FR at 55510. As such, DHS opted to publish any future annual numerical... phase-in of Federal immigration law. See 76 FR at 55510. The numerical limitations set forth in...

  14. 75 FR 12962 - Transitional Safe Harbor Protection for Treatment by the Federal Deposit Insurance Corporation as...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-18

    ..., 2010 (74 FR 59066) . FOR FURTHER INFORMATION CONTACT: Michael Krimminger, Office of the Chairman, 202... concerns, the FDIC published an Interim Final Rule on November 17, 2010 (74 FR 59066) that addressed... Connection With a Securitization or Participation After March 31, 2010, 75 FR 934, January 7, 2010)....

  15. 76 FR 15859 - Tobacco Transition Payment Program; Cigar and Cigarette Per Unit Assessments

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-22

    ... published December 10, 2010 (75 FR 76921-76923), explaining this policy regarding Step A and clarifying the.... The final rule implementing TTPP was published on February 10, 2005 (70 FR ] 7007-7014). There is a... was amended by a final rule published in the Federal Register on April 4, 2005 (70 FR...

  16. 75 FR 14330 - Transitional Safe Harbor Protection for Treatment by the Federal Deposit Insurance Corporation as...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-25

    ...) is correcting a final rule that appeared in the Federal Register of March 18, 2010 (75 FR 12962). The... the final rule published in the Federal Register of March 18, 2010 (75 FR 12962), an incorrect date... changes, the interim rule published on November 17, 2009 (74 FR 59066) . 2. On page 12963, the...

  17. 78 FR 18725 - Homeless Emergency Assistance and Rapid Transition to Housing: Rural Housing Stability Assistance...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-27

    ... with a proposed rule, which published on April 20, 2010 (75 FR 20541) and titled ``Defining Homeless...,'' was published on December 5, 2011 (76 FR 75994). On December 5, 2011, HUD also published an interim rule, titled the ``Emergency Solutions Grants Rule.'' (See 76 FR 75954.) This interim rule...

  18. 77 FR 45421 - Homeless Emergency Assistance and Rapid Transition to Housing: Continuum of Care Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-31

    ... proposed rule, entitled ``Defining Homeless'' on April 20, 2010 (75 FR 20541), which was followed by a final rule that was published on December 5, 2011 (76 FR 75994). The Defining Homeless rule clarified... Emergency Solutions Grants program (76 FR 75954). This interim rule established the program requirements...

  19. 75 FR 62695 - Physical Protection of Irradiated Reactor Fuel in Transit

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-13

    ..., 1979 (44 FR 34466), NRC published an interim final rule in the Federal Register that established its... 3, 1980 (45 FR 37399). The current Sec. 73.37 has changed little since its promulgation in 1980... petition and a request for public comment on September 13, 1999 (64 FR 49410). The Commission review...

  20. 78 FR 29519 - Physical Protection of Irradiated Reactor Fuel in Transit

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-20

    ... Register (44 FR 34466) an interim final rule that established requirements for the physical protection of... June 3, 1980 (45 FR 37399). Section 73.37 has changed little since its promulgation in 1980. The... for public comment a notice of receipt of PRM-73-10 on September 13, 1999 (64 FR 49410). The...

  1. Cosmographic bounds on the cosmological deceleration-acceleration transition redshift in f(R) gravity

    NASA Astrophysics Data System (ADS)

    Capozziello, Salvatore; Farooq, Omer; Luongo, Orlando; Ratra, Bharat

    2014-08-01

    We examine the observational viability of a class of f(R) gravity cosmological models. Particular attention is devoted to constraints from the recent observational determination of the redshift of the cosmological deceleration-acceleration transition. Making use of the fact that the Ricci scalar is a function of redshift z in these models, R =R(z), and so is f(z), we use cosmography to relate a f(z) test function evaluated at higher z to late-time cosmographic bounds. First, we consider a model-independent procedure to build up a numerical f(z) by requiring that at z=0 the corresponding cosmological model reduces to standard ΛCDM. We then infer late-time observational constraints on f(z) in terms of bounds on the Taylor expansion cosmographic coefficients. In doing so we parametrize possible departures from the standard ΛCDM model in terms of a two-parameter logarithmic correction. The physical meaning of the two parameters is also discussed in terms of the post-Newtonian approximation. Second, we provide numerical estimates of the cosmographic series terms by using type Ia supernova apparent magnitude data and Hubble parameter measurements. Finally, we use these estimates to bound the two parameters of the logarithmic correction. We find that the deceleration parameter in our model changes sign at a redshift consistent with what is observed.

  2. Adenovirus E1B 19-kilodalton protein overcomes the cytotoxicity of E1A proteins.

    PubMed Central

    White, E; Cipriani, R; Sabbatini, P; Denton, A

    1991-01-01

    Infection with adenovirus mutants carrying either point mutations or deletions in the coding region for the 19-kDa E1B gene product (19K protein) causes degradation of host cell and viral DNAs (deg phenotype) and enhanced cytopathic effect (cyt phenotype). Therefore, one function of the E1B 19K protein is to protect nuclear DNA integrity and preserve cytoplasmic architecture during productive adenovirus infection. When placed in the background of a virus incapable of expressing a functional E1A gene product, however, E1B 19K gene mutations do not result in the appearance of the cyt and deg phenotypes. This demonstrated that expression of the E1A proteins was responsible for inducing the appearance of the cyt and deg phenotypes. By constructing a panel of viruses possessing E1A mutations spanning each of the three E1A conserved regions in conjunction with E1B 19K gene mutations, we mapped the induction of the cyt and deg phenotypes to the amino-terminal region of E1A. Viruses that fail to express conserved region 3 (amino acids 140 to 185) and/or 2, (amino acids 121 to 185) or nonconserved sequences between conserved regions 2 and 1 of E1A (amino acids 86 to 120) were still capable of inducing cyt and deg. This indicated that activities associated with these regions, such as transactivation and binding to the product of the retinoblastoma susceptibility gene, were dispensable for induction of E1A-dependent cytotoxic effects. In contrast, deletion of sequences in the amino terminus of E1A (amino acids 22 to 107) resulted in extragenic suppression of the cyt and deg phenotypes. Therefore, a function affected by deletion of amino acids 22 to 86 of E1A is responsible for exerting cytotoxic effects in virally infected cells. Furthermore, transient high-level expression of the E1A region using a cytomegalovirus promoter plasmid expression vector was sufficient to induce the cyt and deg phenotypes, demonstrating that E1A expression alone is sufficient to exert these

  3. Identification and characterization of an hnRNP E1 translational silencing motif

    PubMed Central

    Brown, Andrew S.; Mohanty, Bidyut K.; Howe, Philip H.

    2016-01-01

    Non-canonical transforming growth factor β (TGFβ) signaling through protein kinase B (Akt2) induces phosphorylation of heterogeneous nuclear ribonucleoprotein E1 (hnRNP E1) at serine-43 (p-hnRNP E1). This post-translational modification (PTM) of hnRNP E1 promotes its dissociation from a 3′ untranslated region (UTR) nucleic acid regulatory motif, driving epithelial to mesenchymal transition (EMT) and metastasis. We have identified an hnRNP E1 consensus-binding motif and genomically resolved a subset of genes in which it is contained. This study characterizes the binding kinetics of the consensus-binding motif and hnRNP E1, its various K-homology (KH) domains and p-hnRNP E1. Levels of p-hnRNP E1 are highly upregulated in metastatic cancer cells and low in normal epithelial tissue. We show a correlation between this PTM and levels of Akt2 and its activated form, phosphorylated serine-474 (p-Akt2). Using cellular progression models of metastasis, we observed a signature high level of Akt2, p-Akt2 and p-hnRNP E1 protein expression, coupled to a significantly reduced level of total hnRNP E1 in metastatic cells. Genes that are translationally silenced by hnRNP E1 and expressed by its dissociation are highly implicated in the progression of EMT and metastasis. This study provides insight into a non-canonical TGFβ signaling cascade that is responsible for inducing EMT by aberrant expression of hnRNP E1 silenced targets. The relevance of this system in metastatic progression is clearly shown in cellular models by the high abundance of p-hnRNP E1 and low levels of hnRNP E1. New insights provided by the resolution of this molecular mechanism provide targets for therapeutic intervention and give further insight into the role of the TGFβ microenvironment. PMID:27067543

  4. 76 FR 69119 - Commonwealth of the Northern Mariana Islands Transitional Worker Classification: Correction

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-08

    ..., published in the Federal Register on September 7, 2011 at 76 FR 55502, DHS intended to revise only the.... 107-296, 116 Stat. 2135 (6 U.S.C. 1 et seq.), E.O. 12356, 47 FR 14874, 15557, 3 CFR, 1982 Comp., p... Classification: Correction AGENCY: U.S. Citizenship and Immigration Services, DHS. ACTION: Final rule;...

  5. 76 FR 1376 - Physical Protection of Irradiated Reactor Fuel in Transit Extension of Comment Period

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-10

    ...: Extension of comment period. SUMMARY: On October 13, 2010 (75 FR 62695), the U.S. Nuclear Regulatory... was published on October 13, 2010 (75 FR 62695) and the public comment period was scheduled to expire... nuclear fuel'' (SNF) are used interchangeably). This proposed rule would establish generically...

  6. 76 FR 19710 - Tobacco Transition Payment Program; Cigar and Cigarette Per Unit Assessments; Correction

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-08

    ... 0560-AI12 and include the volume, date, and page number (March 22, 2011, 76 FR 15859-15864) of the..., 2011, CCC published a Request for Comments (76 FR 15859-15864) requesting comments about the... Payment Program; Cigar and Cigarette Per Unit Assessments; Correction AGENCY: Commodity Credit...

  7. 77 FR 7080 - Changes To Implement Transitional Program for Covered Business Method Patents

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-10

    ... Flexibility Analysis for Patent-Related Regulations, 71 FR 67109 (Nov. 20, 2006), 1313 Off. Gaz. Pat. Office... Regulations, 71 FR at 67112 (Nov 20, 2006), 1313 Off. Gaz. Pat. Office at 63 (Dec. 12, 2006). As discussed... Covered Business Method Patents AGENCY: United States Patent and Trademark Office, Commerce....

  8. 76 FR 31639 - Comment Request for Information Collection for Enhanced Transitional Jobs Demonstration, New...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-01

    ... Request for Information Collection for Enhanced Transitional Jobs Demonstration, New Collection AGENCY... the Enhanced Transitional Jobs Demonstration project (ETJD). A copy of the proposed information...@dol.gov . SUPPLEMENTARY INFORMATION: I. Background In applying for the Enhanced Transitional...

  9. 76 FR 44394 - Public Transportation on Indian Reservations Program; Tribal Transit Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-25

    ... Federal Transit Administration Public Transportation on Indian Reservations Program; Tribal Transit... availability of $15,075,000 in funding provided by the Public Transportation on Indian Reservations Program... establishing the Public Transportation on Indian Reservations Program (Tribal Transit Program) (TTP)....

  10. 77 FR 63920 - New Jersey Transit Corporation-Acquisition Exemption-Norfolk Southern Railway Company

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-17

    ... Surface Transportation Board New Jersey Transit Corporation--Acquisition Exemption--Norfolk Southern Railway Company The New Jersey Transit Corporation (NJ Transit), a noncarrier, has filed a verified notice..., N.J., from milepost 8.616 to milepost 9.905 (the Line). NJ Transit states that, under the...

  11. 78 FR 10253 - Federal Fiscal Year 2013 Annual List of Certifications and Assurances for Federal Transit...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-13

    ..., Allocations, Program Information and Interim Guidance,'' 77 FR 63670, October 16, 2012 (FTA FY 2013... marijuana use for medical or recreational purposes, your Applicant must comply with Federal (not...

  12. 76 FR 59495 - Presidential Determination on Major Illicit Drug Transit or Major Illicit Drug Producing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-26

    ... Sig.) THE WHITE HOUSE, Washington, September 15, 2011 [FR Doc. 2011-24887 Filed 9-23-11; 11:15 am... necessarily an adverse reflection of its government's counternarcotics efforts or level of cooperation...

  13. 78 FR 36431 - Safety Zone; Inbound Transit of M/V TEAL, Savannah River; Savannah, GA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-18

    ... DHS Department of Homeland Security FR Federal Register NPRM Notice of Proposed Rulemaking STS Ship to... River to the Georgia Ports Authority, Garden City Terminal Container Berth 8 (CB8). This safety...

  14. Prostaglandin E1 in hand angiography

    SciTech Connect

    Levy, J.M.; Joseph, R.B.; Bodell, L.S.; Nykamp, P.W.; Hessel, S.J.

    1983-11-01

    Prostaglandin E1 (PG1) is a rapid, potent vasodilator which, when infused into the arterial system in low doses by bolus injection, has no significant systemic effects and has a relatively long duration of action. Sixty-three hand angiograms were done on 55 patients, comparing PGE1 to tolazoline and to angiograms done with no vasodilation. There was no significant difference between PGE1 and tolazoline in digital artery opacification; however, venous opacification was very significantly better with PGE1. PGE1 should be a drug of choice in hand angiography.

  15. Origin of replication of colicin E1 plasmid DNA.

    PubMed Central

    Tomizawa, J I; Ohmori, H; Bird, R E

    1977-01-01

    Cleavage maps of colicin E1 plasmid DNA and its smaller derivative, pNT1 DNA, were constructed by using restriction endonucleases. The nucleotide sequence of a region that contains the orgin of replication was determined. The site of the nucleotide from which DNA replication is initiated was determined with 6S L-fragments, the DNA fragment first made on colicin E1 plasmid DNA. The fragments were labeled with [gamma-32P]ATP and polynucleotide 5'-hydroxyl-kinase (ATP:5'-dephosphopolynucleotide 5'-phosphotransferase, EC 2.7.1.78) at the 5'-OH groups which were uncovered by alkali treatment. The site is one of three consecutive nucleotides, dA, dA, and dC, located at a unique position. One or a few rA residues were found to be attached to some of the DNA molecules. The transition from the primer RNA to DNA occurs in a region consisting of a segment of five A residues. Both sides of this segment are rich in G and C. Images PMID:325558

  16. 77 FR 1779 - Meeting and Webinar on Integrated Dynamic Transit Operations; Notice of Public Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-11

    ... for Mobility program is to improve public transportation by increasing transit productivity... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF TRANSPORTATION Meeting and Webinar on Integrated Dynamic Transit Operations; Notice of Public Meeting AGENCY:...

  17. 75 FR 14243 - Pipeline Safety: Girth Weld Quality Issues Due to Improper Transitioning, Misalignment, and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-24

    ... Improper Transitioning, Misalignment, and Welding Practices of Large Diameter Line Pipe AGENCY: Pipeline... girth weld failures due to welding quality issues. Misalignment during welding of large diameter line... bevel and wall thickness transitions, and other improper welding practices that occurred...

  18. 75 FR 38506 - Office of Postsecondary Education: Overview Information; Coordinating Center for Transition and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-02

    ... Postsecondary Programs for Students With Intellectual Disabilities; Notice Inviting Applications for New Awards... transition and postsecondary programs for students with intellectual disabilities, including institutions that have grants authorized under the Transition Programs for Students with Intellectual...

  19. 77 FR 52131 - FY 2012 Discretionary Funding Opportunity: Paul S. Sarbanes Transit in Parks Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-28

    ... agreements, transit-related intelligent transportation systems, relocation assistance, acquiring replacement... qualifying alternative transportation systems, including the development of related...

  20. 77 FR 28421 - Supplemental Draft Environmental Impact Statement for the Central Corridor Light Rail Transit...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-14

    ... Light Rail Transit Project, Minneapolis and Saint Paul, MN AGENCY: Federal Transit Administration (FTA... prepare a Supplemental Draft Environmental Impact Statement (SDEIS) for the Central Corridor Light Rail... miles long and consists of 23 Central Corridor Light Rail Transit (LRT) stations. The SDEIS...

  1. 77 FR 14465 - Public Transportation on Indian Reservations Program; Tribal Transit Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-09

    ... Federal Transit Administration Public Transportation on Indian Reservations Program; Tribal Transit... Surface and Air Transportation Programs Extension Act of 2011, Public Law No.112-30 continues the... establishing the Public Transportation on Indian Reservations Program (Tribal Transit Program or TTP)....

  2. 76 FR 60587 - Environmental Impact Statement; North Corridor Transit Project, Seattle (WA) Metropolitan Area...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-29

    ... County. ] Alternatives Analysis and Results The North Corridor Transit Project Alternatives Analysis (AA... for transit projects seeking New Starts funding (Title 49 United States Code 5309.) The AA report also... Supplemental EIS on the Regional Transit Long-Range Plan (June 2005). The North Corridor AA considered...

  3. 78 FR 13748 - Environmental Impact Statement for the East San Fernando Valley Transit Corridor Project, Los...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-28

    ...The Federal Transit Administration (FTA) and the Los Angeles County Metropolitan Transportation Authority (LACMTA) are issuing this Notice of Intent (NOI) to advise other agencies and the public that they will jointly prepare an Environmental Impact Statement (EIS) for proposed transit improvements in the East San Fernando Valley Transit Project Corridor in Los Angeles County, California. The......

  4. 75 FR 20541 - Homeless Emergency Assistance and Rapid Transition to Housing: Defining “Homeless”

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-20

    ... the Emergency Solutions Grant Program and the Rural Housing Stability Program. The HEARTH Act also... Rural Housing Stability program replaces the Rural Homelessness Grant program. The HEARTH Act also... the proposal by name and docket number (FR-5333-P-01) and must be sent to: HUD Desk Officer, Office...

  5. 76 FR 17629 - Applications for New Awards; Transition to Teaching Grant Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-30

    ... December 15, 2010 (75 FR 78486). For FY 2011 and any subsequent year in which we make awards from the list... Science, Technology, Engineering, and Mathematics (STEM) Education. Projects that are designed to address... workforce. According to the U.S. Department of Education, Institute of Education Sciences, nearly...

  6. 77 FR 58915 - Presidential Determination on Major Illicit Drug Transit or Major Illicit Drug Producing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-24

    ... Register. (Presidential Sig.) THE WHITE HOUSE, Washington, September 14, 2012. [FR Doc. 2012-23640 Filed 9..., Dominican Republic, Ecuador, El Salvador, Guatemala, Haiti, Honduras, India, Jamaica, Laos, Mexico... Nations Office on Drugs and Crime (UNODC) estimate that cultivation in Helmand decreased between 35 and...

  7. 78 FR 58855 - Presidential Determination on Major Drug Transit or Major Illicit Drug Producing Countries for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-25

    ... WHITE HOUSE, Washington, September 13, 2013. [FR Doc. 2013-23433 Filed 9-24-13; 8:45 am] Billing code..., Honduras, India, Jamaica, Laos, Mexico, Nicaragua, Pakistan, Panama, Peru, and Venezuela. A country's... citizen safety by fostering a wide range of crime prevention programs. Although the problems are...

  8. 77 FR 64120 - Agency Information Collection Activities: Petition for CNMI-Only Nonimmigrant Transition Worker...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-18

    ... Register on August 3, 2012, at 77 FR 46446, allowing for a 60-day public comment period. USCIS did receive... via email at oira_submission@omb.eop.gov and via the Federal eRulemaking Portal Web site at http://www... submissions will be posted, without change, to the Federal eRulemaking Portal at...

  9. 75 FR 60494 - Notice of Proposed Guidance and Request for Comment on the Federal Transit Administration's...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-30

    ... Privacy Act Statement in the Federal Register published April 11, 2000, (65 FR 19477), or you may visit... (TEAM system), the development of pre-applications or white papers, the development of formal... (MPR) in TEAM and clarifies ] the development of Quarterly Narrative Reports. Section 4 also...

  10. 76 FR 75994 - Homeless Emergency Assistance and Rapid Transition to Housing: Defining “Homeless”

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-05

    .... The April 2010 Proposed Rule On April 20, 2010, HUD published a proposed rule (75 FR 20541) to... statutory language of the definition in section 103 of the McKinney- Vento Act, as amended by the HEARTH Act... consistent with HUD's longstanding interpretation of the statutory language ``lacks a fixed, regular...

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

    PubMed Central

    Krömmelbein, Natascha; Wiebusch, Lüder; Schiedner, Gudrun; Büscher, Nicole; Sauer, Caroline; Florin, Luise; Sehn, Elisabeth; Wolfrum, Uwe; Plachter, Bodo

    2016-01-01

    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. PMID:26848680

  12. 75 FR 5172 - Solicitation of Nominations for Members of the Transit Rail Advisory Committee for Safety

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-01

    ..., transit agencies, rider advocacy groups, State safety oversight agencies, and industry associations... interested in keeping TRACS free of individuals who currently are registered Federal lobbyists. The...

  13. 75 FR 27114 - Public Transportation on Indian Reservations Program; Tribal Transit Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-13

    ... Federal Transit Administration Public Transportation on Indian Reservations Program; Tribal Transit... availability of $15,074,963 million in funding provided by the Public Transportation on Indian Reservations.... Overview Section 3013 of SAFETEA-LU, amended 49 U.S.C. 5311(c) by establishing the Public Transportation...

  14. 77 FR 5876 - Notice of Meeting of the Transit Rail Advisory Committee for Safety (TRACS)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-06

    ... Transit Administrator on matters relating to the safety of public transportation systems. DATES: The TRACS... Secretary and the Federal Transit Administrator on matters pertaining to the safety of public transportation... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF...

  15. 78 FR 28285 - Notice of Meeting of the Transit Rail Advisory Committee for Safety (TRACS)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-14

    ... Transit Administrator on matters relating to the safety of public transportation systems. DATES: The TRACS... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF TRANSPORTATION... public meeting of the Transit Rail Advisory Committee for Safety (TRACS). TRACS is a Federal...

  16. 75 FR 9343 - Nomenclature Change Relating to the Network Distribution Center Transition

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-02

    ... 111 and 121 Nomenclature Change Relating to the Network Distribution Center Transition AGENCY: Postal... to the ongoing transition of USPS bulk mail centers (BMC) to network distribution centers (NDC), by... Gambhir at 202-268-6256. SUPPLEMENTARY INFORMATION: Background: The BMC network was established in...

  17. 75 FR 53639 - Best Practices for Transit, Transshipment, and Reexport of Items Subject to the Export...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-01

    ... Bureau of Industry and Security Best Practices for Transit, Transshipment, and Reexport of Items Subject... public comments on a set of proposed ``Best Practices for Transit, Transshipment, and Reexport of Items... dialogue with industry regarding new transshipment principles and best practices that complement...

  18. 75 FR 67751 - Medicare Program: Community-Based Care Transitions Program (CCTP) Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-03

    ... HUMAN SERVICES Centers for Medicare & Medicaid Services Medicare Program: Community-Based Care... about the upcoming Community-based Care Transitions Program. The meeting is open to the public, but... will be posted on the CMS Care Transitions Web site at...

  19. 78 FR 27284 - Public Transportation on Indian Reservations Program; Tribal Transit Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-09

    ...This Notice accomplishes several purposes. First, the U.S. Department of Transportation (DOT), Federal Transit Administration (FTA) summarizes and responds to written comments FTA received in response to a November 9, 2012, Federal Register Notice regarding proposed grant program provisions for this modified program. Second, this Notice establishes the framework for the Tribal Transit Program,......

  20. In Vitro and In Vivo Biology of Recombinant Adenovirus Vectors with E1, E1/E2A, or E1/E4 Deleted

    PubMed Central

    Lusky, M.; Christ, M.; Rittner, K.; Dieterle, A.; Dreyer, D.; Mourot, B.; Schultz, H.; Stoeckel, F.; Pavirani, A.; Mehtali, M.

    1998-01-01

    Isogenic, E3-deleted adenovirus vectors defective in E1, E1 and E2A, or E1 and E4 were generated in complementation cell lines expressing E1, E1 and E2A, or E1 and E4 and characterized in vitro and in vivo. In the absence of complementation, deletion of both E1 and E2A completely abolished expression of early and late viral genes, while deletion of E1 and E4 impaired expression of viral genes, although at a lower level than the E1/E2A deletion. The in vivo persistence of these three types of vectors was monitored in selected strains of mice with viral genomes devoid of transgenes to exclude any interference by immunogenic transgene-encoded products. Our studies showed no significant differences among the vectors in the short-term maintenance and long-term (4-month) persistence of viral DNA in liver and lung cells of immunocompetent and immunodeficient mice. Furthermore, all vectors induced similar antibody responses and comparable levels of adenovirus-specific cytotoxic T lymphocytes. These results suggest that in the absence of transgenes, the progressive deletion of the adenovirus genome does not extend the in vivo persistence of the transduced cells and does not reduce the antivirus immune response. In addition, our data confirm that, in the absence of transgene expression, mouse cellular immunity to viral antigens plays a minor role in the progressive elimination of the virus genome. PMID:9499056

  1. 26 CFR 1.167(e)-1 - Change in method.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... to December 30, 2003 (§ 1.167(e)-1 as contained in 26 CFR part 1 edition revised as of April 1, 2003). ... 26 Internal Revenue 2 2010-04-01 2010-04-01 false Change in method. 1.167(e)-1 Section 1.167(e)-1...) INCOME TAXES (CONTINUED) Itemized Deductions for Individuals and Corporations § 1.167(e)-1 Change...

  2. 78 FR 69524 - Preparation of an Environmental Impact Statement for High Capacity Transit Improvements for the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-19

    ... Indianapolis Metropolitan Planning Organization (Indianapolis MPO) and Indianapolis Public Transportation... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF TRANSPORTATION... Counties of Marion and Hamilton AGENCY: Federal Transit Administration, U.S. Department of...

  3. 75 FR 37771 - Office of Postsecondary Education; Overview Information; Transition Programs for Students with...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-30

    ... Intellectual Disabilities Into Higher Education (TPSID)--Model Comprehensive Transition and Postsecondary Programs for Students With Intellectual Disabilities; Notice Inviting Applications for New Awards for... and postsecondary programs for students with intellectual disabilities. Priorities: This...

  4. Enhanced spin-dependent parity-nonconservation effect in the 7 s 1/2 2S →6 d 5/2 2D transition in Fr: A possibility for unambiguous detection of the nuclear anapole moment

    NASA Astrophysics Data System (ADS)

    Sahoo, B. K.; Aoki, T.; Das, B. P.; Sakemi, Y.

    2016-03-01

    Employing the relativistic coupled-cluster method, comparative studies of the parity nonconserving electric dipole amplitudes for the 7 s 1/2 2S →6 d 5/2 2D transitions in 210Fr and 211Fr isotopes have been carried out. It is found that these transition amplitudes, sensitive only to the nuclear spin-dependent effects, are enhanced substantially owing to the very large contributions from the electron core-polarization effects in Fr. This translates to a relatively large and, in principle, measurable induced light shift, which would be a signature of nuclear spin-dependent parity nonconservation that is dominated by the nuclear anapole moment in a heavy atom like Fr. A plausible scheme to measure this quantity using the Cyclotron and Radioisotope Center (CYRIC) facility at Tohoku University has been outlined.

  5. CYP2E1 and Oxidative Liver Injury by Alcohol

    PubMed Central

    Lu, Yongke; Cederbaum, Arthur I.

    2008-01-01

    Ethanol-induced oxidative stress appears to play a major role in mechanisms by which ethanol causes liver injury. Many pathways have been suggested to contribute to the ability of ethanol to induce a state of oxidative stress. One central pathway appears to be the induction of cytochrome P450 2E1 (CYP2E1) by ethanol. CYP2E1 metabolizes and activates many toxicological substrates, including ethanol, to more reactive, toxic products. Levels of CYP2E1 are elevated under a variety of physiological and pathophysiological conditions, and after acute and chronic alcohol treatment. CYP2E1 is also an effective generator of reactive oxygen species such as the superoxide anion radical and hydrogen peroxide, and in the presence of iron catalysts, produces powerful oxidants such as the hydroxyl radical. This Review Article summarizes some of the biochemical and toxicological properties of CYP2E1, and briefly describes the use of cell lines developed to constitutively express CYP2E1 in assessing the actions of CYP2E1. Possible therapeutic implications for treatment of alcoholic liver injury by inhibition of CYP2E1 or CYP2E1-dependent oxidative stress will be discussed, followed by some future directions which may help to understand the actions of CYP2E1 and its role in alcoholic liver injury. PMID:18078827

  6. Activation of adenovirus 5 E1A transcription by region E1B in transformed primary rat cells.

    PubMed Central

    Jochemsen, A G; Peltenburg, L T; te Pas, M F; de Wit, C M; Bos, J L; van der Eb, A J

    1987-01-01

    The human adenovirus 5 E1A region can immortalize primary cultures of baby rat kidney cells, but requires the presence of the E1B region for complete oncogenic transformation. One of the effects of the E1B region in the transformation process is the activation of E1A expression. We have investigated the mechanism of this stimulation of E1A expression using nuclear run-on assays with nuclei from Ad5 E1A- and Ad5 E1-transformed cells. It was found that E1B enhances E1A at the level of transcription-initiation. This activation is mainly observed when the E1A and E1B regions are integrated simultaneously into the cellular genome and only minimally when these genes are integrated separately, strongly suggesting that a close physical linkage of these regions is essential for the observed effect. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. PMID:2962857

  7. Activation of NF-κB by Human Papillomavirus 16 E1 Limits E1-Dependent Viral Replication through Degradation of E1

    PubMed Central

    Nakahara, Tomomi; Tanaka, Katsuyuki; Ohno, Shin-ichi; Egawa, Nagayasu; Yugawa, Takashi

    2015-01-01

    ABSTRACT NF-κB is a family of transcription factors that regulate gene expression involved in many processes, such as the inflammatory response and cancer progression. Little is known about associations of NF-κB with the human papillomavirus (HPV) life cycle. We have developed a tissue culture system to conditionally induce E1-dependent replication of the human papillomavirus 16 (HPV16) genome in human cervical keratinocytes and found that expression of HPV16 E1, a viral helicase, results in reduction of IκBα and subsequent activation of NF-κB in a manner dependent on helicase activity. Exogenous expression of a degradation-resistant mutant of IκBα, which inhibits the activation of NF-κB, enhanced E1-dependent replication of the viral genome. Wortmannin, a broad inhibitor of phosphoinositide 3-kinases (PI3Ks), and, to a lesser extent, VE-822, an ATR kinase inhibitor, but not KU55933, an ATM kinase inhibitor, suppressed the activation of NF-κB and augmented E1-dependent replication of the HPV16 genome. Interestingly, the enhancement of E1-dependent replication of the viral genome was associated with increased stability of E1 in the presence of wortmannin as well as the IκBα mutant. Collectively, we propose that expression of E1 induces NF-κB activation at least in part through the ATR-dependent DNA damage response and that NF-κB in turn limits E1-dependent replication of HPV16 through degradation of E1, so that E1 and NF-κB may constitute a negative feedback loop. IMPORTANCE A major risk factor in human papillomavirus (HPV)-associated cancers is persistent infection with high-risk HPVs. To eradicate viruses from infected tissue, it is important to understand molecular mechanisms underlying the establishment and maintenance of persistent infection. In this study, we obtained evidence that human papillomavirus 16 (HPV16) E1, a viral DNA helicase essential for amplification of the viral genomes, induces NF-κB activation and that this limits E1-dependent

  8. Optimization of Acidothermus Celluloyticus Endoglucanase (E1) Production in Transgenic Tobacco Plants by Transcriptional, Post-transcription and Post-Translational Modification

    SciTech Connect

    Dai, Ziyu; Hooker, Brian S.; Quesenberry, Ryan D.; Thomas, S. R.

    2005-10-01

    Biochemical characteristics of Acidothermus cellulolyticus endoglucanase (E1) and its physiological effects in transgenic tobacco (Nicotiana tabacum) has been studied previously. In an attempt to obtain a high level of production of intact E1 in transgenic plants, the E1 gene was expressed under the control of strong Mac promoter (a hybrid promoter of manopine synthase promoter and cauliflower mosaic virus 35S promoter enhancer region) or tomato Rubisco small subunit (RbcS-3C) promoter with different 5’ untranslated leader (UTL) sequence and targeted to different subcellular comartmentations with various transit peptides. The expression of E1 protein in transgenic tobacco plants was determined via E1 activity, protein immunobloting, and RNA gel-blotting analyses. Effects of different transit peptides on E1 protein production and its stability were examined in transgenic tobacco plants carrying one of six transgene expression vectors with the same (Mac) promoter and transcription terminator (Tmas). Transgenic tobacco plants with apoplast transit peptide (Mm-apo) had the highest average E1 activity and protein accumulation , while E1 protein was more stable in transgenic plants with no transit peptide (Mm) than others. The E1 expression under tomato RbcS-3C promoter was higher than that under Mac promoter based on the average E1 activity, E1 protein accumulation, and RNA gel-blotting. The E1 expression was increased more than two fold when the 5’-UTL of alfalfa mosaic virus RNA4 gene replaced the UTL of RbcS-3C promoter, while the UTL of alfalfa mosaic virus RNA4 gene was less effective than the UTL of Mac promoter. The optimal combination of promoter, 5’-UTL, and subcellular compartmentation (transit peptide) for E1 protein production in transgenic tobacco plants are discussed.

  9. 77 FR 41801 - Solicitation for a Cooperative Agreement-Transition From Jail to the Community (TJC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-16

    ... National Institute of Corrections Solicitation for a Cooperative Agreement--Transition From Jail to the... for a Cooperative Agreement. SUMMARY: The National Institute of Corrections (NIC) is soliciting proposals from organizations, groups, or individuals interested in entering into a 30-month...

  10. 78 FR 64245 - AG Survey of Transitional Housing Assistance for Victims of Domestic Violence, Dating Violence...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-28

    ... Survey of Transitional Housing Assistance for Victims of Domestic Violence, Dating Violence, Stalking, or... notice. The Department of Justice, Office on Violence Against Women (OVW) will be submitting the... collection. If you have questions concerning the collection, please Cathy Poston, Office on Violence...

  11. 76 FR 207 - Intent To Prepare an Environmental Impact Statement for Proposed Transit Improvements to the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-03

    ... Improvements to the North Red and Purple Lines, Cook County, IL AGENCY: Federal Transit Administration, U.S... Authority (CTA) intend to prepare a Tier 1 Environmental Impact Statement (Tier 1 EIS) for the North Red and... North Red and Purple lines up to a state of good repair from the track structure immediately north...

  12. 75 FR 51523 - Notice of Meeting of the Transit Rail Advisory Committee for Safety (TRACS)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-20

    ... Transit Administrator on matters relating to the safety of public transportation systems. DATES: The TRACS... pertaining to the safety of public transportation systems. TRACS is composed of 21 members representing a... Department of Transportation Richard W. Clark, California Public Utilities Commission Diane Davidson,...

  13. 76 FR 16854 - Notice of Meeting of the Transit Rail Advisory Committee for Safety (TRACS)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-25

    ... Administrator on matters relating to the safety of public transportation systems. DATES: The TRACS meeting will... of the Federal Transit Administration on matters relating to the safety of public transportation... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF...

  14. 78 FR 67212 - Notice of Meeting of the Transit Rail Advisory Committee for Safety (TRACS)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-08

    ... Secretary and the Federal Transit Administrator on matters relating to the safety of public transportation... (FTA) on matters relating to the safety of public transportation systems. TRACS is currently composed... National Public Transportation Safety Plan (4) Review of the Draft Letter Report on Public...

  15. 76 FR 75953 - Homeless Emergency Assistance and Rapid Transition to Housing: Emergency Solutions Grants Program...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-05

    ...The Homeless Emergency Assistance and Rapid Transition to Housing Act of 2009 (HEARTH Act), enacted into law on May 20, 2009, consolidates three of the separate homeless assistance programs administered by HUD under the McKinney-Vento Homeless Assistance Act into a single grant program, and revises the Emergency Shelter Grants program and renames it as the Emergency Solutions Grants (ESG)......

  16. 76 FR 11433 - Federal Transition To Secure Hash Algorithm (SHA)-256

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-02

    ...The Civilian Agency Acquisition Council, and the Defense Acquisition Regulations Council (Councils), are hosting the first of at least two public meetings to start a dialogue with industry and Government agencies about ways for the acquisition community to transition to Secure Hash Algorithm SHA-256. SHA-256 is a cryptographic hash function that is used in digital signatures, and......

  17. 75 FR 18942 - FY 2010 Discretionary Sustainability Funding Opportunity; Transit Investments for Greenhouse Gas...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-13

    ... Investments for Greenhouse Gas and Energy Reduction (TIGGER) Program and Clean Fuels Grant Program, Augmented... clean energy sources that will both enhance the environment through improved air quality and curb our... funds in Fiscal Year (FY) 2010 for the Transit Investments for Greenhouse Gas and Energy...

  18. 75 FR 3956 - Intent To Prepare an Environmental Impact Statement for Proposed Transit Improvements in the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-25

    ... system in Los Angeles County. The proposed project would provide a continuation of the Metro Gold Line... transportation and land use plans. Phase 2 would expand upon the Gold Line Eastside Extension investment and... provide the study area with improved fixed-guideway east-west transit service from the Metro Gold...

  19. 77 FR 55813 - Transition of DOE-ID Public Reading Room

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-11

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Transition of DOE-ID Public Reading Room AGENCY: Idaho Operations Office, Department of Energy. ACTION... Department of Energy Idaho Operations Office Public Reading Room has been relocated to the INL...

  20. 75 FR 67019 - Presidential Determination on Major Illicit Drug Transit or Major Illicit Drug Producing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-01

    ... From the Federal Register Online via the Government Publishing Office #0; #0; #0; Presidential Documents #0; #0; #0;#0;Federal Register / Vol. 75 , No. 210 / Monday, November 1, 2010 / Presidential Documents#0;#0; ] Presidential Determination No. 2011-16 of September 15, 2010 Presidential Determination on Major Illicit Drug Transit or Major Illicit Drug...

  1. 76 FR 71464 - Defense Federal Acquisition Regulation Supplement; Transition to the System for Award Management...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-18

    ... Integrated Acquisition Environment systems to the new System for Award Management architecture. DATES... the IAE to the new System for Award Management (SAM) architecture has begun. Phase One will transition... Representations and Certifications Application (ORCA) to the new SAM architecture. This rule provides the...

  2. 77 FR 47692 - Notice of Transportation Services' Transition From Paper to Electronic Fare Media Comments...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-09

    ...On March 29, 2011, and April 2, 2012, U.S. Department of Transportation's Office of Transportation Services (TRANServe), located within the Office of the Assistant Secretary for Administration, published for public comment Notices of the adoption of a new program distribution methodology for transit benefits. To date, TRANServe has implemented its plan in three of the eight TRANServe Services......

  3. 75 FR 10799 - Transitions Optical, Inc.; Analysis to Aid Public Comment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-09

    ... Transitions Optical, Inc.; Analysis to Aid Public Comment AGENCY: Federal Trade Commission. ACTION: Proposed... prohibiting unfair or deceptive acts or practices or unfair methods of competition. The attached Analysis to... public record for a period of thirty (30) days. The following Analysis to Aid Public Comment...

  4. 76 FR 31354 - Notice of Issuance of Final Determination Concerning the Transit Connect Electric Vehicle

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-31

    ... and Border Protection (``CBP'') has issued a final determination concerning the country of origin of... determination that the United States is the country of origin of the vehicle for purposes of U.S. Government... final determination concerning the country of origin of the Transit Connect Electric Vehicle which...

  5. Evidence for the onset of reflection asymmetry in sup 216 Fr

    SciTech Connect

    Debray, M.E.; Davidson, J.; Davidson, M.; Kreiner, A.J.; Hojman, D.; Santos, D. ); Ahn, K.; Fossan, D.B.; Liang, Y.; Ma, R.; Paul, E.S.; Piel, W.F. Jr.; Xu, N. )

    1990-05-01

    States in doubly odd {sup 216}Fr have been studied using in-beam {alpha}, {gamma}, and {ital e}{sup {minus}} spectroscopy techniques through the {sup 208}Pb({sup 11}B3{ital n}) fusion-evaporation reaction. {sup 216}Fr shows a band structure with interleaved states of alternating parities connected by enhanced {ital B}({ital E}1) transitions. It represents the lowest-mass corner of the region ({ital Z}{ge}87,{ital N}{ge}129) in which this phenomenon is observed.

  6. The nuclear receptor NR2E1/TLX controls senescence

    PubMed Central

    Krusche, Benjamin; Pemberton, Helen; Alonso, Marta M.; Chandler, Hollie; Brookes, Sharon; Parrinello, Simona; Peters, Gordon; Gil, Jesús

    2014-01-01

    The nuclear receptor NR2E1 (also known as TLX or tailless) controls the self-renewal of neural stem cells (NSCs) and has been implied as an oncogene which initiates brain tumours including glioblastomas. Despite NR2E1 regulating targets like p21CIP1 or PTEN we still lack a full explanation for its role in NSC self-renewal and tumorigenesis. We know that Polycomb repressive complexes (PRC) also control stem cell self-renewal and tumorigenesis, but so far, no formal connection has been established between NR2E1 and PRCs. In a screen for transcription factors regulating the expression of the Polycomb protein CBX7, we identified NR2E1 as one of its more prominent regulators. NR2E1 binds at the CBX7 promoter, inducing its expression. Notably CBX7 represses NR2E1 as part of a regulatory loop. Ectopic NR2E1 expression inhibits cellular senescence, extending cellular lifespan in fibroblasts via CBX7-mediated regulation of p16INK4a and direct repression of p21CIP1. In addition NR2E1 expression also counteracts oncogene-induced senescence (OIS). The importance of NR2E1 to restrain senescence is highlighted through the process of knocking down its expression, which causes premature senescence in human fibroblasts and epithelial cells. We also confirmed that NR2E1 regulates CBX7 and restrains senescence in NSCs. Finally, we observed that the expression of NR2E1 directly correlates with that of CBX7 in human glioblastoma multiforme. Overall we identified control of senescence and regulation of Polycomb action as two possible mechanisms that can join those so far invoked to explain the role of NR2E1 in control of NSC self-renewal and cancer. PMID:25328137

  7. Calculation of Radiative Corrections to E1 matrix elements in the Neutral Alkalis

    SciTech Connect

    Sapirstein, J; Cheng, K T

    2004-09-28

    Radiative corrections to E1 matrix elements for ns-np transitions in the alkali metal atoms lithium through francium are evaluated. They are found to be small for the lighter alkalis but significantly larger for the heavier alkalis, and in the case of cesium much larger than the experimental accuracy. The relation of the matrix element calculation to a recent decay rate calculation for hydrogenic ions is discussed, and application of the method to parity nonconservation in cesium is described.

  8. The multiple roles of cyclin E1 in controlling cell cycle progression and cellular morphology of Trypanosoma brucei.

    PubMed

    Gourguechon, Stéphane; Savich, Jason M; Wang, Ching C

    2007-05-11

    Regulation of eukaryotic cell cycle progression requires sequential activation and inactivation of cyclin-dependent kinases. Previous RNA interference (RNAi) experiments in Trypanosoma brucei indicated that cyclin E1, cdc2-related kinase (CRK)1 and CRK2 are involved in regulating G1/S transition, whereas cyclin B2 and CRK3 play a pivotal role in controlling the G2/M checkpoint. To search for potential interactions between the other cyclins and CRKs that may not have been revealed by the RNAi assays, we used the yeast two-hybrid system and an in vitro glutathione-S-transferase pulldown assay and observed interactions between cyclin E1 and CRK1, CRK2 and CRK3. Cyclins E1-E4 are homologues of yeast Pho80 cyclin. But yeast complementation assays indicated that none of them possesses a Pho80-like function. Analysis of cyclin E1+CRK1 and cyclin E1+CRK2 double knockdowns in the procyclic form of T. brucei indicated that the cells were arrested more extensively in the G1 phase beyond the cumulative effect of individual knockdowns. But BrdU incorporation was impaired significantly only in cyclin E1+CRK1-depleted cells, whereas a higher percentage of cyclin E1+CRK2 knockdown cells assumed a grossly elongated posterior end morphology. A double knockdown of cyclin E1 and CRK3 arrested cells in G2/M much more efficiently than if only CRK3 was depleted. Taken together, these data suggest multiple functions of cyclin E1: it forms a complex with CRK1 in promoting G1/S phase transition; it forms a complex with CRK2 in controlling the posterior morphogenesis during G1/S transition; and it forms a complex with CRK3 in promoting passage across the G2/M checkpoint in the trypanosome. PMID:17376478

  9. THE MULTIPLE ROLES OF CYCLIN E1 IN CONTROLLING CELL CYCLE PROGRESSION AND CELLULAR MORPHOLOGY OF TRYPANOSOMA BRUCEI

    PubMed Central

    Gourguechon, Stéphane; Savich, Jason M.; Wang, Ching C.

    2009-01-01

    SUMMARY Regulation of eukaryotic cell cycle progression requires sequential activation and inactivation of cyclin-dependent kinases. Previous RNA interference (RNAi) experiments in Trypanosoma brucei indicated that cyclin E1, cdc2-related kinase (CRK)1 and CRK2 are involved in regulating G1/S transition, whereas cyclin B2 and CRK3 play a pivotal role in controlling the G2/M checkpoint. To search for potential interactions between the other cyclins and CRKs that may not have been revealed by the RNAi assays, we used the yeast two-hybrid system and an in vitro GST pulldown assay and observed interactions between cyclin E1 and CRK1, CRK2 and CRK3. Cyclins E1-E4 are homologues of yeast Pho80 cyclin. But yeast complementation assays indicated that none of them possesses a Pho80-like function. Analysis of cyclin E1+CRK1 and cyclin E1+CRK2 double knockdowns in the procyclic form of T. brucei indicated that the cells were arrested more extensively in the G1 phase beyond the cumulative effect of individual knockdowns. But BrdU incorporation was significantly impaired only in cyclin E1+CRK1 depleted cells, whereas a higher percentage of cyclin E1+CRK2 knockdown cells assumed a grossly elongated posterior end morphology. A double knockdown of cyclin E1 and CRK3 arrested cells in G2/M much more efficiently than if CRK3 was depleted alone. Taken together, these data suggest multiple functions of cyclin E1. It forms a complex with CRK1 in promoting G1/S phase transition, with CRK2 in controlling the posterior morphogenesis during G1/S transition and with CRK3 in promoting passage across the G2/M checkpoint in the trypanosome. PMID:17376478

  10. Chemical characteristics for optimizing CYP2E1 inhibition.

    PubMed

    van de Wier, B; Balk, J M; Bast, A; Koek, G H; Haenen, G R M M

    2015-12-01

    Cytochrome P450 2E1 (CYP2E1) expression and activity in the liver is associated with the degree of liver damage in patients with alcoholic steatohepatitis (ASH) as well as non-alcoholic steatohepatitis (NASH). CYP2E1 is known to generate reactive oxygen species, which leads to oxidative stress, one of the hallmarks of both diseases. Apart from ROS, toxic metabolites can be formed by CYP2E1 metabolism, further potentiating liver injury. Therefore, CYP2E1 is implicated in the pathogenesis of ASH and NASH. The aim of this study was to determine the chemical characteristics of compounds that are important to inhibit CYP2E1. To this end, structurally related analogs that differed in their lipophilic, steric and electronic properties were tested. In addition, homologues series of aliphatic primary alcohols, secondary alcohols, aldehydes, ketones and carboxylic acids were tested. It was found that inhibition of the CYP2E1 activity is primarily governed by lipophilicity. The optimal log D7.4 (octanol/water distribution coefficient at pH 7.4) value for inhibition of CYP2E1 was approximately 2.4. In the carboxylic acids series the interaction of the carboxylate group with polar residues lining the CYP2E1 active site also has to be considered. This study sketches the basic prerequisites in the search for inhibitors of CYP2E1, which would strengthen our therapeutic armamentarium against CYP2E1 associated diseases, such as ASH and NASH. PMID:26428356

  11. 26 CFR 1.665(e)-1 - Preceding taxable year.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Preceding taxable year. 1.665(e)-1 Section 1.665... (CONTINUED) INCOME TAXES Treatment of Excess Distributions of Trusts Applicable to Taxable Years Beginning Before January 1, 1969 § 1.665(e)-1 Preceding taxable year. (a) Definition. For purposes of subpart...

  12. 26 CFR 1.665(e)-1 - Preceding taxable year.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 8 2011-04-01 2011-04-01 false Preceding taxable year. 1.665(e)-1 Section 1.665... (CONTINUED) INCOME TAXES (CONTINUED) Treatment of Excess Distributions of Trusts Applicable to Taxable Years Beginning Before January 1, 1969 § 1.665(e)-1 Preceding taxable year. (a) Definition. For purposes...

  13. 26 CFR 1.927(e)-1 - Special sourcing rule.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...(e)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Earned Income of Citizens of United States § 1.927(e)-1 Special sourcing rule. (a) Source rules for related persons—(1) In general. The income of a person described in...

  14. 26 CFR 1.927(e)-1 - Special sourcing rule.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...(e)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Earned Income of Citizens of United States § 1.927(e)-1 Special sourcing rule. (a) Source rules for related persons—(1) In general. The income of a person described in section 482 from...

  15. 26 CFR 1.514(e)-1 - Allocation rules.

    Code of Federal Regulations, 2010 CFR

    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 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Taxation of Business Income of Certain Exempt Organizations §...

  16. 26 CFR 1.642(e)-1 - Depreciation and depletion.

    Code of Federal Regulations, 2010 CFR

    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...

  17. 26 CFR 1.665(e)-1 - Preceding taxable year.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 8 2012-04-01 2012-04-01 false Preceding taxable year. 1.665(e)-1 Section 1.665... (CONTINUED) INCOME TAXES (CONTINUED) Treatment of Excess Distributions of Trusts Applicable to Taxable Years Beginning Before January 1, 1969 § 1.665(e)-1 Preceding taxable year. (a) Definition. For purposes...

  18. 26 CFR 1.665(e)-1 - Preceding taxable year.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 8 2014-04-01 2014-04-01 false Preceding taxable year. 1.665(e)-1 Section 1.665... (CONTINUED) INCOME TAXES (CONTINUED) Treatment of Excess Distributions of Trusts Applicable to Taxable Years Beginning Before January 1, 1969 § 1.665(e)-1 Preceding taxable year. (a) Definition. For purposes...

  19. 78 FR 49600 - Notice of Intent To Prepare an Environmental Impact Statement for the Virginia Beach Transit...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-14

    ...The Federal Transit Administration (FTA) and Hampton Roads Transit (HRT) are planning to prepare an Environmental Impact Statement (EIS) for the Virginia Beach Transit Extension Study (VBTES). The VBTES will examine extending transit service from the eastern terminus of Norfolk's existing Light Rail Transit (LRT) system, ``The Tide,'' at Newtown Road to the Virginia Beach Oceanfront either......

  20. Resolvin E1 Regulates ADP Activation of Human Platelets

    PubMed Central

    Fredman, Gabrielle; Van Dyke, Thomas E.; Serhan, Charles N.

    2010-01-01

    Objective Resolvin E1 (RvE1) is an eicosapentaenoic acid (EPA)-derived specialized pro-resolving mediator generated during resolution of acute inflammation. RvE1 exhibits potent organ-protective actions in vivo and acts on specific cell types including platelets. Here, we investigated the ability of RvE1 to regulate adenosine diphosphate (ADP) activation of platelets via specific receptors because RvE1 reduces platelet aggregation with certain agonists including ADP. Methods and Results RvE1 (0.1nM–100nM) incubated with platelets gave reduced ADP-stimulated P-selectin mobilization (IC50 ~1.6×10−12 M) and polymerized actin content compared to control platelets. RvE1 (1–100nM) did not stimulate or block intracellular calcium mobilization. Using a new P2Y12-β-arrestin-coupled cell system, ADP-activated P2Y12 with an EC50 of 5×10−6 M and RvE1 did not directly stimulate P2Y12 or block ADP-P2Y12 signals. In this system, another eicosanoid LTE4 (EC50 1.3×10−11 M) dose dependently activated P2Y12. When recombinant P2Y12-expressing cells were transiently transfected with an RvE1 receptor, human ChemR23 (present on human platelets), addition of RvE1 (0.1nM-10.0nM) blocked ADP signals (IC50 ~1.6×10−11 M) in P2Y12-ChemR23-expressing cells compared to mock transfections. Conclusions These results demonstrate that RvE1’s regulatory actions (i.e reducing ADP-stimulated P-selectin mobilization and actin polymerization) are hChemR23-dependent. Moreover, they document specific platelet actions of RvE1 selectively engaged with ADP-activated platelets that illuminate a new cellular mechanism and impact of omega-3 EPA that may contribute to both resolution of vascular inflammation and ADP-dependent platelet activation relevant in pathologic cardiovascular events. PMID:20702811

  1. Molecular basis of maple syrup urine disease: Novel mutations at the E1[alpha] locus that impair E1([alpha][sub 2][beta][sub 2]) assembly or decrease steady-state E1[alpha] mRNA levels of branched-chain [alpha]-keto acid dehydrogenase complex

    SciTech Connect

    Chuang, J.L.; Fisher, C.R.; Chuang, D.T.; Cox, R.P. )

    1994-08-01

    The authors report the occurrence of three novel mutations in the E1[alpha] (BCKDHA) locus of the branched-chain [alpha]-keto acid dehydrogenase (BCKAD) complex that cause maple syrup urine disease (MSUD). An 8-bp deletion in exon 7 is present in one allele of a compound-heterozygous patient (GM-649). A single C nucleotide insertion in exon 2 occurs in one allele of an intermediate-MSUD patient (Lo). The second allele of patient Lo carries an A-to-G transition in exon 9 of the E1[alpha] gene. This missense mutation changes Tyr-368 to Cys (Y368C) in the E1[alpha] subunit. Both the 8-bp deletion and the single C insertion generate a downstream nonsense codon. Both mutations appear to be associated with a low abundance of the mutant E1[alpha] mRNA, as determined by allele-specific oligonucleotide probing. Transfection studies strongly suggest that the Y368C substitution in the E1[alpha] subunit impairs its proper assembly with the normal E1[beta]. Unassembled as well as misassembled E1[alpha] and E1[beta] subunits are degraded in the cell. 32 refs., 8 figs.

  2. Establishment of Class e1 Mass Standard of 50 kg

    NASA Astrophysics Data System (ADS)

    Yao, Hong; Wang, Jian; Ding, Jingan; Zhong, Ruilin; Ren, Xiaoping

    Because of the equipment limit, the dissemination of large mass has been realized by a large amount of higher class of 20 kg weights since 1950s in China. But with improvement of the technique and customer's requirements, it is necessary to establish the mass standard of 50 kg weight. In 1990s, mass standard laboratory has set up Class E1 weight sets from 20 kg to 1 mg. To extend the mass capacity up to 50 kg of Class E1, it is not only to produce Class E1 50 kg weight and import a mass comparator, but also need to lift the heavy weight from weight box to balance receptor safely. Up to now, the mass comparator has been installed in Hepingli campus of NIM. Two pieces of Class E1 50 kg weights are determined by combination weighing method. A lifting device has been mounted close to the mass comparator in order to move the 50 kg easily.

  3. Influence of neutron surface on E1 resonance properties

    NASA Astrophysics Data System (ADS)

    Goncharova, N. G.; Tretyakova, T. Yu.; Fedorov, N. A.

    2016-01-01

    The E1 strength distributions in even-even Si isotopes were calculated in the "particle-core coupling" version of the shell model taking into account the fragmentation of the hole configuration among the states of the daughter nuclei. The comparison of calculated strength distributions in different isotopes of the same element shows the peculiarities of a neutron surface influence on the E1 resonance fragmentation.

  4. Impotence evaluated by the use of prostaglandin E1

    SciTech Connect

    Hwang, T.I.; Yang, C.R.; Wang, S.J.; Chang, C.L.; Tzai, T.S.; Chang, C.H.; Wu, H.C.

    1989-06-01

    We screened 80 patients at our hospital for the differential diagnosis of impotence using intracavernous injection of prostaglandin E1 (20 micrograms). The rate of positive response was 78.8 per cent (63 patients). Neither systemic reactions nor priapism occurred. However, a considerable incidence (23.8 per cent, 19 of 80 patients) of tolerable injection pain was encountered. The 133-xenon penile washout study was conducted routinely in impotent men for hemodynamic evaluation of penile vascularity. In 80 patients a positive correlation between the response of intracavernous prostaglandin E1 injection and the result of the washout study was found (r equals 0.381, p less than 0.0002). We selected 14 subjects randomly to receive additional intravenous infusions of prostaglandin E1 (6 ampules, 120 micrograms total) for 3 days, after which another 133-xenon washout study was done. The washout studies before and after intravenous prostaglandin E1 infusion were compared, and 10 patients (71.4 per cent) appeared to obtain improvement in half-time clearance and penile blood flow. However, only 3 patients noticed improvement subjectively. We suggest that prostaglandin E1 could be a desirable alternative for the diagnosis and treatment of impotence.

  5. Oncolytic Replication of E1b-Deleted Adenoviruses

    PubMed Central

    Cheng, Pei-Hsin; Wechman, Stephen L.; McMasters, Kelly M.; Zhou, Heshan Sam

    2015-01-01

    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 viral mRNA export, and cell cycle disruption. PMID:26561828

  6. Oncolytic Replication of E1b-Deleted Adenoviruses.

    PubMed

    Cheng, Pei-Hsin; Wechman, Stephen L; McMasters, Kelly M; Zhou, Heshan Sam

    2015-11-01

    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. PMID:26561828

  7. Optimization of Acidothermus cellulolyticus endoglucanase (E1) production in transgenic tobacco plants by transcriptional, post-transcription and post-translational modification.

    PubMed

    Dai, Ziyu; Hooker, Brian S; Quesenberry, Ryan D; Thomas, Steven R

    2005-10-01

    An attempt was made to obtain a high-level production of intact Acidothermus cellulolyticus endoglucanase (E1) in transgenic tobacco plants. The E1 expression was examined under the control of the constitutive and strong Mac promoter or light-inducible tomato Rubisco small sub-unit (RbcS-3C) promoter with its original or Alfalfa Mosaic Virus (AMV) RNA4 5'-untranslated leader (UTL) and targeted to different sub-cellular compartments via transit peptides. The transit peptides included native E1, endoplasmic reticulum, vacuole, apoplast, and chloroplast. E1 expression and its stability in transgenic plants were determined via E1 activity, protein immunoblotting, and RNA gel-blotting analyses. Effects of sub-cellular compartments on E1 production and its stability were determined in transgenic tobacco plants carrying one of six transgene expression vectors, where the E1 was under the control of Mac promoter, mannopine synthase transcription terminator, and one of the five transit peptides. Transgenic tobacco plants with an apoplastic transit peptide had the highest average E1 activity and protein accumulation, which was about 0.25% of total leaf soluble proteins estimated via E1 specific activity and protein gel blots. Intercellular fluid analyses confirmed that E1 signal peptide functioned properly in tobacco cells to secret E1 protein into the apoplast. By replacing RbcS-3C UTL with AMV RNA4 UTL E1 production was enhanced more than twofold, while it was less effective than the mannopine synthase UTL. It was observed that RbcS-3C promoter was more favorable for E1 expression in transgenic plants than the Mac promoter. E1 activity in dried tobacco seeds stored one year at room temperature was 45% higher than that observed immediately after harvesting, suggesting that E1 protein can be stored at room temperature for a long period. E1 stability in different sub-cellular compartments and the optimal combination of promoter, 5'-UTL, and sub-cellular compartmentation for

  8. The Soybean-Specific Maturity Gene E1 Family of Floral Repressors Controls Night-Break Responses through Down-Regulation of FLOWERING LOCUS T Orthologs1[OPEN

    PubMed Central

    Xu, Meilan; Yamagishi, Noriko; Zhao, Chen; Takeshima, Ryoma; Kasai, Megumi; Watanabe, Satoshi; Kanazawa, Akira; Yoshikawa, Nobuyuki; Liu, Baohui; Yamada, Tetsuya; Abe, Jun

    2015-01-01

    Photoperiodism is a rhythmic change of sensitivity to light, which helps plants to adjust flowering time according to seasonal changes in daylength and to adapt to growing conditions at various latitudes. To reveal the molecular basis of photoperiodism in soybean (Glycine max), a facultative short-day plant, we analyzed the transcriptional profiles of the maturity gene E1 family and two FLOWERING LOCUS T (FT) orthologs (FT2a and FT5a). E1, a repressor for FT2a and FT5a, and its two homologs, E1-like-a (E1La) and E1Lb, exhibited two peaks of expression in long days. Using two different approaches (experiments with transition between light and dark phases and night-break experiments), we revealed that the E1 family genes were expressed only during light periods and that their induction after dawn in long days required a period of light before dusk the previous day. In the cultivar Toyomusume, which lacks the E1 gene, virus-induced silencing of E1La and E1Lb up-regulated the expression of FT2a and FT5a and led to early flowering. Therefore, E1, E1La, and E1Lb function similarly in flowering. Regulation of E1 and E1L expression by light was under the control of E3 and E4, which encode phytochrome A proteins. Our data suggest that phytochrome A-mediated transcriptional induction of E1 and its homologs by light plays a critical role in photoperiodic induction of flowering in soybean. PMID:26134161

  9. The Soybean-Specific Maturity Gene E1 Family of Floral Repressors Controls Night-Break Responses through Down-Regulation of FLOWERING LOCUS T Orthologs.

    PubMed

    Xu, Meilan; Yamagishi, Noriko; Zhao, Chen; Takeshima, Ryoma; Kasai, Megumi; Watanabe, Satoshi; Kanazawa, Akira; Yoshikawa, Nobuyuki; Liu, Baohui; Yamada, Tetsuya; Abe, Jun

    2015-08-01

    Photoperiodism is a rhythmic change of sensitivity to light, which helps plants to adjust flowering time according to seasonal changes in daylength and to adapt to growing conditions at various latitudes. To reveal the molecular basis of photoperiodism in soybean (Glycine max), a facultative short-day plant, we analyzed the transcriptional profiles of the maturity gene E1 family and two FLOWERING LOCUS T (FT) orthologs (FT2a and FT5a). E1, a repressor for FT2a and FT5a, and its two homologs, E1-like-a (E1La) and E1Lb, exhibited two peaks of expression in long days. Using two different approaches (experiments with transition between light and dark phases and night-break experiments), we revealed that the E1 family genes were expressed only during light periods and that their induction after dawn in long days required a period of light before dusk the previous day. In the cultivar Toyomusume, which lacks the E1 gene, virus-induced silencing of E1La and E1Lb up-regulated the expression of FT2a and FT5a and led to early flowering. Therefore, E1, E1La, and E1Lb function similarly in flowering. Regulation of E1 and E1L expression by light was under the control of E3 and E4, which encode phytochrome A proteins. Our data suggest that phytochrome A-mediated transcriptional induction of E1 and its homologs by light plays a critical role in photoperiodic induction of flowering in soybean. PMID:26134161

  10. Acetaldehyde and parkinsonism: role of CYP450 2E1

    PubMed Central

    Vaglini, Francesca; Viaggi, Cristina; Piro, Valentina; Pardini, Carla; Gerace, Claudio; Scarselli, Marco; Corsini, Giovanni Umberto

    2013-01-01

    The present review update the relationship between acetaldehyde (ACE) and parkinsonism with a specific focus on the role of P450 system and CYP 2E1 isozyme particularly. We have indicated that ACE is able to enhance the parkinsonism induced in mice by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, a neurotoxin able to damage the nigrostriatal dopaminergic pathway. Similarly diethyldithiocarbamate, the main metabolite of disulfiram, a drug widely used to control alcoholism, diallylsulfide (DAS) and phenylisothiocyanate also markedly enhance the toxin-related parkinsonism. All these compounds are substrate/inhibitors of CYP450 2E1 isozyme. The presence of CYP 2E1 has been detected in the dopamine (DA) neurons of rodent Substantia Nigra (SN), but a precise function of the enzyme has not been elucidated yet. By treating CYP 2E1 knockout (KO) mice with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, the SN induced lesion was significantly reduced when compared with the lesion observed in wild-type animals. Several in vivo and in vitro studies led to the conclusion that CYP 2E1 may enhance the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity in mice by increasing free radical production inside the dopaminergic neurons. ACE is a good substrate for CYP 2E1 enzyme as the other substrate-inhibitors and by this way may facilitate the susceptibility of dopaminergic neurons to toxic events. The literature suggests that ethanol and/or disulfiram may be responsible for toxic parkinsonism in human and it indicates that basal ganglia are the major targets of disulfiram toxicity. A very recent study reports that there are a decreased methylation of the CYP 2E1 gene and increased expression of CYP 2E1 mRNA in Parkinson's disease (PD) patient brains. This study suggests that epigenetic variants of this cytochrome contribute to the susceptibility, thus confirming multiples lines of evidence which indicate a link between environmental toxins and PD. PMID:23801948

  11. The emission spectroscopy of the e1Π-a1Δ system of VN molecule

    NASA Astrophysics Data System (ADS)

    Fan, Qunchao; Hu, Shi; Sun, Weiguo; Wang, Qi

    2013-10-01

    Vanadium nitride is an important metallurgical additive and a good electrode material molecule. It is necessary to understand its intrinsic microstructure for better applications. Four groups of known experimental transition data of low-lying rotational quantum states and the analytical formula developed recently by Sun group are used to study the Ree, Pee, Rff and Pff-branch emission spectra of the (0, 0) band of the e1Π-a1Δ system of VN molecule respectively. The results not only reproduce all known experimental spectral lines accurately, but also generate valid data of the unknown spectral lines up to J = 80 that may not be available experimentally.

  12. Calculation of radiative corrections to E1 matrix elements in the neutral alkali metals

    SciTech Connect

    Sapirstein, J.; Cheng, K.T.

    2005-02-01

    Radiative corrections to E1 matrix elements for ns-np transitions in the alkali-metal atoms lithium through francium are evaluated. They are found to be small for the lighter alkali metals but significantly larger for the heavier alkali metals, and in the case of cesium much larger than the experimental accuracy. The relation of the matrix element calculation to a recent decay rate calculation for hydrogenic ions is discussed, and application of the method to parity nonconservation in cesium is described.

  13. 75 FR 45008 - Intent To Prepare an Environmental Impact Statement for a Proposed Light Rail Transit Line in...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-30

    ... Federal Transit Administration Intent To Prepare an Environmental Impact Statement for a Proposed Light... Impact Statement (EIS) for the proposed Woodward Avenue Light Rail Transit (LRT) project in Detroit... selected Woodward Avenue as the Locally Preferred Alternative (LPA) with Light Rail Transit as...

  14. 78 FR 38796 - Intent To Prepare an Environmental Impact Statement for Increased Transit Service to King of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-27

    ... Federal Transit Administration Intent To Prepare an Environmental Impact Statement for Increased Transit... (NOI) to prepare an Environmental Impact Statement and Section 4(f) Evaluation. SUMMARY: The FTA and... Environmental Impact Statement (EIS) and Section 4(f) Evaluation for increased transit service to King...

  15. 77 FR 31337 - Department of Defense Task Force on the Care, Management, and Transition of Recovering Wounded...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-25

    ... of the Secretary Department of Defense Task Force on the Care, Management, and Transition of... the Care, Management, and Transition of Recovering Wounded, Ill, and Injured Members of the Armed... Defense Task Force on the Care, Management, and Transition of Recovering Wounded, Ill, and Injured...

  16. 76 FR 71331 - Department of Defense Task Force on the Care, Management, and Transition of Recovering Wounded...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-17

    ... of the Secretary Department of Defense Task Force on the Care, Management, and Transition of... on the Care, Management, and Transition of Recovering Wounded, Ill, and Injured Members of the Armed... Department of Defense Task Force on the Care, Management, and Transition of Recovering Wounded, Ill,...

  17. 76 FR 38118 - Meeting of the Department of Defense Task Force on the Care, Management, and Transition of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-29

    ... Transition of Recovering Wounded, Ill, and Injured Members of the Armed Forces AGENCY: Department of Defense... Committee meeting of the Department of Defense Task Force on the Care, Management, and Transition of... Defense Task Force on the Care, Management, and Transition of Recovering Wounded, Ill, and Injured...

  18. 76 FR 1501 - Preparation of Environmental Impact Statement for Transit Improvements in the US 90A/Southwest...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-10

    ...The Federal Transit Administration (FTA) and the Metropolitan Transit Authority of Harris County (METRO) intend to prepare an Environmental Impact Statement (EIS) in accordance with the National Environmental Policy Act (NEPA), to evaluate the proposed transit improvements in the US 90A/Southwest Rail corridor in the Houston metropolitan area (Harris County). The US 90A/Southwest Rail corridor......

  19. Multi-Laboratory Validation of Estrone (E1) ELISA Methods

    EPA Science Inventory

    This project is a round-robin evaluation of commercially available Enzyme-Linked Immunosorbent Assay (ELISA) technology to quantitatively or qualitatively measure the hormone estrone (E1) in combined animal feeding operation (CAFO) receiving streams. ELISA is meant to be a simpl...

  20. 26 CFR 53.4941(e)-1 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... TAXES (CONTINUED) FOUNDATION AND SIMILAR EXCISE TAXES Taxes on Self-Dealing § 53.4941(e)-1 Definitions... and the liabilities of the parties have been fixed. Thus, for example, if a private foundation gives a disqualified person a binding option on June 15, 1971, to purchase property owned by the foundation at any...

  1. 26 CFR 53.4941(e)-1 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... TAXES (CONTINUED) FOUNDATION AND SIMILAR EXCISE TAXES Taxes on Self-Dealing § 53.4941(e)-1 Definitions... and the liabilities of the parties have been fixed. Thus, for example, if a private foundation gives a disqualified person a binding option on June 15, 1971, to purchase property owned by the foundation at any...

  2. 26 CFR 53.4941(e)-1 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... TAXES (CONTINUED) FOUNDATION AND SIMILAR EXCISE TAXES Taxes on Self-Dealing § 53.4941(e)-1 Definitions... and the liabilities of the parties have been fixed. Thus, for example, if a private foundation gives a disqualified person a binding option on June 15, 1971, to purchase property owned by the foundation at any...

  3. 26 CFR 53.4941(e)-1 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... TAXES (CONTINUED) FOUNDATION AND SIMILAR EXCISE TAXES Taxes on Self-Dealing § 53.4941(e)-1 Definitions... and the liabilities of the parties have been fixed. Thus, for example, if a private foundation gives a disqualified person a binding option on June 15, 1971, to purchase property owned by the foundation at any...

  4. 26 CFR 53.4941(e)-1 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... TAXES (CONTINUED) FOUNDATION AND SIMILAR EXCISE TAXES Taxes on Self-Dealing § 53.4941(e)-1 Definitions... and the liabilities of the parties have been fixed. Thus, for example, if a private foundation gives a disqualified person a binding option on June 15, 1971, to purchase property owned by the foundation at any...

  5. 24. SPILLWAY CHANNEL WALLS REINFORCEMENT DETAILS; MONOLITHS E1 TO ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    24. SPILLWAY CHANNEL WALLS - REINFORCEMENT DETAILS; MONOLITHS E-1 TO F-4 INCL. & NO. 34. Sheet S-11, June, 1939. File no. SA 342/24(?). - Prado Dam, Spillway, Santa Ana River near junction of State Highways 71 & 91, Corona, Riverside County, CA

  6. PPARgamma ligands suppress the feedback loop between E2F2 and cyclin-E1.

    PubMed

    Komatsu, Yoko; Ito, Ichiaki; Wayama, Mitsutoshi; Fujimura, Akiko; Akaogi, Kensuke; Machida, Hikaru; Nakajima, Yuka; Kuroda, Takao; Ohmori, Kazuji; Murayama, Akiko; Kimura, Keiji; Yanagisawa, Junn

    2008-05-23

    PPARgamma is a nuclear hormone receptor that plays a key role in the induction of peroxisome proliferation. A number of studies showed that PPARgamma ligands suppress cell cycle progression; however, the mechanism remains to be determined. Here, we showed that PPARgamma ligand troglitazone inhibited G1/S transition in colon cancer cells, LS174T. Troglitazone did not affect on either expression of CDK inhibitor (p18) or Wnt signaling pathway, indicating that these pathways were not involved in the troglitazone-dependent cell cycle arrest. GeneChip and RT-PCR analyses revealed that troglitazone decreased mRNA levels of cell cycle regulatory factors E2F2 and cyclin-E1 whose expression is activated by E2F2. Down-regulation of E2F2 by troglitazone results in decrease of cyclin-E1 transcription, which could inhibit phosphorylation of Rb protein, and consequently evoke the suppression of E2F2 transcriptional activity. Thus, we propose that troglitazone suppresses the feedback loop containing E2F2, cyclin-E1, and Rb protein. PMID:18355447

  7. Bursts of energetic electron induced large surface charging observed by Chang'E-1

    NASA Astrophysics Data System (ADS)

    Wang, X. Y.; Zhang, A. B.; Zhang, X. G.; Reme, H.; Kong, L. G.; Zhang, S. Y.; Yu, D. J.; Wang, S. J.; Zhu, G. W.

    2012-10-01

    A relationship between surface charging and bursts of energetic electron (BEE) event is presented in this paper. In a 200 km lunar polar orbit, during quiet time, 0.1-2.0 MeV BEE events were observed by High Energetic Particles Detectors (HPD) on board Chang'E-1, on December 22, 2007, when the spacecraft was within the inner terrestrial magnetosheath. At the same time, a large surface charging of ∼-5.4 kV was observed by Chang'E-1, which was evidenced by increasing the ions energy observed by Solar Wind Ion Detectors (SWIDs). We found that the surface charging is strongly correlated with BEE events, and the potentials of spacecraft surface charging was experientially expressed as U≈3.6×10-5·fT (kV). The BEE events did occur in the solar wind, geomagnetic tail and magnetosheath alternately, whereas the surface charging during the BEE events is in the magnetosheath or transition region of boundaries. Though the observed surface charging was fewer than the BEE events, it is expected that the occurrence of the charging events caused by the bursts of energetic electrons should be more frequent than the Chang'E-1 observations. Meanwhile, the spacecraft charging indicates the lunar surface can be charged to negative kilovolt-scale by the BEE events even in quiet times.

  8. 76 FR 23644 - Solicitation of Nominations for Members of the Transit Rail Advisory Committee for Safety (TRACS)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-27

    ..., FTA issued an initial notice (75 FR 5172) soliciting nominations to serve on TRACS. From that... knowledge base with professionals who have done academic research in the safety field. DATES: Applications... agencies. The FTA Administrator is now seeking to increase the representation from members of the...

  9. 77 FR 75521 - Community Reinvestment Act Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-21

    ... 1, 2005. 70 FR 44256 (Aug. 2, 2005). As explained in the SUPPLEMENTARY INFORMATION section of these... Home Mortgage Disclosure Act (HMDA). 70 FR 12148 (Mar. 11, 2005). See 12 U.S.C. 2808; 12 CFR 203.2(e)(1... the other federal banking agencies in its CRA rule set forth at 12 CFR part 563e. 72 FR 13429 (Mar....

  10. 78 FR 74119 - Department of Defense Task Force on the Care, Management, and Transition of Recovering Wounded...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-10

    ... of the Secretary Department of Defense Task Force on the Care, Management, and Transition of... of the Department of Defense Task Force on the Care, Management, and Transition of Recovering Wounded, Ill, and Injured Members of the Armed Forces (subsequently referred to as the Task Force)....

  11. 75 FR 61553 - National Transit Database: Amendments to the Urbanized Area Annual Reporting Manual and to the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-05

    ... Transit (RB), Commuter Bus (CB), Streetcar Rail (SR), and Hybrid Rail (YR). These definitions, like all... overhead catenaries and with frequent stops. Hybrid Rail (YR): This mode is for rail transit systems... Otherwise Classified'' (e.g. slip and fall/electric shock/other) on the S&S-50 Form and on the ``Number...

  12. 77 FR 14364 - Comment Sought on Funding Pilot Program Participants Transitioning Out of the Rural Health Care...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-09

    ... COMMISSION Comment Sought on Funding Pilot Program Participants Transitioning Out of the Rural Health Care... to fund Rural Health Care Pilot Program (Pilot Program) participants who will exhaust funding... year to provide time to establish a process to transition them into the permanent Rural Health...

  13. 77 FR 4787 - Department of Defense Task Force on the Care, Management, and Transition of Recovering Wounded...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-31

    ... Forces. The meeting notice published in the January 24, 2012 edition of the Federal Register (77 FR 3454.... Bannick 9:30-9:45 a.m. Break 9:45-10:45 a.m. OSD Office of Military Community and Family Policy (MCFP) 10... Review & Administration 9:30-9:45 a.m. Break 9:45-10:45 a.m. Continue Site Visit Review...

  14. RP-1 delivered to E-1 Test Stand

    NASA Technical Reports Server (NTRS)

    2010-01-01

    NASA John C. Stennis Space Center employee Dustan Ladner (left) assists tanker driver David Velasco in transferring RP-1 fuel to a 20,000-gallon underground tank at the E-1 Test Stand during a March 30 delivery. The rocket propellant will be used for testing Aerojet AJ26 rocket engines beginning this summer. Stennis is testing the engines for Orbital Sciences Corporation, which has partnered with NASA to provide eight supply missions to the International Space Station through 2015. The partnership is part of NASA's Commercial Orbital Transportation Services initiative to work closer with companies to provide commercial space transport once the space shuttle is retired later this year.

  15. E1 strength in Pb208 within the shell model

    NASA Astrophysics Data System (ADS)

    Schwengner, R.; Massarczyk, R.; Brown, B. A.; Beyer, R.; Dönau, F.; Erhard, M.; Grosse, E.; Junghans, A. R.; Kosev, K.; Nair, C.; Rusev, G.; Schilling, K. D.; Wagner, A.

    2010-05-01

    The dipole response of the doubly magic nuclide Pb208 was studied in photon-scattering experiments at the electron linear accelerator ELBE with bremsstrahlung produced at kinetic electron energies of 9.0 and 15.0 MeV. The present (γ,γ') data combined with (γ,n) data from the literature are compared with results of shell-model calculations and calculations using a quasiparticle random-phase approximation. The shell-model calculations including (2p-2h) excitations describe the experimental E1 strength well and reproduce the spreading of the giant dipole resonance by applying a small smearing width only.

  16. 75 FR 59645 - Radio Broadcast Services and Multichannel Video and Cable Television Service; Clarification...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-28

    ... longer pending OMB approval for the sections listed: 73.6027--69 FR 69331, November 29, 2004. 76.5(ll)--61 FR 6137, February 16, 1996. 76.913(b)(1)--62 FR 6495, February 12, 1997. 76.924(e)(1)(iii) and (e)(2)(iii)--61 FR 9367, March 8, 1996. 76.925--60 FR 52119, October 5, 1995. 76.942(f)--60 FR...

  17. Influence of GSTs, CYP2E1 and mEH polymorphisms on 1, 3-butadiene-induced micronucleus frequency in Chinese workers

    SciTech Connect

    Tan Hongshan; Wang Qi; Wang Aihong; Ye Yunjie; Feng Nannan; Feng Xiaoqing; Lu Lingeng; Au, William; Zheng Yuxin; Xia Zhaolin

    2010-09-15

    1,3-butadiene (BD) has been classified as a human carcinogen, however, the relationship between chromosomal damage and its metabolic polymorphisms is not clear. The present study used the CBMN assay to detect chromosomal damage in the peripheral lymphocytes of 166 exposed workers and 41 non-exposed healthy individuals. PCR and PCR-RFLP were applied to detect GSTT1, GSTM1, CYP2E1 c1c2 and mEH Tyr113His, His139Arg polymorphisms. The results demonstrated that the micronucleus (MN) frequency of the exposed workers was significantly higher than controls (P < 0.01). Among the exposed workers, the individuals with high BD exposures are more susceptible to chromosomal damage than those with low exposures (FR = 1.30, 95% CI 1.14-1.53; P < 0.05). Gender-difference was also found in our study: males got lower micronucleus frequency than females. Workers who carried the genotypes of GSTM1 (+), CYP2E1 (c1c2/c2c2) and mEH intermediate (I) group had significantly higher MN frequency than those carrying the genotypes of GSTM1 (-) (FR = 1.29, 95% CI 1.05-1.59; P < 0.05), CYP2E1 (c1c1) (FR = 1.55, 95% CI 1.24-1.93; P < 0.01) or mEH high (H) group (FR = 1.57, 95% CI 1.08-2.34; P < 0.05), respectively. Our data indicated that the current BD exposure level could cause significantly higher MN frequency in workers than controls. Polymorphisms of GSTM1, CYP2E1 and mEH are susceptible to altered chromosome damage.

  18. Discovery of low-lying E1 and M1 strengths in {sup 232}Th

    SciTech Connect

    Adekola, A. S.; Hammond, S. L.; Hill, A.; Karwowski, H. J.; Angell, C. T.; Howell, C. R.; Kwan, E.; Kelley, J. H.

    2011-03-15

    Properties of low-energy dipole states in {sup 232}Th have been investigated with the nuclear resonance fluorescence technique. The present work used monoenergetic {gamma}-ray beams at energies of 2-4 MeV from the high-intensity {gamma}-ray source at Triangle Universities Nuclear Laboratory. Over 40 transitions corresponding to deexcitation to the ground state and first excited state were observed for the first time. Excitation energies, integrated cross sections, decay widths, branching ratios, and transition strengths for those states in {sup 232}Th were determined and compared with quasiparticle random-phase-approximation calculations. A large number of E1 transitions were observed for the first time in actinide nuclei with summed strength of 3.28(69)x10{sup -3} e{sup 2} fm{sup 2}. The observed summed M1 strength of 4.26(63){mu}{sub N}{sup 2} is in good agreement with the other actinides and with the systematics of the scissors mode in deformed rare-earth nuclei.

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

    NASA Astrophysics Data System (ADS)

    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.

  20. 78 FR 53187 - Early Scoping Notification for the Alternatives Analysis of the GA 400 Transit Initiative in...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-28

    ... that offers an alternative to automobile travel. This notice invites the public and agency officials to... study area by providing a more robust transit network that offers an alternative to automobile...

  1. 78 FR 7415 - Department of Defense Task Force on the Care, Management, and Transition of Recovering Wounded...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-01

    ....-10:15 a.m. Break 10:15 a.m.-12:00 p.m. Army Warrior Transition Command Survey Program 12:00 p.m.-1:00 p.m. Additional Questions for Army Warrior Transition Command 1:00 p.m.-2:00 p.m. Break for Lunch 2....defense.gov/rwtf/to view the Charter. Individuals making presentations will be notified by...

  2. Buserelin acetate microparticle dispersion effects drug release and plasma E(1) levels.

    PubMed

    Usami, Makiko; Misawa, Kazumasa; Yagi, Naomi; Sekikawa, Hitoshi; Nabeshima, Toshitaka

    2007-07-18

    We investigated the effect of different dispersion methods on release behavior and efficacy onset following microparticle administration of buserelin acetate (BA) sustained-release injection. In this in vitro release study, the initial dispersion of BA increased with increased stirring speed (p<0.01). Stability of BA was studied over 7 days after BA release. The initial BA release rate was higher (p<0.01) after a 1-min vibration dispersion method (VDM) using a test tube mixer (2000 rpm) compared with the standard dispersion method (SDM) by hand. Without shaking, powder aggregation was observed, and BA release was lower than in either the SDM or VDM methods. In this study using 4-week-old Sprague-Dawley female rats, the initial plasma estrone (E(1)) concentrations were lower (p<0.05) in the VDM method than in the SDM method. Observations by optical microscope and scanning microscope showed no change in microparticle shape or distribution of size induced by SDM, VDM or the ultrasonication dispersion method. These results suggest that different dispersion methods do not change the shape and distribution of microparticle size, but clearly change the BA release rate and the transition in plasma E(1) concentrations that can affect drug efficacy. PMID:17398044

  3. Metabolism of prostaglandin E1 in dog kidneys

    PubMed Central

    Nakano, J.

    1970-01-01

    1. The biotransformation of prostaglandin E1 (PGE1) was studied in the isolated, perfused dog kidneys. 2. An average 43% of PGE1 was converted into the less polar metabolite I by a single passage through the kidney. As the re-circulation of the perfusate continued, PGE1 was converted not only into metabolite I but also the least polar metabolite II. The velocity of the conversion of PGE1 into metabolite I was significantly greater than that into metabolite II. Usually, six passages elapsed before maximum degradation of PGE1 occurred. 3. Further separation with silicic acid column chromatography and gas-liquid chromatography showed that metabolite II consists of two individual metabolites, metabolite IIa and metabolite IIb. 4. The present study indicates that the kidney biotransforms PGE1 rather rapidly into three metabolites which are less polar than PGE1. PMID:5492900

  4. 78 FR 66902 - Department of Defense Task Force on the Care, Management, and Transition of Recovering Wounded...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-07

    ...The Department of Defense is publishing this notice to announce the following Federal Advisory Committee meeting of the Department of Defense Task Force on the Care, Management, and Transition of Recovering Wounded, Ill, and Injured Members of the Armed Forces (subsequently referred to as the Task...

  5. 77 FR 63669 - Notice of FTA Transit Program Changes, Authorized Funding Levels and Implementation of the Moving...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-16

    ...This notice announces changes in the Federal Transit Administration (FTA) programs in accordance with the Moving Ahead for Progress in the 21st Century Act (MAP-21), which authorizes surface transportation programs of the Department of Transportation for Federal fiscal years (FY) 2013 and 2014. This notice provides preliminary implementation instructions and guidance for the new and revised......

  6. 75 FR 44233 - Notice of Proposed Extension of Project Period and Waiver for the National Secondary Transition...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-28

    ... Transition Technical Assistance Center to receive funding from October 1, 2010 through September 30, 2011. DATES: We must receive your comments on or before August 12, 2010. ADDRESSES: Address all comments about... CONTACT. Background On March 8, 2005, the Department published a notice in the Federal Register (70...

  7. 76 FR 57044 - Announcement of Requirements and Registration for “Ensuring Safe Transitions From Hospital to Home”

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-15

    ... to stimulate innovative approaches to care transitions and improving patient safety. Nearly one in... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND... Hospital to Home'' Authority: 15 U.S.C. 3719. AGENCY: Office of the National Coordinator for...

  8. 78 FR 28580 - Department of Defense Task Force on the Care, Management, and Transition of Recovering Wounded...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-15

    ... of the Secretary Department of Defense Task Force on the Care, Management, and Transition of Recovering Wounded, Ill, and Injured Members of the Armed Forces AGENCY: Office of the Assistant Secretary of... Federal Advisory Committee meeting of the Department of Defense Task Force on the Care, Management,...

  9. 75 FR 76422 - Meeting of the Department of Defense Task Force on the Care, Management, and Transition of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-08

    ... of the Secretary Meeting of the Department of Defense Task Force on the Care, Management, and Transition of Recovering Wounded, Ill, and Injured Members of the Armed Forces (Subsequently Referred to as the Task Force) AGENCY: Department of Defense. ACTION: Notice. SUMMARY: Pursuant to Section 10...

  10. 75 FR 59323 - Early Scoping for the Alternatives Analysis of the North Corridor Transit Project in Metropolitan...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-27

    ... (NEPA) and is part of a planning Alternatives Analysis (AA) required by Title 49 United States Code (U.S...-assisted major capital transit investment. The AA process results in the selection or confirmation of a... public comments on the scope of the AA study, including the transportation problems to be addressed,...

  11. 76 FR 56743 - Department of Defense Task Force on the Care, Management, and Transition of Recovering Wounded...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-14

    ... Team Briefing on TBI management in the Theater. 3 p.m. Department of Labor. 4 p.m. Open. 5 p.m. Closing... of the Secretary Department of Defense Task Force on the Care, Management, and Transition of Recovering Wounded, Ill, and Injured Members of the Armed Forces; Meeting AGENCY: Department of...

  12. 78 FR 42156 - Sonoma-Marin Area Rail Transit District-Acquisition Exemption-In Marin County, Cal.

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-15

    ... Surface Transportation Board Sonoma-Marin Area Rail Transit District--Acquisition Exemption-- In Marin County, Cal. AGENCY: Surface Transportation Board, DOT. ACTION: Notice of Exemption. SUMMARY: The Board... to Docket No. FD 35732, must be filed with the Surface Transportation Board, 395 E Street...

  13. 77 FR 21098 - Notice of Meeting of the Environmental Financial Advisory Board (EFAB), and Transit-Oriented...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-09

    ... Development Workshop AGENCY: Environmental Protection Agency (EPA). ACTION: Notice. SUMMARY: The United States... 22-23, 2012 and a Transit-Oriented Development Workshop on May 24, 2012. EFAB is an EPA advisory..., Agency priorities and to discuss progress with work projects under EFAB's current Strategic Action...

  14. 78 FR 48537 - Small Business Innovation Research and Small Business Technology Transfer Programs...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-08

    ... STTR Policy Directives at 77 FR 46806 and 77 FR 46855 respectively. Section 4(a)(3) of these Policy... 16, 2012 at 77 FR 63410. The Transition Rate benchmark sets the minimum ratio of Phase II to Phase I... (77 FR 46806) and the STTR Policy Directive (77 FR 46855). Pravina Raghavan, Deputy...

  15. 78 FR 23204 - Privacy Act of 1974, System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-18

    ... of users and the purpose of such uses: USAID's routine uses, see 42 FR 47371 (September 20, 1977) and 59 FR 52954 (October 20, 1994), apply to this system of records. As additional routine uses for this...); (d); (e)(1); (e)(4)(G), (H), and (I); and (f) of 5 U.S.C. 552a. See 57 FR 38276, 38280-81 (August...

  16. Fast electric dipole transitions in Ra-Ac nuclei

    SciTech Connect

    Ahmad, I.

    1985-01-01

    Lifetime of levels in /sup 225/Ra, /sup 225/Ac, and /sup 227/Ac have been measured by delayed coincidence techniques and these have been used to determine the E1 gamma-ray transition probabilities. The reduced E1 transition probabilities. The reduced E1 transition probabilities in /sup 225/Ra and /sup 225/Ac are about two orders of magnitude larger than the values in mid-actinide nuclei. On the other hand, the E1 rate in /sup 227/Ac is similar to those measured in heavier actinides. Previous studies suggest the presence of octupole deformation in all the three nuclei. The present investigation indicates that fast E1 transitions occur for nuclei with octupole deformation. However, the studies also show that there is no one-to-one correspondence between E1 rate and octupole deformation. 13 refs., 4 figs.

  17. Experimental and computational studies on zwitterionic (E)-1-((4-phenoxyphenyliminio)methyl)naphthalen-2-olate

    NASA Astrophysics Data System (ADS)

    Alpaslan, Gökhan; Macit, Mustafa; Erdönmez, Ahmet; Büyükgüngör, Orhan

    2011-06-01

    The Schiff base compound (E)-1-((4-phenoxyphenyliminio)methyl)naphthalen-2-olate has been synthesized and characterized by IR, UV-Vis, and X-ray single-crystal determination. Molecular geometry of the title compound in the ground state have been calculated using the density functional method (DFT) with 6-31G(d,p) basis set and compared with the experimental data. The calculated results show that the optimized geometry can well reproduce the crystal structure. By using TD-DFT method, electronic absorption spectra of the title compound have been predicted and a good agreement with the TD-DFT method and the experimental ones is determined. Molecular orbital coefficient analyses reveal that the electronic transitions are mainly assigned to n → p∗ and p → p∗ electronic transitions. To investigate the tautomeric stability, optimization calculations at B3LYP/6-31G(d,p) level were performed for the NH and OH forms of the title compound. Calculated results reveal that the OH form is more stable than NH form. In addition, molecular electrostatic potential and non-linear optical properties of the title compound were performed at B3LYP/6-31G(d,p) level of theory.

  18. Human adenovirus 2 E1B-19K and E1B-53K tumor antigens: antipeptide antibodies targeted to the NH2 and COOH termini.

    PubMed Central

    Green, M; Brackmann, K H; Lucher, L A; Symington, J S; Kramer, T A

    1983-01-01

    The human adenovirus 2 (Ad2) transforming region is located in the left 11.1% of the viral genome and encodes two early transcription units, E1A and E1B. Based on the amino acid sequence deduced from the Ad2 E1B DNA sequence (Gingeras et al., J. Biol. Chem. 257:13475-13491, 1982), we have prepared antibodies against synthetic peptides, 8 to 16 amino acids in length, encoded at the NH2 and COOH termini of the major E1B-19K and E1B-53K tumor antigens. The antipeptide antibodies immunoprecipitated the targeted E1B-19K or E1B-53K tumor antigens from extracts of Ad2-infected cells. The specificity of the peptide competition studies. Antipeptide antibodies directed to the NH2 and COOH termini immunoprecipitated the E1B-19K and E1B-53K tumor antigens from two Ad2-transformed rat cell lines, F17 and F4, providing evidence that identical tumor antigens are synthesized in Ad2-infected and Ad2-transformed cells. These results show that the E1B-19K and E1B-53K T antigens are not processed proteolytically at either the NH2 or COOH terminus. Our data provide strong evidence at the protein level that the E1B-19K and E1B-53K tumor antigens partially overlap in DNA sequence, with the E1B-19K initiating translation at the first ATG at nucleotide 1711 in translation reading frame 1 and the E1B-53K tumor antigen initiating translation at the second ATG at nucleotide 2016 in reading frame 3. This confirms the results of others on the N-terminal amino acid sequence of E1B-19K and theoretical deductions based on the DNA sequence. Our findings prove that the large E1B-53K T antigen initiates translation at the second ATG at nucleotide 2016 and not at equally plausible initiation codons located farther downstream at nucleotides 2202 and 2235. Thus, the E1B-53K T antigen is another example of a protein which initiates translation at an internal ATG rather than at the 5'-proximal ATG. Images PMID:6632083

  19. Lack of cytochrome P450 2E1 (CYP2E1) induction in the rat liver by starvation without coprophagy.

    PubMed

    Chung, H C; Sung, S H; Kim, J S; Kim, Y C; Kim, S G

    2001-03-01

    Starvation potentiates the hepatotoxicity of a variety of small molecules, including chlorinated hydrocarbons and nitrosamines, through the induction of CYP2E1. A change in CYP2E1 expression during starvation may also alter the pharmacokinetic profiles of xenobiotics. Northern blot and Western blot analyses revealed that hepatic CYP2E1 was not induced during starvation in rats placed in metabolic or wire-bottom cages in contrast to the induction of CYP2E1 in animals housed in solid-bottom cages. We studied the effect of coprophagy on the expression of hepatic CYP2E1 during starvation. The extent of coprophagy was 24% in fed rats. Fecal matter of starving rats was reduced to 14% of control and starving rats re-ingested ~1.6 g of feces per day. The effect of fecal matter on CYP2E1 expression (i.e., 1.6 g/kg/day for 3 days) was assessed in fed or starving rats. Starving rats gavaged with fecal matter for 3 days resulted in a 3.5-fold increase in the level of CYP2E1 mRNA, while fed rats gavaged with feces failed to show an increase in the mRNA. The increase in the CYP2E1 mRNA level accompanied the induction of CYP2E1. Starving rats gavaged with methanol extract of feces (500 mg/kg/day for 3 days) showed a 3.3-fold increase in CYP2E1 mRNA level in the liver. These results provide evidence that CYP2E1 is not induced by starvation without coprophagy, raising the contention that the mechanistic basis for CYP2E1 induction by starvation should be reevaluated. PMID:11181486

  20. Two classes of human papillomavirus type 16 E1 mutants suggest pleiotropic conformational constraints affecting E1 multimerization, E2 interaction, and interaction with cellular proteins.

    PubMed Central

    Yasugi, T; Vidal, M; Sakai, H; Howley, P M; Benson, J D

    1997-01-01

    Random mutagenesis of human papillomavirus type 16 (HPV16) E1 was used to generate E1 missense mutants defective for interaction with either hUBC9 or 16E1-BP, two cDNAs encoding proteins that have been identified by their ability to interact with HPV16 E1 in two-hybrid assays. hUBC9, the human counterpart of Saccharomyces cerevisiae UBC9, is a ubiquitin-conjugating enzyme known to be involved in cell cycle progression. 16E1-BP encodes a protein of no known function but does contain an ATPase signature motif. Eight hUBC9 or 16E1-BP interaction-defective HPV16 E1 missense mutants were identified and characterized for origin-dependent transient DNA replication, ATPase activity, and various protein-protein interaction phenotypes. Six of these mutant E1 proteins were significantly impaired for replication. Among these, two classes of replication-defective HPV16 E1 missense mutants were observed. One class, represented by the S330R replication-defective mutant (containing an S-to-R change at position 330), remained competent for all protein-protein interactions tested, with the exception of hUBC9 association. Furthermore, this mutant, unlike the other replication-defective HPV16 E1 missense mutants, had a strong dominant negative replication phenotype in transient-replication assays. The other class, represented by five of the missense mutants, was defective for multiple protein-protein interactions, usually including, but not limited to, the interaction defect for which each mutant was originally selected. In many cases, a single missense mutation in one region of HPV16 E1 had pleiotropic effects, even upon activities thought to be associated with other domains of HPV16 E1. This suggests that E1 proteins are not modular but may instead be composed of multiple structurally and/or functionally interdependent domains. PMID:9223484

  1. 77 FR 23667 - Department of Defense Task Force on the Care, Management, and Transition of Recovering Wounded...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-20

    ... Medical Center--Portsmouth, and Iowa Joint Forces Headquarters. 9:30-9:45 a.m. Break. 9:45-10:45 a.m... Briefing. 1:45-2 p.m. Break. 2-3 p.m. 2011 Recommendation Review. Review the 2011 Recommendations see what.... Break. 3:15-5 p.m. Task Force Recommendation Development Review of Transition Outcomes,...

  2. 78 FR 14272 - Department of Defense Task Force on the Care, Management, and Transition of Recovering Wounded...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-05

    ...Under the provisions of the Federal Advisory Committee Act of 1972 (5 U.S.C., Appendix, as amended), the Government in the Sunshine Act of 1976 (5 U.S.C. 552b, as amended), and 41 CFR 102-3.150, the Department of Defense announces that the following Federal Advisory Committee meeting of the Department of Defense Task Force on the Care, Management, and Transition of Recovering Wounded, Ill, and......

  3. Crystal structure of the DNA binding domain of the replication initiation protein E1 from papillomavirus.

    PubMed

    Enemark, E J; Chen, G; Vaughn, D E; Stenlund, A; Joshua-Tor, L

    2000-07-01

    Papillomaviral infection causes both benign and malignant lesions and is a necessary cause of cervical carcinoma. Replication of this virus requires the replication initiation proteins E1 and E2, which bind cooperatively at the origin of replication (ori) as an (E1)2-(E2)2-DNA complex. This is a precursor to larger E1 complexes that distort and unwind the ori. We present the crystal structure of the E1 DNA binding domain refined to 1.9 A resolution. Residues critical for DNA binding are located on an extended loop and an alpha helix. We identify the E1 dimerization surface by selective mutations at an E1/E1 interface observed in the crystal and propose a model for the (E1)2-DNA complex. These and other observations suggest how the E1 DNA binding domain orchestrates assembly of the hexameric helicase on the ori. PMID:10949036

  4. The dual effect of adenovirus type 5 E1A 13S protein on NF-kappaB activation is antagonized by E1B 19K.

    PubMed Central

    Schmitz, M L; Indorf, A; Limbourg, F P; Städtler, H; Traenckner, E B; Baeuerle, P A

    1996-01-01

    The genomes of human adenoviruses encode several regulatory proteins, including the two differentially spliced gene products E1A and E1B. Here, we show that the 13S but not the 12S splice variant of E1A of adenovirus type 5 can activate the human transcription factor NF-kappaB in a bimodal fashion. One mode is the activation of NF-kappaB containing the p65 subunit from the cytoplasmic NF-kappaB-IkappaB complex. This activation required reactive oxygen intermediates and the phosphorylation of IkappaBalpha at serines 32 and 36, followed by IkappaBalpha degradation and the nuclear uptake of NF-kappaB. In addition, 13S E1A stimulated the transcriptional activity of the C-terminal 80 amino acids of p65 at a core promoter with either a TATA box or an initiator (INR) element. The C-terminal 80 amino acids of p65 were found to associate with E1A in vitro. The activation of NF-kappaB-dependent reporter gene transcription by E1A was potently suppressed upon coexpression of the E1B 19-kDa protein (19K). E1B 19K prevented both the activation of NF-kappaB and the E1A-mediated transcriptional enhancement of p65. These inhibitory effects were not found for the 55-kDa splice variant of the E1B protein. We suggest that the inductive effect of E1A 13S on the host factor NF-kappaB, whose activation is important for the transcription of various adenovirus genes, must be counteracted by the suppressive effect of E1B 19K so that the adenovirus-infected cell can escape the immune-stimulatory and apoptotic effects of NF-kappaB. PMID:8754803

  5. 76 FR 52046 - Final Policy Statement on the Eligibility of Pedestrian and Bicycle Improvements Under Federal...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-19

    ... of Joint Development Projects under Federal Transit Law at 72 FR 5788. B. Transit Enhancement... Investment Projects, 75 FR 31383 (June 3, 2010). ] F. Access to Public Transportation for Individuals With... Statement on the Eligibility of Pedestrian and Bicycle Improvements under Federal Transit Law, 74 FR...

  6. The Human Adenovirus Type 5 E4orf6/E1B55K E3 Ubiquitin Ligase Complex Enhances E1A Functional Activity

    PubMed Central

    Dallaire, Frédéric; Schreiner, Sabrina; Blair, G. Eric; Dobner, Thomas; Branton, Philip E.

    2015-01-01

    ABSTRACT Human adenovirus (Ad) E1A proteins have long been known as the central regulators of virus infection as well as the major source of adenovirus oncogenic potential. Not only do they activate expression of other early viral genes, they make viral replication possible in terminally differentiated cells, at least in part, by binding to the retinoblastoma (Rb) tumor suppressor family of proteins to activate E2F transcription factors and thus viral and cellular DNA synthesis. We demonstrate in an accompanying article (F. Dallaire et al., mSphere 1:00014-15, 2016) that the human adenovirus E3 ubiquitin ligase complex formed by the E4orf6 and E1B55K proteins is able to mimic E1A activation of E2F transactivation factors. Acting alone in the absence of E1A, the Ad5 E4orf6 protein in complex with E1B55K was shown to bind E2F, disrupt E2F/Rb complexes, and induce hyperphosphorylation of Rb, leading to induction of viral and cellular DNA synthesis, as well as stimulation of early and late viral gene expression and production of viral progeny. While these activities were significantly lower than those exhibited by E1A, we report here that this ligase complex appeared to enhance E1A activity in two ways. First, the E4orf6/E1B55K complex was shown to stabilize E1A proteins, leading to higher levels in infected cells. Second, the complex was demonstrated to enhance the activation of E2F by E1A products. These findings indicated a new role of the E4orf6/E1B55K ligase complex in promoting adenovirus replication. IMPORTANCE Following our demonstration that adenovirus E3 ubiquitin ligase formed by the viral E4orf6 and E1B55K proteins is able to mimic the activation of E2F by E1A, we conducted a series of studies to determine if this complex might also promote the ability of E1A to do so. We found that the complex both significantly stabilizes E1A proteins and also enhances their ability to activate E2F. This finding is of significance because it represents an entirely new

  7. The Human Adenovirus Type 5 E4orf6/E1B55K E3 Ubiquitin Ligase Complex Enhances E1A Functional Activity.

    PubMed

    Dallaire, Frédéric; Schreiner, Sabrina; Blair, G Eric; Dobner, Thomas; Branton, Philip E; Blanchette, Paola

    2016-01-01

    Human adenovirus (Ad) E1A proteins have long been known as the central regulators of virus infection as well as the major source of adenovirus oncogenic potential. Not only do they activate expression of other early viral genes, they make viral replication possible in terminally differentiated cells, at least in part, by binding to the retinoblastoma (Rb) tumor suppressor family of proteins to activate E2F transcription factors and thus viral and cellular DNA synthesis. We demonstrate in an accompanying article (F. Dallaire et al., mSphere 1:00014-15, 2016) that the human adenovirus E3 ubiquitin ligase complex formed by the E4orf6 and E1B55K proteins is able to mimic E1A activation of E2F transactivation factors. Acting alone in the absence of E1A, the Ad5 E4orf6 protein in complex with E1B55K was shown to bind E2F, disrupt E2F/Rb complexes, and induce hyperphosphorylation of Rb, leading to induction of viral and cellular DNA synthesis, as well as stimulation of early and late viral gene expression and production of viral progeny. While these activities were significantly lower than those exhibited by E1A, we report here that this ligase complex appeared to enhance E1A activity in two ways. First, the E4orf6/E1B55K complex was shown to stabilize E1A proteins, leading to higher levels in infected cells. Second, the complex was demonstrated to enhance the activation of E2F by E1A products. These findings indicated a new role of the E4orf6/E1B55K ligase complex in promoting adenovirus replication. IMPORTANCE Following our demonstration that adenovirus E3 ubiquitin ligase formed by the viral E4orf6 and E1B55K proteins is able to mimic the activation of E2F by E1A, we conducted a series of studies to determine if this complex might also promote the ability of E1A to do so. We found that the complex both significantly stabilizes E1A proteins and also enhances their ability to activate E2F. This finding is of significance because it represents an entirely new function for

  8. The adenovirus E1A proteins induce apoptosis, which is inhibited by the E1B 19-kDa and Bcl-2 proteins.

    PubMed Central

    Rao, L; Debbas, M; Sabbatini, P; Hockenbery, D; Korsmeyer, S; White, E

    1992-01-01

    Cooperation between the adenovirus E1A and E1B oncogenes is required for transformation of primary quiescent rodent cells. Although expression of E1A alone will stimulate cell proliferation sufficient to initiate transformed focus formation, proliferation fails to be sustained and foci degenerate. Coexpression of either the 19-kDa or 55-kDa E1B oncoproteins with E1A permits high-frequency transformation by overcoming this cytotoxic response. Without E1B 19-kDa protein expression, however, transformants remain susceptible to induction of cell death. Rapid loss of viability is coincident with nucleolytic cleavage of DNA in intranucleosomal regions and chromatin condensation, hallmarks of programmed cell death (apoptosis). Furthermore, overexpression of a known suppressor of apoptosis, the Bcl-2 protooncogene, can rescue E1A-induced focus degeneration. Thus E1A-dependent stimulation of cell proliferation is accompanied by apoptosis and thereby insufficient to singly induce transformation. High-frequency transformation requires a second function encoded by the E1B 19-kDa protein to block apoptosis. Images PMID:1457005

  9. Sequence-independent autoregulation of the adenovirus type 5 E1A transcription unit.

    PubMed Central

    Hearing, P; Shenk, T

    1985-01-01

    The adenovirus E1A gene is known to be autoregulated at the level of transcription. Autoregulation was found to be mediated by products of the E1A 13S mRNA, which induced a fivefold increase in E1A transcription rate. Deletion analysis suggested that the autoregulation did not require any specific sequence in the E1A transcriptional control region. This conclusion was reinforced by the demonstration that a cellular alpha-globin gene substituted for the E1A gene on the adenovirus chromosome was also positively regulated by E1A gene products. Images PMID:2943984

  10. Metabolic inactivation of resolvin E1 and stabilization of its anti-inflammatory actions.

    PubMed

    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. PMID:16757471

  11. Functional conservation and diversification of the soybean maturity gene E1 and its homologs in legumes

    PubMed Central

    Zhang, Xingzheng; Zhai, Hong; Wang, Yaying; Tian, Xiaojie; Zhang, Yupeng; Wu, Hongyan; Lü, Shixiang; Yang, Guang; Li, Yuqiu; Wang, Lu; Hu, Bo; Bu, Qingyun; Xia, Zhengjun

    2016-01-01

    Gene regulatory networks involved in flowering time and photoperiodic responses in legumes remain unknown. Although the major maturity gene E1 has been successfully deciphered in soybean, knowledge on the functional conservation of this gene is limited to a certain extent to E1 homologs in legumes. The ectopic expression of Phvul.009G204600 (PvE1L), an E1 homolog from common bean, delayed the onset of flowering in soybean. By contrast, the ectopic expression of Medtr2g058520 (MtE1L) from Medicago truncatula did not affect the flowering of soybean. Characterization of the late-flowering mte1l mutant indicated that MtE1L promoted flowering in Medicago truncatula. Moreover, all transgenic E1, PvE1L and MtE1L soybean lines exhibited phenotypic changes in terms of plant height. Transgenic E1 or PvE1L plants were taller than the wild-type, whereas transgenic MtE1L plants produced dwarf phenotype with few nodes and short internode. Thus, functional conservation and diversification of E1 family genes from legumes in the regulation of flowering and plant growth may be associated with lineage specification and genomic duplication. PMID:27405888

  12. Improved Plant-based Production of E1 endoglucanase Using Potato: Expression Optimization and Tissue Targeting

    SciTech Connect

    Dai, Ziyu; Hooker, Brian S.; Anderson, Daniel B.; Thomas, Steven R.

    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.

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

    SciTech Connect

    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.

    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.

  14. Cell-based analysis of Chikungunya virus E1 protein in membrane fusion

    PubMed Central

    2012-01-01

    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. Cells bearing the V178

  15. Transition Planning

    ERIC Educational Resources Information Center

    Statfeld, Jenna L.

    2011-01-01

    Post-school transition is the movement of a child with disabilities from school to activities that occur after the completion of school. This paper provides information about: (1) post-school transition; (2) transition plan; (3) transition services; (4) transition planning; (5) vocational rehabilitation services; (6) services that are available…

  16. 26 CFR 1.501(e)-1 - Cooperative hospital service organizations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... state they were in on completion of the exempt function (e.g., the sale of silver waste produced in the...(e)-1 Section 1.501(e)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Exempt Organizations § 1.501(e)-1...

  17. 26 CFR 1.501(e)-1 - Cooperative hospital service organizations.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... state they were in on completion of the exempt function (e.g., the sale of silver waste produced in the...(e)-1 Section 1.501(e)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Exempt Organizations § 1.501(e)-1...

  18. 26 CFR 1.501(e)-1 - Cooperative hospital service organizations.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... state they were in on completion of the exempt function (e.g., the sale of silver waste produced in the....501(e)-1 Section 1.501(e)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Exempt Organizations § 1.501(e)-1...

  19. 26 CFR 1.501(e)-1 - Cooperative hospital service organizations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... state they were in on completion of the exempt function (e.g., the sale of silver waste produced in the....501(e)-1 Section 1.501(e)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Exempt Organizations § 1.501(e)-1...

  20. 26 CFR 1.501(e)-1 - Cooperative hospital service organizations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... state they were in on completion of the exempt function (e.g., the sale of silver waste produced in the...(e)-1 Section 1.501(e)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Exempt Organizations § 1.501(e)-1...

  1. 26 CFR 1.1397E-1 - Qualified zone academy bonds.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 11 2010-04-01 2010-04-01 true Qualified zone academy bonds. 1.1397E-1 Section 1.1397E-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Empowerment Zone Employment Credit § 1.1397E-1 Qualified zone...

  2. 26 CFR 1.669(e)-1A - Pro rata portion of taxes deemed distributed.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Pro rata portion of taxes deemed distributed. 1.669(e)-1A Section 1.669(e)-1A Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... Taxable Years Beginning Before January 1, 1969 § 1.669(e)-1A Pro rata portion of taxes deemed...

  3. 26 CFR 1.924(e)-1 - Activities relating to the disposition of export property.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 10 2010-04-01 2010-04-01 false Activities relating to the disposition of export property. 1.924(e)-1 Section 1.924(e)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Earned Income of Citizens of United States § 1.924(e)-1 Activities relating to...

  4. 26 CFR 1.1402(e)-1A - Application of regulations under section 1402(e).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 12 2010-04-01 2010-04-01 false Application of regulations under section 1402(e). 1.1402(e)-1A Section 1.1402(e)-1A Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Tax on Self-Employment Income §...

  5. 26 CFR 1.1402(e)-1A - Application of regulations under section 1402(e).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 12 2011-04-01 2011-04-01 false Application of regulations under section 1402(e). 1.1402(e)-1A Section 1.1402(e)-1A Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Tax on Self-Employment Income §...

  6. 26 CFR 1.263(e)-1 - Expenditures in connection with certain railroad rolling stock.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... by the Interstate Commerce Commission (49 CFR Part 1201), but only if (i) such unit exclusively moves... rolling stock. 1.263(e)-1 Section 1.263(e)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Items Not Deductible § 1.263(e)-1 Expenditures...

  7. 26 CFR 1.1059(e)-1 - Non-pro rata redemptions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 11 2011-04-01 2011-04-01 false Non-pro rata redemptions. 1.1059(e)-1 Section 1... (CONTINUED) INCOME TAXES (CONTINUED) Special Rules § 1.1059(e)-1 Non-pro rata redemptions. (a) In general... under section 1059(e)(1). For example, if a redemption of stock is not pro rata as to all...

  8. 26 CFR 1.669(e)-1A - Pro rata portion of taxes deemed distributed.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 8 2011-04-01 2011-04-01 false Pro rata portion of taxes deemed distributed. 1.669(e)-1A Section 1.669(e)-1A Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... Applicable to Taxable Years Beginning Before January 1, 1969 § 1.669(e)-1A Pro rata portion of taxes...

  9. 26 CFR 1.509(e)-1 - Definition of gross investment income.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 7 2010-04-01 2010-04-01 true Definition of gross investment income. 1.509(e)-1 Section 1.509(e)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Private Foundations § 1.509(e)-1 Definition of...

  10. 26 CFR 1.509(e)-1 - Definition of gross investment income.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 7 2011-04-01 2009-04-01 true Definition of gross investment income. 1.509(e)-1 Section 1.509(e)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Private Foundations § 1.509(e)-1 Definition of...

  11. 26 CFR 1.149(e)-1 - Information reporting requirements for tax-exempt bonds.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 2 2010-04-01 2010-04-01 false Information reporting requirements for tax-exempt bonds. 1.149(e)-1 Section 1.149(e)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Tax Exemption Requirements for State and Local Bonds § 1.149(e)-1...

  12. 26 CFR 1.6050E-1 - Reporting of State and local income tax refunds.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    .... 1.6050E-1 Section 1.6050E-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Information Returns § 1.6050E-1 Reporting of... individual in any calendar year. (b) Definitions. For purposes of this section— (1) The term refund...

  13. 26 CFR 1.6050E-1 - Reporting of State and local income tax refunds.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    .... 1.6050E-1 Section 1.6050E-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Information Returns § 1.6050E-1 Reporting of... individual in any calendar year. (b) Definitions. For purposes of this section— (1) The term refund...

  14. 26 CFR 1.6050E-1 - Reporting of State and local income tax refunds.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    .... 1.6050E-1 Section 1.6050E-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Information Returns § 1.6050E-1 Reporting of State and local... year. (b) Definitions. For purposes of this section— (1) The term refund officer means the officer...

  15. 42 CFR 52e.1 - To what programs do these regulations apply?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false To what programs do these regulations apply? 52e.1 Section 52e.1 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL HEART, LUNG, AND BLOOD INSTITUTE GRANTS FOR PREVENTION AND CONTROL PROJECTS § 52e.1 To what programs...

  16. 42 CFR 52e.1 - To what programs do these regulations apply?

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false To what programs do these regulations apply? 52e.1 Section 52e.1 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL HEART, LUNG, AND BLOOD INSTITUTE GRANTS FOR PREVENTION AND CONTROL PROJECTS § 52e.1 To what programs...

  17. 42 CFR 52e.1 - To what programs do these regulations apply?

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false To what programs do these regulations apply? 52e.1 Section 52e.1 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL HEART, LUNG, AND BLOOD INSTITUTE GRANTS FOR PREVENTION AND CONTROL PROJECTS § 52e.1 To what programs...

  18. 42 CFR 52e.1 - To what programs do these regulations apply?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false To what programs do these regulations apply? 52e.1 Section 52e.1 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL HEART, LUNG, AND BLOOD INSTITUTE GRANTS FOR PREVENTION AND CONTROL PROJECTS § 52e.1 To what programs...

  19. Identification of a nuclear export signal sequence for bovine papillomavirus E1 protein

    SciTech Connect

    Rosas-Acosta, German; Wilson, Van G.

    2008-03-30

    Recent studies have demonstrated nuclear export by papillomavirus E1 proteins, but the requisite export sequence(s) for bovine papillomavirus (BPV) E1 were not defined. In this report we identify three functional nuclear export sequences (NES) present in BPV E1, with NES2 being the strongest in reporter assays. Nuclear localization of BPV1 E1 was modulated by over- or under-expression of CRM1, the major cellular exportin, and export was strongly reduced by the CRM1 inhibitor, Leptomycin B, indicating that E1 export occurs primarily through a CRM1-dependent process. Consistent with the in vivo functional results, E1 bound CRM1 in an in vitro pull-down assay. In addition, sumoylated E1 bound CRM1 more effectively than unmodified E1, suggesting that E1 export may be regulated by SUMO modification. Lastly, an E1 NES2 mutant accumulated in the nucleus to a greater extent than wild-type E1, yet was defective for viral origin replication in vivo. However, NES2 exhibited no intrinsic replication defect in an in vitro replication assay, implying that nucleocytoplasmic shuttling may be required to maintain E1 in a replication competent state.

  20. 40 CFR Figure E-1 to Subpart E of... - Designation Testing Checklist

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 5 2010-07-01 2010-07-01 false Designation Testing Checklist E Figure E-1 to Subpart E of Part 53 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Equivalent Methods for PM2.5 or PM10â2.5 Pt. 53, Subpt. E, Fig. E-1 Figure E-1 to Subpart E of Part...

  1. 26 CFR 48.4216(e)-1 - Exclusion of local advertising charges from sale price.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... sale price. 48.4216(e)-1 Section 48.4216(e)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF... Provisions Applicable to Manufacturers Taxes § 48.4216(e)-1 Exclusion of local advertising charges from sale price. (a) In general. Section 4216(e) deals with the treatment to be accorded charges made by...

  2. 26 CFR 48.4216(e)-1 - Exclusion of local advertising charges from sale price.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... sale price. 48.4216(e)-1 Section 48.4216(e)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF... Provisions Applicable to Manufacturers Taxes § 48.4216(e)-1 Exclusion of local advertising charges from sale price. (a) In general. Section 4216(e) deals with the treatment to be accorded charges made by...

  3. 17 CFR 270.10e-1 - Death, disqualification, or bona fide resignation of directors.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... bona fide resignation of directors. 270.10e-1 Section 270.10e-1 Commodity and Securities Exchanges....10e-1 Death, disqualification, or bona fide resignation of directors. If a registered investment company, by reason of the death, disqualification, or bona fide resignation of any director, does not...

  4. 78 FR 52607 - Unified Registration System

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-23

    ... published on January 17, 2008 (73 FR 3316), or you may visit http://edocket.access.gpo.gov/2008/pdf/E8-785... Regulations FR Federal Register FTA Federal Transit Administration GVWR Gross Vehicle Weight Rating HHG... American Free Trade Agreement (NAFTA) Long-Haul Trucking Provisions, 76 FR 40420 (July 8, 2011); see...

  5. Two-quasiparticle isomer, E1 hindrances and residual interactions in {sup 172}Tm

    SciTech Connect

    Hughes, R. O.; Lane, G. J.; Dracoulis, G. D.; Kibedi, T.; Nieminen, P.; Watanabe, H.

    2008-04-15

    The structure of the neutron-rich nucleus {sup 172}Tm has been studied using incomplete fusion of {sup 7}Li on an {sup 170}Er target at 30 MeV. A 190-{mu}s isomer at an excitation energy of 476 keV was identified using chopped beams and {gamma}-ray spectroscopy. The isomer decays with very inhibited E1 transitions to the rotational bands based on the parallel and antiparallel couplings of the {nu}5/2{sup -}[512] x {pi}1/2{sup +}[411] configuration, the latter (K{sup {pi}}=2{sup -}) being the ground state. The isomeric state has been assigned J{sup {pi}}=6{sup +}, arising from the energetically favored (parallel) coupling of the {nu}5/2{sup -}[512] x {pi}7/2{sup -}[523] configuration. The proton-neutron residual interaction was deduced for the configuration of the isomeric state and is found to agree with previous empirical studies.

  6. Energy levels and transition rates for helium-like ions with Z = 10-36

    NASA Astrophysics Data System (ADS)

    Si, R.; Guo, X. L.; Wang, K.; Li, S.; Yan, J.; Chen, C. Y.; Brage, T.; Zou, Y. M.

    2016-08-01

    Aims: Helium-like ions provide an important X-ray spectral diagnostics in astrophysical and high-temperature fusion plasmas. An interpretation of the observed spectra provides information on temperature, density, and chemical compositions of the plasma. Such an analysis requires information for a wide range of atomic parameters, including energy levels and transition rates. Our aim is to provide a set of accurate energy levels and transition rates for helium-like ions with Z = 10-36. Methods: The second-order many-body perturbation theory (MBPT) was adopted in this paper. To support our MBPT results, we performed an independent calculation using the multiconfiguration Dirac-Hartree-Fock (MCDHF) method. Results: We provide accurate energies for the lowest singly excited 70 levels among 1snl(n ≤ 6,l ≤ (n-1)) configurations and the lowest doubly excited 250 levels arising from the K-vacancy 2ln'l'(n' ≤ 6,l' ≤ (n'-1)) configurations of helium-like ions with Z = 10-36. Wavelengths, transition rates, oscillator strengths, and line strengths are calculated for the E1, M1, E2, and M2 transitions among these levels. The radiative lifetimes are reported for all the calculated levels. Conclusions: Our MBPT results for singly excited n ≤ 2 levels show excellent agreement with other elaborate calculations, while those for singly excited n ≥ 3 and doubly excited levels show significant improvements over previous theoretical results. Our results will be very helpful for astrophysical line identification and plasma diagnostics. Full Tables 1 and 2 are only available at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/592/A141

  7. 78 FR 79283 - Community Reinvestment Act Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-30

    ... CRA purposes by the OCC, Board, and FDIC on August 2, 2005, effective September 1, 2005. 70 FR 44256... Act (HMDA). 70 FR 12148 (Mar. 11, 2005). See 12 U.S.C. 2808; 12 CFR 203.2(e)(1). On March 22, 2007... other federal banking agencies in its CRA rule previously set forth at 12 CFR 563e. 72 FR 13429 (Mar....

  8. 76 FR 79529 - Community Reinvestment Act Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-22

    ... adopted for CRA purposes by the OCC, Board, and FDIC on August 2, 2005, effective September 1, 2005. 70 FR... Disclosure Act (HMDA). 70 FR 12148 (Mar. 22, 2007). See 12 U.S.C. 2808; 12 CFR 203.2(e)(1). On March 22, 2007... federal banking agencies in its CRA rule set forth at 12 CFR 563e. 72 FR 13429. Pursuant to the...

  9. Subcellular localization of rat CYP2E1 impacts metabolic efficiency toward common substrates.

    PubMed

    Hartman, Jessica H; Martin, H Cass; Caro, Andres A; Pearce, Amy R; Miller, Grover P

    2015-12-01

    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 subcellular fractions from rat liver. For all substrates, metabolic efficiency changed with substrate concentration for erCYP2E1 reflected in non-hyperbolic kinetic profiles but not for mtCYP2E1. Hyperbolic kinetic profiles for the mitochondrial enzyme were consistent with Michaelis-Menten mechanism in which metabolic efficiency was constant. By contrast, erCYP2E1 metabolism of 4-nitrophenol led to a loss of enzyme efficiency at high substrate concentrations when substrate inhibited the reaction. Similarly, aniline metabolism by erCYP2E1 demonstrated negative cooperativity as metabolic efficiency decreased with increasing substrate concentration. The opposite was observed for erCYP2E1 oxidation of styrene; the sigmoidal kinetic profile indicated increased efficiency at higher substrate concentrations. These mechanisms and CYP2E1 levels in mitochondria and endoplasmic reticulum were used to estimate the impact of CYP2E1 subcellular localization on metabolic flux of pollutants. Those models showed that erCYP2E1 mainly carries out aniline metabolism at all aniline concentrations. Conversely, mtCYP2E1 dominates styrene oxidation at low styrene concentrations and erCYP2E1 at higher concentrations. Taken together, subcellular localization of CYP2E1 results in distinctly different enzyme activities that could impact overall metabolic clearance and/or activation of substrates and thus impact the interpretation and prediction of toxicological outcomes. PMID:26463279

  10. 17 CFR 274.127e-1 - Form N-27E-1, notice to periodic payment plan certificate holders of 18-month surrender rights...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    .... Editorial Note: For Federal Register citations affecting Form N-27E-1, see the List of CFR Sections Affected... EXCHANGE COMMISSION (CONTINUED) FORMS PRESCRIBED UNDER THE INVESTMENT COMPANY ACT OF 1940 Forms for...

  11. 78 FR 14620 - Joint Development: Proposed Circular

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-06

    ... published guidance on the eligibility of joint development activities for FTA funding. 72 FR 5788 (Feb. 7... review DOT's complete Privacy Act Statement published in the Federal Register on April 11, 2000 (65 FR... Federal Transit Administration Joint Development: Proposed Circular AGENCY: Federal Transit...

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

    SciTech Connect

    Wang, Jimin Li, Yue; Modis, Yorgo

    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 E1–E2 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 E1–E2 disulfide bond formation are proposed for E1 residues. • Implications for E1 ectodomain structure and disulfide bonding pattern are discussed.

  13. ColE1 plasmid incompatibility: localization and analysis of mutations affecting incompatibility.

    PubMed Central

    Hashimoto-Gotoh, T; Inselburg, J

    1979-01-01

    Deletion mutants of plasmid ColE1 that involve the replication origin and adjacent regions of the plasmid have been studied to determine the mechanism by which those mutations affect the expression of plasmid incompatibility. It was observed that (i) a region of ColE1 that is involved in the expression of plasmid incompatibility lies between base pairs -185 and -684; (ii) the integrity of at least part of the region of ColE1 DNA between base pairs -185 and -572 is essential for the expression of ColE1 incompatibility; (iii) the expression of incompatibility is independent of the ability of the ColE1 genome to replicate autonomously; (iv) plasmid incompatibility is affected by plasmid copy number; and (v) ColE1 plasmid-mediated DNA replication of the lambda phage-ColE1 chimera lambda imm434 Oam29 Pam3 ColE1 is inhibited by ColE1-incompatible but not by ColE1-compatible plasmids. Images PMID:378980

  14. Adenovirus type 5 E1A sensitizes hepatocellular carcinoma cells to gemcitabine.

    PubMed

    Lee, Wei-Ping; Tai, Dar-In; Tsai, Sun-Lung; Yeh, Chau-Ting; Chao, Yee; Lee, Shou-Dong; Hung, Mien-Chie

    2003-10-01

    Hepatocellular carcinoma (HCC) is resistant to conventional chemotherapy. A few clinical trials have shown that the cytidine analogue gemcitabine appears to have antitumor activity for HCC, but the overall survival times remain to be improved. In this study, we examined the synergistic effect of adenovirus type 5 E1A (E1A) and gemcitabine on HCC and found that E1A sensitized J5, J7, Huh7, and HepG2 HCC cells to gemcitabine. To further study the E1A-mediated chemosensitization, we established stable cell lines that expressed the E1A gene and then examined whether E1A could have proapoptotic activity while expressed in HCC cells. Our results clearly showed that E1A sensitized HCC cells to gemcitabine through induction of apoptosis. To study the underlying mechanism, we tested nuclear factor (NF)-kappaB activity and found that NF-kappaB was activated in HCC cells treated with gemcitabine but not in HCC cells that expressed E1A. Occurrence of apoptosis entails cleavage of poly (ADP-ribose) polymerase (PARP), a nuclear protein involved in DNA repair, genome stability, and maintenance of telomere length. Our study showed that gemcitabine enhanced PARP expression. However, E1A did not induce PARP cleavage but rather suppressed PARP expression at the transcriptional level. Further study showed that both NF-kappaB and PARP played protective roles in the prevention of E1A+gemcitabine-induced apoptosis. PMID:14559808

  15. [Induction of rat hepatic CYP2E1 expression by arecoline in vivo].

    PubMed

    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. PMID:27405178

  16. Emergence and Phase Transitions

    NASA Astrophysics Data System (ADS)

    Sikkema, Arnold

    2006-05-01

    Phase transitions are well defined in physics through concepts such as spontaneous symmetry breaking, order parameter, entropy, and critical exponents. But emergence --- also exhibiting whole-part relations (such as top-down influence), unpredictability, and insensitivity to microscopic detail --- is a loosely-defined concept being used in many disciplines, particularly in psychology, biology, philosophy, as well as in physics[1,2]. I will review the concepts of emergence as used in the various fields and consider the extent to which the methods of phase transitions can clarify the usefulness of the concept of emergence both within the discipline of physics and beyond.1. Robert B. Laughlin, A Different Universe: Reinventing Physics from the Bottom Down (New York: Basic Books, 2005). 2. George F.R. Ellis, ``Physics and the Real World'', Physics Today, vol. 58, no. 7 (July 2005) pp. 49-54.

  17. 76 FR 81727 - Approval and Promulgation of Implementation Plans; Oklahoma; Federal Implementation Plan for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-28

    ... elements of Oklahoma's SIP. 76 FR 16168. Today, we are taking final action by partially approving and..., we published the proposal on which we are now taking final action. 76 FR 16168. We proposed to... because ODEQ ``did not properly follow the requirements of section 51.308(e)(1)(ii)(A).'' 76 FR 16168,...

  18. 75 FR 21008 - Office of Biotechnology Activities; Recombinant DNA Research: Proposed Actions Under the NIH...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-22

    ...) to address biosafety for research with synthetic nucleic acids (74 FR 9411). The proposal included... the proposed changes to Section III-E-1 (74 FR 9411), a substantively revised proposal has been...-1 and the other proposed revisions included in the March 2009 Federal Register (FR) notice....

  19. The frequency of cytochrome P450 2E1 polymorphisms in Black South Africans.

    PubMed

    Chelule, Paul K; Pegoraro, Rosemary J; Gqaleni, Nceba; Dutton, Michael F

    2006-01-01

    Polymorphisms in the promoter region of the Cytochrome P4502E1 (CYP2E1) gene reportedly modify the metabolic activity of CYP2E1 enzyme, and have been associated with increased susceptibility to squamous cell carcinoma (SCC) of the oesophagus in high prevalence areas such as China. To assess the frequency of these polymorphisms in Black South Africans, a population with a high incidence of oesophageal SCC, this study examined genomic DNA from 331 subjects for restriction fragment length polymorphisms in the CYP2E1 (RsaI and PstI digestion). The frequency of the CYP2E1 c1/c1 and c1/c3 genotypes was 95% and 5% respectively. The frequency of the CYP2E1 allele distribution was found to be markedly different between Chinese and South African populations; hence it is important to place racial differences into consideration when proposing allelic variants as genetic markers for cancer. PMID:17264406

  20. 26 CFR 1.1059(e)-1 - Non-pro rata redemptions.

    Code of Federal Regulations, 2010 CFR

    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...

  1. 26 CFR 1.414(e)-1 - Definition of church plan.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 5 2010-04-01 2010-04-01 false Definition of church plan. 1.414(e)-1 Section 1.414(e)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.414(e)-1 Definition of church plan. (a) General rule. For the...

  2. Largazole and Its Derivatives Selectively Inhibit Ubiquitin Activating Enzyme (E1)

    PubMed Central

    Nasveschuk, Christopher G.; Wang, Wei; Quade, Bettina; Zhang, Gan; Kuchta, Robert D.; Phillips, Andrew J.; Liu, Xuedong

    2012-01-01

    Protein ubiquitination plays an important role in the regulation of almost every aspect of eukaryotic cellular function; therefore, its destabilization is often observed in most human diseases and cancers. Consequently, developing inhibitors of the ubiquitination system for the treatment of cancer has been a recent area of interest. Currently, only a few classes of compounds have been discovered to inhibit the ubiquitin-activating enzyme (E1) and only one class is relatively selective in E1 inhibition in cells. We now report that Largazole and its ester and ketone analogs selectively inhibit ubiquitin conjugation to p27Kip1 and TRF1 in vitro. The inhibitory activity of these small molecules on ubiquitin conjugation has been traced to their inhibition of the ubiquitin E1 enzyme. To further dissect the mechanism of E1 inhibition, we analyzed the effects of these inhibitors on each of the two steps of E1 activation. We show that Largazole and its derivatives specifically inhibit the adenylation step of the E1 reaction while having no effect on thioester bond formation between ubiquitin and E1. E1 inhibition appears to be specific to human E1 as Largazole ketone fails to inhibit the activation of Uba1p, a homolog of E1 in Schizosaccharomyces pombe. Moreover, Largazole analogs do not significantly inhibit SUMO E1. Thus, Largazole and select analogs are a novel class of ubiquitin E1 inhibitors and valuable tools for studying ubiquitination in vitro. This class of compounds could be further developed and potentially be a useful tool in cells. PMID:22279528

  3. Expression and characterization of a soluble rubella virus E1 envelope protein.

    PubMed

    Seto, N O; Gillam, S

    1994-10-01

    Individual specific antigenic rubella virus (RV) structural proteins are required for accurate serological diagnosis of acute and congenital rubella infections as well as rubella immune status. The RV envelope glycoprotein E1 is the major target antigen and plays an important role in viral-specific immune responses. The native virion is difficult to produce in large quantities and the protein subunits are also difficult to isolate without loss of antigenicity. The production of a soluble RV E1 (designated E1 delta Tm) using the baculovirus-insect cell expression system is described. In contrast to wild-type RV E1, the genetically engineered E1 delta Tm protein lacks a transmembrane anchor. It behaved as a secretory protein and was secreted abundantly from insect cells. Pulse-chase studies were used to examine the synthesis, glycosylation, and secretion of E1 delta Tm by the insect cells. The secreted E1 delta Tm protein was purified from serum-free medium by one-step immunochromatography. The purified E1 delta Tm protein retained full antigenicity and may be a convenient source of E1 protein for use in diagnostic assay and rubella vaccine development. PMID:7852960

  4. Identification and characterization of multiple conserved nuclear localization signals within adenovirus E1A

    SciTech Connect

    Marshall, Kris S.; Cohen, Michael J.; Fonseca, Greg J.; Todorovic, Biljana; King, Cason R.; Yousef, Ahmed F.; Zhang, Zhiying; Mymryk, Joe S.

    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. Optical properties of Ge-rich G e1 -xS ix alloys: Compositional dependence of the lowest direct and indirect gaps

    NASA Astrophysics Data System (ADS)

    Xu, Chi; Gallagher, J. D.; Senaratne, C. L.; Menéndez, J.; Kouvetakis, J.

    2016-03-01

    Ge-rich G e1 -xS ix alloys have been investigated using spectroscopic ellipsometry and photoluminescence at room temperature. Special emphasis was placed on the compositional dependence of the lowest-energy interband transitions. For x ≤0.05 , a compositional range of particular interest for modern applications, we find E0=0.799 (1 ) +3.214 (45 ) x +0.080 (44 ) x2 (in eV) for the lowest direct gap. The compositional dependence of the indirect gap is obtained from photoluminescence as Eind=0.659 (4 ) +1.18 (17 ) x (in eV). We find no significant discrepancies between these results and the extrapolations from measurements at higher Si concentrations. Such discrepancies had been suggested by recent work on G e1 -xS ix films on Si. Accurate knowledge of the interband transition energies is an important requirement for the design of devices incorporating Ge-rich G e1 -xS ix alloys and for the understanding of more complex systems, such as ternary G e1 -x -yS ixS ny alloys, in terms of its binary constituents.

  6. Sex steroid hormones regulate constitutive expression of Cyp2e1 in female mouse liver

    PubMed Central

    Cheng, Jie; Gonzalez, Frank J.

    2013-01-01

    CYP2E1 is of paramount toxicological significance because it metabolically activates a large number of low-molecular-weight toxicants and carcinogens. In this context, factors that interfere with Cyp2e1 regulation may critically affect xenobiotic toxicity and carcinogenicity. The aim of this study was to investigate the role of female steroid hormones in the regulation of CYP2E1, as estrogens and progesterone are the bases of contraceptives and hormonal replacement therapy in menopausal women. Interestingly, a fluctuation in the hepatic expression pattern of Cyp2e1 was revealed in the different phases of the estrous cycle of female mice, with higher Cyp2e1 expression at estrus (E) and lower at methestrus (ME), highly correlated with that in plasma gonadal hormone levels. Depletion of sex steroids by ovariectomy repressed Cyp2e1 expression to levels similar to those detected in males and cyclic females at ME. Hormonal supplementation brought Cyp2e1 expression back to levels detected at E. The role of progesterone appeared to be more prominent than that of 17β-estradiol. Progesterone-induced Cyp2e1 upregulation could be attributed to inactivation of the insulin/PI3K/Akt/FOXO1 signaling pathway. Tamoxifen, an anti-estrogen, repressed Cyp2e1 expression potentially via activation of the PI3K/Akt/FOXO1 and GH/STAT5b-linked pathways. The sex steroid hormone-related changes in hepatic Cyp2e1 expression were highly correlated with those observed in Hnf-1α, β-catenin, and Srebp-1c. In conclusion, female steroid hormones are clearly involved in the regulation of CYP2E1, thus affecting the metabolism of a plethora of toxicants and carcinogenic agents, conditions that may trigger several pathologies or exacerbate the outcomes of various pathophysiological states. PMID:23548611

  7. Ubiquitin-dependent Proteasomal Degradation of Human Liver Cytochrome P450 2E1

    PubMed Central

    Wang, YongQiang; Guan, Shenheng; Acharya, Poulomi; Koop, Dennis R.; Liu, Yi; Liao, Mingxiang; Burlingame, Alma L.; Correia, Maria Almira

    2011-01-01

    Human liver CYP2E1 is a monotopic, endoplasmic reticulum-anchored cytochrome P450 responsible for the biotransformation of clinically relevant drugs, low molecular weight xenobiotics, carcinogens, and endogenous ketones. CYP2E1 substrate complexation converts it into a stable slow-turnover species degraded largely via autophagic lysosomal degradation. Substrate decomplexation/withdrawal results in a fast turnover CYP2E1 species, putatively generated through its futile oxidative cycling, that incurs endoplasmic reticulum-associated ubiquitin-dependent proteasomal degradation (UPD). CYP2E1 thus exhibits biphasic turnover in the mammalian liver. We now show upon heterologous expression of human CYP2E1 in Saccharomyces cerevisiae that its autophagic lysosomal degradation and UPD pathways are evolutionarily conserved, even though its potential for futile catalytic cycling is low due to its sluggish catalytic activity in yeast. This suggested that other factors (i.e. post-translational modifications or “degrons”) contribute to its UPD. Indeed, in cultured human hepatocytes, CYP2E1 is detectably ubiquitinated, and this is enhanced on its mechanism-based inactivation. Studies in Ubc7p and Ubc5p genetically deficient yeast strains versus corresponding isogenic wild types identified these ubiquitin-conjugating E2 enzymes as relevant to CYP2E1 UPD. Consistent with this, in vitro functional reconstitution analyses revealed that mammalian UBC7/gp78 and UbcH5a/CHIP E2-E3 ubiquitin ligases were capable of ubiquitinating CYP2E1, a process enhanced by protein kinase (PK) A and/or PKC inclusion. Inhibition of PKA or PKC blocked intracellular CYP2E1 ubiquitination and turnover. Here, through mass spectrometric analyses, we identify some CYP2E1 phosphorylation/ubiquitination sites in spatially associated clusters. We propose that these CYP2E1 phosphorylation clusters may serve to engage each E2-E3 ubiquitination complex in vitro and intracellularly. PMID:21209460

  8. Nr2e1 Deficiency Augments Palmitate-Induced Oxidative Stress in Beta Cells

    PubMed Central

    Shi, Xiaoli; Deng, Haohua; Dai, Zhe; Xu, Yancheng; Xiong, Xiaokan; Ma, Pei; Cheng, Jing

    2016-01-01

    Nuclear receptor subfamily 2 group E member 1 (Nr2e1) has been regarded as an essential regulator of the growth of neural stem cells. However, its function elsewhere is unknown. In the present study, we generated Nr2e1 knockdown MIN6 cells and studied whether Nr2e1 knockdown affected basal beta cell functions such as proliferation, cell death, and insulin secretion. We showed that knockdown of Nr2e1 in MIN6 cells resulted in increased sensitivity to lipotoxicity, decreased proliferation, a partial G0/G1 cell-cycle arrest, and higher rates of apoptosis. Moreover, Nr2e1 deficiency exaggerates palmitate-induced impairment in insulin secretion. At the molecular level, Nr2e1 deficiency augments palmitate-induced oxidative stress. Nr2e1 deficiency also resulted in decreases in antioxidant enzymes and expression level of Nrf2. Together, this study indicated a potential protective effect of Nr2e1 on beta cells, which may serve as a target for the development of novel therapies for diabetes. PMID:26649147

  9. 26 CFR 1.665(e)-1A - Preceding taxable year.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 8 2011-04-01 2011-04-01 false Preceding taxable year. 1.665(e)-1A Section 1... (CONTINUED) INCOME TAXES (CONTINUED) Treatment of Excess Distributions of Trusts Applicable to Taxable Years Beginning on Or After January 1, 1969 § 1.665(e)-1A Preceding taxable year. (a) Definition—(1)...

  10. 26 CFR 1.665(e)-1A - Preceding taxable year.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Preceding taxable year. 1.665(e)-1A Section 1... (CONTINUED) INCOME TAXES Treatment of Excess Distributions of Trusts Applicable to Taxable Years Beginning on Or After January 1, 1969 § 1.665(e)-1A Preceding taxable year. (a) Definition—(1) Domestic...

  11. 26 CFR 48.4216(e)-1 - Exclusion of local advertising charges from sale price.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 16 2011-04-01 2011-04-01 false Exclusion of local advertising charges from sale price. 48.4216(e)-1 Section 48.4216(e)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) MISCELLANEOUS EXCISE TAXES MANUFACTURERS AND RETAILERS EXCISE TAXES Special Provisions Applicable to Manufacturers Taxes §...

  12. 26 CFR 1.263(e)-1 - Expenditures in connection with certain railroad rolling stock.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... by the Interstate Commerce Commission (49 CFR Part 1201), but only if (i) such unit exclusively moves... rolling stock. 1.263(e)-1 Section 1.263(e)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Items Not Deductible §...

  13. Resolvin E1 and chemokine-like receptor 1 mediate bone preservation.

    PubMed

    Gao, Li; Faibish, Dan; Fredman, Gabrielle; Herrera, Bruno S; Chiang, Nan; Serhan, Charles N; Van Dyke, Thomas E; Gyurko, Robert

    2013-01-15

    The polyunsaturated ω-3 fatty acid eicosapentaenoic acid-derived resolvin E1 (RvE1) enhances resolution of inflammation, prevents bone loss, and induces bone regeneration. Although the inflammation-resolving actions of RvE1 are characterized, the molecular mechanism of its bone-protective actions are of interest. To test the hypothesis that receptor-mediated events impact bone changes, we prepared transgenic mice overexpressing the RvE1 receptor chemokine-like receptor 1 (chemR23) on leukocytes. In zymosan-initiated peritonitis, neutrophil polymorphonuclear leukocyte infiltration in response to RvE1 was limited requiring log order lower doses in chemR23tg mice. Ligature-induced alveolar bone loss was diminished in chemR23tg mice. Local RvE1 treatment of uniform craniotomy in the parietal bone significantly accelerated regeneration of the bone defect. In in vitro bone cultures, RvE1 significantly enhanced expression of osteoprotegerin (OPG) without inducing change in receptor activator of NF-κB ligand levels, whereas the osteogenic markers alkaline phosphatase, bone sialoprotein, and Runt-related transcription factor 2 remained unchanged. These results indicate that RvE1 modulates osteoclast differentiation and bone remodeling by direct actions on bone, rescuing OPG production and restoring a favorable receptor activator of NF-κB ligand/OPG ratio, in addition to known anti-inflammatory and proresolving actions. PMID:23241890

  14. 26 CFR 1.1031(e)-1 - Exchange of livestock of different sexes.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 11 2014-04-01 2014-04-01 false Exchange of livestock of different sexes. 1.1031(e)-1 Section 1.1031(e)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... Exchange of livestock of different sexes. Section 1031(e) provides that livestock of different sexes...

  15. 26 CFR 1.1031(e)-1 - Exchange of livestock of different sexes.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 11 2012-04-01 2012-04-01 false Exchange of livestock of different sexes. 1.1031(e)-1 Section 1.1031(e)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... Exchange of livestock of different sexes. Section 1031(e) provides that livestock of different sexes...

  16. 26 CFR 1.1031(e)-1 - Exchange of livestock of different sexes.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 11 2013-04-01 2013-04-01 false Exchange of livestock of different sexes. 1.1031(e)-1 Section 1.1031(e)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... Exchange of livestock of different sexes. Section 1031(e) provides that livestock of different sexes...

  17. 26 CFR 1.1031(e)-1 - Exchange of livestock of different sexes.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 11 2010-04-01 2010-04-01 true Exchange of livestock of different sexes. 1.1031(e)-1 Section 1.1031(e)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... livestock of different sexes. Section 1031(e) provides that livestock of different sexes are not property...

  18. 26 CFR 1.1031(e)-1 - Exchange of livestock of different sexes.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 11 2011-04-01 2011-04-01 false Exchange of livestock of different sexes. 1.1031(e)-1 Section 1.1031(e)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... Exchange of livestock of different sexes. Section 1031(e) provides that livestock of different sexes...

  19. 26 CFR 31.3121(e)-1 - State, United States, and citizen.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 15 2011-04-01 2011-04-01 false State, United States, and citizen. 31.3121(e)-1... § 31.3121(e)-1 State, United States, and citizen. (a) When used in the regulations in this subpart, the..., the term “United States”, when used in a geographical sense, means the several states (including...

  20. 17 CFR 270.30e-1 - Reports to stockholders of management companies.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Reports to stockholders of management companies. 270.30e-1 Section 270.30e-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE... stockholders of management companies. (a) Every registered management company shall transmit to...

  1. 26 CFR 1.509(e)-1 - Definition of gross investment income.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 7 2013-04-01 2013-04-01 false Definition of gross investment income. 1.509(e)-1 Section 1.509(e)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... gross investment income. For the distinction between gross receipts and gross investment income, see §...

  2. CK2 Phosphorylation Inactivates DNA Binding by the Papillomavirus E1 and E2 Proteins

    PubMed Central

    Schuck, Stephen; Ruse, Cristian

    2013-01-01

    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. PMID:23637413

  3. Resolvin E1 inhibits dendritic cell migration in the skin and attenuates contact hypersensitivity responses.

    PubMed

    Sawada, Yu; Honda, Tetsuya; Hanakawa, Sho; Nakamizo, Satoshi; Murata, Teruasa; Ueharaguchi-Tanada, Yuri; Ono, Sachiko; Amano, Wataru; Nakajima, Saeko; Egawa, Gyohei; Tanizaki, Hideaki; Otsuka, Atsushi; Kitoh, Akihiko; Dainichi, Teruki; Ogawa, Narihito; Kobayashi, Yuichi; Yokomizo, Takehiko; Arita, Makoto; Nakamura, Motonobu; Miyachi, Yoshiki; Kabashima, Kenji

    2015-10-19

    Resolvin E1 (RvE1) is a lipid mediator derived from ω3 polyunsaturated fatty acids that exerts potent antiinflammatory roles in several murine models. The antiinflammatory mechanism of RvE1 in acquired immune responses has been attributed to attenuation of cytokine production by dendritic cells (DCs). In this study, we newly investigated the effect of RvE1 on DC motility using two-photon microscopy in a contact hypersensitivity (CHS) model and found that RvE1 impaired DC motility in the skin. In addition, RvE1 attenuated T cell priming in the draining lymph nodes and effector T cell activation in the skin, which led to the reduced skin inflammation in CHS. In contrast, leukotriene B4 (LTB4) induced actin filament reorganization in DCs and increased DC motility by activating Cdc42 and Rac1 via BLT1, which was abrogated by RvE1. Collectively, our results suggest that RvE1 attenuates cutaneous acquired immune responses by inhibiting cutaneous DC motility, possibly through LTB4-BLT1 signaling blockade. PMID:26438363

  4. Resolvin E1 inhibits dendritic cell migration in the skin and attenuates contact hypersensitivity responses

    PubMed Central

    Sawada, Yu; Hanakawa, Sho; Nakamizo, Satoshi; Murata, Teruasa; Ueharaguchi-Tanada, Yuri; Ono, Sachiko; Amano, Wataru; Nakajima, Saeko; Egawa, Gyohei; Tanizaki, Hideaki; Otsuka, Atsushi; Kitoh, Akihiko; Dainichi, Teruki; Ogawa, Narihito; Kobayashi, Yuichi; Yokomizo, Takehiko; Arita, Makoto; Nakamura, Motonobu; Miyachi, Yoshiki

    2015-01-01

    Resolvin E1 (RvE1) is a lipid mediator derived from ω3 polyunsaturated fatty acids that exerts potent antiinflammatory roles in several murine models. The antiinflammatory mechanism of RvE1 in acquired immune responses has been attributed to attenuation of cytokine production by dendritic cells (DCs). In this study, we newly investigated the effect of RvE1 on DC motility using two-photon microscopy in a contact hypersensitivity (CHS) model and found that RvE1 impaired DC motility in the skin. In addition, RvE1 attenuated T cell priming in the draining lymph nodes and effector T cell activation in the skin, which led to the reduced skin inflammation in CHS. In contrast, leukotriene B4 (LTB4) induced actin filament reorganization in DCs and increased DC motility by activating Cdc42 and Rac1 via BLT1, which was abrogated by RvE1. Collectively, our results suggest that RvE1 attenuates cutaneous acquired immune responses by inhibiting cutaneous DC motility, possibly through LTB4-BLT1 signaling blockade. PMID:26438363

  5. 26 CFR 1.665(e)-1A - Preceding taxable year.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 8 2012-04-01 2012-04-01 false Preceding taxable year. 1.665(e)-1A Section 1... (CONTINUED) INCOME TAXES (CONTINUED) Treatment of Excess Distributions of Trusts Applicable to Taxable Years Beginning on Or After January 1, 1969 § 1.665(e)-1A Preceding taxable year. (a) Definition—(1)...

  6. 26 CFR 1.665(e)-1A - Preceding taxable year.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 8 2014-04-01 2014-04-01 false Preceding taxable year. 1.665(e)-1A Section 1... (CONTINUED) INCOME TAXES (CONTINUED) Treatment of Excess Distributions of Trusts Applicable to Taxable Years Beginning on Or After January 1, 1969 § 1.665(e)-1A Preceding taxable year. (a) Definition—(1)...

  7. Distinct Features of Cap Binding by eIF4E1b Proteins

    PubMed Central

    Kubacka, Dorota; Miguel, Ricardo Núñez; Minshall, Nicola; Darzynkiewicz, Edward; Standart, Nancy; Zuberek, Joanna

    2015-01-01

    eIF4E1b, closely related to the canonical translation initiation factor 4E (eIF4E1a), cap-binding protein is highly expressed in mouse, Xenopus and zebrafish oocytes. We have previously characterized eIF4E1b as a component of the CPEB mRNP translation repressor complex along with the eIF4E-binding protein 4E-Transporter, the Xp54/DDX6 RNA helicase and additional RNA-binding proteins. eIF4E1b exhibited only very weak interactions with m7GTP-Sepharose and, rather than binding eIF4G, interacted with 4E-T. Here we undertook a detailed examination of both Xenopus and human eIF4E1b interactions with cap analogues using fluorescence titration and homology modeling. The predicted structure of eIF4E1b maintains the α + β fold characteristic of eIF4E proteins and its cap-binding pocket is similarly arranged by critical amino acids: Trp56, Trp102, Glu103, Trp166, Arg112, Arg157 and Lys162 and residues of the C-terminal loop. However, we demonstrate that eIF4E1b is 3-fold less well able to bind the cap than eIF4E1a, both proteins being highly stimulated by methylation at N7 of guanine. Moreover, eIF4E1b proteins are distinguishable from eIF4E1a by a set of conserved amino acid substitutions, several of which are located near to cap-binding residues. Indeed, eIF4E1b possesses several distinct features, namely, enhancement of cap binding by a benzyl group at N7 position of guanine, a reduced response to increasing length of the phosphate chain and increased binding to a cap separated by a linker from Sepharose, suggesting differences in the arrangement of the protein's core. In agreement, mutagenesis of the amino acids differentiating eIF4E1b from eIF4E1a reduces cap binding by eIF4E1a 2-fold, demonstrating their role in modulating cap binding. PMID:25463438

  8. Oxidative stress mediated toxicity exerted by ethanol-inducible CYP2E1

    SciTech Connect

    Wu Defeng; Cederbaum, Arthur I. . E-mail: arthur.cederbaum@mssm.edu

    2005-09-01

    Induction of CYP2E1 by ethanol is one of the central pathways by which ethanol generates a state of oxidative stress in hepatocytes. To study the biochemical and toxicological actions of CYP2E1, our laboratory established HepG2 cell lines which constitutively overexpress CYP2E1 and characterized these cells with respect to ethanol toxicity. Addition of ethanol or an unsaturated fatty acid such as arachidonic acid or iron was toxic to the CYP2E1-expressing cells but not control cells. This toxicity was associated with elevated lipid peroxidation and could be prevented by antioxidants and inhibitors of CYP2E1. Apoptosis occurred in the CYP2E1-expressing cells exposed to ethanol, arachidonic acid, or iron. Removal of GSH caused a loss of viability in the CYP2E1-expressing cells even in the absence of added toxin or pro-oxidant. This was associated with mitochondrial damage and decreased mitochondrial membrane potential. Low concentrations of iron and arachidonic acid synergistically interacted with CYP2E1 to produce cell toxicity, suggesting these nutrients may act as priming or sensitizing agents to alcohol-induced liver injury. Surprisingly, CYP2E1-expressing cells had elevated GSH levels, due to transcriptional activation of glutamate cysteine ligase. Similarly, levels of catalase, alpha-, and microsomal glutathione transferase were also increased, suggesting that upregulation of these antioxidant genes may reflect an adaptive mechanism to remove CYP2E1-derived oxidants. Using co-cultures, interaction between CYP2E1-derived diffusible mediators to activate collagen production in hepatic stellate cells was found. While it is likely that several mechanisms contribute to alcohol-induced liver injury, the linkage between CYP2E1-dependent oxidative stress, mitochondrial injury, stellate cell activation, and GSH homeostasis may contribute to the toxic action of ethanol on the liver. HepG2 cell lines overexpressing CYP2E1 may be a valuable model to characterize the

  9. The Equine Herpesvirus 2 E1 Open Reading Frame Encodes a Functional Chemokine Receptor

    PubMed Central

    Camarda, Grazia; Spinetti, Gaia; Bernardini, Giovanni; Mair, Catherine; Davis-Poynter, Nick; Capogrossi, Maurizio C.; Napolitano, Monica

    1999-01-01

    Several herpesviruses contain open reading frames (ORFs) that encode potential homologs of eucaryotic genes. Equine herpesvirus 2 (EHV-2) is a gammaherpesvirus related to other lymphotropic herpesviruses such as herpesvirus saimiri and Epstein-Barr virus. The E1 ORF of EHV-2, a G protein-coupled receptor homolog, shows 31 to 47% amino acid identity with known CC chemokine receptors. To investigate whether E1 may encode a functional receptor, we cloned the E1 ORF and expressed it in stably transfected cell lines. We report here the identification of the CC chemokine eotaxin as a functional ligand for the EHV-2 E1 receptor. Chemokines are likely to play a role in the regulation of immune functions in equine hosts during EHV-2 infection and, via interaction with E1, may affect viral replication and/or escape from immune responses. PMID:10559296

  10. Beyond Oncolytics: E1B55K-Deleted Adenovirus as a Vaccine Delivery Vector.

    PubMed

    Thomas, Michael A; Nyanhete, Tinashe; Tuero, Iskra; Venzon, David; Robert-Guroff, Marjorie

    2016-01-01

    Type 5 human adenoviruses (Ad5) deleted of genes encoding the early region 1B 55-kDa (E1B55K) protein including Onyx-015 (dl1520) and H101 are best known for their oncolytic potential. As a vaccine vector the E1B55K deletion may allow for the insertion of a transgene nearly 1,000 base pairs larger than now possible. This has the potential of extending the application for which the vectors are clinically known. However, the immune priming ability of E1B55K-deleted vectors is unknown, undermining our ability to gauge their usefulness in vaccine applications. For this reason, we created an E1B55K-deleted Ad5 vector expressing full-length single chain HIVBaLgp120 attached to a flexible linker and the first two domains of rhesus CD4 (rhFLSC) in exchange for the E3 region. In cell-based experiments the E1B55K-deleted vector promoted higher levels of innate immune signals including chemokines, cytokines, and the NKG2D ligands MIC A/B compared to an E1B55K wild-type vector expressing the same immunogen. Based on these results we evaluated the immune priming ability of the E1B55K-deleted vector in mice. The E1B55K-deleted vector promoted similar levels of Ad5-, HIVgp120, and rhFLSC-specific cellular and humoral immune responses as the E1B55K wild-type vector. In pre-clinical HIV-vaccine studies the wild-type vector has been employed as part of a very effective prime-boost strategy. This study demonstrates that E1B55K-deleted adenoviruses may serve as effective vaccine delivery vectors. PMID:27391605

  11. Role of CYP2E1 in thioacetamide-induced mouse hepatotoxicity

    SciTech Connect

    Kang, Jin Seok; Wanibuchi, Hideki; Morimura, Keiichirou; Wongpoomchai, Rawiwan; Chusiri, Yaowares; Gonzalez, Frank J.; Fukushima, Shoji

    2008-05-01

    Previous experiments showed that treatment of mice and rats with thioacetamide (TAA) induced liver cell damage, fibrosis and/or cirrhosis, associated with increased oxidative stress and activation of hepatic stellate cells. Some experiments suggest that CYP2E1 may be involved in the metabolic activation of TAA. However, there is no direct evidence on the role of CYP2E1 in TAA-mediated hepatotoxicity. To clarify this, TAA-induced hepatotoxicity was investigated using Cyp2e1-null mice. Male wild-type and Cyp2e1-null mice were treated with TAA (200 mg/kg of body weight, single, i.p.) at 6 weeks of age, and hepatotoxicity examined 24 and 48 h after TAA treatment. Relative liver weights of Cyp2e1-null mice were significantly different at 24 h compared to wild-type mice (p < 0.01). Serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) in Cyp2e1-null mice were significantly different at both time points compared to wild-type mice (p < 0.01). Histopathological examination showed Cyp2e1-null mice represented no hepatototoxic lesions, in clear contrast to severe centriobular necrosis, inflammation and hemorrhage at both time points in wild-type mice. Marked lipid peroxidation was also only limited to wild-type mice (p < 0.01). Similarly, TNF-{alpha}, IL-6 and glutathione peroxidase mRNA expression in Cyp2e1-null mice did not significantly differ from the control levels, contrasting with the marked alteration in wild-type mice (p < 0.01). Western blot analysis further revealed no increase in iNOS expression in Cyp2e1-null mice. These results reveal that CYP2E1 mediates TAA-induced hepatotoxicity in wild-type mice as a result of increased oxidative stress.

  12. Architecture of the hepatitis C virus E1 glycoprotein transmembrane domain studied by NMR.

    PubMed

    Zazrin, Hadas; Shaked, Hadassa; Chill, Jordan H

    2014-03-01

    Oligomerization of hepatitis C viral envelope proteins E1 and E2 is essential to virus fusion and assembly. Although interactions within the transmembrane (TM) domains of these glycoproteins have proven contributions to the E1/E2 heterodimerization process and consequent infectivity, there is little structural information on this entry mechanism. Here, as a first step towards our long-term goal of understanding the interaction between E1 and E2 TM-domains, we have expressed, purified and characterized E1-TM using structural biomolecular NMR methods. An MBP-fusion expression system yielded sufficient quantities of pure E1-TM, which was solubilized in two membrane-mimicking environments, SDS- and LPPG-micelles, affording samples amenable to NMR studies. Triple resonance assignment experiments and relaxation measurements provided information on the secondary structure and global fold of E1-TM in these environments. In SDS micelles E1-TM adopts a helical conformation, with helical stretches at residues 354-363 and 371-379 separated by a more flexible segment of residues 364-370. In LPPG micelles a helical conformation was observed for residues 354-377 with greater flexibility in the 366-367 dyad, suggesting LPPG provides a more native environment for the peptide. Replacement of key positively charged residue K370 with an alanine did not affect the secondary structure of E1-TM but did change the relative positioning within the micelle of the two helices. These results lay the foundation for structure determination of E1-TM and a molecular understanding of how E1-TM flexibility enhances its interaction with E2-TM during heterodimerization and membrane fusion. PMID:24192053

  13. Molecular mechanism of trichloroethylene-induced hepatotoxicity mediated by CYP2E1

    SciTech Connect

    Ramdhan, Doni Hikmat; Kamijima, Michihiro; Yamada, Naoyasu; Ito, Yuki; Yanagiba, Yukie; Nakamura, Daichi; Okamura, Ai; Ichihara, Gaku; Aoyama, Toshifumi; Gonzalez, Frank J.; Nakajima, Tamie

    2008-09-15

    Cytochrome P450 (CYP) 2E1 was suggested to be the major enzyme involved in trichloroethylene (TRI) metabolism and TRI-induced hepatotoxicity, although the latter molecular mechanism is not fully understood. The involvement of CYP2E1 in TRI-induced hepatotoxicity and its underlying molecular mechanism were studied by comparing hepatotoxicity in cyp2e1{sup +/+} and cyp2e1{sup -/-} mice. The mice were exposed by inhalation to 0 (control), 1000, or 2000 ppm of TRI for 8 h a day, for 7 days, and TRI-hepatotoxicity was assessed by measuring plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and histopathology. Urinary metabolites of trichloroethanol and trichloroacetic acid (TCA) were considerably greater in cyp2e1{sup +/+} compared to cyp2e1{sup -/-} mice, suggesting that CYP2E1 is the major P450 involved in the formation of these metabolites. Consistent with elevated plasma ALT and AST activities, cyp2e1{sup +/+} mice in the 2000 ppm group showed histopathological inflammation. TRI significantly upregulated PPAR{alpha}, which might function to inhibit NF{kappa}B p50 and p65 signalling. In addition, TRI-induced NF{kappa}B p52 mRNA, and significantly positive correlation between NF{kappa}B p52 mRNA expression and plasma ALT activity levels were observed, suggesting the involvement of p52 in liver inflammation. Taken together, the current study directly demonstrates that CYP2E1 was the major P450 involved in the first step of the TRI metabolism, and the metabolites produced may have two opposing roles: one inducing hepatotoxicity and the other protecting against the toxicity. Intermediate metabolite(s) from TRI to chloral hydrate produced by CYP2E1-mediated oxidation may be involved in the former, and TCA in the latter.

  14. Beyond Oncolytics: E1B55K-Deleted Adenovirus as a Vaccine Delivery Vector

    PubMed Central

    Thomas, Michael A.; Nyanhete, Tinashe; Tuero, Iskra; Venzon, David; Robert-Guroff, Marjorie

    2016-01-01

    Type 5 human adenoviruses (Ad5) deleted of genes encoding the early region 1B 55-kDa (E1B55K) protein including Onyx-015 (dl1520) and H101 are best known for their oncolytic potential. As a vaccine vector the E1B55K deletion may allow for the insertion of a transgene nearly 1,000 base pairs larger than now possible. This has the potential of extending the application for which the vectors are clinically known. However, the immune priming ability of E1B55K-deleted vectors is unknown, undermining our ability to gauge their usefulness in vaccine applications. For this reason, we created an E1B55K-deleted Ad5 vector expressing full-length single chain HIVBaLgp120 attached to a flexible linker and the first two domains of rhesus CD4 (rhFLSC) in exchange for the E3 region. In cell-based experiments the E1B55K-deleted vector promoted higher levels of innate immune signals including chemokines, cytokines, and the NKG2D ligands MIC A/B compared to an E1B55K wild-type vector expressing the same immunogen. Based on these results we evaluated the immune priming ability of the E1B55K-deleted vector in mice. The E1B55K-deleted vector promoted similar levels of Ad5-, HIVgp120, and rhFLSC-specific cellular and humoral immune responses as the E1B55K wild-type vector. In pre-clinical HIV-vaccine studies the wild-type vector has been employed as part of a very effective prime-boost strategy. This study demonstrates that E1B55K-deleted adenoviruses may serve as effective vaccine delivery vectors. PMID:27391605

  15. Crystal structure of a Na+-bound Na+,K+-ATPase preceding the E1P state.

    PubMed

    Kanai, Ryuta; Ogawa, Haruo; Vilsen, Bente; Cornelius, Flemming; Toyoshima, Chikashi

    2013-10-10

    Na(+),K(+)-ATPase pumps three Na(+) ions out of cells in exchange for two K(+) taken up from the extracellular medium per ATP molecule hydrolysed, thereby establishing Na(+) and K(+) gradients across the membrane in all animal cells. These ion gradients are used in many fundamental processes, notably excitation of nerve cells. Here we describe 2.8 Å-resolution crystal structures of this ATPase from pig kidney with bound Na(+), ADP and aluminium fluoride, a stable phosphate analogue, with and without oligomycin that promotes Na(+) occlusion. These crystal structures represent a transition state preceding the phosphorylated intermediate (E1P) in which three Na(+) ions are occluded. Details of the Na(+)-binding sites show how this ATPase functions as a Na(+)-specific pump, rejecting K(+) and Ca(2+), even though its affinity for Na(+) is low (millimolar dissociation constant). A mechanism for sequential, cooperative Na(+) binding can now be formulated in atomic detail. PMID:24089211

  16. Cytochrome P450 2E1 (CYP2E1) regulates the response to oxidative stress and migration of breast cancer cells

    PubMed Central

    2013-01-01

    Introduction The cytochrome P450 (CYP) enzymes are a class of heme-containing enzymes involved in phase I metabolism of a large number of xenobiotics. The CYP family member CYP2E1 metabolises many xenobiotics and pro-carcinogens, it is not just expressed in the liver but also in many other tissues such as the kidney, the lung, the brain, the gastrointestinal tract and the breast tissue. It is induced in several pathological conditions including cancer, obesity, and type II diabetes implying that this enzyme is implicated in other biological processes beyond its role in phase I metabolism. Despite the detailed description of the role of CYP2E1 in the liver, its functions in other tissues have not been extensively studied. In this study, we investigated the functional significance of CYP2E1 in breast carcinogenesis. Methods Cellular levels of reactive oxygen species (ROS) were measured by H2DCFDA (2 2.9.2 2′,7′-dichlorodihydrofluorescein diacetate) staining and autophagy was assessed by tracing the cellular levels of autophagy markers using western blot assays. The endoplasmic reticulum stress and the unfolded protein response (UPR) were detected by luciferase assays reflecting the splicing of mRNA encoding the X-box binding protein 1 (XBP1) transcription factor and cell migration was evaluated using the scratch wound assay. Gene expression was recorded with standard transcription assays including luciferase reporter and chromatin immunoprecipitation. Results Ectopic expression of CYP2E1 induced ROS generation, affected autophagy, stimulated endoplasmic reticulum stress and inhibited migration in breast cancer cells with different metastatic potential and p53 status. Furthermore, evidence is presented indicating that CYP2E1 gene expression is under the transcriptional control of the p53 tumor suppressor. Conclusions These results support the notion that CYP2E1 exerts an important role in mammary carcinogenesis, provide a potential link between ethanol metabolism

  17. 78 FR 70396 - Parts and Accessories Necessary for Safe Operation; Renewal of Exemption for Con-Way Freight, TK...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-25

    ..., 2010 (73 FR 82132) or you may visit http://edocket/ access.gpo.gov/2008/pdf/E8-785.pdf . FOR FURTHER... asked for public comment (75 FR 33666). Section 393.60(e)(1) of the FMCSRs prohibits the obstruction of... report described above. 2011 Notice of Final Disposition On November 18, 2011 (76 FR 71619),...

  18. 78 FR 6407 - Ability-to-Repay and Qualified Mortgage Standards Under the Truth in Lending Act (Regulation Z)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-30

    ... underwriting standards. See 73 FR 44524 (July 30, 2008). The following discussion provides background... rulemaking authority by section 1029 of the Dodd- Frank Act). 76 FR 79768 (Dec. 22, 2011). This rule did not... Regulation Z. See 60 FR 15463 (Mar. 24, 1995). In particular, Sec. 226.32(e)(1) \\42\\ implemented TILA...

  19. Orthogonal Ubiquitin Transfer through Engineered E1-E2 Cascades for Protein Ubiquitination

    PubMed Central

    Zhao, Bo; Bhuripanyo, Karan; Zhang, Keya; Kiyokawa, Hiroaki; Schindelin, Hermann; Yin, Jun

    2014-01-01

    SUMMARY Protein modification by ubiquitin (UB) controls diverse cellular processes. UB is conjugated to cellular proteins by sequential transfer through an E1-E2-E3 enzymatic cascade. The cross-activities of 2 E1s, 50 E2s and thousands of E3s encoded by the human genome make it difficult to identify the substrate proteins of a specific E3 enzyme in the cell. One way to solve this problem is to engineer an orthogonal UB transfer (OUT) cascade in which the engineered UB (xUB) is relayed by engineered E1, E2 and E3 enzymes (xE1, xE2, xE3) to modify the substrate proteins of a specific E3. Here, we use phage display and mutagenesis to construct xUB-xE1 and xE1-xE2 pairs that are orthogonal to the native E1 and E2 enzymes. Our work on engineering the UB transfer cascades will enable us to use OUT to map the signal transduction networks mediated by protein ubiquitination. PMID:23102221

  20. Intranuclear location of the adenovirus type 5 E1B 55-kilodalton protein.

    PubMed Central

    Smiley, J K; Young, M A; Flint, S J

    1990-01-01

    The intracellular location of the adenovirus type 5 E1B 55-kilodalton (kDa) protein, particularly the question of whether it is associated with nuclear pore complexes, was examined. Fractionation of adenovirus type 5-infected HeLa cell nuclei by an established procedure (N. Dwyer and G. Blobel, J. Cell. Biol. 70:581-591, 1976) yielded one population of E1B 55-kDa protein molecules released by digestion of nuclei with RNase A and a second population recovered in the pore complex-lamina fraction. Free and E1B 55-kDa protein-bound forms of the E4 34-kDa protein (P. Sarnow, C. A. Sullivan, and A. J. Levine, Virology 120:387-394, 1982) were largely recovered in the pore complex-lamina fraction. Nevertheless, the association of E1B 55-kDa protein molecules with this nuclear envelope fraction did not depend on interaction of the E1B 55-kDa protein with the E4 34-kDa protein. Comparison of the immunofluorescence patterns observed with antibodies recognizing the E1B 55-kDa protein or cellular pore complex proteins and of the behavior of these viral and cellular proteins during in situ fractionation suggests that the E1B 55-kDa protein does not become intimately or stably associated with pore complexes in adenovirus-infected cells. Images PMID:2143545

  1. Evidence for a tissue-specific induction of cutaneous CYP2E1 by dexamethasone.

    PubMed

    Sampol, E; Mirrione, A; Villard, P H; Piccerelle, P; Scoma, H; Berbis, P; Barra, Y; Durand, A; Lacarelle, B

    1997-06-27

    We studied in mouse the effect of topical application of dexamethasone or salicylic acid, on CYP2E1 and CYP3A expression (proteins and/or mRNA) in liver and skin. Dexamethasone was also administered by intraperitoneal injection. Topical application or intraperitoneal injection of dexamethasone increased cutaneous CYP2E1 (8 and 4-fold respectively) whereas the hepatic level of this isoform showed a slight decrease and hepatic CYP3A expression was increased (3-fold). Cutaneous CYP2E1 was increased (3-fold) after topical treatment by salicylic acid. This compound had no effect on hepatic CYP3A and CYP2E1 expression. Cutaneous CYP3A (protein and mRNA) was not detectable in all groups (control or treated animals). Dexamethasone and salicylic acid increased cutaneous CYP2E1 mRNA level (2.5 and 1.4-fold respectively). In conclusion, dexamethasone and salicylic acid induced cutaneous CYP2E1 protein and mRNA level. Cutaneous CYP2E1 induction by dexamethasone is a tissue-specific process. PMID:9207195

  2. E1A activates transcription of p73 and Noxa to induce apoptosis.

    PubMed

    Flinterman, Marcella; Guelen, Lars; Ezzati-Nik, Samira; Killick, Richard; Melino, Gerry; Tominaga, Kazuya; Mymryk, Joe S; Gäken, Joop; Tavassoli, Mahvash

    2005-02-18

    p73, a member of the p53 family of proteins, transcriptionally activates a number of genes involved in the control of cell cycle and apoptosis. Overexpression of p73 was detected in a large number of primary head and neck cancers, and in the established cell lines examined, these all contained inactivating p53 mutations. The significance of p73 overexpression in the pathogenesis of head and neck cancer is currently unclear. We have shown that the expression of adenovirus 5 E1A in a panel of head and neck cancer cell lines induces apoptosis independently of their p53 status. In this study we examined the role of p73 and its transcriptional targets in E1A-mediated induction of apoptosis. E1A expression resulted in significant activation of the TAp73 promoter but had no effect on the alternative, DeltaNp73 promoter. E1A also increased expression of endogenous TAp73 mRNA and protein. E1A mutants lacking the p300- and/or pRB-binding sites showed reduced ability to activate the TAp73 promoter. Additionally, mutations in the E2F1-binding sites in the TAp73 promoter impaired activation by E1A. Importantly, expression of the 13S isoform of E1A substantially induced the p53 apoptotic target Noxa in several p53-deficient cancer cell lines. Our results indicate that E1A activation of p73 and the p53 apoptotic target Noxa can occur in the absence of a functional p53. This activation is likely to play a key role in the mechanism of p53-independent apoptosis induced by E1A in some cancers and may provide an avenue for future cancer therapies. PMID:15572378

  3. Selective Time- and NADPH-Dependent Inhibition of Human CYP2E1 by Clomethiazole.

    PubMed

    Stresser, David M; Perloff, Elke S; Mason, Andrew K; Blanchard, Andrew P; Dehal, Shangara S; Creegan, Timothy P; Singh, Ritu; Gangl, Eric T

    2016-08-01

    The sedative clomethiazole (CMZ) has been used in Europe since the mid-1960s to treat insomnia and alcoholism. It has been previously demonstrated in clinical studies to reversibly inhibit human CYP2E1 in vitro and decrease CYP2E1-mediated elimination of chlorzoxazone. We have investigated the selectivity of CMZ inhibition of CYP2E1 in pooled human liver microsomes (HLMs). In a reversible inhibition assay of the major drug-metabolizing cytochrome P450 (P450) isoforms, CYP2A6 and CYP2E1 exhibited IC50 values of 24 µM and 42 µM, respectively with all other isoforms exhibiting values >300 µM. When CMZ was preincubated with NADPH and liver microsomal protein for 30 minutes before being combined with probe substrates, however, more potent inhibition was observed for CYP2E1 and CYP2B6 but not CYP2A6 or other P450 isoforms. The substantial increase in potency of CYP2E1 inhibition upon preincubation enables the use of CMZ to investigate the role of human CYP2E1 in xenobiotic metabolism and provides advantages over other chemical inhibitors of CYP2E1. The KI and kinact values obtained with HLM-catalyzed 6-hydroxylation of chlorzoxazone were 40 µM and 0.35 minute(-1), respectively, and similar to values obtained with recombinant CYP2E1 (41 µM, 0.32 minute(-1)). The KI and kinact values, along with other parameters, were used in a mechanistic static model to explain earlier observations of a profound decrease in the rate of chlorzoxazone elimination in volunteers despite the absence of detectable CMZ in blood. PMID:27149898

  4. Involvement of CYP 2E1 enzyme in ovotoxicity caused by 4-vinylcyclohexene and its metabolites.

    PubMed

    Rajapaksa, Kathila S; Cannady, Ellen A; Sipes, I Glenn; Hoyer, Patricia B

    2007-06-01

    4-Vinylcyclohexene (VCH) is bioactivated by hepatic CYP 2A and 2B to a monoepoxide (VCM) and subsequently to an ovotoxic diepoxide metabolite (VCD). Studies suggest that the ovary can directly bioactivate VCH via CYP 2E1. The current study was designed to evaluate the role of ovarian CYP 2E1 in VCM-induced ovotoxicity. Postnatal day 4 B6C3F(1) and CYP 2E1 wild-type (+/+) and null (-/-) mouse ovaries were cultured (15 days) with VCD (30 microM), 1,2-VCM (125-1000 microM), or vehicle. Twenty-eight days female CYP 2E1 +/+ and -/- mice were dosed daily (15 days; ip) with VCH, 1,2-VCM, VCD or vehicle. Following culture or in vivo dosing, ovaries were histologically evaluated. In culture, VCD decreased (p<0.05) primordial and primary follicles in ovaries from all three groups of mice. 1,2-VCM decreased (p<0.05) primordial follicles in B6C3F(1) and CYP 2E1 +/+ ovaries, but not in CYP 2E1 -/- ovaries in culture. 1,2-VCM did not affect primary follicles in any group of mouse ovaries. Conversely, following in vivo dosing, primordial and primary follicles were reduced (p<0.05) by VCD and VCM in CYP2E1 +/+ and -/-, and by VCH in +/+ mice. The data demonstrate that, whereas in vitro ovarian bioactivation of VCM requires CYP 2E1 enzyme, in vivo CYP 2E1 plays a minimal role. Thus, the findings support that hepatic metabolism dominates the contribution made by the ovary in bioactivation of VCM to its ovotoxic metabolite, VCD. This study also demonstrates the use of a novel ovarian culture system to evaluate ovary-specific metabolism of xenobiotics. PMID:17462685

  5. Involvement of CYP 2E1 enzyme in ovotoxicity caused by 4-vinylcyclohexene and its metabolites

    SciTech Connect

    Rajapaksa, Kathila S.; Cannady, Ellen A.; Sipes, I. Glenn; Hoyer, Patricia B. . E-mail: hoyer@u.arizona.edu

    2007-06-01

    4-Vinylcyclohexene (VCH) is bioactivated by hepatic CYP 2A and 2B to a monoepoxide (VCM) and subsequently to an ovotoxic diepoxide metabolite (VCD). Studies suggest that the ovary can directly bioactivate VCH via CYP 2E1. The current study was designed to evaluate the role of ovarian CYP 2E1 in VCM-induced ovotoxicity. Postnatal day 4 B6C3F{sub 1} and CYP 2E1 wild-type (+/+) and null (-/-) mouse ovaries were cultured (15 days) with VCD (30 {mu}M), 1,2-VCM (125-1000 {mu}M), or vehicle. Twenty-eight days female CYP 2E1 +/+ and -/- mice were dosed daily (15 days; ip) with VCH, 1,2-VCM, VCD or vehicle. Following culture or in vivo dosing, ovaries were histologically evaluated. In culture, VCD decreased (p < 0.05) primordial and primary follicles in ovaries from all three groups of mice. 1,2-VCM decreased (p < 0.05) primordial follicles in B6C3F{sub 1} and CYP 2E1 +/+ ovaries, but not in CYP 2E1 -/- ovaries in culture. 1,2-VCM did not affect primary follicles in any group of mouse ovaries. Conversely, following in vivo dosing, primordial and primary follicles were reduced (p < 0.05) by VCD and VCM in CYP2E1 +/+ and -/-, and by VCH in +/+ mice. The data demonstrate that, whereas in vitro ovarian bioactivation of VCM requires CYP 2E1 enzyme, in vivo CYP 2E1 plays a minimal role. Thus, the findings support that hepatic metabolism dominates the contribution made by the ovary in bioactivation of VCM to its ovotoxic metabolite, VCD. This study also demonstrates the use of a novel ovarian culture system to evaluate ovary-specific metabolism of xenobiotics.

  6. Origin of low-lying enhanced E1 strength in rare-Earth nuclei.

    PubMed

    Spieker, M; Pascu, S; Zilges, A; Iachello, F

    2015-05-15

    The experimental E1 strength distribution below 4 MeV in rare-earth nuclei suggests a local breaking of isospin symmetry. In addition to the octupole states, additional J^{π}=1^{-} states with enhanced E1 strength have been observed in rare-earth nuclei by means of (γ,γ') experiments. By reproducing the experimental results, the spdf interacting boson model calculations provide further evidence for the formation of an α cluster in medium-mass nuclei and might provide a new understanding of the origin of low-lying E1 strength. PMID:26024168

  7. 78 FR 12826 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-25

    ... the Tracks of the General Railroad System by Light Rail and Conventional Equipment, 65 FR 42529 (July... General Railroad System by Conventional Railroads and Light Rail Transit Systems, 65 FR 42626 (July 10... (65 FR 19477). Issued in Washington, DC, on February 20, 2013. Robert C. Lauby, Deputy...

  8. 78 FR 13154 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-26

    ... Railroad System by Light Rail and Conventional Equipment, 65 FR 42529 (July 10, 2000). See also Joint... Conventional Railroads and Light ] Rail Transit Systems, 65 FR 42626 (July 10, 2000).) FRA assigned the... Statement in the Federal Register published on April 11, 2000 (65 FR 19477). Issued in Washington, DC,...

  9. 78 FR 11987 - Cable Television Act of 1992

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-21

    ... cable rates are reasonable and expands the opportunities for cable programmers to reach viewers. DATES: The amendments to 47 CFR 76.922(e)(1) and (2) published in the Federal Register at 59 FR 62614...-286, published in the Federal Register, 59 FR 62614, December 6, 1994, the Commission adopted...

  10. The Search for the CP-violating emission of an E1 photon from the K(L) ---> pi+ pi- gamma decay

    SciTech Connect

    Shields, John Michael

    2005-01-01

    A search for the CP-violating electric dipole (E1) direct emission contribution to the K{sub L} {yields} {pi}{sup +}{pi}{sup -}{gamma} decay is performed using data from the 1997 KTeV/E832 experiment. Because the K{sub L} {yields} {pi}{sup +}{pi}{sup -}{gamma} 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{sub E1}| < 0.14 (90% CL) is reported. In the process of obtaining this upper limit, high resolution measurements of fit parameters ({tilde g}{sub M1} and a{sub 1}/a{sub 2}) associated with the size and shape of the M1 direct emission peak are also extracted. The fit results for these parameters: {tilde g}{sub M1} = 1.229 {+-} 0.035 (stat) {+-} 0.087 (syst); a{sub 1}/a{sub 2} = -0.733 {+-} 0.007 (stat) {+-} 0.014 (syst) are in strong agreement with previous measurements.

  11. CPEB and miR-15/16 Co-Regulate Translation of Cyclin E1 mRNA during Xenopus Oocyte Maturation

    PubMed Central

    Wilczynska, Ania; Git, Anna; Argasinska, Joanna; Belloc, Eulàlia; Standart, Nancy

    2016-01-01

    Cell cycle transitions spanning meiotic maturation of the Xenopus oocyte and early embryogenesis are tightly regulated at the level of stored inactive maternal mRNA. We investigated here the translational control of cyclin E1, required for metaphase II arrest of the unfertilised egg and the initiation of S phase in the early embryo. We show that the cyclin E1 mRNA is regulated by both cytoplasmic polyadenylation elements (CPEs) and two miR-15/16 target sites within its 3’UTR. Moreover, we provide evidence that maternal miR-15/16 microRNAs co-immunoprecipitate with CPE-binding protein (CPEB), and that CPEB interacts with the RISC component Ago2. Experiments using competitor RNA and mutated cyclin E1 3’UTRs suggest cooperation of the regulatory elements to sustain repression of the cyclin E1 mRNA during early stages of maturation when CPEB becomes limiting and cytoplasmic polyadenylation of repressed mRNAs begins. Importantly, injection of anti-miR-15/16 LNA results in the early polyadenylation of endogenous cyclin E1 mRNA during meiotic maturation, and an acceleration of GVBD, altogether strongly suggesting that the proximal CPEB and miRNP complexes act to mutually stabilise each other. We conclude that miR-15/16 and CPEB co-regulate cyclin E1 mRNA. This is the first demonstration of the co-operation of these two pathways. PMID:26829217

  12. Effects of orbital and spin current interference in E1 and M2 nuclear excitations

    SciTech Connect

    Goncharova, N. G.

    2015-12-15

    The interference of contributions from the orbital and spin currents to the E1 and M2 resonances is investigated. The results of the current interference analysis within the shell model are compared with the experimental data.

  13. Hepatitis C Virus Envelope Glycoprotein E1 Forms Trimers at the Surface of the Virion

    PubMed Central

    Falson, Pierre; Bartosch, Birke; Alsaleh, Khaled; Tews, Birke Andrea; Loquet, Antoine; Ciczora, Yann; Riva, Laura; Montigny, Cédric; Montpellier, Claire; Duverlie, Gilles; Pécheur, Eve-Isabelle; le Maire, Marc; Cosset, François-Loïc

    2015-01-01

    ABSTRACT In hepatitis C virus (HCV)-infected cells, the envelope glycoproteins E1 and E2 assemble as a heterodimer. To investigate potential changes in the oligomerization of virion-associated envelope proteins, we performed SDS-PAGE under reducing conditions but without thermal denaturation. This revealed the presence of SDS-resistant trimers of E1 in the context of cell-cultured HCV (HCVcc) as well as in the context of HCV pseudoparticles (HCVpp). The formation of E1 trimers was found to depend on the coexpression of E2. To further understand the origin of E1 trimer formation, we coexpressed in bacteria the transmembrane (TM) domains of E1 (TME1) and E2 (TME2) fused to reporter proteins and analyzed the fusion proteins by SDS-PAGE and Western blotting. As expected for strongly interacting TM domains, TME1–TME2 heterodimers resistant to SDS were observed. These analyses also revealed homodimers and homotrimers of TME1, indicating that such complexes are stable species. The N-terminal segment of TME1 exhibits a highly conserved GxxxG sequence, a motif that is well documented to be involved in intramembrane protein-protein interactions. Single or double mutations of the glycine residues (Gly354 and Gly358) in this motif markedly decreased or abrogated the formation of TME1 homotrimers in bacteria, as well as homotrimers of E1 in both HCVpp and HCVcc systems. A concomitant loss of infectivity was observed, indicating that the trimeric form of E1 is essential for virus infectivity. Taken together, these results indicate that E1E2 heterodimers form trimers on HCV particles, and they support the hypothesis that E1 could be a fusion protein. IMPORTANCE HCV glycoproteins E1 and E2 play an essential role in virus entry into liver cells as well as in virion morphogenesis. In infected cells, these two proteins form a complex in which E2 interacts with cellular receptors, whereas the function of E1 remains poorly understood. However, recent structural data suggest that E1

  14. Mechanistic analysis of local ori melting and helicase assembly by the papillomavirus E1 protein

    PubMed Central

    Schuck, Stephen; Stenlund, Arne

    2011-01-01

    Summary Preparation of DNA templates for replication requires opening of the duplex to expose single stranded (ss) DNA. The locally melted DNA is required for replicative DNA helicases to initiate unwinding. How local melting is generated in eukaryotic replicons is unknown, but initiator proteins from a handful of eukaryotic viruses can perform this function. Here we dissect the local melting process carried out by the papillomavirus E1 protein. We characterize the melting process kinetically and identify mutations in the E1 helicase and in the ori that arrest the local melting process. We show that a subset of these mutants have specific defects for melting of the center of the ori containing the binding sites for E1 and demonstrate that these mutants fail to untwist the ori DNA. This newfound understanding of how E1 generates local melting suggests possible mechanisms for local melting in other replicons. PMID:21884978

  15. Accurate measurements of transition frequencies and isotope shifts of laser-trapped francium.

    PubMed

    Sanguinetti, S; Calabrese, R; Corradi, L; Dainelli, A; Khanbekyan, A; Mariotti, E; de Mauro, C; Minguzzi, P; Moi, L; Stancari, G; Tomassetti, L; Veronesi, S

    2009-04-01

    An interferometric method is used to improve the accuracy of the 7S-7P transition frequencies of three francium isotopes by 1 order of magnitude. The deduced isotope shifts for 209-211Fr confirm the ISOLDE data. The frequency of the D2 transition of 212Fr--the accepted reference for all Fr isotope shifts--is revised, and a significant difference with the ISOLDE value is found. Our results will be a benchmark for the accuracy of the theory of Fr energy levels, a necessary step to investigate fundamental symmetries. PMID:19340162

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

    PubMed Central

    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 envelope proteins E1 and E2 and to develop a CHIKV subunit vaccine, C-terminally his-tagged E1 and E2 envelope glycoproteins were produced at high levels in insect cells with baculovirus vectors using their native signal peptides located in CHIKV 6K and E3, respectively. Results Expression in the presence of either tunicamycin or furin inhibitor showed that a substantial portion of recombinant intracellular E1 and precursor E3E2 was glycosylated, but that a smaller fraction of E3E2 was processed by furin into mature E3 and E2. Deletion of the C-terminal transmembrane domains of E1 and E2 enabled secretion of furin-cleaved, fully processed E1 and E2 subunits, which could then be efficiently purified from cell culture fluid via metal affinity chromatography. Confocal laser scanning microscopy on living baculovirus-infected Sf21 cells revealed that full-length E1 and E2 translocated to the plasma membrane, suggesting similar posttranslational processing of E1 and E2, as in a natural CHIKV infection. Baculovirus-directed expression of E1 displayed fusogenic activity as concluded from syncytia formation. CHIKV-E2 was able to induce neutralizing antibodies in rabbits. Conclusions Chikungunya virus glycoproteins could be functionally expressed at high levels in insect cells and are properly glycosylated and cleaved by furin. The ability of purified, secreted CHIKV-E2 to induce neutralizing antibodies in rabbits underscores the potential use of E2 in a subunit vaccine to prevent CHIKV infections. PMID:21762510

  17. 11 CFR 300.60 - Scope (2 U.S.C. 441i(e)(1)).

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...) REGULATIONS NON-FEDERAL FUNDS Federal Candidates and Officeholders § 300.60 Scope (2 U.S.C. 441i(e)(1)). This subpart applies to: (a) Federal candidates; (b) Individuals holding Federal office (see 11 CFR 300.2(o... 11 Federal Elections 1 2010-01-01 2010-01-01 false Scope (2 U.S.C. 441i(e)(1)). 300.60 Section...

  18. 11 CFR 300.60 - Scope (2 U.S.C. 441i(e)(1)).

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...) REGULATIONS NON-FEDERAL FUNDS Federal Candidates and Officeholders § 300.60 Scope (2 U.S.C. 441i(e)(1)). This subpart applies to: (a) Federal candidates; (b) Individuals holding Federal office (see 11 CFR 300.2(o... 11 Federal Elections 1 2011-01-01 2011-01-01 false Scope (2 U.S.C. 441i(e)(1)). 300.60 Section...

  19. Resolvin E1 regulates osteoclast fusion via DC-STAMP and NFATc1

    PubMed Central

    Zhu, Min; Van Dyke, Thomas E.; Gyurko, Robert

    2013-01-01

    Interactions between the immune and skeletal systems in inflammatory bone diseases are well appreciated, but the underlying molecular mechanisms that coordinate the resolution phase of inflammation and bone turnover have not been unveiled. Here we investigated the direct actions of the proresolution mediator resolvin E1 (RvE1) on bone-marrow-cell-derived osteoclasts in an in vitro murine model of osteoclast maturation and inflammatory bone resorption. Investigation of the actions of RvE1 treatment on the specific stages of osteoclast maturation revealed that RvE1 targeted late stages of osteoclast maturation to decrease osteoclast formation by 32.8%. Time-lapse vital microscopy and migration assays confirmed that membrane fusion of osteoclast precursors was inhibited. The osteoclast fusion protein DC-STAMP was specifically targeted by RvE1 receptor binding and was down-regulated by 65.4%. RvE1 did not affect the induction of the essential osteoclast transcription factor nuclear factor of activated T cells c1 (NFATc1) or its nuclear translocation; however, NFATc1 binding to the DC-STAMP promoter was significantly inhibited by 60.9% with RvE1 treatment as shown in electrophoresis mobility shift assay. Our findings suggest that proresolution mediators act directly on osteoclasts, in addition to down-regulation of inflammation, providing a novel mechanism for modulating osteoclast signaling in osteolytic inflammatory disease.—Zhu, M., Van Dyke, T. E., Gyurko, R. Resolvin E1 regulates osteoclast fusion via DC-STAMP and NFATc1. PMID:23629863

  20. 40 CFR Figure E-1 to Subpart E of... - Designation Testing Checklist

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Equivalent Methods for PM2.5 or PM10â2.5 Pt. 53, Subpt. E, Fig. E-1 Figure E-1 to Subpart E of Part 53... 40 CFR Part 53 or 40 CFR Part 50, Appendix L Verification Comments (Includes documentation of who...-7.4.10) Application Specification Tests Field Precision (§ 53.58) (L-5.1) Meets all Appendix...

  1. 78 FR 17871 - Changes To Implement the Technical Corrections to the Leahy-Smith America Invents Act as to Inter...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-25

    ... Appeal Board and Judicial Review of Patent Trial and Appeal Board Decisions, 77 FR 48612 (Aug. 14, 2012... Transitional Program for Covered Business Method Patents, 77 FR 48680 (Aug. 14, 2012) (final rule); Transitional Program for Covered Business Method Patents--Definition of Technological Invention, 77 FR...

  2. Response of an Escherichia coli-Bound Fluorescent Probe to Colicin E1

    PubMed Central

    Cramer, W. A.; Phillips, S. K.

    1970-01-01

    The fluorescent probe, 8-anilino-1-napthalenesulfonate (ANS) binds to Escherichia coli, showing an enhanced fluorescence. The interaction of colicin E1 with sensitive cells causes an increase of about 100% in the fluorescence of the bound ANS, and this change at equilibrium has an apparent “all-or-none” nature as a function of E1 multiplicity. Approximately 6 to 8% of the ANS is bound to the cells at equilibrium. The colicin E1-induced fluorescence increase can be attributed partly to an increase in ANS binding and partly to an increase in the fluorescence yield of the bound ANS. The kinetics of the E1-induced fluorescence increase in sensitive cells are very similar to those of the adenosine triphosphate decrease. The phosphorylation uncoupler p-trifluoromethoxy-carbonylcyanidephenylhydrazone also causes a large change in the fluorescence of bound ANS. Colicin E2 or E3 does not cause any fluorescence change, nor does colicin E1 cause fluorescence change with a colicinogenic strain. ANS appears to be a probe of structural or conformational change in the cell envelope that is closely associated with the colicin E1-induced adenosine triphosphate decrease. PMID:4923074

  3. ATF4 deficiency protects hepatocytes from oxidative stress via inhibiting CYP2E1 expression

    PubMed Central

    Wang, Chunxia; Li, Houkai; Meng, Qingshu; Du, Ying; Xiao, Fei; Zhang, Qian; Yu, Junjie; Li, Kai; Chen, Shanghai; Huang, Zhiying; Liu, Bin; Guo, Feifan

    2014-01-01

    Activating transcription factor (ATF) 4 is involved in the regulation of oxidative stress in fibroblasts and neurons. The role of ATF4 in hepatocytes, however, is unknown. The aim of this study was to investigate the role of ATF4 in hepatocytes in oxidative stress under a high-fat diet (HFD). Here, we showed that palmitate-stimulated reactive oxygen species (ROS) production and triglyceride (TG) accumulation is blocked by ATF4 deficiency in primary hepatocytes. Consistently, HFD-induced oxidative stress, TG accumulation and expression of cytochrome P450, family 2, subfamily, polypeptide 1 (CYP2E1) are also blocked by knocking down ATF4 expression in the mouse liver. This suggests that ATF4 might regulate oxidative stress viaCYP2E1 under an HFD. In addition, we observed that expression of CYP2E1 is indirectly regulated by ATF4 in a cAMP-responsive element binding protein (CREB)-dependent manner, which can directly activate the CYP2E1 promoter activity. Notably, ATF4-stimulated ROS production is inhibited in vivo by treatment with diallyl sulphide, a selective CYP2E1 inhibitor. Finally, we showed that ATF4 expression in the liver is responsible for the protective effects against HFD-induced CYP2E1 expression, oxidative stress, and TG accumulation. Taken together, these observations suggest that ATF4 is a novel regulator of oxidative stress as well as accumulation of TG in response to HFD. PMID:24373582

  4. E1A inhibits transforming growth factor-beta signaling through binding to Smad proteins.

    PubMed

    Nishihara, A; Hanai, J; Imamura, T; Miyazono, K; Kawabata, M

    1999-10-01

    Smads form a recently identified family of proteins that mediate intracellular signaling of the transforming growth factor (TGF)-beta superfamily. Smads bind to DNA and act as transcriptional regulators. Smads interact with a variety of transcription factors, and the interaction is likely to determine the target specificity of gene induction. Smads also associate with transcriptional coactivators such as p300 and CBP. E1A, an adenoviral oncoprotein, inhibits TGF-beta-induced transactivation, and the ability of E1A to bind p300/CBP is required for the inhibition. Here we determined the Smad interaction domain (SID) in p300 and found that two adjacent regions are required for the interaction. One of the regions is the C/H3 domain conserved between p300 and CBP, and the other is a nonconserved region. p300 mutants containing SID inhibit transactivation by TGF-beta in a dose-dependent manner. E1A inhibits the interaction of Smad3 with a p300 mutant that contains SID but lacks the E1A binding domain. We found that E1A interacts specifically with receptor-regulated Smads, suggesting a novel mechanism whereby E1A antagonizes TGF-beta signaling. PMID:10497242

  5. In vitro characterization of the NAD(+) synthetase NadE1 from Herbaspirillum seropedicae.

    PubMed

    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. PMID:26802007

  6. Specific uptake of radioiodinated fragment E1 by venous thrombi in pigs

    SciTech Connect

    Knight, L.C.; Olexa, S.A.; Malmud, L.S.; Budzynski, A.Z.

    1983-12-01

    Fragment E1, a product of plasmic digestion of cross-linked fibrin, binds specifically in vitro to polymerized fibrin but not to fibrinogen. Purified human Fragment E1 was radiolabeled with /sup 125/I or /sup 131/I by the Iodogen technique. The uptake of radioiodinated Fragment E1 in vitro into forming or preformed clots was demonstrated. Animal biodistribution studies of radioiodinated Fragment E1 showed its rapid removal from the circulation; radioactive catabolites did not reside long in any organ and were excreted in the urine. The uptake in vivo was evaluated in pigs with preexisting venous thrombi of various ages from 1 h up to 5 d at the time of intravenous systemic injection of the tracer. Radioiodinated fibrinogen was also injected into the same animals to compare the uptake of the two tracers. Thrombus-to-blood ratios for Fragment E1 averaged 43:1 (range 10-108) and 29:1 (range 8-107) in thrombi 1-6 h and 1-5 d old, respectively. In contrast, mean thrombus-to-blood ratios for fibrinogen were, in the same time intervals, 26:1 (range 17-41) and 2:1 (range 0.5-3.9), respectively. It is concluded that radioiodinated Fragment E1 is a specific marker of thrombi in vivo: its uptake by fresh thrombi is better than that of labeled fibrinogen and, in contrast to radioiodinated fibrinogen, this fragment is incorporated into old thrombi as well.

  7. Resolvin D1 and E1 promote resolution of inflammation in microglial cells in vitro.

    PubMed

    Rey, C; Nadjar, A; Buaud, B; Vaysse, C; Aubert, A; Pallet, V; Layé, S; Joffre, C

    2016-07-01

    Sustained inflammation in the brain together with microglia activation can lead to neuronal damage. Hence limiting brain inflammation and activation of microglia is a real therapeutic strategy for inflammatory disease. Resolvin D1 (RvD1) and resolvin E1 (RvE1) derived from n-3 long chain polyunsaturated fatty acids are promising therapeutic compounds since they actively turn off the systemic inflammatory response. We thus evaluated the anti-inflammatory activities of RvD1 and RvE1 in microglia cells in vitro. BV2 cells were pre-incubated with RvD1 or RvE1 before lipopolysaccharide (LPS) treatment. RvD1 and RvE1 both decreased LPS-induced proinflammatory cytokines (TNF-α, IL-6 and IL-1β) gene expression, suggesting their proresolutive activity in microglia. However, the mechanisms involved are distinct as RvE1 regulates NFκB signaling pathway and RvD1 regulates miRNAs expression. Overall, our findings support that pro-resolving lipids are involved in the resolution of brain inflammation and can be considered as promising therapeutic agents for brain inflammation. PMID:26718448

  8. Replication-associated activities of purified human papillomavirus type 11 E1 helicase.

    PubMed

    Rocque, W J; Porter, D J; Barnes, J A; Dixon, E P; Lobe, D C; Su, J L; Willard, D H; Gaillard, R; Condreay, J P; Clay, W C; Hoffman, C R; Overton, L K; Pahel, G; Kost, T A; Phelps, W C

    2000-03-01

    Replication of human papillomavirus type11 (HPV11) requires both the E1 and the E2 proteins. E1 is structurally and functionally similar to SV40 large T-antigen and is a DNA helicase/NTPase that binds to the origin of replication and initiates viral DNA replication. The biochemical characterization of HPV E1 is incompletely documented in the literature in part because of difficulties in expressing and purifying the protein. Herein, we report a method for the overexpression of full-length, untagged E1 (73.5 kDa) in baculovirus-infected Trichoplusia ni insect cells and the purification to homogeneity using a two-step procedure. The purified protein is a nonspecific NTPase that hydrolyzes ATP, dATP, UTP, or GTP equally well. Point mutations were made in the putative NTPase domain to verify that the activities observed were encoded by E1. Purified mutant D523N had negligible ATPase and helicase activities but retained DNA-binding activity. Sedimentation equilibrium ultracentrifugation and glycerol gradient centrifugation demonstrated that the wild-type protein is primarily a hexamer in its purified form. Secondary structure determination by circular dichroism revealed a large percentage of alpha-helical structure consistent with secondary structure predictions. These data define a fundamental set of biochemical and kinetic parameters for HPV E1 which are a critical prerequisite to future mechanistic studies of the enzyme. PMID:10686145

  9. Diabetes mellitus increases the in vivo activity of cytochrome P450 2E1 in humans

    PubMed Central

    Wang, Zaiqi; Hall, Stephen D; Maya, Juan F; Li, Lang; Asghar, Ali; Gorski, J C

    2003-01-01

    Aim Cytochrome P450 2E1 (CYP2E1) is thought to activate a number of protoxins, and has been implicated in the development of liver disease. Increased hepatic expression of CYP2E1 occurs in rat models of diabetes but it is unclear whether human diabetics display a similar up-regulation. This study was designed to test the hypothesis that human diabetics experience enhanced CYP2E1 expression. Methods The pharmacokinetics of a single dose of chlorzoxazone (500 mg), used as an index of hepatic CYP2E1 activity, was determined in healthy subjects (n = 10), volunteers with Type I (n = 13), and Type II (n = 8) diabetes mellitus. Chlorzoxazone and 6-hydroxychlorzoxazone in serum and urine were analysed by high-performance liquid chromatography. The expression of CYP2E1 mRNA in peripheral blood mononuclear cells was quantified by reverse transcriptase-polymerase chain reaction. Results The mean ± s.d. (90% confidence interval of the difference) chlorzoxazone area under the plasma concentration-time curve was significantly (P ≤ 0.05) reduced in obese Type II diabetics (15.7 ± 11.3 µg h ml−1; 9, 22) compared with healthy subjects (43.5 ± 16.9 µg h ml−1; 16, 40) and Type I diabetics (32.8 ± 9.2 µg h ml−1; 9, 25). There was a significant two-fold increase in the oral clearance of chlorzoxazone in obese Type II diabetics compared with healthy volunteers and Type I diabetics. The protein binding of chlorzoxazone was not significantly different between the three groups. In contrast, Type 1 diabetics and healthy volunteers demonstrated no difference in the oral clearance of chlorzoxazone. The urinary recovery of 6-hydroxychlorzoxazone as a percentage of the administered dose was not different between healthy, Type I and obese Type II diabetics. The elimination half-life of chlorzoxazone did not differ between the three groups. CYP2E1 mRNA was significantly elevated in Type I and obese Type II diabetics compared with healthy volunteers. The oral clearance of

  10. Autophagy Protects against CYP2E1/Chronic Ethanol-Induced Hepatotoxicity

    PubMed Central

    Lu, Yongke; Cederbaum, Arthur I.

    2015-01-01

    Autophagy is an intracellular pathway by which lysosomes degrade and recycle long-lived proteins and cellular organelles. The effects of ethanol on autophagy are complex but recent studies have shown that autophagy serves a protective function against ethanol-induced liver injury. Autophagy was found to also be protective against CYP2E1-dependent toxicity in vitro in HepG2 cells which express CYP2E1 and in vivo in an acute alcohol/CYPE1-dependent liver injury model. The goal of the current report was to extend the previous in vitro and acute in vivo experiments to a chronic ethanol model to evaluate whether autophagy is also protective against CYP2E1-dependent liver injury in a chronic ethanol-fed mouse model. Wild type (WT), CYP2E1 knockout (KO) or CYP2E1 humanized transgenic knockin (KI), mice were fed an ethanol liquid diet or control dextrose diet for four weeks. In the last week, some mice received either saline or 3-methyladenine (3-MA), an inhibitor of autophagy, or rapamycin, which stimulates autophagy. Inhibition of autophagy by 3-MA potentiated the ethanol-induced increases in serum transaminase and triglyceride levels in the WT and KI mice but not KO mice, while rapamycin prevented the ethanol liver injury. Treatment with 3-MA enhanced the ethanol-induced fat accumulation in WT mice and caused necrosis in the KI mice; little or no effect was found in the ethanol-fed KO mice or any of the dextrose-fed mice. 3-MA treatment further lowered the ethanol-decrease in hepatic GSH levels and further increased formation of TBARS in WT and KI mice, whereas rapamycin blunted these effects of ethanol. Neither 3-MA nor rapamycin treatment affected CYP2E1 catalytic activity or content or the induction CYP2E1 by ethanol. The 3-MA treatment decreased levels of Beclin-1 and Atg 7 but increased levels of p62 in the ethanol-fed WT and KI mice whereas rapamycin had the opposite effects, validating inhibition and stimulation of autophagy, respectively. These results suggest

  11. Cytochrome p450 2E1 polymorphisms and the risk of gastric cardia cancer

    PubMed Central

    Cai, Lin; Zheng, Zong-Li; Zhang, Zuo-Feng

    2005-01-01

    AIM: Genetic polymorphisms of drug-metabolizing enzymes have recently been shown to affect susceptibility to chemical carcinogenesis. Cytochrome P450 2E1 (CYP2E1) enzyme catalyzes the metabolism of many procarcinogens, such as N-nitrosamines and related compounds. The gene coding for this enzyme is polymorphic and thus may play a role in gastric cardia cancer (GCC) etiology. In this hospital-based case-control study, we evaluate the relationship between genetic polymorphisms of CYP2E1 and the risk of GCC. METHODS: The study subjects comprised 159 histologically confirmed GCC cases identified via hospital cancer registry and surgical records at five hospitals in Fuzhou, Fujian Province, China, between April and November 2001. Controls were 192 patients admitted to the same hospitals for nonmalignant conditions. The genotypes of CYP2E1 were detected by a PCR-based RFLP assay. The odds ratios were estimated by logistic regression analyses and were adjusted for potential confounding factors. RESULTS: The distribution of three genotypes of CYP2E1 in GCC cases and controls was significantly different (χ2 = 16.04, P<0.01). The frequency of the CYP2E1 (c1/c1) genotype in GCC cases and controls was 60.4% and 40.1%, respectively. The CYP2E1 (c1/c1) genotype was associated with an increased risk for GCC (the adjusted (OR) was 2.37, 95% confidence interval (CI): 1.52-3.70). Subjects who carried the CYP2E1 (c1/c1) genotype and were habitual smokers were at a significantly higher risk of developing GCC (OR = 4.68, 95%CI: 2.19-10.04) compared with those who had the CYP2E1 (c1/c2 or c2/c2) genotype and did not smoke. CONCLUSION: These results suggest that the CYP2E1 genotype may influence individual susceptibility to development of GCC, and that the risk increases significantly in smokers. PMID:15793883

  12. Redox Regulation of Human Estrogen Sulfotransferase (hSULT1E1)†

    PubMed Central

    Maiti, Smarajit; Zhang, Jimei; Chen, Guangping

    2007-01-01

    Sulfotransferases (SULTs) are enzymes that catalyze the sulfation of hydroxyl-containing compounds. Sulfation regulates hormone activities and detoxifies xenobiotics. Human estrogen sulfotransferase (hSULT1E1) catalyzes the sulfation of estrogens and regulates estrogen bioactivities. Oxidative regulation provides a biological mechanism for regulating enzyme activities in vivo. The oxidative regulation of human SULTs has not been reported. In this study, we used amino acid modification, manipulation of intracellular redox state, and site-directed mutagenesis to study the redox regulation of human SULTs and specifically the mechanism of hSULT1E1 inhibitory regulation by oxidized glutathione (GSSG). Of the four major human SULTs, hSULT1A1, hSULT1A3, and hSULT2A1 do not undergo redox regulation; hSULT1E1, on the other hand, can be redox regulated. GSSG inactivated hSULT1E1 activity in an efficient, time- and concentration-dependant manner. The co-enzyme adenosine 3′-phosphate 5′-phosphosulfate protected hSULT1E1 from GSSG-associated inactivation. A reduced glutathione (GSH) inducer (N-acetyl cysteine) significantly increased while a GSH depletor (buthionine sulfoxamine) significantly decreased hSULT1E1 activity, but both failed to affect the amount of hSULT1E1 protein in human hepatocyte carcinoma Hep G2 cells. Crystal structure suggested that no Cys residues exist near the active sites of hSULT1A1, hSULT1A3, and hSULT2A1, but Cys residues do exist within the active site of hSULT1E1. Site-directed mutagenesis demonstrated that Cys83 is critical for the redox regulation of hSULT1E1. This first report on the redox regulation of human SULTs suggests that the redox regulation of hSULT1E1 may interrupt the regulation and function of estrogens under various physiological and pathological conditions. PMID:17266938

  13. 75 FR 63535 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-15

    ... Railroads and Light Rail Transit Systems, 65 FR 42626 (July 10, 2000). On August 19, 1999, UTA filed a... System by Light Rail and Conventional Equipment, 65 FR 42529 (July 10, 2000); see also Joint Statement of... the FRA Railroad Safety Board on August 19, 1999, for the Sandy/Salt Lake TRAX Light Rail Transit...

  14. Requirement for the E1 Helicase C-Terminal Domain in Papillomavirus DNA Replication In Vivo

    PubMed Central

    Bergvall, Monika; Gagnon, David; Titolo, Steve; Lehoux, Michaël; D'Abramo, Claudia M.

    2016-01-01

    ABSTRACT The papillomavirus (PV) E1 helicase contains a conserved C-terminal domain (CTD), located next to its ATP-binding site, whose function in vivo is still poorly understood. The CTD is comprised of an alpha helix followed by an acidic region (AR) and a C-terminal extension termed the C-tail. Recent biochemical studies on bovine papillomavirus 1 (BPV1) E1 showed that the AR and C-tail regulate the oligomerization of the protein into a double hexamer at the origin. In this study, we assessed the importance of the CTD of human papillomavirus 11 (HPV11) E1 in vivo, using a cell-based DNA replication assay. Our results indicate that combined deletion of the AR and C-tail drastically reduces DNA replication, by 85%, and that further truncation into the alpha-helical region compromises the structural integrity of the E1 helicase domain and its interaction with E2. Surprisingly, removal of the C-tail alone or mutation of highly conserved residues within the domain still allows significant levels of DNA replication (55%). This is in contrast to the absolute requirement for the C-tail reported for BPV1 E1 in vitro and confirmed here in vivo. Characterization of chimeric proteins in which the AR and C-tail from HPV11 E1 were replaced by those of BPV1 indicated that while the function of the AR is transferable, that of the C-tail is not. Collectively, these findings define the contribution of the three CTD subdomains to the DNA replication activity of E1 in vivo and suggest that the function of the C-tail has evolved in a PV type-specific manner. IMPORTANCE While much is known about hexameric DNA helicases from superfamily 3, the papillomavirus E1 helicase contains a unique C-terminal domain (CTD) adjacent to its ATP-binding site. We show here that this CTD is important for the DNA replication activity of HPV11 E1 in vivo and that it can be divided into three functional subdomains that roughly correspond to the three conserved regions of the CTD: an alpha helix, needed

  15. The adenovirus E1A protein overrides the requirement for cellular ras in initiating DNA synthesis.

    PubMed Central

    Stacey, D W; Dobrowolski, S F; Piotrkowski, A; Harter, M L

    1994-01-01

    The adenovirus E1A protein can induce cellular DNA synthesis in growth-arrested cells by interacting with the cellular protein p300 or pRb. In addition, serum- and growth factor-dependent cells require ras activity to initiate DNA synthesis and recently we have shown that Balb/c 3T3 cells can be blocked in either early or late G1 following microinjection of an anti-ras antibody. In this study, the E1A 243 amino acid protein is shown through microinjection not only to shorten the G0 to S phase interval but, what is more important, to override the inhibitory effects exerted by the anti-ras antibody in either early or late G1. Specifically, whether E1A is co-injected with anti-ras into quiescent cells or injected 18 h following a separate injection of anti-ras after serum stimulation, it efficiently induces cellular DNA synthesis in cells that would otherwise be blocked in G0/G1. Moreover, injection of a mutant form of E1A that can no longer associate with p300 is just as efficient as wild-type E1A in stimulating DNA synthesis in cells whose ras activity has been neutralized by anti-ras. The results presented here show that E1A is capable of overriding the requirement of cellular ras activity in promoting the entry of cells into S phase. Moreover, the results suggest the possibility that pRb and/or pRb-related proteins may function in a ras-dependent pathway that enables E1A to achieve this activity. Images PMID:7813447

  16. Mutation in E1, the Ubiquitin Activating Enzyme, Reduces Drosophila Lifespan and Results in Motor Impairment

    PubMed Central

    Liu, Hsiu-Yu; Pfleger, Cathie M.

    2013-01-01

    Neurodegenerative diseases cause tremendous suffering for those afflicted and their families. Many of these diseases involve accumulation of mis-folded or aggregated proteins thought to play a causal role in disease pathology. Ubiquitinated proteins are often found in these protein aggregates, and the aggregates themselves have been shown to inhibit the activity of the proteasome. These and other alterations in the Ubiquitin Pathway observed in neurodegenerative diseases have led to the question of whether impairment of the Ubiquitin Pathway on its own can increase mortality or if ongoing neurodegeneration alters Ubiquitin Pathway function as a side-effect. To address the role of the Ubiquitin Pathway in vivo, we studied loss-of-function mutations in the Drosophila Ubiquitin Activating Enzyme, Uba1 or E1, the most upstream enzyme in the Ubiquitin Pathway. Loss of only one functional copy of E1 caused a significant reduction in adult lifespan. Rare homozygous hypomorphic E1 mutants reached adulthood. These mutants exhibited further reduced lifespan and showed inappropriate Ras activation in the brain. Removing just one functional copy of Ras restored the lifespan of heterozygous E1 mutants to that of wild-type flies and increased the survival of homozygous E1 mutants. E1 homozygous mutants also showed severe motor impairment. Our findings suggest that processes that impair the Ubiquitin Pathway are sufficient to cause early mortality. Reduced lifespan and motor impairment are seen in the human disease X-linked Infantile Spinal Muscular Atrophy, which is associated with mutation in human E1 warranting further analysis of these mutants as a potential animal model for study of this disease. PMID:23382794

  17. 75 FR 27443 - [alpha]-[p-(1,1,3,3-Tetramethylbutyl)phenyl]-[omega]- hydroxypoly(oxyethylene); Time-Limited...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-17

    ... Register of March 25, 2009 (74 FR 12856) (FRL-8399- 4), EPA issued a notice pursuant to section 408(d)(3... Register of August 9, 2006 (71 FR 45415) (FRL- 8084-1) in which the Agency revoked, under section 408(e)(1... was later extended to August 9, 2009, in the Federal Register of August 4, 2008 (73 ] FR 45317)...

  18. Multiple transcriptional regulatory domains in the human immunodeficiency virus type 1 long terminal repeat are involved in basal and E1A/E1B-induced promoter activity.

    PubMed Central

    Kliewer, S; Garcia, J; Pearson, L; Soultanakis, E; Dasgupta, A; Gaynor, R

    1989-01-01

    The human immunodeficiency virus (HIV) type 1 long terminal repeat (LTR) is the site of activation of the HIV tat protein. However, additional transactivators, such as the adenovirus E1A and herpesvirus ICPO proteins, have also been shown to be capable of activating the HIV LTR. Analysis of adenovirus mutants indicated that complete transactivation of the HIV LTR was dependent on both the E1A and E1B proteins. To determine which regions of the HIV LTR were important for complete E1A/E1B activation, a variety of oligonucleotide-directed mutations in HIV transcriptional regulatory domains were assayed both in vivo and in vitro. S1 nuclease analysis of RNA prepared after transfection of these HIV constructs into HeLa cells infected with wild-type adenovirus indicated that the enhancer, SP1, TATA, and a portion of the transactivation-responsive element were each required for complete E1A/E1B-mediated activation of the HIV LTR. These same promoter elements were required for both basal and E1A/E1B-induced levels of transcription in in vitro transcription reactions performed with cellular extracts prepared from cells infected with dl434, an E1A/E1B deletion mutant, or wild-type adenovirus. No mutations were found that reduced only E1A/E1B-induced expression without proportionally reducing basal levels of transcription, suggesting that E1A/E1B-mediated induction of the HIV LTR requires multiple promoter elements which are also required for basal transcriptional levels. Unlike activation by the tat protein, there was not a rigid dependence on maintenance of the transactivation-responsive stem base pairing for E1A/E1B-mediated activation either in vivo or in vitro, indicating that activation occurs by a mechanism distinct from that of tat induction. Images PMID:2529378

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

    PubMed

    Wang, Jimin; Li, Yue; Modis, Yorgo

    2014-04-01

    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 E1-E2 heterodimers. The membrane anchor models provide structural constraints for the disulfide bonding pattern and overall backbone conformation of the E1 ectodomain. PMID:24725935

  20. Dual E1 activation systems for ubiquitin differentially regulate E2 enzyme charging.

    PubMed

    Jin, Jianping; Li, Xue; Gygi, Steven P; Harper, J Wade

    2007-06-28

    Modification of proteins with ubiquitin or ubiquitin-like proteins (UBLs) by means of an E1-E2-E3 cascade controls many signalling networks. Ubiquitin conjugation involves adenylation and thioesterification of the carboxy-terminal carboxylate of ubiquitin by the E1-activating enzyme Ube1 (Uba1 in yeast), followed by ubiquitin transfer to an E2-conjugating enzyme through a transthiolation reaction. Charged E2s function with E3s to ubiquitinate substrates. It is currently thought that Ube1/Uba1 is the sole E1 for charging of E2s with ubiquitin in animals and fungi. Here we identify a divergent E1 in vertebrates and sea urchin, Uba6, which specifically activates ubiquitin but not other UBLs in vitro and in vivo. Human Uba6 and Ube1 have distinct preferences for E2 charging in vitro, and their specificity depends in part on their C-terminal ubiquitin-fold domains, which recruit E2s. In tissue culture cells, Uba6 is required for charging a previously uncharacterized Uba6-specific E2 (Use1), whereas Ube1 is required for charging the cell-cycle E2s Cdc34A and Cdc34B. Our data reveal unexpected complexity in the pathways that control the conjugation of ubiquitin, in which dual E1s orchestrate the charging of distinct cohorts of E2s. PMID:17597759

  1. Sub-meter Precision Lunar Figures from Chang'E-1 and SELENE Laser Altimetry

    NASA Astrophysics Data System (ADS)

    Baki Iz, H.; Shum, C. K.; Chen, Y. Q.; Dai, C. L.

    2010-05-01

    The selenocentric radial footprint radial distances of 8.8 million Chang'E-1, and 8.5 million SELENE laser altimetry measurements were used used to estimate improved triaxial, biaxial and spherical lunar figure parameters together with their geometric centers with respect to the center of mass of the Moon. The estimated equatorial semi-major, minor, and polar axes of the triaxial ellipsoid's shape parameters from the Chang'E-1 and SELENE solutions differ by 143 m, 3 m and 49 m and -186 m, -3 m, and -52 m in their geometric center positions with respect to the lunar center of mass. The new missions' laser altimetry measurements data reveals a more spherical lunar figure and are in better agreement with each other compared to the ULCN 2005's geometrically best fitting lunar figure. The RMS misclosures calculated for Chang'E-1 and SELENE data using all the estimated parameters were used to assess the goodness of fit of each solution. The estimates for geometrically best fitting solution from Chang'E-1's data give the smallest RMS misclosures for both Chang'E-1 and SELENE data. Overall, the spherical harmonic topographical models' RMS misclosures are larger than those best fitting solutions.

  2. Mitochondrial pyruvate dehydrogenase. Molecular cloning of the E1 alpha subunit and expression analysis.

    PubMed Central

    Grof, C P; Winning, B M; Scaysbrook, T P; Hill, S A; Leaver, C J

    1995-01-01

    A polymerase chain reaction-based approach was used to isolate cDNA clones encoding the E1 alpha subunit of the mitochondrial pyruvate dehydrogenase from higher plants. Putative full-length clones were identified on the basis of similarity to E1 alpha sequences from nonplant sources. Southern blot analysis revealed a small family of genes in potato (Solanum tuberosum L.), whereas in cucumber (Cucumis sativus) there are only one or two genes. Tissue-specific variation in the relative amounts of E1 alpha mRNA was observed in northern blot analysis of different potato tissues, with the highest steady-state transcript levels found in floral tissue. Measurement of pyruvate dehydrogenase activity in cucumber cotyledons showed that there is a transient increase to a maximum at 4 to 5 d postimbibition. Western blot analysis revealed that the amount of E1 alpha protein also peaks at this time. Steady-state transcript levels in germinating cucumber cotyledons also show transient accumulation, peaking 2 d postimbibition. These data are consistent with regulation of E1 alpha at the level of transcription and/or mRNA stability in postgerminative cucumber cotyledons. PMID:7659754

  3. Expression and Characterization of Acidothermus celluloyticus E1 Endoglucanase in Transgenic Duckweed Lemna minor 8627

    SciTech Connect

    Sun, Y.; Cheng, J. J.; Himmel, M. E.; Skory, C. D.; Adney, W. S.; Thomas, S. R.; Tisserat, B.; Nishimura, Y.; Yamamoto, Y. T.

    2007-01-01

    Endoglucanase E1 from Acidothermus cellulolyticus was expressed cytosolically under control of the cauliflower mosaic virus 35S promoter in transgenic duckweed, Lemna minor 8627 without any obvious observable phenotypic effects on morphology or rate of growth. The recombinant enzyme co-migrated with the purified catalytic domain fraction of the native E1 protein on western blot analysis, revealing that the cellulose-binding domain was cleaved near or in the linker region. The duckweed-expressed enzyme was biologically active and the expression level was up to 0.24% of total soluble protein. The endoglucanase activity with carboxymethylcellulose averaged 0.2 units mg protein{sup -1} extracted from fresh duckweed. The optimal temperature and pH for E1 enzyme activity were about 80 C and pH 5, respectively. While extraction with HEPES (N-[2-hydroxyethyl]piperazine-N{prime}-[2-ethanesulfonic acid]) buffer (pH 8) resulted in the highest recovery of total soluble proteins and E1 enzyme, extraction with citrate buffer (pH 4.8) at 65 C enriched relative amounts of E1 enzyme in the extract. This study demonstrates that duckweed may offer new options for the expression of cellulolytic enzymes in transgenic plants.

  4. Cooperative effects for CYP2E1 differ between styrene and its metabolites

    PubMed Central

    Hartman, Jessica H.; Boysen, Gunnar; Miller, Grover P.

    2014-01-01

    Cooperative interactions are frequently observed in the metabolism of drugs and pollutants by cytochrome P450s; nevertheless, the molecular determinants for cooperativity remain elusive. Previously, we demonstrated that steady-state styrene metabolism by CYP2E1 exhibits positive cooperativity.We hypothesized that styrene metabolites have lower affinity than styrene toward CYP2E1 and limited ability to induce cooperative effects during metabolism. To test the hypothesis, we determined the potency and mechanism of inhibition for styrene and its metabolites toward oxidation of 4-nitrophenol using CYP2E1 Supersomes® and human liver microsomes.Styrene inhibited the reaction through a mixed cooperative mechanism with high affinity for the catalytic site (67 μM) and lower affinity for the cooperative site (1100 μM), while increasing substrate turnover at high concentrations. Styrene oxide and 4-vinylphenol possessed similar affinity for CYP2E1. Styrene oxide behaved cooperatively like styrene, but 4-vinylphenol decreased turnover at high concentrations. Styrene glycol was a very poor competitive inhibitor. Among all compounds, there was a positive correlation with binding and hydrophobicity.Taken together, these findings for CYP2E1 further validate contributions of cooperative mechanisms to metabolic processes, demonstrate the role of molecular structure on those mechanisms and underscore the potential for heterotropic cooperative effects between different compounds. PMID:23327532

  5. Genetic mapping of a major site of phosphorylation in adenovirus type 2 E1A proteins

    SciTech Connect

    Tsukamotot, A.S.; Ponticelli, A.; Berk, A.J.; Gaynor, R.B.

    1986-07-01

    Adenovirus early region 1A (E1A) encodes two acidic phosphoproteins which are required for transactivation of viral transcription, efficient viral DNA replication in phase G/sub 0/-arrested human cells, and oncogenic transformation of rodent cells. Biochemical analysis of in vivo /sup 32/P-labeled adenovirus type 2 E1A proteins purified with monoclonal antibodies demonstrated that these proteins were phosphorylated at multiple serine residues. Two-dimensional phosphotryptic peptide maps of wild-type and mutant E1A proteins were used to locate a major site of E1A protein phosphorylation at serine-219 of the large E1A protein. Although this serine fell within a consensus sequence for phosphorylation by the cyclic AMP-dependent protein kinases, experiments with mutant CHO cells defective in these enzymes indicated that it was not. Oligonucleotide-directed mutagenesis was used to substitute an alanine for serine-219. This mutation prevented phosphorylation at this site. Nonetheless, the mutant was indistinguishable from the wild type for early gene transactivation, replication on G/sub 0/-arrested WI-38 cells, and transformation of cloned rat embryo fibroblast cells.

  6. Effect of BI-1 on insulin resistance through regulation of CYP2E1

    PubMed Central

    Lee, Geum-Hwa; Oh, Kyoung-Jin; Kim, Hyung-Ryong; Han, Hye-Sook; Lee, Hwa-Young; Park, Keun-Gyu; Nam, Ki-Hoan; Koo, Seung-Hoi; Chae, Han-Jung

    2016-01-01

    Diet-induced obesity is a major contributing factor to the progression of hepatic insulin resistance. Increased free fatty acids in liver enhances endoplasmic reticulum (ER) stress and production of reactive oxygen species (ROS), both are directly responsible for dysregulation of hepatic insulin signaling. BI-1, a recently studied ER stress regulator, was examined to investigate its association with ER stress and ROS in insulin resistance models. To induce obesity and insulin resistance, BI-1 wild type and BI-1 knock-out mice were fed a high-fat diet for 8 weeks. The BI-1 knock-out mice had hyperglycemia, was associated with impaired glucose and insulin tolerance under high-fat diet conditions. Increased activity of NADPH-dependent CYP reductase-associated cytochrome p450 2E1 (CYP2E1) and exacerbation of ER stress in the livers of BI-1 knock-out mice was also observed. Conversely, stable expression of BI-1 in HepG2 hepatocytes was shown to reduce palmitate-induced ER stress and CYP2E1-dependent ROS production, resulting in the preservation of intact insulin signaling. Stable expression of CYP2E1 led to increased ROS production and dysregulation of insulin signaling in hepatic cells, mimicking palmitate-mediated hepatic insulin resistance. We propose that BI-1 protects against obesity-induced hepatic insulin resistance by regulating CYP2E1 activity and ROS production. PMID:27576594

  7. Effect of BI-1 on insulin resistance through regulation of CYP2E1.

    PubMed

    Lee, Geum-Hwa; Oh, Kyoung-Jin; Kim, Hyung-Ryong; Han, Hye-Sook; Lee, Hwa-Young; Park, Keun-Gyu; Nam, Ki-Hoan; Koo, Seung-Hoi; Chae, Han-Jung

    2016-01-01

    Diet-induced obesity is a major contributing factor to the progression of hepatic insulin resistance. Increased free fatty acids in liver enhances endoplasmic reticulum (ER) stress and production of reactive oxygen species (ROS), both are directly responsible for dysregulation of hepatic insulin signaling. BI-1, a recently studied ER stress regulator, was examined to investigate its association with ER stress and ROS in insulin resistance models. To induce obesity and insulin resistance, BI-1 wild type and BI-1 knock-out mice were fed a high-fat diet for 8 weeks. The BI-1 knock-out mice had hyperglycemia, was associated with impaired glucose and insulin tolerance under high-fat diet conditions. Increased activity of NADPH-dependent CYP reductase-associated cytochrome p450 2E1 (CYP2E1) and exacerbation of ER stress in the livers of BI-1 knock-out mice was also observed. Conversely, stable expression of BI-1 in HepG2 hepatocytes was shown to reduce palmitate-induced ER stress and CYP2E1-dependent ROS production, resulting in the preservation of intact insulin signaling. Stable expression of CYP2E1 led to increased ROS production and dysregulation of insulin signaling in hepatic cells, mimicking palmitate-mediated hepatic insulin resistance. We propose that BI-1 protects against obesity-induced hepatic insulin resistance by regulating CYP2E1 activity and ROS production. PMID:27576594

  8. Epitope-mapped monoclonal antibodies against the HPV16E1--E4 protein.

    PubMed

    Doorbar, J; Ely, S; Coleman, N; Hibma, M; Davies, D H; Crawford, L

    1992-03-01

    The human papillomavirus (HPV) E1--E4 protein is the only nonstructural late protein encoded by the virus. We have isolated three hybridomas producing monoclonal antibodies to the E1--E4 protein of HPV16, which is the HPV type most frequently associated with cervical cancer. The three antibodies (TVG 401, 402, and 403) detect adjacent epitopes within the major seroreactive region of the molecule and show no reactivity against the E4 proteins of HPV1, HPV2, HPV4, or HPV6. The E1--E4 protein migrates as a 10K species on SDS-gel electrophoresis and forms cytoplasmic inclusion granules in infected cells in vitro similar in appearance to those produced by HPV1 in benign warts. In naturally occurring HPV16-induced tumors the E1--E4 protein was detected in the cytoplasm of cells in the upper layers of the lesion in areas in which HPV16 DNA replication was occurring, as determined by in situ hybridization. Although the epitopes recognized by these monoclonal antibodies survive brief fixation in 5% formaldehyde, reactivity was destroyed by prolonged fixation. These monoclonal antibodies represent the first against HPV16 E1--E4 and should complement those already available to E7 and L1 for the screening of frozen sections of clinical biopsies and will be of value in monitoring the progression of HPV infection from benign lesions to invasive cancer. PMID:1371027

  9. E1B and E4 oncoproteins of adenovirus antagonize the effect of apoptosis inducing factor

    SciTech Connect

    Turner, Roberta L.; Wilkinson, John C.; Ornelles, David A.

    2014-05-15

    Adenovirus inundates the productively infected cell with linear, double-stranded DNA and an abundance of single-stranded DNA. The cellular response to this stimulus is antagonized by the adenoviral E1B and E4 early genes. A mutant group C adenovirus that fails to express the E1B-55K and E4ORF3 genes is unable to suppress the DNA-damage response. Cells infected with this double-mutant virus display significant morphological heterogeneity at late times of infection and frequently contain fragmented nuclei. Nuclear fragmentation was due to the translocation of apoptosis inducing factor (AIF) from the mitochondria into the nucleus. The release of AIF was dependent on active poly(ADP-ribose) polymerase-1 (PARP-1), which appeared to be activated by viral DNA replication. Nuclear fragmentation did not occur in AIF-deficient cells or in cells treated with a PARP-1 inhibitor. The E1B-55K or E4ORF3 proteins independently prevented nuclear fragmentation subsequent to PARP-1 activation, possibly by altering the intracellular distribution of PAR-modified proteins. - Highlights: • E1B-55K or E4orf3 prevents nuclear fragmentation. • Nuclear fragmentation requires AIF and PARP-1 activity. • Adenovirus DNA replication activates PARP-1. • E1B-55K or E4orf3 proteins alter the distribution of PAR.

  10. Enantioselective Rhodium-Catalyzed Cycloisomerization of (E)-1,6-Enynes.

    PubMed

    Deng, Xu; Ni, Shao-Fei; Han, Zheng-Yu; Guan, Yu-Qing; Lv, Hui; Dang, Li; Zhang, Xu-Mu

    2016-05-17

    An enantioselective rhodium(I)-catalyzed cycloisomerization reaction of challenging (E)-1,6-enynes is reported. This novel process enables (E)-1,6-enynes with a wide range of functionalities, including nitrogen-, oxygen-, and carbon-tethered (E)-1,6-enynes, to undergo cycloisomerization with excellent enantioselectivity, in a high-yielding and operationally simple manner. Moreover, this Rh(I) -diphosphane catalytic system also exhibited superior reactivity and enantioselectivity for (Z)-1,6-enynes. A rationale for the striking reactivity difference between (E)- and (Z)-1,6-enynes using Rh(I) -BINAP and Rh(I) -TangPhos is outlined using DFT studies to provide the necessary insight for the design of new catalyst systems and the application to synthesis. PMID:27061132

  11. E1 and M1 γ-strength functions in 144Nd

    SciTech Connect

    Voinov, A. V.; Grimes, S. M.

    2015-12-14

    Both E1 and M1 γ-strength functions below the neutron separation energy were analyzed based on experimental data from 143Nd(n,γ)144Nd and 143Nd(n,γα)140Ce reactions. It is confirmed that the commonly adopted E1 model based on the temperature dependence of the width of the giant dipole resonance works well. The popular M1 strength function due to the spin-flip magnetic resonance located near the neutron binding energy is not capable of reproducing experimental data. As a result, the low-energy enhancement of the M1 strength or the energy-independent model of Weisskopf, both leading to the low-energy strength sizable to E1 one, fit experimental data best.

  12. Regulation of the effects of CYP2E1-induced oxidative stress by JNK signaling

    PubMed Central

    Schattenberg, Jörn M.; Czaja, Mark J.

    2014-01-01

    The generation of excessive amounts of reactive oxygen species (ROS) leads to cellular oxidative stress that underlies a variety of forms of hepatocyte injury and death including that from alcohol. Although ROS can induce cell damage through direct effects on cellular macromolecules, the injurious effects of ROS are mediated largely through changes in signal transduction pathways such as the mitogen-activated protein kinase c-Jun N-terminal kinase (JNK). In response to alcohol, hepatocytes have increased levels of the enzyme cytochrome P450 2E1 (CYP2E1) which generates an oxidant stress that promotes the development of alcoholic steatosis and liver injury. These effects are mediated in large part through overactivation of JNK that alters cell death pathways. Targeting the JNK pathway or its downstream effectors may be a useful therapeutic approach to the oxidative stress generated by CYP2E1 in alcoholic liver disease. PMID:25462060

  13. E1 and M1 γ-strength functions in 144Nd

    DOE PAGESBeta

    Voinov, A. V.; Grimes, S. M.

    2015-12-14

    Both E1 and M1 γ-strength functions below the neutron separation energy were analyzed based on experimental data from 143Nd(n,γ)144Nd and 143Nd(n,γα)140Ce reactions. It is confirmed that the commonly adopted E1 model based on the temperature dependence of the width of the giant dipole resonance works well. The popular M1 strength function due to the spin-flip magnetic resonance located near the neutron binding energy is not capable of reproducing experimental data. As a result, the low-energy enhancement of the M1 strength or the energy-independent model of Weisskopf, both leading to the low-energy strength sizable to E1 one, fit experimental data best.

  14. E 1 and M 1 γ -strength functions in 144Nd

    NASA Astrophysics Data System (ADS)

    Voinov, A. V.; Grimes, S. M.

    2015-12-01

    Both E 1 and M 1 γ -strength functions below the neutron separation energy were analyzed based on experimental data from 143Nd(n ,γ )144Nd and 143Nd(n ,γ α )140Ce reactions. It is confirmed that the commonly adopted E 1 model based on the temperature dependence of the width of the giant dipole resonance works well. The popular M 1 strength function due to the spin-flip magnetic resonance located near the neutron binding energy is not capable of reproducing experimental data. The low-energy enhancement of the M 1 strength or the energy-independent model of Weisskopf, both leading to the low-energy strength sizable to E 1 one, fit experimental data best.

  15. Two distinct regions of the BPV1 E1 replication protein interact with the activation domain of E2.

    PubMed

    Moscufo, N; Sverdrup, F; Breiding, D E; Androphy, E J

    1999-12-15

    Papillomavirus E1 and E2 proteins co-operation in viral DNA replication is mediated by protein-protein interactions that lead to formation of an E1-E2 complex. To identify the domains involved, portions of the two proteins were expressed as fusions to the DNA-binding protein LexA or the transactivation domain of VP16 and analyzed by the yeast two-hybrid system. The C-terminal 266 amino acids of BPV1 E1 (E1C266) interacted strongly with E2 in the yeast system and in a mammalian two-hybrid assay. VP16-E1C266 interacted with a region encompassing amino acids 1-200 of the transactivation domain of E2 that was fused to LexA. The interaction between E1 full length and E2 was clearly observed only when E1 was expressed as LexA-E1 chimera. In addition, we found that in the LexA context also the N-terminal region encompassing the first 340 amino acids of E1 (E1N340) interacted with E2 full length. The interactions of E1N340 and E1C266 with E2 were confirmed also by in vitro binding studies. These observations demonstrate that two distinct regions of E1 mediate the interaction with E2 in vivo. PMID:10581387

  16. Genetic study of the functional organization of the colicin E1 molecule.

    PubMed Central

    Suit, J L; Fan, M L; Kayalar, C; Luria, S E

    1985-01-01

    Colicin E1 fragments obtained by genetic manipulations of the ColE1 plasmid were tested for bactericidal activity, binding to bacterial cells, and reactions with a series of anticolicin monoclonal antibodies. Two of the fragments were also tested for ability to form channels in liposomal vesicles. The results are in agreement with studies from chemically and enzymatically derived colicin fragments, assigning the receptor binding activity to the central part of the molecule and the killing activity to a region near the carboxyl terminus. PMID:2579061

  17. CYP2E1-dependent elevation of serum cholesterol, triglycerides, and hepatic bile acids by isoniazid

    SciTech Connect

    Cheng, Jie; Krausz, Kristopher W.; Li, Feng; Ma, Xiaochao; Gonzalez, Frank J.

    2013-01-15

    Isoniazid is the first-line medication in the prevention and treatment of tuberculosis. Isoniazid is known to have a biphasic effect on the inhibition–induction of CYP2E1 and is also considered to be involved in isoniazid-induced hepatotoxicity. However, the full extent and mechanism of involvement of CYP2E1 in isoniazid-induced hepatotoxicity remain to be thoroughly investigated. In the current study, isoniazid was administered to wild-type and Cyp2e1-null mice to investigate the potential toxicity of isoniazid in vivo. The results revealed that isoniazid caused no hepatotoxicity in wild-type and Cyp2e1-null mice, but produced elevated serum cholesterol and triglycerides, and hepatic bile acids in wild-type mice, as well as decreased abundance of free fatty acids in wild-type mice and not in Cyp2e1-null mice. Metabolomic analysis demonstrated that production of isoniazid metabolites was elevated in wild-type mice along with a higher abundance of bile acids, bile acid metabolites, carnitine and carnitine derivatives; these were not observed in Cyp2e1-null mice. In addition, the enzymes responsible for bile acid synthesis were decreased and proteins involved in bile acid transport were significantly increased in wild-type mice. Lastly, treatment of targeted isoniazid metabolites to wild-type mice led to similar changes in cholesterol, triglycerides and free fatty acids. These findings suggest that while CYP2E1 is not involved in isoniazid-induced hepatotoxicity, while an isoniazid metabolite might play a role in isoniazid-induced cholestasis through enhancement of bile acid accumulation and mitochondria β-oxidation. -- Highlights: ► Isoniazid metabolites were elevated only in wild-type mice. ► Isoniazid caused no hepatotoxicity in wild-type and Cyp2e1-null mice. ► Isoniazid elevated serum cholesterol and triglycerides, and hepatic bile acids. ► Bile acid transporters were significantly decreased in isoniazid-treated mice.

  18. Substitution of specific cysteine residues in E1 glycoprotein of classical swine fever virus strain Brescia affects formation of E1-E2 heterodimers and alters virulence in swine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    E1, along with E^rns and E2, is one of the three envelope glycoproteins of Classical Swine Fever Virus (CSFV). E1 and E2 are anchored to the virus envelope at their carboxyl termini and E^rns loosely associates with the viral envelope. In infected cells, E2 forms homodimers and heterodimers with E1,...

  19. 76 FR 56363 - Capital Project Management

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-13

    ... September 1, 1989, at 49 CFR part 633 (54 FR 36708). At the time, UMTA's capital programs were comparatively... agency published on September 10, 2009, at 74 FR 46515-21. This proposed rule would transform the current... Federal Transit Administration 49 CFR Part 633 RIN 2132-AA92 Capital Project Management AGENCY:...

  20. 78 FR 32116 - TRICARE Young Adult

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-29

    .... Overview An interim final rule was published in the Federal Register on April 27, 2011 (76 FR 23479-23485... (76 FR 23479-23485). No comments were received. OMB approved the TYA application form and assigned the... Transitional Compensation Program (TCP) under 10 U.S.C 1059 as defined in Sec. 199.3(b)(2)(iii) of this...

  1. 78 FR 44399 - Semiannual Regulatory Flexibility Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-23

    ... adopted on April 9, 2013, (78 FR 21019) a regulation to permit banking organizations under its supervision... Regulation CC to facilitate the banking industry's ongoing transition to fully electronic interbank check... whether a deposited check has been returned unpaid. Timetable: Action Date FR Cite Board Requested...

  2. 78 FR 16511 - Delegation of Authority

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-15

    ... necessary to complete the transition of the Administration on Intellectual and Developmental Disabilities to... with the Federal Register notice of reorganization as last amended, 77 FR 23250-23260, April 18,...

  3. 26 CFR 1.72(e)-1T - Treatment of distributions where substantially all contributions are employee contributions...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 72(o) are disregarded in their entirety (i.e., treated as neither employee contributions nor employer... all contributions are employee contributions (temporary). 1.72(e)-1T Section 1.72(e)-1T Internal... TAXES (CONTINUED) Items Specifically Included in Gross Income § 1.72(e)-1T Treatment of...

  4. 26 CFR 1.1033(e)-1 - Sale or exchange of livestock solely on account of drought.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... of drought. 1.1033(e)-1 Section 1.1033(e)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF... § 1.1033(e)-1 Sale or exchange of livestock solely on account of drought. (a) The sale or exchange of... applicable if the sale or exchange of such livestock by the taxpayer is solely on account of drought....

  5. 26 CFR 1.1033(e)-1 - Sale or exchange of livestock solely on account of drought.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... of drought. 1.1033(e)-1 Section 1.1033(e)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF... § 1.1033(e)-1 Sale or exchange of livestock solely on account of drought. (a) The sale or exchange of... applicable if the sale or exchange of such livestock by the taxpayer is solely on account of drought....

  6. 26 CFR 1.1033(e)-1 - Sale or exchange of livestock solely on account of drought.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... of drought. 1.1033(e)-1 Section 1.1033(e)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF... § 1.1033(e)-1 Sale or exchange of livestock solely on account of drought. (a) The sale or exchange of... applicable if the sale or exchange of such livestock by the taxpayer is solely on account of drought....

  7. 26 CFR 1.1033(e)-1 - Sale or exchange of livestock solely on account of drought.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... of drought. 1.1033(e)-1 Section 1.1033(e)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF... § 1.1033(e)-1 Sale or exchange of livestock solely on account of drought. (a) The sale or exchange of... applicable if the sale or exchange of such livestock by the taxpayer is solely on account of drought....

  8. Cytochrome P450 2E1 inhibition prevents hepatic carcinogenesis induced by diethylnitrosamine in alcohol-fed rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chronic alcohol ingestion increases hepatic cytochrome P450 2E1 (CYP2E1), which is associated with hepatocarcinogenesis. We investigated whether treatment with chlormethiazole (CMZ), a CYP2E1 inhibitor, protects against alcohol-associated hepatic carcinogenesis in rats. Rats were fed either an ethan...

  9. 26 CFR 1.72(e)-1T - Treatment of distributions where substantially all contributions are employee contributions...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... all contributions are employee contributions (temporary). 1.72(e)-1T Section 1.72(e)-1T Internal... TAXES (CONTINUED) Items Specifically Included in Gross Income § 1.72(e)-1T Treatment of distributions... Reform Act (TRA) of 1984 change the law with regard to the treatment of non-annuity distributions...

  10. 26 CFR 1.72(e)-1T - Treatment of distributions where substantially all contributions are employee contributions...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... all contributions are employee contributions (temporary). 1.72(e)-1T Section 1.72(e)-1T Internal... TAXES (CONTINUED) Items Specifically Included in Gross Income § 1.72(e)-1T Treatment of distributions... Reform Act (TRA) of 1984 change the law with regard to the treatment of non-annuity distributions...

  11. 26 CFR 301.6223(e)-1 - Effect of Internal Revenue Service's failure to provide notice.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... years beginning prior to October 4, 2001, see § 301.6223(e)-1T contained in 26 CFR part 1, revised April...: Example 1. Partnership ABC has as one of its partners, A, a partnership with three partners, X, Y, and Z. ABC does not have more than 100 partners, and partnership A is entitled to notice under section...

  12. 26 CFR 301.6223(e)-1 - Effect of Internal Revenue Service's failure to provide notice.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... years beginning prior to October 4, 2001, see § 301.6223(e)-1T contained in 26 CFR part 1, revised April...: Example 1. Partnership ABC has as one of its partners, A, a partnership with three partners, X, Y, and Z. ABC does not have more than 100 partners, and partnership A is entitled to notice under section...

  13. 26 CFR 301.6223(e)-1 - Effect of Internal Revenue Service's failure to provide notice.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... years beginning prior to October 4, 2001, see § 301.6223(e)-1T contained in 26 CFR part 1, revised April...: Example 1. Partnership ABC has as one of its partners, A, a partnership with three partners, X, Y, and Z. ABC does not have more than 100 partners, and partnership A is entitled to notice under section...

  14. 26 CFR 301.6223(e)-1 - Effect of Internal Revenue Service's failure to provide notice.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... years beginning prior to October 4, 2001, see § 301.6223(e)-1T contained in 26 CFR part 1, revised April...: Example 1. Partnership ABC has as one of its partners, A, a partnership with three partners, X, Y, and Z. ABC does not have more than 100 partners, and partnership A is entitled to notice under section...

  15. 26 CFR 301.6223(e)-1 - Effect of Internal Revenue Service's failure to provide notice.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... years beginning prior to October 4, 2001, see § 301.6223(e)-1T contained in 26 CFR part 1, revised April...: Example 1. Partnership ABC has as one of its partners, A, a partnership with three partners, X, Y, and Z. ABC does not have more than 100 partners, and partnership A is entitled to notice under section...

  16. NOVEL ASSAY TO ASSESS CYP-2E1-LIKE ACTIVITY IN THE JAPANESE MEDAKA (ORYZIAS LATIPES).

    EPA Science Inventory

    Liver microsomes and S-9 fraction of Japanese medaka (Oryzias latipes) metabolized the CYP2E1 specific substrate, p-nitrophenol (PNP), to a single hydroxylated product, 4-nitrocatechol. The use of liver S-9 fraction proved to be a viable alternative to liver microsomes and allowe...

  17. 26 CFR 1.1397E-1 - Qualified zone academy bonds.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... apply to bonds issued under section 1397E pursuant to allocations of the national qualified zone academy... 26 Internal Revenue 11 2012-04-01 2012-04-01 false Qualified zone academy bonds. 1.1397E-1 Section... academy bonds. (a) In general—(1) Overview. In general, a qualified zone academy bond (QZAB or QZABs) is...

  18. E1 Ubiquitin-Activating Enzyme UBA-1 Plays Multiple Roles throughout C. elegans Development

    PubMed Central

    Kulkarni, Madhura; Smith, Harold E.

    2008-01-01

    Poly-ubiquitination of target proteins typically marks them for destruction via the proteasome and provides an essential mechanism for the dynamic control of protein levels. The E1 ubiquitin-activating enzyme lies at the apex of the ubiquitination cascade, and its activity is necessary for all subsequent steps in the reaction. We have isolated a temperature-sensitive mutation in the Caenorhabditis elegans uba-1 gene, which encodes the sole E1 enzyme in this organism. Manipulation of UBA-1 activity at different developmental stages reveals a variety of functions for ubiquitination, including novel roles in sperm fertility, control of body size, and sex-specific development. Levels of ubiquitin conjugates are substantially reduced in the mutant, consistent with reduced E1 activity. The uba-1 mutation causes delays in meiotic progression in the early embryo, a process that is known to be regulated by ubiquitin-mediated proteolysis. The uba-1 mutation also demonstrates synthetic lethal interactions with alleles of the anaphase-promoting complex, an E3 ubiquitin ligase. The uba-1 mutation provides a sensitized genetic background for identifying new in vivo functions for downstream components of the ubiquitin enzyme cascade, and it is one of the first conditional mutations reported for the essential E1 enzyme in a metazoan animal model. PMID:18636104

  19. 26 CFR 301.6229(e)-1 - Information with respect to unidentified partner.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 CFR part 1, revised April 1, 2001. ... 26 Internal Revenue 18 2010-04-01 2010-04-01 false Information with respect to unidentified....6229(e)-1 Information with respect to unidentified partner. (a) In general. A partner who is...

  20. The 8-Pyrrole-Benzothiazinones Are Noncovalent Inhibitors of DprE1 from Mycobacterium tuberculosis.

    PubMed

    Makarov, Vadim; Neres, João; Hartkoorn, Ruben C; Ryabova, Olga B; Kazakova, Elena; Šarkan, Michal; Huszár, Stanislav; Piton, Jérémie; Kolly, Gaëlle S; Vocat, Anthony; Conroy, Trent M; Mikušová, Katarína; Cole, Stewart T

    2015-08-01

    8-Nitro-benzothiazinones (BTZs), such as BTZ043 and PBTZ169, inhibit decaprenylphosphoryl-β-d-ribose 2'-oxidase (DprE1) and display nanomolar bactericidal activity against Mycobacterium tuberculosis in vitro. Structure-activity relationship (SAR) studies revealed the 8-nitro group of the BTZ scaffold to be crucial for the mechanism of action, which involves formation of a semimercaptal bond with Cys387 in the active site of DprE1. To date, substitution of the 8-nitro group has led to extensive loss of antimycobacterial activity. Here, we report the synthesis and characterization of the pyrrole-benzothiazinones PyrBTZ01 and PyrBTZ02, non-nitro-benzothiazinones that retain significant antimycobacterial activity, with MICs of 0.16 μg/ml against M. tuberculosis. These compounds inhibit DprE1 with 50% inhibitory concentration (IC50) values of <8 μM and present favorable in vitro absorption-distribution-metabolism-excretion/toxicity (ADME/T) and in vivo pharmacokinetic profiles. The most promising compound, PyrBTZ01, did not show efficacy in a mouse model of acute tuberculosis, suggesting that BTZ-mediated killing through DprE1 inhibition requires a combination of both covalent bond formation and compound potency. PMID:25987616

  1. The 8-Pyrrole-Benzothiazinones Are Noncovalent Inhibitors of DprE1 from Mycobacterium tuberculosis

    PubMed Central

    Makarov, Vadim; Neres, João; Hartkoorn, Ruben C.; Ryabova, Olga B.; Kazakova, Elena; Šarkan, Michal; Huszár, Stanislav; Piton, Jérémie; Kolly, Gaëlle S.; Vocat, Anthony; Conroy, Trent M.; Mikušová, Katarína

    2015-01-01

    8-Nitro-benzothiazinones (BTZs), such as BTZ043 and PBTZ169, inhibit decaprenylphosphoryl-β-d-ribose 2′-oxidase (DprE1) and display nanomolar bactericidal activity against Mycobacterium tuberculosis in vitro. Structure-activity relationship (SAR) studies revealed the 8-nitro group of the BTZ scaffold to be crucial for the mechanism of action, which involves formation of a semimercaptal bond with Cys387 in the active site of DprE1. To date, substitution of the 8-nitro group has led to extensive loss of antimycobacterial activity. Here, we report the synthesis and characterization of the pyrrole-benzothiazinones PyrBTZ01 and PyrBTZ02, non-nitro-benzothiazinones that retain significant antimycobacterial activity, with MICs of 0.16 μg/ml against M. tuberculosis. These compounds inhibit DprE1 with 50% inhibitory concentration (IC50) values of <8 μM and present favorable in vitro absorption-distribution-metabolism-excretion/toxicity (ADME/T) and in vivo pharmacokinetic profiles. The most promising compound, PyrBTZ01, did not show efficacy in a mouse model of acute tuberculosis, suggesting that BTZ-mediated killing through DprE1 inhibition requires a combination of both covalent bond formation and compound potency. PMID:25987616

  2. Defective human retinoblastoma protein identified by lack of interaction with the E1A oncoprotein.

    PubMed

    Paggi, M G; Martelli, F; Fanciulli, M; Felsani, A; Sciacchitano, S; Varmi, M; Bruno, T; Carapella, C M; Floridi, A

    1994-02-15

    Inactivating mutations of the retinoblastoma susceptibility gene (Rb) are involved in the pathogenesis of hereditary and sporadic retinoblastoma. Alterations in the Rb gene have also been found in several other human tumors occurring with epidemiological incidence higher than that of retinoblastoma. Four human malignant glioma cell lines were examined for abnormalities in the retinoblastoma gene product (pRb), using a procedure based on the interaction of pRb with an in vitro-translated adenovirus E1A oncoprotein. In the CRS-A2 cell line, derived from a glioblastoma multiforme, pRb did not bind with the in vitro-translated E1A protein. Restriction analysis of the CRS-A2 Rb gene and Rb mRNA expression provided patterns that could not be distinguished from the other glioma cell lines. Further investigation revealed the presence of a truncated pRb in the CRS-A2 cell line, due to a nucleotide insertion in the coding sequence at position 2550. In addition, this truncated Rb protein was undetectable in phosphorylated form. The binding assay with the in vitro-translated E1A was also used to study other cell lines with known mutations in the Rb gene. This method, which evaluates the interaction between in vitro-translated E1A and the pRb, is proposed as a rapid screening for detecting functional alterations in the retinoblastoma protein. PMID:8313367

  3. 26 CFR 301.6511(e)-1 - Special rules applicable to manufactured sugar.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 18 2014-04-01 2014-04-01 false Special rules applicable to manufactured sugar... Assessment and Collection § 301.6511(e)-1 Special rules applicable to manufactured sugar. (a) Use as... the person entitled thereto. Such right accrues as of the date the manufactured sugar, or...

  4. 26 CFR 301.6511(e)-1 - Special rules applicable to manufactured sugar.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 18 2011-04-01 2011-04-01 false Special rules applicable to manufactured sugar... Assessment and Collection § 301.6511(e)-1 Special rules applicable to manufactured sugar. (a) Use as... the person entitled thereto. Such right accrues as of the date the manufactured sugar, or...

  5. 26 CFR 301.6511(e)-1 - Special rules applicable to manufactured sugar.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 18 2013-04-01 2013-04-01 false Special rules applicable to manufactured sugar... Assessment and Collection § 301.6511(e)-1 Special rules applicable to manufactured sugar. (a) Use as... the person entitled thereto. Such right accrues as of the date the manufactured sugar, or...

  6. 26 CFR 301.6511(e)-1 - Special rules applicable to manufactured sugar.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 18 2010-04-01 2010-04-01 false Special rules applicable to manufactured sugar... Assessment and Collection § 301.6511(e)-1 Special rules applicable to manufactured sugar. (a) Use as... the person entitled thereto. Such right accrues as of the date the manufactured sugar, or...

  7. 26 CFR 301.6511(e)-1 - Special rules applicable to manufactured sugar.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 18 2012-04-01 2012-04-01 false Special rules applicable to manufactured sugar... Assessment and Collection § 301.6511(e)-1 Special rules applicable to manufactured sugar. (a) Use as... the person entitled thereto. Such right accrues as of the date the manufactured sugar, or...

  8. E-1 Dynamic Fluid-Flow Model Update: EASY/ROCETS Enhancement and Model Development Support

    NASA Technical Reports Server (NTRS)

    Follett, Randolph F.; Taylor, Robert P.

    1998-01-01

    This report documents the research conducted to update computer models for dynamic fluid flow simulation of the E-1 test stand subsystems at te NASA John C. Stennis Space Center.Work also involved significant upgrades to the capabilities of EASY/ROCKETS library through the inclusion of the NIST-12 thermodynamic property database and development of new control system modules.

  9. 26 CFR 301.6501(e)-1T - Omission from return (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... and Collection § 301.6501(e)-1T Omission from return (temporary). (a) Income taxes—(1) General rule. (i) If the taxpayer omits from the gross income stated in the return of a tax imposed by subtitle A... the gross income so stated, the tax may be assessed, or a proceeding in court for the collection...

  10. 26 CFR 1.401(e)-1 - Definitions relating to plans covering self-employed individuals.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., Stock Bonus Plans, Etc. § 1.401(e)-1 Definitions relating to plans covering self-employed individuals...), (f), (g), (h), and (i), are also generally applicable to any plan covering a self-employed individual. However, in addition to such requirements and special rules, any plan covering a self-employed...

  11. Induction of CYP2E1 in non-alcoholic fatty liver diseases.

    PubMed

    Aljomah, Ghanim; Baker, Susan S; Liu, Wensheng; Kozielski, Rafal; Oluwole, Janet; Lupu, Benita; Baker, Robert D; Zhu, Lixin

    2015-12-01

    Mounting evidence supports a contribution of endogenous alcohol metabolism in the pathogenesis of non-alcoholic steatohepatitis (NASH). However, it is not known whether the expression of alcohol metabolism genes is altered in the livers of simple steatosis. There is also a current debate on whether fatty acids induce CYP2E1 in fatty livers. In this study, expression of alcohol metabolizing genes in the liver biopsies of simple steatosis patients was examined by quantitative real-time PCR (qRT-PCR), in comparison to biopsies of NASH livers and normal controls. Induction of alcohol metabolizing genes was also examined in cultured HepG2 cells treated with ethanol or oleic acid, by qRT-PCR and Western blots. We found that the mRNA expression of alcohol metabolizing genes including ADH1C, ADH4, ADH6, catalase and CYP2E1 was elevated in the livers of simple steatosis, to similar levels found in NASH livers. In cultured HepG2 cells, ethanol induced the expression of CYP2E1 mRNA and protein, but not ADH4 or ADH6; oleic acid did not induce any of these genes. These results suggest that elevated alcohol metabolism may contribute to the pathogenesis of NAFLD at the stage of simple steatosis as well as more severe stages. Our in vitro data support that CYP2E1 is induced by endogenous alcohol but not by fatty acids. PMID:26551085

  12. Identification and Mechanistic Studies of a Novel Ubiquitin E1 Inhibitor

    PubMed Central

    Ungermannova, Dana; Parker, Seth J.; Nasveschuk, Christopher G.; Chapnick, Douglas A.; Phillips, Andrew J.; Kuchta, Robert D.; Liu, Xuedong

    2012-01-01

    Protein degradation via the ubiquitin-proteasome pathway is important for a diverse number of cellular processes ranging from cell signaling to development. Disruption of the ubiquitin pathway occurs in a variety of human diseases, including several cancers and neurological disorders. Excessive proteolysis of tumor suppressor proteins, such as p27, occurs in numerous aggressive human tumors. To discover small-molecule inhibitors that potentially prevent p27 degradation, we developed a series of screening assays, including a cell-based screen of a small-molecule compound library and two novel nucleotide exchange assays. Several small-molecule inhibitors, including NSC624206, were identified and subsequently verified to prevent p27 ubiquitination in vitro. The mechanism of NSC624206 inhibition of p27 ubiquitination was further unraveled using the nucleotide exchange assays and shown to be due to antagonizing ubiquitin activating enzyme (E1). We determined that NSC624206 and PYR-41, a recently reported inhibitor of ubiquitin E1, specifically block ubiquitin-thioester formation but have no effect on ubiquitin adenylation. These studies reveal a novel E1 inhibitor that targets a specific step of the E1 activation reaction. NSC624206 could, therefore, be potentially useful for the control of excessive ubiquitin-mediated proteolysis in vivo. PMID:22274912

  13. 26 CFR 1.414(e)-1 - Definition of church plan.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... (CONTINUED) INCOME TAXES (CONTINUED) Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.414(e)-1 Definition... is paid to, employees employed in connection with an unrelated trade or business. The determination... employees not employed in connection with an unrelated trade or business unless it fails to meet...

  14. Specific estrogen sulfotransferase (SULT1E1) substrates and molecular imaging probe candidates

    PubMed Central

    Cole, Graham B.; Keum, Gyochang; Liu, Jie; Small, Gary W.; Satyamurthy, Nagichettiar; Kepe, Vladimir; Barrio, Jorge R.

    2010-01-01

    This work focuses on the development of specific substrates for estrogen sulfotransferase (SULT1E1) to produce molecular imaging probes for this enzyme. SULT1E1 is a key enzyme in estrogen homeostasis, playing a central role in the prevention and development of human disease. In vitro sulfation assays showed alkyl and aryl substitutions to a fused heterocyclic system modeled after β-naphthol (βN), based on compounds that interact with the estrogen receptor, rendered several molecules with enhanced specificity for SULT1E1 over SULT1A1*1, SULT1A1*2, SULT1A3, and SULT2A1. Several 6-hydroxy-2-arylbenzothiazoles tested demonstrated excellent affinity—Vmax/Km ratios—and specificity for SULT1E1. Km values ranged from 0.12–2.36 μM. A strong correlation was observed between polarity of the 4′-sustituent on the 2-aryl moiety (Hammett σp) and the log(Vmax/Km) (r = 0.964). Substrate sensitivity is influenced by the acidity of the 6-phenolic group demonstrated by correlating its 1H NMR chemical shift (δOH) with the log(Vmax/Km) (r = 0.963). Acidity is mediated by the electron withdrawing capacity of the 4′-substituent outlined by the correlation of the C-2 13C NMR chemical shift (δC2) with the log(Vmax/Km) (r = 0.987). 2-[4-(Methylamino)phenyl]-6-hydroxybenzothiazole (2b) was radiolabeled with carbon-11 (11C-(2b)) and used in vivo for microPET scanning and tissue metabolite identification. High PET signal was paralleled with the presence of radiolabeled 11C-(2b)-6-O-sulfate and the SULT1E1 protein detected by western blot. Because this and other members of this family presenting specificity for SULT1E1 can be labeled with carbon-11 or fluorine-18, in vivo assays of SULT1E1 functional activity are now feasible in humans. PMID:20304798

  15. [Improved kidney function with intravenous prostaglandin E1 in patients with terminal heart failure].

    PubMed

    Wutte, M; Hülsmann, M; Berger, R; Rödler, S; Frey, B; Stanek, B; Pacher, R

    1998-07-31

    In end stage congestive heart failure activation of a series of compensatory mechanisms increase renal vascular resistance and impair renal function. Prostaglandin E1 is increasingly used in the treatment of severe heart failure for its vasodilating actions. In various experimental settings prostaglandin E analogues are known to improve renal function by modulating renal filtration pressure and redistribution of renal blood flow. However, prostaglandin E1 decreases systemic blood pressure and thus, also renal perfusion pressure, a fact by which renal function might be further compromized in heart failure patients. The aim of the study was to evaluate the effects of prostaglandin E1 on excretory renal function in patients with end stage heart failure and to prove the hypothesis, that the well known local actions of prostaglandins on renal microcirculation might outweigh the negative impact of an expected decrease in perfusion pressure. 25 patients with terminal congestive heart failure were investigated. 13 patients received prostaglandin E1 at a dose of 13.5 +/- 1.9 ng/kg/min in combination with constant rates of dopamine and dobutamine (group A), 12 patients received prostaglandin E1 at a dose of 10.3 +/- 1.7 ng/kg/min without catecholamines (group B). There was no significant difference in prostaglandin dosages between groups. Kidney function was assessed by measuring plasma creatinine and urea nitrogen, urinary output, creatinine clearance, osmotic and free water clearance at baseline and after 72 h of infusion therapy. Hemodynamic parameters were measured by using a balloon tipped pulmonary arterial catheter. Hemodynamic measurements during infusion showed a significant improvement in all patients. At the same time as expected mean arterial pressure decreased in both groups (p < 0.001). Nevertheless, in both groups a significant increase of creatinine clearance during infusion was observed (in group A from 45 ml/min to 78 ml/min., p < 0.05, in group B from 59

  16. Osteogenic gene expression of murine osteoblastic (MC3T3-E1) cells under cyclic tension

    NASA Astrophysics Data System (ADS)

    Kao, C. T.; Chen, C. C.; Cheong, U.-I.; Liu, S. L.; Huang, T. H.

    2014-08-01

    Low-level laser therapy (LLLT) can promote cell proliferation. The remodeling ability of the tension side of orthodontic teeth affects post-orthodontic stability. The purpose of the present study was to investigate the osteogenic effects of LLLT on osteoblast-like cells treated with a simulated tension system that provides a mechanical tension regimen. Murine osteoblastic (MC3T3-E1) cells were cultured in a Flexcell strain unit with programmed loads of 12% elongation at a frequency of 0.5 Hz for 24 and 48 h. The cultured cells were treated with a low-level diode laser using powers of 5 J and 10 J. The proliferation of MC3T3-E1 cells was determined using the Alamar Blue assay. The expression of osteogenic genes (type I collagen (Col-1), osteopontin (OPN), osteocalcin (OC), osteoprotegerin (OPG), receptor activator of nuclear factor kappa B ligand (RANKL), bone morphologic protein (BMP-2), and bone morphologic protein (BMP-4)) in MC3T3-E1 cells was analyzed using reverse transcription polymerase chain reaction (RT-PCR). The data were analyzed using one-way analysis of variance. The proliferation rate of tension-cultured MC3T3-E1 cells under 5 J and 10 J LLLT increased compared with that of the control group (p < 0.05). Prominent mineralization of the MC3T3-E1 cells was visible using a von Kossa stain in the 5 J LLLT group. Osteogenic genes (Col-1, OC, OPG and BMP-2) were significantly expressed in the MC3T3-E1 cells treated with 5 J and 10 J LLLT (p < 0.05). LLLT in tension-cultured MC3T3-E1 cells showed synergistic osteogenic effects, including increases in cell proliferation and Col-1, OPN, OC, OPG and BMP-2 gene expression. LLLT might be beneficial for bone remodeling on the tension side of orthodontics.

  17. Benzene metabolism by human liver microsomes in relation to cytochrome P450 2E1 activity.

    PubMed

    Seaton, M J; Schlosser, P M; Bond, J A; Medinsky, M A

    1994-09-01

    Low levels of benzene from sources including cigarette smoke and automobile emissions are ubiquitous in the environment. Since the toxicity of benzene probably results from oxidative metabolites, an understanding of the profile of biotransformation of low levels of benzene is critical in making a valid risk assessment. To that end, we have investigated metabolism of a low concentration of [14C]benzene (3.4 microM) by microsomes from human, mouse and rat liver. The extent of phase I benzene metabolism by microsomal preparations from 10 human liver samples and single microsomal preparations from both mice and rats was then related to measured activities of cytochrome P450 (CYP) 2E1. Measured CYP 2E1 activities, as determined by hydroxylation of p-nitrophenol, varied 13-fold (0.253-3.266 nmol/min/mg) for human samples. The fraction of benzene metabolized in 16 min ranged from 10% to 59%. Also at 16 min, significant amounts of oxidative metabolites were formed. Phenol was the main metabolite formed by all but two human microsomal preparations. In those samples, both of which had high CYP 2E1 activity, hydroquinone was the major metabolite formed. Both hydroquinone and catechol formation showed a direct correlation with CYP 2E1 activity over the range of activities present. A simulation model was developed based on a mechanism of competitive inhibition between benzene and its oxidized metabolites, and was fit to time-course data for three human liver preparations. Model calculations for initial rates of benzene metabolism ranging from 0.344 to 4.442 nmol/mg/min are directly proportional to measured CYP 2E1 activities. The model predicted the dependence of benzene metabolism on the measured CYP 2E1 activity in human liver samples, as well as in mouse and rat liver samples. These results suggest that differences in measured hepatic CYP 2E1 activity may be a major factor contributing to both interindividual and interspecies variations in hepatic metabolism of benzene

  18. CYP2E1 and NQO1 genotypes and bladder cancer risk in a Lebanese population.

    PubMed

    Basma, Hussein A; Kobeissi, Loulou H; Jabbour, Michel E; Moussa, Mohamad A; Dhaini, Hassan R

    2013-01-01

    Urinary bladder cancer incidence in Lebanon ranks among the highest in the world. Cytochrome P450 2E1 (CYP2E1), NAD(P)H quinone oxidoreductase1 (NQO1), and N-Acetyltransferase1 (NAT1), are drug-metabolizing enzymes (DMEs) involved in the metabolism of carcinogens, such as arylamines and heterocyclic amines, implicated in bladder cancer. The present study attempts to investigate the role of these DMEs genetic polymorphism in bladder cancer risk among Lebanese men. 54 cases and 106 controls were recruited from two hospitals in Beirut. An interview-based questionnaire was administered to assess suspected environmental and occupational risk factors. PCR-RFLP was performed on blood-based DNA samples to determine DMEs genotypes. Associations between bladder cancer and putative risk factors were measured using adjusted odds ratios (ORs) and their 95% confidence intervals (CIs). Results showed CYP2E1 c1/c1, NAT1*14A, and smoking, to be risk factors for bladder cancer. No significant differences in frequency distribution of the NQO1 genotypes were found in cases versus controls. The odds of carrying the CYP2E1 c1/c1 genotype were 4 times higher in cases compared to controls (OR=3.97, 95% CI: 0.48-32.7). The odds of carrying at least one NAT1*14A allele were 14 times higher in cases versus controls (OR=14.4, 95% CI: 1.016-204.9). Our study suggests CYP2E1 c1/c1, NAT1*14A, and smoking, as potential risk factors for bladder cancer in Lebanese. Further studies with larger samples must be conducted to confirm these findings. PMID:24319536

  19. CYP2E1 and NQO1 genotypes and bladder cancer risk in a Lebanese population

    PubMed Central

    Basma, Hussein A; Kobeissi, Loulou H; Jabbour, Michel E; Moussa, Mohamad A; Dhaini, Hassan R

    2013-01-01

    Urinary bladder cancer incidence in Lebanon ranks among the highest in the world. Cytochrome P450 2E1 (CYP2E1), NAD(P)H quinone oxidoreductase1 (NQO1), and N-Acetyltransferase1 (NAT1), are drug-metabolizing enzymes (DMEs) involved in the metabolism of carcinogens, such as arylamines and heterocyclic amines, implicated in bladder cancer. The present study attempts to investigate the role of these DMEs genetic polymorphism in bladder cancer risk among Lebanese men. 54 cases and 106 controls were recruited from two hospitals in Beirut. An interview-based questionnaire was administered to assess suspected environmental and occupational risk factors. PCR-RFLP was performed on blood-based DNA samples to determine DMEs genotypes. Associations between bladder cancer and putative risk factors were measured using adjusted odds ratios (ORs) and their 95% confidence intervals (CIs). Results showed CYP2E1 c1/c1, NAT1*14A, and smoking, to be risk factors for bladder cancer. No significant differences in frequency distribution of the NQO1 genotypes were found in cases versus controls. The odds of carrying the CYP2E1 c1/c1 genotype were 4 times higher in cases compared to controls (OR=3.97, 95% CI: 0.48-32.7). The odds of carrying at least one NAT1*14A allele were 14 times higher in cases versus controls (OR=14.4, 95% CI: 1.016-204.9). Our study suggests CYP2E1 c1/c1, NAT1*14A, and smoking, as potential risk factors for bladder cancer in Lebanese. Further studies with larger samples must be conducted to confirm these findings. PMID:24319536

  20. Structural basis of inhibition of Mycobacterium tuberculosis DprE1 by benzothiazinone inhibitors

    PubMed Central

    Batt, Sarah M.; Jabeen, Talat; Bhowruth, Veemal; Quill, Lee; Lund, Peter A.; Eggeling, Lothar; Alderwick, Luke J.; Fütterer, Klaus; Besra, Gurdyal S.

    2012-01-01

    Resistance against currently used antitubercular therapeutics increasingly undermines efforts to contain the worldwide tuberculosis (TB) epidemic. Recently, benzothiazinone (BTZ) inhibitors have shown nanomolar potency against both drug-susceptible and multidrug-resistant strains of the tubercle bacillus. However, their proposed mode of action is lacking structural evidence. We report here the crystal structure of the BTZ target, FAD-containing oxidoreductase Mycobacterium tuberculosis DprE1, which is essential for viability. Different crystal forms of ligand-free DprE1 reveal considerable levels of structural flexibility of two surface loops that seem to govern accessibility of the active site. Structures of complexes with the BTZ-derived nitroso derivative CT325 reveal the mode of inhibitor binding, which includes a covalent link to conserved Cys387, and reveal a trifluoromethyl group as a second key determinant of interaction with the enzyme. Surprisingly, we find that a noncovalent complex was formed between DprE1 and CT319, which is structurally identical to CT325 except for an inert nitro group replacing the reactive nitroso group. This demonstrates that binding of BTZ-class inhibitors to DprE1 is not strictly dependent on formation of the covalent link to Cys387. On the basis of the structural and activity data, we propose that the complex of DrpE1 bound to CT325 is a representative of the BTZ-target complex. These results mark a significant step forward in the characterization of a key TB drug target. PMID:22733761

  1. 77 FR 5252 - Federal Travel Regulation; GSA E-Gov Travel Service (ETS) Transition to E-Gov Travel Service 2...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-02

    ... ADMINISTRATION Federal Travel Regulation; GSA E-Gov Travel Service (ETS) Transition to E-Gov Travel Service 2..., DC 22202 E-GOV TRAVEL SERVICE GSA Bulletin ETS 12-01 TO: Heads of Federal Agencies SUBJECT: GSA E-Gov... Regulation (FTR) Part 301-73 requires all agencies to deploy and implement an E-Gov Travel Service (ETS)....

  2. Metric transition

    NASA Technical Reports Server (NTRS)

    1992-01-01

    This report describes NASA's metric transition in terms of seven major program elements. Six are technical areas involving research, technology development, and operations; they are managed by specific Program Offices at NASA Headquarters. The final program element, Institutional Management, covers both NASA-wide functional management under control of NASA Headquarters and metric capability development at the individual NASA Field Installations. This area addresses issues common to all NASA program elements, including: Federal, state, and local coordination; standards; private industry initiatives; public-awareness initiatives; and employee training. The concluding section identifies current barriers and impediments to metric transition; NASA has no specific recommendations for consideration by the Congress.

  3. Microwave Spectrum and Molecular Structure of the ARGON-(E)-1-CHLORO-1,2-DIFLUOROETHYLENE Complex

    NASA Astrophysics Data System (ADS)

    Marshall, Mark D.; Leung, Helen O.; Tandon, Hannah K.; Messinger, Joseph P.; Mlaver, Eli

    2014-06-01

    Previous studies of argon complexes with fluoroethylenes have revealed a preference for a geometry that maximizes the contact of the argon atom with heavy atoms on the fluoroethylene. We have observed a continuation of this trend when one of the fluorine atoms is replaced by chlorine. The argon-(E)-1-chloro-1,2-difluoroethylene complex provides two competing heavy atom cavities, FCCF and FCCl, and the opportunity to examine whether the number of heavy atoms or the associated increase in polarizability is determinative of structure. The 5.6 -- 18.1 GHz chirped-pulse Fourier transform microwave spectrum of this species provides initial assignments and predictions for spectra obtained in a more sensitive and higher precision Balle-Flygare instrument. Transitions for both the 35Cl and 37Cl isotopologues are observed and analyzed to provide geometric parameters for this non-planar complex. The spectrum is consistent with the argon atom located in the FCCl cavity, and the structure agrees well with ab initio predictions. Comparisons are made with Ar-1-chloro-1-fluoroethylene, (Z)-1-chloro-2-fluoroethylene, and Ar-vinyl chloride. Z. Kisiel, P.W. Fowler, and A.C. Legon, J. Chem. Phys. 95, 2283 (1991).

  4. Theoretical studies of the long lifetimes of the 6 d D 3 /2 ,5 /2 2 states in Fr: Implications for parity-nonconservation measurements

    NASA Astrophysics Data System (ADS)

    Sahoo, B. K.; Das, B. P.

    2015-11-01

    Lifetimes of the 6 d D 3 /2 2 and 6 d D 5 /2 2 states in Fr are determined from calculations of the radiative transition amplitudes of the allowed electric dipole (E 1 ) and the forbidden electric quadrupole (E 2 ) and magnetic dipole (M 1 ) channels which were performed using the second-order many-body perturbation theory and the coupled-cluster method at different levels of approximations in the relativistic framework. The values obtained for these two quantities are 540(10) and 1704(32) ns, respectively. These relatively long lifetimes and the large electric dipole parity-non-conserving amplitudes of 7 s S 1 /2 2 →6 d D 3 /2 ,5 /2 2 transitions strongly favor Fr as a leading candidate for the measurement of parity nonconservation arising from the neutral-current weak interaction and the nuclear anapole moment. In another important application, these 6 D states in Fr can be used efficiently for resonance ionization spectroscopic techniques to carry out precise measurements of the properties of the higher excited states due to the long lifetimes of these states.

  5. Novel Manifestation of {alpha}-Clustering Structures: New '{alpha}+{sup 208}Pb' States in {sup 212}Po Revealed by Their Enhanced E1 Decays

    SciTech Connect

    Astier, A.; Porquet, M.-G.; Petkov, P.; Delion, D. S.; Schuck, P.

    2010-01-29

    Excited states in {sup 212}Po were populated by {alpha} transfer using the {sup 208}Pb({sup 18}O,{sup 14}C) reaction, and their deexcitation {gamma} rays were studied with the Euroball array. Several levels were found to decay by a unique E1 transition (E{sub {gamma}}<1 MeV) populating the yrast state with the same spin value. Their lifetimes were measured by the Doppler-shift attenuation method. The values, found in the range 0.1-1.4 ps, lead to very enhanced transitions, B(E1)=2x10{sup -2}-1x10{sup -3} W.u. These results are discussed in terms of an {alpha}-cluster structure which gives rise to states with non-natural-parity values, provided that the composite system cannot rotate collectively, as expected in the '{alpha}+{sup 208}Pb' case. Such states due to the oscillatory motion of the {alpha}-core distance are observed for the first time.

  6. Heterologous expression of human cytochrome P450 2E1 in HepG2 cell line

    PubMed Central

    Zhuge, Jian; Luo, Ye; Yu, Ying-Nian

    2003-01-01

    AIM: Human cytochrome P-450 2E1 (CYP2E1) takes part in the biotransformation of ethanol, acetone, many small-molecule substrates and volatile anesthetics. CYP2E1 is involved in chemical activation of many carcinogens, procarcinogens, and toxicants. To assess the metabolic and toxicological characteristics of CYP2E1, we cloned CYP2E1 cDNA and established a HepG2 cell line stably expressing recombinant CYP 2E1. METHODS: Human CYP2E1 cDNA was amplified with reverse transcription-polymerase chain reaction (RT-PCR) from total RNAs extracted from human liver and cloned into pGEM-T vector. The cDNA segment was identified by DNA sequencing and subcloned into a mammalian expression vector pREP9. A transgenic cell line was established by transfecting the recombinant plasmid of pREP9-CYP2E1 to HepG2 cells. The expression of CYP2E1 mRNA was validated by RT-PCR. The enzyme activity of CYP2E1 catalyzing oxidation of 4-nitrophenol in postmitochondrial supernate (S9) fraction of the cells was determined by spectrophotometry. The metabolic activation of HepG2-CYP2E1 cells was assayed by N-nitrosodiethylamine (NDEA) cytotoxicity and micronucleus test. RESULTS: The cloned CYP2E1 cDNA segment was identical to that reported by Umeno et al (GenBank access No. J02843). HepG2-CYP2E1 cells expressed CYP2E1 mRNA and had 4-nitrophenol hydroxylase activity (0.162 ± 0.025 nmol·min-1·mg-1 S9 protein), which were undetectable in parent HepG2 cells. HepG2-CYP2E1 cells increased the cytotoxicity and micronucleus rate of NDEA in comparison with those of HepG2 cells. CONCLUSION: The cDNA of human CYP2E1 can be successfully cloned, and a cell line, HepG2-CYP2E1, which can efficiently express mRNA and has CYP2E1 activity, is established. The cell line is useful for testing the cytotoxicity, mutagenicity and metabolism of xenobiotics, which may possibly be activated or metabolized by CYP2E1. PMID:14669323

  7. 77 FR 76861 - Removal of Job Training Partnership Act Implementing Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-31

    ... electronically at http://www.gpo.gov/fdsys/browse/collection.action?collectionCode=FR . SUPPLEMENTARY INFORMATION... April 15, 1999. See 64 FR 18662. In that IFR, the Department explicitly provided for the phased transition of the JTPA programs to WIA, to be fully completed by July 1, 2000. See 64 FR 18662, 18663...

  8. 77 FR 69546 - Agency Information Collection Activities; Information Collection Renewal; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-19

    ..., Transition Provisions, and Prompt Corrective Action (77 FR 52792); Regulatory Capital Rules: Standardized Approach for Risk- Weighted Assets; Market Discipline and Disclosure Requirements (77 FR 52888); and Regulatory Capital Rules: Advanced Approaches Risk-based Capital Rules; Market Risk Capital Rule (77 FR...

  9. 75 FR 56530 - Public Information Collections Approved by Office of Management and Budget

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-16

    ... Transition; Public Information Collection Approved by Office of Management and Budget, 75 FR 9113 (March 1... Proposed Rulemaking, FCC 10- 16 (rel. January 15, 2010); 75 FR 3622 (January 22, 2010). To effectuate the... Requested, 75 FR 3731 (January 22, 2010). \\3\\ See Revisions to Rules Authorizing the Operation of Low...

  10. 77 FR 52715 - Request for Comment on Letters Seeking a Waiver of the Renewable Fuel Standard

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-30

    ..., 2010 (75 FR 14670) (referred to as RFS2). The transition from the RFS1 requirements of EPAct to the... 2012 compliance year were published in the Federal ] Register on January 9, 2012 (77 FR 1320). Under... of a State, region, or the United States (73 FR 47168, August 13, 2008). EPA's 2008 denial of...

  11. 76 FR 77315 - Agency Information Collection Activities: Submission for OMB Review; Joint Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-12

    ...; savings associations will begin to file the Call Report as of the March 31, 2012, report date (76 FR 39986... pertained (76 FR 44987). After considering the comments received on these revisions, the transition guidance... loan definitions in its February 2011 final rule on assessments (76 FR 10672) to determine...

  12. 77 FR 48679 - Changes to Implement Inter Partes Review Proceedings, Post-Grant Review Proceedings, and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-14

    ...); (4) Changes to Implement Transitional Program for Covered Business Method Patents, 77 FR 7080 (Feb... Business Method Patents-- Definition of Technological Invention, 77 FR 7095 (Feb. 10, 2012), to add a new... method patents (RIN 0651-AC75); and (6) Changes to Implement Derivation Proceedings, 77 FR 7028 ]...

  13. 77 FR 35862 - Approval and Promulgation of Implementation Plans; State of Florida: New Source; Review...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-15

    ... to approve the aforementioned changes to Florida's NSR PSD program. See 77 FR 20582. Comments on the... NAAQS transition. See 70 FR 71612. The NSR permitting requirements established in the rule included the... subpart 1 and subpart 2 of the CAA. See 69 FR 23951. The Phase II Rule made changes to federal...

  14. 78 FR 9915 - Agency Information Collection Activities: Submission for OMB Review; Comment Request; Basel II...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-12

    ..., Capital Adequacy, Transition Provisions, and Prompt Corrective Action (77 FR 52792); Regulatory Capital... FR 52888); Regulatory Capital Rules: Advanced Approaches Risk-Based Capital Rule; Market Risk Capital Rule (77 FR 52978), and OMB review and action on proposed changes to the collection arising from...

  15. 77 FR 44242 - Medicare Program; Hospice Wage Index for Fiscal Year 2013

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-27

    ... wage index final rule (70 FR 45130), we implemented a 1-year transition policy using a 50/50 blend of... index. In the August 8, 1997 Federal Register (62 FR 42860), we published a final rule implementing a... the BNAF. The FY 2010 Hospice Wage Index final rule (74 FR 39384) finalized a provision for a...

  16. 78 FR 22659 - Revisions to the Export Administration Regulations: Initial Implementation of Export Control Reform

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-16

    ... Determines No Longer Warrant Control under the United States Munitions List (USML) (76 FR 41958) (hereinafter... Retrospective Regulatory Review (77 FR 37524) (hereinafter ``June 21 (transition) rule''). That rule proposed... President Determines No Longer Warrant Control Under the United States Munitions List (USML), (, 76 FR...

  17. Prenatal antidepressant exposure associated with CYP2E1 DNA methylation change in neonates

    PubMed Central

    Gurnot, Cécile; Martin-Subero, Ignacio; Mah, Sarah M; Weikum, Whitney; Goodman, Sarah J; Brain, Ursula; Werker, Janet F; Kobor, Michael S; Esteller, Manel; Oberlander, Tim F; Hensch, Takao K

    2015-01-01

    Some but not all neonates are affected by prenatal exposure to serotonin reuptake inhibitor antidepressants (SRI) and maternal mood disturbances. Distinguishing the impact of these 2 exposures is challenging and raises critical questions about whether pharmacological, genetic, or epigenetic factors can explain the spectrum of reported outcomes. Using unbiased DNA methylation array measurements followed by a detailed candidate gene approach, we examined whether prenatal SRI exposure was associated with neonatal DNA methylation changes and whether such changes were associated with differences in birth outcomes. Prenatal SRI exposure was first associated with increased DNA methylation status primarily at CYP2E1(βNon-exposed = 0.06, βSRI-exposed = 0.30, FDR = 0); however, this finding could not be distinguished from the potential impact of prenatal maternal depressed mood. Then, using pyrosequencing of CYP2E1 regulatory regions in an expanded cohort, higher DNA methylation status—both the mean across 16 CpG sites (P < 0.01) and at each specific CpG site (P < 0.05)—was associated with exposure to lower 3rd trimester maternal depressed mood symptoms only in the SRI-exposed neonates, indicating a maternal mood x SRI exposure interaction. In addition, higher DNA methylation levels at CpG2 (P = 0.04), CpG9 (P = 0.04) and CpG10 (P = 0.02), in the interrogated CYP2E1 region, were associated with increased birth weight independently of prenatal maternal mood, SRI drug exposure, or gestational age at birth. Prenatal SRI antidepressant exposure and maternal depressed mood were associated with altered neonatal CYP2E1 DNA methylation status, which, in turn, appeared to be associated with birth weight. PMID:25891251

  18. Fluxes and spectra of quasimonochromatic annihilation photons for studying E1 giant resonances in nuclei

    SciTech Connect

    Dzhilavyan, L. Z.

    2014-12-15

    The fluxes and spectra of quasimonochromatic photons originating from the in-flight annihilation of positrons interacting with electrons of targets are analyzed in the energy region characteristic of the excitation of E1 giant resonances in nuclei. Targets of small thickness and low atomic number are used. The dependences of the spectra on the energy and angle (and their scatter) for positrons incident to the target, on the collimation angle for photons, and on the target thickness are studied.

  19. Aminotriazole alleviates acetaminophen poisoning via downregulating P450 2E1 and suppressing inflammation.

    PubMed

    Jing, Yuping; Wu, Kunwei; Liu, Jiashuo; Ai, Qing; Ge, Pu; Dai, Jie; Jiang, Rong; Zhou, Dan; Che, Qian; Wan, Jingyuan; Zhang, Li

    2015-01-01

    Aminotriazole (ATZ) is commonly used as a catalase (CAT) inhibitor. We previously found ATZ attenuated oxidative liver injury, but the underlying mechanisms remain unknown. Acetaminophen (APAP) overdose frequently induces life-threatening oxidative hepatitis. In the present study, the potential hepatoprotective effects of ATZ on oxidative liver injury and the underlying mechanisms were further investigated in a mouse model with APAP poisoning. The experimental data indicated that pretreatment with ATZ dose- and time-dependently suppressed the elevation of plasma aminotransferases in APAP exposed mice, these effects were accompanied with alleviated histological abnormality and improved survival rate of APAP-challenged mice. In mice exposed to APAP, ATZ pretreatment decreased the CAT activities, hydrogen peroxide (H2O2) levels, malondialdehyde (MDA) contents, myeloperoxidase (MPO) levels in liver and reduced TNF-α levels in plasma. Pretreatment with ATZ also downregulated APAP-induced cytochrome P450 2E1 (CYP2E1) expression and JNK phosphorylation. In addition, posttreatment with ATZ after APAP challenge decreased the levels of plasma aminotransferases and increased the survival rate of experimental animals. Posttreatment with ATZ had no effects on CYP2E1 expression or JNK phosphorylation, but it significantly decreased the levels of plasma TNF-α. Our data indicated that the LD50 of ATZ in mice was 5367.4 mg/kg body weight, which is much higher than the therapeutic dose of ATZ in the present study. These data suggested that ATZ might be effective and safe in protect mice against APAP-induced hepatotoxicity, the beneficial effects might resulted from downregulation of CYP2E1 and inhibiton of inflammation. PMID:25884831

  20. Ultrasound associated uptake of chitosan nanoparticles in MC3T3-E1 cells

    NASA Astrophysics Data System (ADS)

    Wu, Junyi

    Chitosan is a natural linear polysaccharide that has been well known for its applications in drug delivery system due to its unique physicochemical and biological properties. However, challenges still remain for it to become a fully realized therapeutic agent. In this study, we investigated the uptake of chitosan nanoparticles (CNP) under the ultrasound stimulation, using a model cell culture system (MC3T3-E1 mouse pre-osteoblasts). The CNP were fabricated by an ionic gelation method and were lyophilized prior to characterization and delivery to cells. Particle size and zeta potential were measured using Dynamic Light Scattering (DLS); the efficiency of chitosan complexation was measured using the ninhydrin assay. Cytotoxicity was examined by neutral red assay within 48 hours after delivery. The effect of ultrasound (US) on the efficiency of nanoparticle delivery to the MC3T3-E1 cells was examined at 1MHz and at either 1 or 2 W/cm2. Fluorescein isothiocyanate (FITC)-conjugated-CNP were used to visualize the internalized particles within the cytosol. The uptake of FITC-CNP exhibits a dose and time dependent effect, a strong FITC fluorescence was detected at the concentration of 500microg/mL under fluorescence microscope. Ultrasound assisted uptake of FITC-CNP performed a significant positive effect at 2W/cm2 with 60s of ultrasound exposure time. CNP displayed a slightly decrease in cell viability from 25microg/mL to 100microg/mL, while higher concentration of CNP facilitates the proliferation of MC3T3-E1 cells. Less than 10% of reduction in cell viability was observed for US at 1W/cm2 and 2W/cm2 with 30s and 60s of exposure time, which suggest a mild effect of US to MC3T3-E1 cell line.

  1. Purification, crystallization and preliminary X-ray diffraction analysis of human enolase-phosphatase E1

    SciTech Connect

    Wang, Hui; Pang, Hai; Ding, Yi; Li, Yi; Wu, Xiao’ai; Rao, Zihe

    2005-05-01

    Recombinant human E1 enzyme has been crystallized using the hanging-drop vapour-diffusion method and diffraction-quality crystals were grown at 291 K using PEG 4000 as precipitant. Enolase-phosphatase E1 (MASA) is a bifunctional enzyme in the ubiquitous methionine-salvage pathway and catalyzes the continuous reaction of 2,3-diketo-5-methylthio-1-phosphopentane to yield the acireductone metabolite. Recombinant human E1 enzyme has been crystallized using the hanging-drop vapour-diffusion method and diffraction-quality crystals were grown at 291 K using PEG 4000 as precipitant. Diffraction data were collected to 1.7 Å resolution from SeMet-derivative crystals at 100 K using synchrotron radiation. The crystals belong to space group P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 54.02, b = 57.55, c = 87.32 Å. The structure was subsequently solved by the multi-wavelength anomalous diffraction (MAD) phasing method.

  2. Evaluation of E1A Double Mutant Oncolytic Adenovectors in Anti-Glioma Gene Therapy

    PubMed Central

    Ulasov, Ilya V.; Tyler, Matthew A.; Rivera, Angel A.; Nettelbeck, Dirk M.; Douglas, Joanne T.; Lesniak, Maciej S.

    2008-01-01

    Malignant glioma, in particular glioblastoma multiforme (GBM), represents one of the most devastating cancers currently known and existing treatment regimens do little to change patient prognosis. Conditionally replicating adenoviral vectors (CRAds) represent attractive experimental anti-cancer agents with potential for clinical application. However, early protein products of the wild type adenovirus backbone—such as E1A—limit CRAds’ replicative specificity. In this study, we evaluated the oncolytic potency and specificity of CRAds in which p300/CPB and/or pRb binding capacities of E1A were ablated to reduce non-specific replicative cytolysis. In vitro cytopathic assays, quantitative PCR analysis, Western blot, and flow cytometry studies demonstrate the superior anti-glioma efficacy of a double-mutated CRAd, Ad2/24CMV, which harbors mutations that reduce E1A binding to p300/CPB and pRb. When compared to its single-mutated and wild type counterparts, Ad2/24CMV demonstrated attenuated replication and cytotoxicity in representative normal human brain while displaying enhanced replicative cytotoxicity in malignant glioma. These results have implications for the development of double-mutated CRAd vectors for enhanced GBM therapy. PMID:18649343

  3. B(E1) Strengths from Coulomb excitation of 11Be

    SciTech Connect

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

    2007-03-06

    The B(E1;1/2{sup +}{yields} 1/2{sup -}) strength for {sup 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 {sup 11}Be+{sup 208}Pb at 38.6 MeV/nucleon is reported. The B(E1) strength of 0.105(12) e{sup 2}fm{sup 2} derived from this measurement is consistent with those made previously at 60 and 64 MeV/nucleon, in 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 combined B(E1) strength of 0.105(7) e{sup 2}fm{sup 2}. This value is in good agreement with the value deduced independently from the lifetime of the 1/2{sup -} state in {sup 11}Be, and has a comparable precision.

  4. E1B and E4 Oncoproteins of Adenovirus Antagonize the Effect of Apoptosis Inducing Factor

    PubMed Central

    Turner, Roberta L.; Wilkinson, John C.; Ornelles, David A.

    2014-01-01

    Adenovirus inundates the productively infected cell with linear, double-stranded DNA and an abundance of single-stranded DNA. The cellular response to this stimulus is antagonized by the adenoviral E1B and E4 early genes. A mutant group C adenovirus that fails to express the E1B-55K and E4orf3 genes is unable to suppress the DNA-damage response. Cells infected with this double-mutant virus display significant morphological heterogeneity at late times of infection and frequently contain fragmented nuclei. Nuclear fragmentation was due to the translocation of apoptosis inducing factor (AIF) from the mitochondria into the nucleus. The release of AIF was dependent on active poly(ADP-ribose) polymerase-1 (PARP-1), which appeared to be activated by viral DNA replication. Nuclear fragmentation did not occur in AIF-deficient cells or in cells treated with a PARP-1 inhibitor. The E1B-55K or E4orf3 proteins independently prevented nuclear fragmentation subsequent to PARP-1 activation, possibly by altering the intracellular distribution of PAR-modified proteins. PMID:24889240

  5. [Intra-arterial administration of prostaglandin E1 in occlusive arterial diseases].

    PubMed

    Davidović, L; Vranes, M; Cernak, I; Kostić, D; Lovrić, A; Sagić, D; Lotina, S

    1992-01-01

    The authors present their result of a two-year follow-up of 106 patients to whom an intra-arterial perfusion of prostaglandin E1 was administered, as limb salvage procedure. The patients were in the IIIrd and IVth stage of occlusive diseases by Fountain, and surgical reconstructions were not possible. All patients were divided into five groups: A--diabetic angiopathy (5), B--distal form of atherosclerosis (40), C--diabetic angiopathy and atherosclerosis (45), D--Burger disease (10) and E--adjuvant therapy in reconstruction with poor run-off (6). The Doppler sonographic and angiographic measurements were performed. After transcutaneous (16 cases), or intraoperative (90 cases) introduction of the catheter into superficial of profunda femoral artery, a continuous intraarterial administration of prostaglandin E1 was carried out in a dose of 10 nanograms/kg body weight/minute (total dosage 3000 nanograms). The patients were controlled immediately after the treatment, as well as 1, 3, 6, 12, 24 and 36 months after the treatment. In efficiency of the treatment was estimated on the following basis: elimination of rest pain, healing of trophic ulceration and demarcation of gangrenous processes. Our late results of intra-arterial administration of prostaglandin E1 proved to be a very successful limb salvage procedure. The treatment was more successful in a connections between the upper knee arterial net and pedal arterial arches were preserved. PMID:1641706

  6. Instanton induced Yukawa couplings from distant E3 and E(-1) instantons

    NASA Astrophysics Data System (ADS)

    Goodsell, Mark D.; Witkowski, Lukas T.

    2016-01-01

    We calculate non-perturbative contributions to Yukawa couplings on D3-branes at orbifold singularities due to E3 and fractional E(-1) instantons which do not intersect the visible sector branes. While distant E3 instantons on bulk cycles typically contribute to Yukawa couplings, we find that distant fractional E(-1) can also give rise to new Yukawa couplings. However, fractional E(-1) instantons only induce Yukawa couplings if they are located at a singularity which shares a collapsed homologous two-cycle with the singularity supporting the visible sector. The non-perturbative contributions to Yukawa couplings exhibit a different flavour structure than the tree-level Yukawa couplings and, as a result, they can be sources of flavour violation. This is particularly relevant for schemes of moduli stabilisation which rely on superpotential contributions from E3 instantons, such as KKLT or the Large Volume Scenario. As a byproduct of our analysis, we shed some new light on the properties of annulus diagrams with matter field insertions in stringy instanton calculus.

  7. Protein binding sites involved in the assembly of the KplE1 prophage intasome.

    PubMed

    Panis, Gaël; Duverger, Yohann; Champ, Stéphanie; Ansaldi, Mireille

    2010-08-15

    The organization of the recombination regions of the KplE1 prophage in Escherichia coli K12 differs from that observed in the lambda prophage. Indeed, the binding sites characterized for the IntS integrase, the TorI recombination directionality factor (RDF) and the integration host factor (IHF) vary in number, spacing and orientation on the attL and attR regions. In this paper, we performed site-directed mutagenesis of the recombination sites to decipher if all sites are essential for the site-specific recombination reaction and how the KplE1 intasome is assembled. We also show that TorI and IntS form oligomers that are stabilized in the presence of their target DNA. Moreover, we found that IHF is the only nucleoid associated protein (NAP) involved in KplE1 recombination, although it is dispensable. This is consistent with the presence of only one functional IHF site on attR and none on attL. PMID:20494389

  8. 77 FR 6479 - Leased Commercial Access; Development of Competition and Diversity in Video Programming...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-08

    ...)(1), 76.1302(d), 76.1302(e)(1), and 76.1302(k) published at 76 FR 60652, September 29, 2011, are... FR 60652, September 29, 2011. The OMB Control Number is 3060-0888. The Commission publishes this... Programming Distribution and Carriage AGENCY: Federal Communications Commission. ACTION: Final...

  9. 75 FR 75711 - Securities Investor Protection Corporation; Notice of Filing of a Proposed Bylaw Change Relating...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-06

    ... Members, Rel. No. SIPA-156, 56 FR 51952 (Oct. 16, 1991). \\6\\ Securities Investor Protection Corporation...-157, 56 FR 60145 (Nov. 27, 1991). II. Need for Public Comment Section 3(e)(1) of SIPA provides that... COMMISSION Securities Investor Protection Corporation; Notice of Filing of a Proposed Bylaw Change...

  10. 77 FR 66196 - Self-Regulatory Organizations; The Options Clearing Corporation; Notice of Extension of Review...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-02

    ... Exchange Act Release No. 67835 (September 12, 2012), 77 FR 57602 (September 18, 2012). \\4\\ Securities Exchange Act Release No. 67906 (September 21, 2012), 77 FR 59431 (September 27, 2012). Section 806(e)(1)(G... Period of Advance Notice To Establish the Legal and Operational Framework for Providing Central...

  11. Heterologous expression of mouse cytochrome P450 2e1 in V79 cells: construction and characterisation of the cell line and comparison with V79 cell lines stably expressing rat P450 2E1 and human P450 2E1.

    PubMed

    Bernauer, Ulrike; Glatt, Hansruedi; Heinrich-Hirsch, Barbara; Liu, Yungang; Muckel, Eva; Vieth, Barbel; Gundert-Remy, Ursula

    2003-01-01

    A V79 Chinese hamster cell line was constructed for stable expression of mouse cytochrome P450 2e1 (Cyp2e1), as an addition to the existing cell battery consisting of cell lines stably expressing rat CYP2E1 and human CYP2E1 (V79 Cell Battery). The aim was to establish a cell battery that offers the in vitro possibility of investigating species-specific differences in the toxicity and metabolism of chemicals representing substrates for CYP2E1. The newly established cell line (V79m2E1) effectively expressed Cyp2e1 in the catalytically active form. The expression of catalytically active CYP2E1 in V79m2E1 cells was maintained over several months in culture, as demonstrated by Western Blotting and chlorzoxazone (CLX) 6-hydroxylase activity. The cells exhibited CLX 6-hydroxylase activity with a Km of 27.8 microM/l and Vmax of 40 pmol/mg protein/minute, compared with a Km of 28.2/28.6 microM/l and a Vmax of 130/60 pmol/mg protein/minute from V79r2E1/V79h2E1 cells. Furthermore, the CYP2E1-dependent mutagenicity of N-nitrosodimethylamine could be demonstrated in the V79m2E1 cells. Therefore, the new cell battery permits the interspecies comparison of CYP2E1-dependent toxicity and of metabolism of chemicals between humans and the two major rodent species--the rat and the mouse--that are usually used in classical toxicity studies. PMID:16221041

  12. Chimeric Derivatives of Hepatitis B Virus Core Particles Carrying Major Epitopes of the Rubella Virus E1 Glycoprotein

    PubMed Central

    Skrastina, Dace; Petrovskis, Ivars; Petraityte, Rasa; Sominskaya, Irina; Ose, Velta; Liekniņa, Ilva; Bogans, Janis; Sasnauskas, Kestutis

    2013-01-01

    Three variants of the major rubella virus (RV) E1 protein virus-neutralizing epitope from position 214 to 285 were exposed on the hepatitis B virus (HBV) C-terminally truncated core (HBcΔ) in a virus-like particle (VLP) vector and were produced in Escherichia coli. All three chimeras demonstrated VLPs in bacterial cell lysates, but only HBcΔ-E1(245-285) demonstrated the correct VLP structure after purification. The other chimeras, HBcΔ-E1(214-285) and HBcΔ-E1(214-240), appeared after purification as non-VLP aggregates of 100 to 900 nm in diameter according to dynamic light scattering data. All three variants possessed the intrinsic antigenic activity of RV E1, since they were recognized by natural human anti-RV E1 antibodies and induced an anti-RV E1 response in mice. HBcΔ-E1(214-240) and HBcΔ-E1(245-285) can be regarded as prototypes for a putative RV vaccine because they were able to induce antibodies recognizing natural RV E1 protein in RV diagnostic kits. PMID:24006140

  13. 76 FR 70730 - Privacy Act of 1974; Department of Homeland Security/U.S. Citizenship and Immigration Services...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-15

    ... Transformation, Increment I'' (August 29, 2011, 76 FR 53764) to allow USCIS to transition to an electronic....g., vaccinations, referrals, communicable disease, physical or mental disorder, prostitution,...

  14. Flight and wind-tunnel correlation of boundary-layer transition on the AEDC transition cone

    NASA Technical Reports Server (NTRS)

    Fisher, D. L.; Dougherty, N. S., Jr.

    1982-01-01

    Transition and fluctuating surface pressure data were acquired on a 10 deg included angle cone, using the same instrumentation and technique over a wide range of Mach and Reynolds numbers in 23 wind tunnels and in flight. Transition was detected with a traversing pitot-pressure probe in contact with the surface. The surface pressure fluctuations were measured with microphones set flush in the cone surface. Good correlation of end of transition Reynolds number RE(T) was obtained between data from the lower disturbance wind tunnels and flight up to a boundary layer edge Mach number, M(e) = 1.2. Above M(e) = 1.2, however, this correlation deteriorates, with the flight Re(T) being 25 to 30% higher than the wind tunnel Re(T) at M(e) = 1.6. The end of transition Reynolds number correlated within + or - 20% with the surface pressure fluctuations, according to the equation used. Broad peaks in the power spectral density distributions indicated that Tollmien-Schlichting waves were the probable cause of transition in flight and in some of the wind tunnels.

  15. Cytochrome P450 2E1 genetic polymorphism and gastric cancer in Changle, Fujian Province

    PubMed Central

    Cai, Lin; Yu, Shun-Zhang; Zhang, Zuo-Feng

    2001-01-01

    AIM: Genetic polymorphism in enzymes of carcinogen metabolism has been found to have the influence on the susceptibility to cancer. Cytochrome P450 2E1 (CYP2E1) is considered to play an important role in the metabolic activation of procarcinogens such as N-nitrosoamines and low molecular weight organic compounds. The purpose of this study is to determine whether CYP450 2E1 polymorphisms are associated with risks of gastric cancer. METHODS: We conducted a population based case-control study in Changle county, Fujian Province, a high-risk region of gastric cancer in China. Ninety-one incident gastric cancer patients and ninety-four healthy controls were included in our study. Datas including demographic characteristcs, diet intake, and alcohol and tobacco consumption of indivduals in our study were completed by a standardized questionnaire. PCR-RFLP revealed three genotypes:heterozygote (C1/C2) and two homozygotes (C1/C1 and C2/C2) in CYP2E1. RESULTS: The frequency of variant genotypes (C1/C2 and C2/C2) in gastric cancer cases and controls was 36.3% and 24.5%, respectively. The rare homozygous C2/C2 genotype was found in 6 indivduals in gastric cancer group (6.6%), whereas there was only one in the control group (1.1%). However, there was no statistically significan difference between the two groups (two-tailed Fisher’s exact test, P = 0.066). Indivduals in gastric cancer group were more likely to carry genotype C1/C2 (odds ratio, OR = 1.50) and C2/C2 (OR = 7.34) than indivduals in control group (χ² = 4.597, for trend P = 0.032). The frequencies of genotypes with the C2 allele (C1/C2 and C2/C2 genotypes) were compared with those of genotypes without C2 allele (C1/C1 genotype) among indivduals in gastric cancer group and control group according to the pattern of gastric cancer risk factors. The results show that indivduals who exposed to these gastric cancer risk factors and carry the C2 allele seemed to have a higher risk of developing gastric cancer. CONCLUSION

  16. [Humanitarian transition].

    PubMed

    Mattei, Jean-François; Troit, Virginie

    2016-02-01

    In two centuries, modern humanitarian action has experienced several fractures often linked to crises. Although its professionalism and intervention force remain indisputable, it faces, since the 2000s, a new context that limits its ability to act and confronts it with new dilemmas, even though it must deal with needs for aid of unprecedented scale. These difficulties reveal a humanitarian transition period that was not anticipated. This transition period reflects the change from a dominant paradigm of North-South solidarity of Western origin to a much more complex model. This article provides a summary of the current mutations that are dominated by the States' assertion of sovereignty. Among the possible solutions, it argues for an ethical approach and a better integration of the research carried out in the Global South, prerequisites for building a true partnership and placing the victims at the heart of the operations which involve them. PMID:26936180

  17. Quantifying macromolecular conformational transition pathways

    NASA Astrophysics Data System (ADS)

    Seyler, Sean; Kumar, Avishek; Thorpe, Michael; Beckstein, Oliver

    2015-03-01

    Diverse classes of proteins function through large-scale conformational changes that are challenging for computer simulations. A range of fast path-sampling techniques have been used to generate transitions, but it has been difficult to compare paths from (and assess the relative strengths of) different methods. We introduce a comprehensive method (pathway similarity analysis, PSA) for quantitatively characterizing and comparing macromolecular pathways. The Hausdorff and Fréchet metrics (known from computational geometry) are used to quantify the degree of similarity between polygonal curves in configuration space. A strength of PSA is its use of the full information available from the 3 N-dimensional configuration space trajectory without requiring additional specific knowledge about the system. We compare a sample of eleven different methods for the closed-to-open transitions of the apo enzyme adenylate kinase (AdK) and also apply PSA to an ensemble of 400 AdK trajectories produced by dynamic importance sampling MD and the Geometrical Pathways algorithm. We discuss the method's potential to enhance our understanding of transition path sampling methods, validate them, and help guide future research toward deeper physical insights into conformational transitions.

  18. Eliminating Transitions

    ERIC Educational Resources Information Center

    Gallick, Barb; Lee, Lisa

    2010-01-01

    Adults often find themselves transitioning from one activity to another in a short time span. Most of the time, they do not feel they have a lot of control over their schedules, but wish that they could carve out extended time to relax and focus on one project. Picture a group of children in the block area who have spent 15 or 20 minutes building…

  19. 78 FR 31399 - Recoupment of Nonrecurring Costs (NCs) on Sales of U.S. Items

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-24

    ... sections 2761(e)(1)(B), 2761 (e)(2), and 2767(b) of Title22, United States Code (U.S.C.) (also known as ``sections 21(e)(1)(B), 21(e)(2), and 27(b) of the Arms Export Control Act, as amended'') for calculating and.... Public Comments The Department of Defense published a proposed rule on November 4, 2011 (76 FR...

  20. 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

    NASA Astrophysics Data System (ADS)

    Carroll, P. Brandon; McGuire, Brett A.; Blake, Geoffrey A.; Apponi, A. J.; Ziurys, L. M.; Remijan, Anthony

    2015-01-01

    An extensive search has been conducted to confirm transitions of trans-ethyl methyl ether (tEME, C2H5OCH3), 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 × 1015 cm-2. This would make tEME at least a factor of two times less abundant than dimethyl ether (CH3OCH3) 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 × 1014 cm-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.

  1. Extended calculations of level and transition properties in the nitrogen isoelectronic sequence: Cr XVIII, Fe XX, Ni XXII, and Zn XXIV

    NASA Astrophysics Data System (ADS)

    Radžiūtė, L.; Ekman, J.; Jönsson, P.; Gaigalas, G.

    2015-10-01

    Extensive multiconfiguration Dirac-Hartree-Fock (MCDHF) calculations and relativistic configuration interaction (RCI) calculations are performed for 272 states of the 2s22p3, 2s2p4, 2p5, 2s22p23l, 2s2p33l, and 2p43l (l = 0,1,2) configurations in the nitrogen-like ions Cr XVIII, Fe XX, Ni XXII, and Zn XXIV. Valence, core-valence, and core-core electron correlation effects are accounted for through large configuration state function expansions. Calculated energy levels are compared with data from other calculations and with experimental data from the NIST database. Landé gJ-factors; hyperfine structures; isotope shifts; and radiative electric dipole (E1), electric quadrupole (E2), and magnetic dipole (M1) transition rates are given for all ions. The accuracy of the calculated energy levels is high enough to facilitate identification of observed spectral lines involving the 2l43l' configurations, for which experimental data are largely missing. Tables 5-21 are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/582/A61

  2. Characterization of novel cytochrome P450 2E1 knockout rat model generated by CRISPR/Cas9.

    PubMed

    Wang, Xin; Tang, Yu; Lu, Jian; Shao, Yanjiao; Qin, Xuan; Li, Yongmei; Wang, Liren; Li, Dali; Liu, Mingyao

    2016-04-01

    A bacterial CRISPR-associated protein-9 nuclease (CRISPR/Cas9) from Streptococcus pyogenes has generated considerable excitement as a new tool to edit the targeted genome. Cytochrome P450 (CYP) 2E1 not only plays an important role in the xenobiotic metabolism and chemical toxicity, but also is involved in many kinds of diseases, such as alcoholic liver diseases and diabetes. Despite its importance, few animal models are used to predict CYP2E1 properties in physiology, pathology, as well as carcinogen activation. To establish a novel model for investigating the functions of CYP2E1 in vivo, this study has successfully generated the Cyp2e1 knockout (KO) rat model without detectable off-target effects using CRISPR/Cas9 system. The Cyp2e1 KO rats were viable and fertile and did not display any obvious physiological abnormities. The absent expression of CYP2E1 in KO rats also resulted in inactive behaviors in the metabolism of CYP2E1 substrates. The Cyp2e1 KO rats as a novel and available rodent animal model provide a powerful tool for the study of CYP2E1 in the chemical metabolism, toxicity, carcinogenicity, and its core factor in drug-drug interactions. PMID:26947455

  3. Human Papillomavirus Type 18 E1 Protein Is Translated from Polycistronic mRNA by a Discontinuous Scanning Mechanism

    PubMed Central

    Remm, Maido; Remm, Anu; Ustav, Mart

    1999-01-01

    Papillomaviruses are small double-stranded DNA viruses that replicate episomally in the nuclei of infected cells. The full-length E1 protein of papillomaviruses is required for the replication of viral DNA. The viral mRNA from which the human papillomavirus type 18 E1 protein is expressed is not known. We demonstrate that in eukaryotic cells, the E1 protein is expressed from polycistronic mRNA containing E6, E7, and E1 open reading frames (ORFs). The translation of adjacent E7 and E1 ORFs is not associated; it is performed by separate populations of ribosomes. The translation of the downstream E1 gene is preceded by ribosome scanning. Scanning happens at least at the 5′ end of the polycistronic mRNA and also approximately 100 bp in front of the E1 gene. Long areas in middle of the mRNA are bypassed by ribosomes, possibly by ribosomal “shunting.” Inactivation of short minicistrons in the upstream area of the E1 gene did not change the expression level of the E1 gene. PMID:10074156

  4. Characterization of papillomavirus E1 helicase mutants defective for interaction with the SUMO-conjugating enzyme Ubc9

    SciTech Connect

    Fradet-Turcotte, Amelie; Brault, Karine; Titolo, Steve; Howley, Peter M.; Archambault, Jacques

    2009-12-20

    The E1 helicase from BPV and HPV16 interacts with Ubc9 to facilitate viral genome replication. We report that HPV11 E1 also interacts with Ubc9 in vitro and in the yeast two-hybrid system. Residues in E1 involved in oligomerization (353-435) were sufficient for binding to Ubc9 in vitro, but the origin-binding and ATPase domains were additionally required in yeast. Nuclear accumulation of BPV E1 was shown previously to depend on its interaction with Ubc9 and sumoylation on lysine 514. In contrast, HPV11 and HPV16 E1 mutants defective for Ubc9 binding remained nuclear even when the SUMO pathway was inhibited. Furthermore, we found that K514 in BPV E1 and the analogous K559 in HPV11 E1 are not essential for nuclear accumulation of E1. These results suggest that the interaction of E1 with Ubc9 is not essential for its nuclear accumulation but, rather, depends on its oligomerization and binding to DNA and ATP.

  5. Downregulation of microRNA miR-520h by E1A Contributes to Anti-cancer Activity

    PubMed Central

    Su, Jen-Liang; Chen, Poshen B.; Chen, Ya-Huey; Chen, Shang-Chih; Chang, Yi-Wen; Jan, Yi-Hua; Cheng, Xiaoyun; Hsiao, Michael; Hung, Mien-Chie

    2010-01-01

    The leading cause of death in cancer patients is cancer metastasis, for which there is no effective treatment. MicroRNAs have been shown to play a significant role in cancer metastasis through regulation of gene expression. The Adenoviral type 5 E1A is associated with multiple tumor suppressing activities including the inhibition of metastasis, and E1A gene therapies have been tested in several clinical trials. However, the mechanisms involved in E1A-mediated tumor suppressing activities are not yet completely defined. Here we demonstrated that E1A down-regulated the expression of miRNA, miR-520h, which was critical for E1A-mediated cancer cell mobility and in vitro invasion activity. In addition, we identified a signal cascade, namely, E1A —| miRNA-520h —| PP2A/C —| IKK → NF-κB → Twist, in which E1A inhibited the expression of Twist through downregulation of miR-520h and the signal cascade. Our results indicated a functional link between miR-520h and tumorigenicity/invasive ability, and provided a new insight into the role of E1A-mediated miRNA regulation in tumor suppression. Therefore, the results identified a new cascade of E1A-mediated tumor suppression activity via downregulation of miRNA-520h expression. PMID:20501832

  6. Ethanol Induction of CYP2A5: Role of CYP2E1-ROS-Nrf2 Pathway

    PubMed Central

    Lu, Yongke; Zhang, Xu Hannah

    2012-01-01

    Chronic ethanol consumption was previously shown to induce CYP2A5 in mice, and this induction of CYP2A5 by ethanol was CYP2E1 dependent. In this study, the mechanisms of CYP2E1-dependent ethanol induction of CYP2A5 were investigated. CYP2E1 was induced by chronic ethanol consumption to the same degree in wild-type (WT) mice and CYP2A5 knockout (Cyp2a5 –/–) mice, suggesting that unlike the CYP2E1-dependent ethanol induction of CYP2A5, ethanol induction of CYP2E1 is not CYP2A5 dependent. Microsomal ethanol oxidation was about 25% lower in Cyp2a5 –/– mice compared with that in WT mice, suggesting that CYP2A5 can oxidize ethanol although to a lesser extent than CYP2E1 does. CYP2A5 was induced by short-term ethanol consumption in human CYP2E1 transgenic knockin (Cyp2e1 –/– KI) mice but not in CYP2E1 knockout (Cyp2e1 –/–) mice. The redox-sensitive transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2) was also induced by acute ethanol in Cyp2e1 –/– KI mice but not in Cyp2e1 –/– mice. Ethanol induction of CYP2A5 in Nrf2 knockout (Nrf2 –/–) mice was lower compared with that in WT mice, whereas CYP2E1 induction by ethanol was comparable in WT and Nrf2 –/– mice. Antioxidants (N-acetyl-cysteine and vitamin C), which blocked oxidative stress induced by chronic ethanol in WT mice and acute ethanol in Cyp2e1 –/– KI mice, also blunted the induction of CYP2A5 and Nrf2 by ethanol but not the induction of CYP2E1 by ethanol. These results suggest that oxidative stress induced by ethanol via induction of CYP2E1 upregulates Nrf2 activity, which in turn regulates ethanol induction of CYP2A5. Results obtained from primary hepatocytes, mice gavaged with binge ethanol or fed chronic ethanol, show that Nrf2-regulated ethanol induction of CYP2A5 protects against ethanol-induced steatosis. PMID:22552773

  7. Structure of the pyruvate dehydrogenase multienzyme complex E1 component from Escherichia coli at 1.85 A resolution.

    PubMed

    Arjunan, Palaniappa; Nemeria, Natalia; Brunskill, Andrew; Chandrasekhar, Krishnamoorthy; Sax, Martin; Yan, Yan; Jordan, Frank; Guest, John R; Furey, William

    2002-04-23

    The crystal structure of the recombinant thiamin diphosphate-dependent E1 component from the Escherichia coli pyruvate dehydrogenase multienzyme complex (PDHc) has been determined at a resolution of 1.85 A. The E. coli PDHc E1 component E1p is a homodimeric enzyme and crystallizes with an intact dimer in an asymmetric unit. Each E1p subunit consists of three domains: N-terminal, middle, and C-terminal, with all having alpha/beta folds. The functional dimer contains two catalytic centers located at the interface between subunits. The ThDP cofactors are bound in the "V" conformation in clefts between the two subunits (binding involves the N-terminal and middle domains), and there is a common ThDP binding fold. The cofactors are completely buried, as only the C2 atoms are accessible from solution through the active site clefts. Significant structural differences are observed between individual domains of E1p relative to heterotetrameric multienzyme complex E1 components operating on branched chain substrates. These differences may be responsible for reported alternative E1p binding modes to E2 components within the respective complexes. This paper represents the first structural example of a functional pyruvate dehydrogenase E1p component from any species. It also provides the first representative example for the entire family of homodimeric (alpha2) E1 multienzyme complex components, and should serve as a model for this class of enzymes. PMID:11955070

  8. Characterization of papillomavirus E1 helicase mutants defective for interaction with the SUMO-conjugating enzyme Ubc9.

    PubMed

    Fradet-Turcotte, Amélie; Brault, Karine; Titolo, Steve; Howley, Peter M; Archambault, Jacques

    2009-12-20

    The E1 helicase from BPV and HPV16 interacts with Ubc9 to facilitate viral genome replication. We report that HPV11 E1 also interacts with Ubc9 in vitro and in the yeast two-hybrid system. Residues in E1 involved in oligomerization (353-435) were sufficient for binding to Ubc9 in vitro, but the origin-binding and ATPase domains were additionally required in yeast. Nuclear accumulation of BPV E1 was shown previously to depend on its interaction with Ubc9 and sumoylation on lysine 514. In contrast, HPV11 and HPV16 E1 mutants defective for Ubc9 binding remained nuclear even when the SUMO pathway was inhibited. Furthermore, we found that K514 in BPV E1 and the analogous K559 in HPV11 E1 are not essential for nuclear accumulation of E1. These results suggest that the interaction of E1 with Ubc9 is not essential for its nuclear accumulation but, rather, depends on its oligomerization and binding to DNA and ATP. PMID:19836047

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

    PubMed

    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. PMID:27049943

  10. E1 of α-ketoglutarate dehydrogenase defends Mycobacterium tuberculosis against glutamate anaplerosis and nitroxidative stress

    PubMed Central

    Maksymiuk, Christina; Balakrishnan, Anand; Bryk, Ruslana; Rhee, Kyu Y.; Nathan, Carl F.

    2015-01-01

    Enzymes of central carbon metabolism (CCM) in Mycobacterium tuberculosis (Mtb) make an important contribution to the pathogen’s virulence. Evidence is emerging that some of these enzymes are not simply playing the metabolic roles for which they are annotated, but can protect the pathogen via additional functions. Here, we found that deficiency of 2-hydroxy-3-oxoadipate synthase (HOAS), the E1 component of the α-ketoglutarate (α-KG) dehydrogenase complex (KDHC), did not lead to general metabolic perturbation or growth impairment of Mtb, but only to the specific inability to cope with glutamate anaplerosis and nitroxidative stress. In the former role, HOAS acts to prevent accumulation of aldehydes, including growth-inhibitory succinate semialdehyde (SSA). In the latter role, HOAS can participate in an alternative four-component peroxidase system, HOAS/dihydrolipoyl acetyl transferase (DlaT)/alkylhydroperoxide reductase colorless subunit gene (ahpC)-neighboring subunit (AhpD)/AhpC, using α-KG as a previously undescribed source of electrons for reductase action. Thus, instead of a canonical role in CCM, the E1 component of Mtb’s KDHC serves key roles in situational defense that contribute to its requirement for virulence in the host. We also show that pyruvate decarboxylase (AceE), the E1 component of pyruvate dehydrogenase (PDHC), can participate in AceE/DlaT/AhpD/AhpC, using pyruvate as a source of electrons for reductase action. Identification of these systems leads us to suggest that Mtb can recruit components of its CCM for reactive nitrogen defense using central carbon metabolites. PMID:26430237

  11. C-E1 fusion protein synthesized by rubella virus DI RNAs maintained during serial passage

    SciTech Connect

    Tzeng, W.-P.; Frey, Teryl K. . E-mail: tfrey@gsu.edu

    2006-12-20

    Rubella virus (RUB) replicons are derivatives of the RUB infectious cDNA clone that retain the nonstructural open reading frame (NS-ORF) that encodes the replicase proteins but not the structural protein ORF (SP-ORF) that encodes the virion proteins. RUB defective interfering (DI) RNAs contain deletions within the SP-ORF and thus resemble replicons. DI RNAs often retain the 5' end of the capsid protein (C) gene that has been shown to modulate virus-specific RNA synthesis. However, when replicons either with or without the C gene were passaged serially in the presence of wt RUB as a source of the virion proteins, it was found that neither replicon was maintained and DI RNAs were generated. The majority DI RNA species contained in-frame deletions in the SP-ORF leading to a fusion between the 5' end of the C gene and the 3' end of the E1 glycoprotein gene. DI infectious cDNA clones were constructed and transcripts from these DI infectious cDNA clones were maintained during serial passage with wt RUB. The C-E1 fusion protein encoded by the DI RNAs was synthesized and was required for maintenance of the DI RNA during serial passage. This is the first report of a functional novel gene product resulting from deletion during DI RNA generation. Thus far, the role of the C-E1 fusion protein in maintenance of DI RNAs during serial passage remained elusive as it was found that the fusion protein diminished rather than enhanced DI RNA synthesis and was not incorporated into virus particles.

  12. Lysophosphatidic acid induces chemotaxis in MC3T3-E1 osteoblastic cells.

    PubMed

    Masiello, Lisa M; Fotos, Joseph S; Galileo, Deni S; Karin, Norman J

    2006-07-01

    Lysophosphatidic acid (LPA) is a bioactive lipid that has pleiotropic effects on a variety of cell types and enhances the migration of endothelial and cancer cells, but it is not known if this lipid can alter osteoblast motility. We performed transwell migration assays using MC3T3-E1 osteoblastic cells and found LPA to be a potent chemotactic agent. Quantitative time-lapse video analysis of osteoblast migration after wounds were introduced into cell monolayers indicated that LPA stimulated both migration velocity and the average migration distance per cell. LPA also elicited substantial changes in cell shape and actin cytoskeletal structure; lipid-treated cells contained fewer stress fibers and displayed long membrane processes that were enriched in F-actin. Quantitative RT-PCR analysis showed that MC3T3-E1 cells express all four known LPA-specific G-protein-coupled receptors (LPA1-LPA4) with a relative mRNA abundance of LPA1>LPA4>LPA2>LPA3. LPA-induced changes in osteoblast motility and morphology were antagonized by both pertussis toxin and Ki16425, a subtype-specific blocker of LPA1 and LPA3 receptor function. Cell migration in many cell types is linked to changes in intracellular Ca2+. Ki16425 also inhibited LPA-induced Ca2+ signaling in a dose-dependent manner, suggesting a link between LPA-induced Ca2+ transients and osteoblast chemotaxis. Our data show that LPA stimulates MC3T3-E1 osteoblast motility via a mechanism that is linked primarily to the G-protein-coupled receptor LPA1. PMID:16487757

  13. Lysophosphatidic acid induces chemotaxis in MC3T3-E1 osteoblastic cells

    SciTech Connect

    Masiello, Lisa M.; Fotos, Joseph S.; Galileo, Deni S.; Karin, Norm J.

    2006-07-01

    Lysophosphatidic acid (LPA) is a bioactive lipid that has pleiotropic effects on a variety of cell types and enhances the migration of endothelial and cancer cells, but it is not known if this lipid can alter osteoblast motility. We performed transwell migration assays using MC3T3-E1 osteoblastic cells and found LPA to be a potent chemotactic agent. Quantitative time-lapse video analysis of osteoblast migration after wounds were introduced into cell monolayers indicated that LPA stimulated both migration velocity and the average migration distance per cell. LPA also elicited substantial changes in cell shape and actin cytoskeletal structure; lipid-treated cells contained fewer stress fibers and displayed long membrane processes that were enriched in F-actin. Quantitative RT-PCR analysis showed that MC3T3-E1 cells express all four known LPA-specific G protein-coupled receptors (LPA1-LPA4) with a relative mRNA abundance of LPA1 > LPA4 > LPA2 >> LPA3. LPA-induced changes in osteoblast motility and morphology were antagonized by both pertussis toxin and Ki16425, a subtype-specific blocker of LPA1 and LPA3 receptor function. Cell migration in many cell types is linked to changes in intracellular Ca2+. Ki16425 also inhibited LPA-induced Ca2+ signaling in a dose-dependent manner, suggesting a link between LPA-induced Ca2+ transients and osteoblast chemotaxis. Our data show that LPA stimulates MC3T3-E1 osteoblast motility via a mechanism that is linked primarily to the G protein-coupled receptor LPA1.

  14. A comparison of substrate dynamics in human CYP2E1 and CYP2A6

    SciTech Connect

    Harrelson, John P. . E-mail: harrelsonj@pacificu.edu; Henne, Kirk R.; Alonso, Darwin O.V.; Nelson, Sidney D.

    2007-01-26

    Considering the dynamic nature of CYPs, methods that reveal information about substrate and enzyme dynamics are necessary to generate predictive models. To compare substrate dynamics in CYP2E1 and CYP2A6, intramolecular isotope effect experiments were conducted, using deuterium labeled substrates: o-xylene, m-xylene, p-xylene, 2,6-dimethylnaphthalene, and 4,4'-dimethylbiphenyl. Competitive intermolecular experiments were also conducted using d{sub 0}- and d{sub 6}-labeled p-xylene. Both CYP2E1 and CYP2A6 displayed full isotope effect expression for o-xylene oxidation and almost complete suppression for dimethylbiphenyl. Interestingly (k {sub H}/k {sub D}){sub obs} for d{sub 3}-p-xylene oxidation ((k {sub H}/k {sub D}){sub obs} = 6.04 and (k {sub H}/k {sub D}){sub obs} = 5.53 for CYP2E1 and CYP2A6, respectively) was only slightly higher than (k {sub H}/k {sub D}){sub obs} for d{sub 3}-dimethylnaphthalene ((k {sub H}/k {sub D}){sub obs} = 5.50 and (k {sub H}/k {sub D}){sub obs} = 4.96, respectively). One explanation is that in some instances (k {sub H}/k {sub D}){sub obs} values are generated by the presence of two substrates-bound simultaneously to the CYP. Speculatively, if this explanation is valid, then intramolecular isotope effect experiments should be useful in the mechanistic investigation of P450 cooperativity.

  15. Cooperativity in CYP2E1 metabolism of acetaminophen and styrene mixtures.

    PubMed

    Hartman, Jessica H; Letzig, Lynda G; Roberts, Dean W; James, Laura P; Fifer, E Kim; Miller, Grover P

    2015-10-01

    Risk assessment for exposure to mixtures of drugs and pollutants relies heavily on in vitro characterization of their bioactivation and/or metabolism individually and extrapolation to mixtures assuming no interaction. Herein, we demonstrated that in vitro CYP2E1 metabolic activation of acetaminophen and styrene mixtures could not be explained through the Michaelis-Menten mechanism or any models relying on that premise. As a baseline for mixture studies with styrene, steady-state analysis of acetaminophen oxidation revealed a biphasic kinetic profile that was best described by negative cooperativity (Hill coefficient=0.72). The best-fit mechanism for this relationship involved two binding sites with differing affinities (Ks=830μM and Kss=32mM). Introduction of styrene inhibited that reaction less than predicted by simple competition and thus provided evidence for a cooperative mechanism within the mixture. Likewise, acetaminophen acted through a mixed-type inhibition mechanism to impact styrene epoxidation. In this case, acetaminophen competed with styrene for CYP2E1 (Ki=830μM and Ksi=180μM for catalytic and effector sites, respectively) and resulted in cooperative impacts on binding and catalysis. Based on modeling of in vivo clearance, cooperative interactions between acetaminophen and styrene resulted in profoundly increased styrene activation at low styrene exposure levels and therapeutic acetaminophen levels. Current Michaelis-Menten based toxicological models for mixtures such as styrene and acetaminophen would fail to detect this concentration-dependent relationship. Hence, future studies must assess the role of alternate CYP2E1 mechanisms in bioactivation of compounds to improve the accuracy of interpretations and predictions of toxicity. PMID:26225832

  16. GALILÉE-1: a validation and processing system for ENDF-6 and GND evaluations

    NASA Astrophysics Data System (ADS)

    Coste-Delclaux, Mireille; Jouanne, Cédric; Moreau, Frédéric; Mounier, Claude

    2016-03-01

    GALILÉE-1 is the new validation and processing system for evaluated data, developed at CEA. This system can handle evaluations stored either in the ENDF-6 format or in the new General Nuclear Data (GND) format. It consists of various components respectively dedicated to read/write the evaluated data whatever the format is, to diagnose inconsistencies in the evaluated data and to provide continuous-energy and multigroup data as well as probability tables for transport and depletion codes. All these components are written in C++ language and share the same objects. This paper describes the state of progress of the various parts of the system and gives some illustrations.

  17. Vinculin expression in MC3T3-E1 cells in response to mechanical stimulus

    PubMed Central

    Cora-Cruz, J.J.; Diffoot-Carlo, N.; Sundaram, P.A.

    2015-01-01

    Loading frequency is known to influence the expression of the focal adhesions of the adherent cells. A small cyclical tensile force was transmitted to mouse pre-osteoblast MC3T3-E1 cells through PDMS substrates of varying stiffness. Changes in cell behavior with respect to proliferation and characteristics of focal adhesions were quantified through immunofluorescence labeling of vinculin. Amount of inactive vinculin was higher on substrates subjected to cyclic stimulation when compared with the results of the static substrates, whereas the number and area of focal adhesion points underwent a reduction. Inactive vinculin appears as a cloud in the cytoplasm in the vicinity of the nucleus. PMID:26858974

  18. Bortezomib alleviates drug-induced liver injury by regulating CYP2E1 gene transcription

    PubMed Central

    PARK, WOO-JAE; KIM, SO-YEON; KIM, YE-RYUNG; PARK, JOO-WON

    2016-01-01

    Acute liver failure, i.e., the fatal deterioration of liver function, is the most common indication that emergency liver transplantation is necessary. Moreover, in the USA, drug-induced liver injury (DILI), including acetaminophen (APAP)-induced hepatotoxicity, is the main cause of acute liver failure. Matching a donor for liver transplantation is extremely difficult, and thus the development of a novel therapy for DILI is urgently needed. Following recent approval by the FDA of the proteasomal inhibitor bortezomib, its therapeutic effects on various human diseases, including solid and hematologic malignancies, have been validated. However, the specific action of proteasomal inhibition in cases of DILI had not been elucidated prior to this study. To examine the effects of proteasomal inhibition in DILI experimentally, male C56Bl/6 mice were injected with 1 mg bortezomib/kg before APAP treatment. Bortezomib not only alleviated APAP-induced hepatotoxicity in a time- and dose-dependent manner, it also alleviated CCl4- and thioacetamide-induced hepatotoxicity. We also noted that bortezomib significantly reduced cytochrome P450 2E1 (CYP2E1) expression and activity in the liver, which was accompanied by the induction of endoplasmic reticulum (ER) stress. In addition, bortezomib decreased hepatocyte nuclear factor-1α-induced promoter activation of CYP2E1 in Hep3B cells. By contrast, another proteasome inhibitor, MG132, did not cause ER stress and did not markedly affect CYP2E1 enzyme activity. Liver injury induced by APAP was aggravated by MG132, possibly via elevation of connexin 32 expression. This study suggests that proteasome inhibition has different effects in cases of DILI depending on the specific inhibitor being used. Furthermore, results from the mouse model indicated that bortezomib, but not MG132, was effective in alleviating DILI. ER stress induced by proteasome inhibition has previously been shown to exert various effects on DILI patients, and thus each

  19. Chikungunya virus with E1-A226V mutation causing two outbreaks in 2010, Guangdong, China

    PubMed Central

    2013-01-01

    Background CHIKV is a mosquito-borne emerging pathogen that has a major health impact in humans in tropical zones around the globe. A new variant of the virus, E1-A226V caused a large outbreak in the Indian Ocean islands and India from 2004–2007. CHIKV outbreak was initially reported in Dongguan region of Guangdong in 2010 in China, another smaller CHIKV outbreak was found in Yangjiang region of Guangdong two weeks later. The viral agent causing the two outbreaks was inferred to be the new E1-A226V variant and Yangjiang CHIKV might be introduced from Dongguan. To confirm the hypothesis and determine the origin of CHIKV causing the outbreaks, we described Yangjiang outbreak in this study, and the molecular characterization of CHIKV from Yangjiang and Dongguang outbreaks were analyzed. Results 27 clinical cases of CHIK fever were reported in outbreak in Yangjiang region. Sera sample from 12 clinical cases were collected from the outbreak, and nucleic acid and antibody tests for CHIKV were performed using Real-time RT-PCR and indirect immunofluorescence. Positive samples of Real-time RT-PCR were subjected to viral isolation. The results showed 3/12 samples positive for Real-time RT-PCR. 7/12 and 4/12 samples were positive for IgM and IgG against CHIKV respectively, two virus strains were isolated. Four viral genomes from Dongguan and Yangjiang were sequenced, characterized and phylogeneticly analyzed. Phylogenetic analysis revealed that the four seqeunced viruses had the closest relationship (99.4~99.6% identify) with the Singapore 2008 isolate belonging to the Indian ocean clade. A common mutation at the site of the E1-A226V was observed among four viruses. Four and three aa substitutions were detected in the CHIKV sequence from the Dongguan and Yangjiang outbreak strains respectively. Conclusion CHIKV with an E1-A226V mutation that originated from Southeast Asia isolates caused two outbreaks in China in 2010, and originated from two different infectious sources

  20. Dynamo Transition

    SciTech Connect

    Verma, M. K.; Yadav, R.; Chandra, M.; Paul, S.; Wahi, P.

    2010-11-23

    In this article we review the experimental and numerical results related to the dynamo transitions. Recent experiments of Von Karman Sodium (VKS) exhibit various dynamo states including constant, time-periodic, and chaotic magnetic fields. Similarly pseudospectral simulations of dynamo show constant, time-periodic, quasiperiodic, and chaotic magnetic field configurations. One of the windows for the magnetic Prandtl number of unity shows period doubling route to chaos. Quasiperiodic route to chaos has been reported for the Prandtl number of 0.5. The dynamo simulations also reveal coexisting multiple attractors that were obtained for different initial conditions.

  1. Fbw7α and Fbw7γ collaborate to shuttle cyclin E1 into the nucleolus for multiubiquitylation.

    PubMed

    Bhaskaran, Nimesh; van Drogen, Frank; Ng, Hwee-Fang; Kumar, Raman; Ekholm-Reed, Susanna; Peter, Matthias; Sangfelt, Olle; Reed, Steven I

    2013-01-01

    Cyclin E1, an activator of cyclin-dependent kinase 2 (Cdk2) that promotes replicative functions, is normally expressed periodically within the mammalian cell cycle, peaking at the G(1)-S-phase transition. This periodicity is achieved by E2F-dependent transcription in late G(1) and early S phases and by ubiquitin-mediated proteolysis. The ubiquitin ligase that targets phosphorylated cyclin E is SCF(Fbw7) (also known as SCF(Cdc4)), a member of the cullin ring ligase (CRL) family. Fbw7, a substrate adaptor subunit, is expressed as three splice-variant isoforms with different subcellular distributions: Fbw7α is nucleoplasmic but excluded from the nucleolus, Fbw7β is cytoplasmic, and Fbw7γ is nucleolar. Degradation of cyclin E in vivo requires SCF complexes containing Fbw7α and Fbw7γ, respectively. In vitro reconstitution showed that the role of SCF(Fbw7α) in cyclin E degradation, rather than ubiquitylation, is to serve as a cofactor of the prolyl cis-trans isomerase Pin1 in the isomerization of a noncanonical proline-proline bond in the cyclin E phosphodegron. This isomerization is required for subsequent binding and ubiquitylation by SCF(Fbw7γ). Here we show that Pin1-mediated isomerization of the cyclin E phosphodegron and subsequent binding to Fbw7γ drive nucleolar localization of cyclin E, where it is ubiquitylated by SCF(Fbw7γ) prior to its degradation by the proteasome. It is possible that this constitutes a mechanism for rapid inactivation of phosphorylated cyclin E by nucleolar sequestration prior to its multiubiquitylation and degradation. PMID:23109421

  2. Fbw7α and Fbw7γ Collaborate To Shuttle Cyclin E1 into the Nucleolus for Multiubiquitylation

    PubMed Central

    Bhaskaran, Nimesh; van Drogen, Frank; Ng, Hwee-Fang; Kumar, Raman; Ekholm-Reed, Susanna; Peter, Matthias

    2013-01-01

    Cyclin E1, an activator of cyclin-dependent kinase 2 (Cdk2) that promotes replicative functions, is normally expressed periodically within the mammalian cell cycle, peaking at the G1-S-phase transition. This periodicity is achieved by E2F-dependent transcription in late G1 and early S phases and by ubiquitin-mediated proteolysis. The ubiquitin ligase that targets phosphorylated cyclin E is SCFFbw7 (also known as SCFCdc4), a member of the cullin ring ligase (CRL) family. Fbw7, a substrate adaptor subunit, is expressed as three splice-variant isoforms with different subcellular distributions: Fbw7α is nucleoplasmic but excluded from the nucleolus, Fbw7β is cytoplasmic, and Fbw7γ is nucleolar. Degradation of cyclin E in vivo requires SCF complexes containing Fbw7α and Fbw7γ, respectively. In vitro reconstitution showed that the role of SCFFbw7α in cyclin E degradation, rather than ubiquitylation, is to serve as a cofactor of the prolyl cis-trans isomerase Pin1 in the isomerization of a noncanonical proline-proline bond in the cyclin E phosphodegron. This isomerization is required for subsequent binding and ubiquitylation by SCFFbw7γ. Here we show that Pin1-mediated isomerization of the cyclin E phosphodegron and subsequent binding to Fbw7γ drive nucleolar localization of cyclin E, where it is ubiquitylated by SCFFbw7γ prior to its degradation by the proteasome. It is possible that this constitutes a mechanism for rapid inactivation of phosphorylated cyclin E by nucleolar sequestration prior to its multiubiquitylation and degradation. PMID:23109421

  3. Adenovirus type 5 early region 4 is responsible for E1A-induced p53-independent apoptosis.

    PubMed Central

    Marcellus, R C; Teodoro, J G; Wu, T; Brough, D E; Ketner, G; Shore, G C; Branton, P E

    1996-01-01

    In the absence of E1B, the 289- and 243-residue E1A products of human adenovirus type 5 induce p53-dependent apoptosis. However, our group has shown recently that the 289-residue E1A protein is also able to induce apoptosis by a p53-independent mechanism (J. G. Teodoro, G. C. Shore, and P. E. Branton, Oncogene 11:467-474, 1995). Preliminary results suggested that p53-independent cell death required expression of one or more additional adenovirus early gene products. Here we show that both the E1B 19-kDa protein and cellular Bcl-2 inhibit or significantly delay p53-independent apoptosis. Neither early region E2 or E3 appeared to be necessary for such cell death. Analysis of a series of E1A mutants indicated that mutations in the transactivation domain and other regions of E1A correlated with E1A-mediated transactivation of E4 gene expression. Furthermore, p53-deficient human SAOS-2 cells infected with a mutant which expresses E1B but none of the E4 gene products remained viable for considerably longer times than those infected with wild-type adenovirus type 5. In addition, an adenovirus vector lacking both E1 and E4 was unable to induce DNA degradation and cell killing in E1A-expressing cell lines. These data showed that an E4 product is essential for E1A-induced p53-independent apoptosis. PMID:8709247

  4. The cognition-enhancing activity of E1R, a novel positive allosteric modulator of sigma-1 receptors

    PubMed Central

    Zvejniece, L; Vavers, E; Svalbe, B; Vilskersts, R; Domracheva, I; Vorona, M; Veinberg, G; Misane, I; Stonans, I; Kalvinsh, I; Dambrova, M

    2014-01-01

    Background and Purpose Here, we describe the in vitro and in vivo effects of (4R,5S)-2-(5-methyl-2-oxo-4-phenyl-pyrrolidin-1-yl)-acetamide (E1R), a novel positive allosteric modulator of sigma-1 receptors. Experimental Approach E1R was tested for sigma receptor binding activity in a [3H](+)-pentazocine assay, in bradykinin (BK)-induced intracellular Ca2+ concentration ([Ca2+]i) assays and in an electrically stimulated rat vas deferens model. E1R's effects on cognitive function were tested using passive avoidance (PA) and Y-maze tests in mice. A selective sigma-1 receptor antagonist (NE-100), was used to study the involvement of the sigma-1 receptor in the effects of E1R. The open-field test was used to detect the effects of E1R on locomotion. Key Results Pretreatment with E1R enhanced the selective sigma-1 receptor agonist PRE-084's stimulating effect during a model study employing electrically stimulated rat vasa deferentia and an assay measuring the BK-induced [Ca2+]i increase. Pretreatment with E1R facilitated PA retention in a dose-related manner. Furthermore, E1R alleviated the scopolamine-induced cognitive impairment during the PA and Y-maze tests in mice. The in vivo and in vitro effects of E1R were blocked by treatment with the selective sigma-1 receptor antagonist NE-100. E1R did not affect locomotor activity. Conclusion and Implications E1R is a novel 4,5-disubstituted derivative of piracetam that enhances cognition and demonstrates efficacy against scopolamine-induced cholinergic dysfunction in mice. These effects are attributed to its positive modulatory action on the sigma-1 receptor and this activity may be relevant when developing new drugs for treating cognitive symptoms related to neurodegenerative diseases. PMID:24490863

  5. Bax inhibitor 1 regulates ER-stress-induced ROS accumulation through the regulation of cytochrome P450 2E1.

    PubMed

    Kim, Hyung-Ryong; Lee, Geum-Hwa; Cho, Eun Yi; Chae, Soo-Wan; Ahn, Taeho; Chae, Han-Jung

    2009-04-15

    This study investigated the molecular mechanism by which Bax inhibitor 1 (BI1) abrogates the accumulation of reactive oxygen species (ROS) in the endoplasmic reticulum (ER). Electron uncoupling between NADPH-dependent cytochrome P450 reductase (NPR) and cytochrome P450 2E1 (P450 2E1) is a major source of ROS on the ER membrane. ER stress produced ROS accumulation and lipid peroxidation of the ER membrane, but BI1 reduced this accumulation. Under ER stress, expression of P450 2E1 in control cells was upregulated more than in BI1-overexpressing cells. In control cells, inhibiting P450 2E1 through chemical or siRNA approaches suppressed ROS accumulation, ER membrane lipid peroxidation and the resultant cell death after ER stress. However, it had little effect in BI1-overexpressing cells. In addition, BI1 knock down also increased ROS accumulation and expression of P450 2E1. In a reconstituted phospholipid membrane containing purified BI1, NPR and P450 2E1, BI1 dose-dependently decreased the production of ROS. BI1 bound to NPR with higher affinity than P450 2E1. Furthermore, BI1 overexpression reduced the interaction of NPR and P450 2E1, and decreased the catalytic activity of P450 2E1, suggesting that the flow of electrons from NPR to P450 2E1 can be modulated by BI1. In summary, BI1 reduces the accumulation of ROS and the resultant cell death through regulating P450 2E1. PMID:19339548

  6. The Human Adenovirus Type 5 E4orf6/E1B55K E3 Ubiquitin Ligase Complex Can Mimic E1A Effects on E2F.

    PubMed

    Dallaire, Frédéric; Schreiner, Sabrina; Blair, G Eric; Dobner, Thomas; Branton, Philip E; Blanchette, Paola

    2016-01-01

    The human adenovirus E4orf6/E1B55K E3 ubiquitin ligase is well known to promote viral replication by degrading an increasing number of cellular proteins that inhibit the efficient production of viral progeny. We report here a new function of the adenovirus 5 (Ad5) viral ligase complex that, although at lower levels, mimics effects of E1A products on E2F transcription factors. When expressed in the absence of E1A, the E4orf6 protein in complex with E1B55K binds E2F, disrupts E2F/retinoblastoma protein (Rb) complexes, and induces hyperphosphorylation of Rb, leading to induction of viral and cellular DNA synthesis as well as stimulation of early and late viral gene expression and production of viral progeny of E1/E3-defective adenovirus vectors. These new and previously undescribed functions of the E4orf6/E1B55K E3 ubiquitin ligase could play an important role in promoting the replication of wild-type viruses. IMPORTANCE During the course of work on the adenovirus E3 ubiquitin ligase formed by the viral E4orf6 and E1B55K proteins, we found, very surprisingly, that expression of these species was sufficient to permit low levels of replication of an adenovirus vector lacking E1A, the central regulator of infection. E1A products uncouple E2F transcription factors from Rb repression complexes, thus stimulating viral gene expression and cell and viral DNA synthesis. We found that the E4orf6/E1B55K ligase mimics these functions. This finding is of significance because it represents an entirely new function for the ligase in regulating adenovirus replication. PMID:27303679

  7. The Human Adenovirus Type 5 E4orf6/E1B55K E3 Ubiquitin Ligase Complex Can Mimic E1A Effects on E2F

    PubMed Central

    Dallaire, Frédéric; Schreiner, Sabrina; Blair, G. Eric; Dobner, Thomas; Branton, Philip E.

    2015-01-01

    ABSTRACT The human adenovirus E4orf6/E1B55K E3 ubiquitin ligase is well known to promote viral replication by degrading an increasing number of cellular proteins that inhibit the efficient production of viral progeny. We report here a new function of the adenovirus 5 (Ad5) viral ligase complex that, although at lower levels, mimics effects of E1A products on E2F transcription factors. When expressed in the absence of E1A, the E4orf6 protein in complex with E1B55K binds E2F, disrupts E2F/retinoblastoma protein (Rb) complexes, and induces hyperphosphorylation of Rb, leading to induction of viral and cellular DNA synthesis as well as stimulation of early and late viral gene expression and production of viral progeny of E1/E3-defective adenovirus vectors. These new and previously undescribed functions of the E4orf6/E1B55K E3 ubiquitin ligase could play an important role in promoting the replication of wild-type viruses. IMPORTANCE During the course of work on the adenovirus E3 ubiquitin ligase formed by the viral E4orf6 and E1B55K proteins, we found, very surprisingly, that expression of these species was sufficient to permit low levels of replication of an adenovirus vector lacking E1A, the central regulator of infection. E1A products uncouple E2F transcription factors from Rb repression complexes, thus stimulating viral gene expression and cell and viral DNA synthesis. We found that the E4orf6/E1B55K ligase mimics these functions. This finding is of significance because it represents an entirely new function for the ligase in regulating adenovirus replication. PMID:27303679

  8. First Selenodetic Result from Chang'E-1 Lunar Orbiter Mission

    NASA Astrophysics Data System (ADS)

    Ping, Jinsong; Huang, Qian; Yan, Jianguo; Shi, Xian; Wang, Guangli; Sha, Kai; Tang, Geshi; Chen, Ming; Cao, Jianfeng

    The first Chinese lunar orbiter, Chang'E-1, was sent to the circle polar orbit of the moon on Nov. 5. During the first month mission checkout period and the following normal mission period, it has been tracked using Range and RR and VLBI method. The tracking data may contribute to both of the OD and the POD of the mission. At the same time, the laser altimeter has been operated to measure the topography of the moon with very high accuracy and spatial resolution. Using the domestic tracking data, POD of Chang'E-1 mission was carried out. It is expected to merge the tracking data with other missions so as to improve the lunar global gravity field. By combining the POD data and attitude information as well as other necessary telemetry messages, the topography of the moon was renewed. Based on the renewed lunar DEM information and the lunar gravity field, the lunar crastial sphere and the Moho surface have been estimated using a downward continuation analyzing method. It may contribute to the selenodetic researches by combining with the historic data.

  9. Poly(L-lactide) crystallization topography directs MC3T3-E1 cells response.

    PubMed

    Li, Wenqiang; Lu, Lu; Jiao, Yanpeng; Zhang, Chaowen; Zhou, Changren

    2016-09-01

    Biomaterial surface topography significantly influences cellular form and function. Using poly(L-lactic acid) films with normal spherulites, banded spherulites, and amorphous surfaces as model substrates, we conducted a systematic assessment of the role for polymer crystallization induced surface morphologies on cell growth and contact guidance. Microscopy and image analysis showed that the MC3T3-E1 cells spread out in a random fashion on the amorphous substrate. At 24 h post-seeding, MC3T3-E1 cells on both types of spherulite surfaces were elongated and aligned along the spherulite radius direction. For the banded spherulite surface with radial stripes and coupling annular grooves, the cell orientation and cell nuclear localization were related to the grooves structure. With increasing time, this orientation preference was weaker. These results demonstrate that the patterning of polymer crystallization structure provide important signals for guiding cells to exhibit characteristic orientation and morphology especially in the early stages of regeneration. PMID:27376548

  10. Construction of an adenovirus type 7a E1A- vector.

    PubMed Central

    Abrahamsen, K; Kong, H L; Mastrangeli, A; Brough, D; Lizonova, A; Crystal, R G; Falck-Pedersen, E

    1997-01-01

    A strategy for constructing replication-defective adenovirus vectors from non-subgroup C viruses has been successfully demonstrated with adenovirus type 7 strain a (Ad7a) as the prototype. An E1A-deleted Ad7a reporter virus expressing the chloramphenicol acetyltransferase (CAT) gene from the cytomegalovirus promoter enhancer was constructed with DNA fragments isolated from Ad7a, an Ad7a recombination reporter plasmid, and the 293 cell line. The Ad7a-CAT virus particle transduces A549 cells as efficiently as Ad5-based vectors. Intravenous infections in a murine model indicate that the Ad7a-CAT virus infects a variety of tissues, with maximal levels of CAT gene expression found in the liver. The duration of Ad7a-CAT transgene expression in the liver was maximally maintained 2 weeks postinfection, with a decline to baseline activity by the week 4 postinfection. Ad7a-CAT represents the first example of a non-subgroup C E1A- adenovirus gene transfer vector. PMID:9343264

  11. Active sites of two orthologous cytochromes P450 2E1: Differences revealed by spectroscopic methods

    SciTech Connect

    Anzenbacherova, Eva; Hudecek, Jiri; Murgida, Daniel; Hildebrandt, Peter; Marchal, Stephane; Lange, Reinhard; Anzenbacher, Pavel . E-mail: anzen@tunw.upol.cz

    2005-12-09

    Cytochromes P450 2E1 of human and minipig origin were examined by absorption spectroscopy under high hydrostatic pressure and by resonance Raman spectroscopy. Human enzyme tends to denature to the P420 form more easily than the minipig form; moreover, the apparent compressibility of the heme active site (as judged from a redshift of the absorption maximum with pressure) is greater than that of the minipig counterpart. Relative compactness of the minipig enzyme is also seen in the Raman spectra, where the presence of planar heme conformation was inferred from band positions characteristic of the low-spin heme with high degree of symmetry. In this respect, the CYP2E1 seems to be another example of P450 conformational heterogeneity as shown, e.g., by Davydov et al. for CYP3A4 [Biochem. Biophys. Res. Commun. 312 (2003) 121-130]. The results indicate that the flexibility of the CYP active site is likely one of its basic structural characteristics.

  12. CD36 is a co-receptor for hepatitis C virus E1 protein attachment

    PubMed Central

    Cheng, Jun-Jun; Li, Jian-Rui; Huang, Meng-Hao; Ma, Lin-Lin; Wu, Zhou-Yi; Jiang, Chen-Chen; Li, Wen-Jing; Li, Yu-Huan; Han, Yan-Xing; Li, Hu; Chen, Jin-Hua; Wang, Yan-Xiang; Song, Dan-Qing; Peng, Zong-Gen; Jiang, Jian-Dong

    2016-01-01

    The cluster of differentiation 36 (CD36) is a membrane protein related to lipid metabolism. We show that HCV infection in vitro increased CD36 expression in either surface or soluble form. HCV attachment was facilitated through a direct interaction between CD36 and HCV E1 protein, causing enhanced entry and replication. The HCV co-receptor effect of CD36 was independent of that of SR-BI. CD36 monoclonal antibodies neutralized the effect of CD36 and reduced HCV replication. CD36 inhibitor sulfo-N-succinimidyl oleate (SSO), which directly bound CD36 but not SR-BI, significantly interrupted HCV entry, and therefore inhibited HCV replication. SSO’s antiviral effect was seen only in HCV but not in other viruses. SSO in combination with known anti-HCV drugs showed additional inhibition against HCV. SSO was considerably safe in mice. Conclusively, CD36 interacts with HCV E1 and might be a co-receptor specific for HCV entry; thus, CD36 could be a potential drug target against HCV. PMID:26898231

  13. A cascading activity-based probe sequentially targets E1-E2-E3 ubiquitin enzymes.

    PubMed

    Mulder, Monique P C; Witting, Katharina; Berlin, Ilana; Pruneda, Jonathan N; Wu, Kuen-Phon; Chang, Jer-Gung; Merkx, Remco; Bialas, Johanna; Groettrup, Marcus; Vertegaal, Alfred C O; Schulman, Brenda A; Komander, David; Neefjes, Jacques; El Oualid, Farid; Ovaa, Huib

    2016-07-01

    Post-translational modifications of proteins with ubiquitin (Ub) and ubiquitin-like modifiers (Ubls), orchestrated by a cascade of specialized E1, E2 and E3 enzymes, control a wide range of cellular processes. To monitor catalysis along these complex reaction pathways, we developed a cascading activity-based probe, UbDha. Similarly to the native Ub, upon ATP-dependent activation by the E1, UbDha can travel downstream to the E2 (and subsequently E3) enzymes through sequential trans-thioesterifications. Unlike the native Ub, at each step along the cascade, UbDha has the option to react irreversibly with active site cysteine residues of target enzymes, thus enabling their detection. We show that our cascading probe 'hops' and 'traps' catalytically active Ub-modifying enzymes (but not their substrates) by a mechanism diversifiable to Ubls. Our founder methodology, amenable to structural studies, proteome-wide profiling and monitoring of enzymatic activity in living cells, presents novel and versatile tools to interrogate Ub and Ubl cascades. PMID:27182664

  14. INITIATIVE RECOVER TRANSITIONAL DISASTER RECOVERY HOUSING (TDRH) PROTOTYPE PROJECT

    EPA Science Inventory

    The intended results of this disaster recovery shelter prototype project are first, to address the urgent need for improved transitional housing stock for future disaster recovery efforts; second, to provide architecture and engineering students with an opportunity to learn fr...

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

    PubMed Central

    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

  16. 26 CFR 1.1033(e)-1 - Sale or exchange of livestock solely on account of drought.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... of drought. 1.1033(e)-1 Section 1.1033(e)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF... Sale or exchange of livestock solely on account of drought. (a) The sale or exchange of livestock... if the sale or exchange of such livestock by the taxpayer is solely on account of drought....

  17. Partition of E1A proteins between soluble and structural fractions of adenovirus-infected and -transformed cells.

    PubMed Central

    Chatterjee, P K; Flint, S J

    1986-01-01

    The partition of E1A proteins between soluble and structural framework fractions of human cells infected or transformed by subgroup C adenoviruses was investigated by using gentle cell fractionation conditions. A polyclonal antibody raised against a trpE-E1A fusion protein (K.R. Spindler, D.S.E. Rosser, and A. J. Berk, J. Virol. 132-141, 1984) synthesized in Escherichia coli was used to measure the steady-state levels of E1A proteins recovered in the various fractions by immunoblotting. The relative concentration of E1A proteins recovered in the soluble fraction of adenovirus type 2-infected cells was at least fivefold greater than the relative concentration in the corresponding fraction of transformed 293 cells. The observed distribution of E1A proteins was not altered by the sulfhydryl-blocking reagent N-ethylmaleimide. E1A proteins were recovered in nuclear matrix, chromatin, and cytoskeleton fractions after further fractionation of the structural framework fraction. However, the E1A protein species that could be identified by one-dimensional gel electrophoresis were not uniformly distributed among the subcellular fractions examined. The results obtained when fractionation was performed in the presence of the oxidation catalysts Cu2+ or (ortho-phenanthroline)2 Cu2+ indicate that E1A proteins can be efficiently cross-linked, via disulfide bonds, to the structural framework of both adenovirus-infected and adenovirus-transformed cells. Images PMID:3023654

  18. Cytochrome P4502E1 inhibitor, chlormethiazole, decreases lipopolysaccharide-induced inflammation in rat Kupffer cells with ethanol treatment

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To investigate the role of Cytochrome P4502E1 in sensitizing Kupffer cells to lipopolysaccharide (LPS)-mediated inflammation after ethanol induction. Sprague-Dawley rats were fed a liquid ethanol diet, control diet or ethanol diet supplemented with CYP2E1 inhibitor, chlormethiazole (CMZ), for 4'week...

  19. RORα switches transcriptional mode of ERRγ that results in transcriptional repression of CYP2E1 under ethanol-exposure

    PubMed Central

    Han, Yong-Hyun; Kim, Don-Kyu; Na, Tae-Young; Ka, Na-Lee; Choi, Hueng-Sik; Lee, Mi-Ock

    2016-01-01

    Increased cytochrome P450 2E1 (CYP2E1) expression is the main cause of oxidative stress, which exacerbates alcoholic liver diseases (ALDs). Estrogen-related receptor gamma (ERRγ) induces CYP2E1 expression and contributes to enhancing alcohol-induced liver injury. Retinoic acid-related orphan receptor alpha (RORα) has antioxidative functions; however, potential cross-talk between ERRγ and RORα in the regulation of CYP2E1 has not been studied. We report that RORα suppressed ERRγ-mediated CYP2E1 expression. A physical interaction of RORα with ERRγ at the ERRγ−response element in the CYP2E1 promoter was critical in this suppression. At this site, coregulator recruitment of ERRγ was switched from coactivator p300 to the nuclear receptor corepressor 1 in the presence of RORα. Cross-talk between ERRγ and RORα was demonstrated in vivo, in that administration of JC1–40, a RORα activator, significantly decreased both CYP2E1 expression and the signs of liver injury in ethanol-fed mice, and this was accompanied by coregulator switching. Thus, this non-classical RORα pathway switched the transcriptional mode of ERRγ, leading to repression of alcohol-induced CYP2E1 expression, and this finding may provide a new therapeutic strategy against ALDs. PMID:26464440

  20. 26 CFR 1.72(e)-1T - Treatment of distributions where substantially all contributions are employee contributions...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 2 2014-04-01 2014-04-01 false Treatment of distributions where substantially all contributions are employee contributions (temporary). 1.72(e)-1T Section 1.72(e)-1T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Items Specifically Included...