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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. pNRQCD determination of E1 radiative transitions

    NASA Astrophysics Data System (ADS)

    Steinbeißer, Sebastian; Segovia, Jorge

    2017-03-01

    This contribution contains the first numerical computation of the complete set of relativistic corrections of relative order v2 for electric dipole (E1) transitions in heavy quarkonium; in particular, for the processes χbj(1P) → ϒ(1S) + γ with J = 0, 1, 2. We assume that the momentum transfer of the heavy mesons involved in the reactions lies in the weak-coupling regime of the low-energy effective field theory potential non-relativistic QCD (pNRQCD) and thus a full perturbative calculation can be performed.

  3. Phenomenology of heavy quarkonium radiative E1 transitions

    SciTech Connect

    Martinez, Hector E.

    2016-01-22

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

  4. 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

  5. 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.

  6. E1, M1, E2 transition energies and probabilities of W54+ ions

    NASA Astrophysics Data System (ADS)

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

    2017-02-01

    A comprehensive theoretical study of the E1, M1, E2 transitions of a Ca-like tungsten ion is presented. Using the multi-configuration Dirac–Fock (MCDF) method with a restricted active space treatment, the wavelengths and probabilities of the M1 and E2 transitions between the multiplets of the ground state configuration ([Ne]3s23p63d2) and of the E1 transitions between [Ne]3s23p53d3 and [Ne]3s23p63d2 have been calculated. The results are in reasonable agreement with available experimental data. The present E1 and M1 calculations are compared with previous theoretical values. For E2 transitions, the importance of electron correlation from 3s and 3p orbitals is pointed out. Several strong E1 transitions are predicted, which have potential advantages for plasma diagnostics.

  7. 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.

  8. Transition metal-free stereospecific access to (E)-(1-fluoro-2-arylvinyl)phosphine borane complexes.

    PubMed

    Rousée, Kevin; Pannecoucke, Xavier; Gaumont, Annie-Claude; Lohier, Jean-François; Morlet-Savary, Fabrice; Lalevée, Jacques; Bouillon, Jean-Philippe; Couve-Bonnaire, Samuel; Lakhdar, Sami

    2017-02-07

    This work describes the first transition metal-free stereospecific synthesis of (E)-(1-fluoro-2-arylvinyl)phosphine boranes through the addition of diarylphosphine-boranes to gem-bromofluoroalkenes in the presence of a base at room temperature. The reaction proceeds well under very mild conditions and tolerates a variety of functionalities. Scope and limitations of the reaction are discussed. Mechanistic investigations have been undertaken and revealed that the reaction takes place through an SRN1 mechanism. The formation of the fluorinated vinyl radical has been evidenced by electron paramagnetic resonance (EPR) experiment.

  9. Evidence for the two-body nature of the E1 transition operator in the sdf-interacting boson model

    NASA Astrophysics Data System (ADS)

    Barfield, A. F.; von Brentano, P.; Dewald, A.; Zell, K. O.; Zamfir, N. V.; Bucurescu, D.; Ivaşcu, M.; Scholten, O.

    1989-03-01

    Two new absolute transition rates are reported for the nucleus144Sm following an ( α, α') Coulomb excitation study. They are B(E3; 3-→ 0+)=(38±3) W.u. and B(E1;3- → 2+)=(2.8±0.4)×10-3 W.u. This large E1 matrix element, along with the previously known B(E1; 1- →+) value support the interpretation of the 1- state in this nucleus as 2-phonon 2+ × 3- excitation. In the frame of the IBM-1 + f-boson model we show the need for a two-body term in the E1 transition operator. Estimates for the strengths of the one and two-body parts of the E1 transition operator are obtained from these experimental data.

  10. 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.

  11. Improvements and testing practical expressions for photon strength functions of E1 gamma-transitions

    NASA Astrophysics Data System (ADS)

    Plujko, Vladimir; Gorbachenko, Oleksandr; Kadenko, Igor; Solodovnyk, Kateryna

    2017-09-01

    Analytical expression for the E1 photon strength functions (PSF) is modified to account for the low-energy enhancement due to nuclear structure effects (presence of pygmy dipole resonance (PDR)). A closed-form expression of the E1 PSF function includes response of two nuclear states - PDR and giant dipole resonance (GDR). Expression for the nuclear response function on electromagnetic field is based on a model of excitation of two coupled damped states. This approach is tested for different data sets for spherical nuclei. Impact on the PSF shape of coupling between the PDR and GDR excitations is considered.

  12. M1 and E1 transition cross sections in D(y->,n) reactions near reaction threshold

    SciTech Connect

    Iwamoto, C.; Akimune, H.; Utsunomiya, H.; Yamagata, T.; Kondo, T.; Kamata, M.; Toyokawa, H.; Harano, H.; Matsumoto, T.; Lui, Y.-W.

    2010-06-01

    M1 and E1 transition cross sections in the D(y->, n) reaction were separately determined by measuring the analyzing power for emitted neutrons with linearly-polarized gamma rays at four energies between 2.26 MeV and 3.70 MeV near reaction threshold at 2.224 MeV. We compared the experimental result with the JENDL evaluated data.

  13. Random-matrix method for the simulation of large atomic E1 transition arrays

    SciTech Connect

    Wilson, B.G.; Rogers, F.; Iglesias, C.

    1988-04-01

    A computationally fast approximate method for the calculation of large atomic-dipole transition arrays is proposed using an adaptation of Wigner's random-matrix theory. Unlike the Gaussian orthogonal ensemble, off-diagonal matrix elements are populated statistically according to a bi-Gaussian distribution function where elements are correlated according to the term value of the parent shell.

  14. Na(+) transport, and the E(1)P-E(2)P conformational transition of the Na(+)/K(+)-ATPase.

    PubMed Central

    Babes, A; Fendler, K

    2000-01-01

    We have used admittance analysis together with the black lipid membrane technique to analyze electrogenic reactions within the Na(+) branch of the reaction cycle of the Na(+)/K(+)-ATPase. ATP release by flash photolysis of caged ATP induced changes in the admittance of the compound membrane system that are associated with partial reactions of the Na(+)/K(+)-ATPase. Frequency spectra and the Na(+) dependence of the capacitive signal are consistent with an electrogenic or electroneutral E(1)P <--> E(2)P conformational transition which is rate limiting for a faster electrogenic Na(+) dissociation reaction. We determine the relaxation rate of the rate-limiting reaction and the equilibrium constants for both reactions at pH 6.2-8.5. The relaxation rate has a maximum value at pH 7.4 (approximately 320 s(-1)), which drops to acidic (approximately 190 s(-1)) and basic (approximately 110 s(-1)) pH. The E(1)P <--> E(2)P equilibrium is approximately at a midpoint position at pH 6.2 (equilibrium constant approximately 0.8) but moves more to the E(1)P side at basic pH 8.5 (equilibrium constant approximately 0.4). The Na(+) affinity at the extracellular binding site decreases from approximately 900 mM at pH 6.2 to approximately 200 mM at pH 8.5. The results suggest that during Na(+) transport the free energy supplied by the hydrolysis of ATP is mainly used for the generation of a low-affinity extracellular Na(+) discharge site. Ionic strength and lyotropic anions both decrease the relaxation rate. However, while ionic strength does not change the position of the conformational equilibrium E(1)P <--> E(2)P, lyotropic anions shift it to E(1)P. PMID:11053130

  15. 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.

  16. 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.

  17. 77 FR 42677 - Special Conditions: General Electric CT7-2E1 Turboshaft Engine

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-20

    ... Federal Aviation Administration 14 CFR Part 33 Special Conditions: General Electric CT7-2E1 Turboshaft.... SUMMARY: This action proposes special conditions for the General Electric CT7-2E1 engine model. This.... Background On September 10, 2009, General Electric applied for an amendment to type certificate E8NE to add...

  18. Single phase Si1-xGex nanocrystals and the shifting of the E1 direct energy transition.

    PubMed

    Ha, Ngo Ngoc; Giang, Nguyen Truong; Thuy, Truong Thi Thanh; Trung, Nguyen Ngoc; Dung, Nguyen Duc; Saeed, Saba; Gregorkiewicz, Tom

    2015-09-18

    We report preparation and characterization of Si1-xGex alloys with varied composition x of a large range from 0-1. The materials have been obtained by co-sputtering, followed by a heat treatment process at 600, 800, and 1000 °C for 30 min in a nitrogen gas atmosphere. X-ray diffraction data have revealed the formation of single-phase nanoparticles in the face-centered cubic (FCC) structure of Si1-xGex alloys. We found that lattice constant a of the Si1-xGex alloys increased linearly with the composition parameter x. Average diameters of the single-phase nanoparticles were estimated to be between 3-10 nm. Further evidence of FCC single-phase [Formula: see text] nanoparticles has been obtained by high resolution transmission electron microscopy. From absorption spectra, the gradual shift of the direct phononless transition identified for the E1 point in the Brillouin zone of bulk Ge is observed in single-phase Si1-xGex nanoparticles as a function of the composition parameter x.

  19. 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.

  20. 78 FR 15597 - Special Conditions: GE Aviation CT7-2E1 Turboshaft Engine Model

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    ...These final special conditions are issued for the General Electric Aviation (GE) CT7-2E1 engine model. This engine model will have a novel or unusual design feature, which is a combination of two existing ratings into a new rating called ``flat 30-second and 2-minute OEI'' rating. This rating is intended for the continuation of flight of a multi-engine rotorcraft after one engine becomes......

  1. 75 FR 43197 - Public Housing Assessment System (PHAS): Asset Management Transition Year 2 Extension

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-23

    ... URBAN DEVELOPMENT Public Housing Assessment System (PHAS): Asset Management Transition Year 2 Extension... 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...

  2. On transition strengths of E1, E2, & E3 in the regions of mixed quadrupole-octupole collectivity

    NASA Astrophysics Data System (ADS)

    Rasmussen, John; Luo, Y. X.; Hamilton, Joseph; Ramayya, A. V.; Donangelo, Raul

    2010-11-01

    We review the main highlights of experiment and theory for the lowest three electric multipolarities, B(E1), B(E2), and B(E3), for nuclei where quadrupole and octupole collectivity may both occur. The principal regions of interest are around 6 to 12 protons and 6 to 12 neutrons beyond the doubly-closed shell nuclei ^132Sn and ^208Pb. We examine microscopic theoretical calculationsootnotetextW. Zhang et al., Phys. Rev. C 81, 034302 (2010) and references therein. in which deformations are driven by Nilsson orbitals near the Fermi energy. We also focus attention on recent experimentalootnotetextP.E. Garrett et al., Phys. Rev. Letts. 103, 062501 (2009) studies of ^152Sm, where the ground band and associated K=1^- band are mirrored by another 0^+ and 1^- band about 0.7 MeV higher in energy. We suggest that a monopole pairing force alone is insufficient to cause this mirroring, and monopole-plus-quadrupole pairing or a more realistic nucleon-nucleon force is needed.

  3. E1 Transitions from the Υ'' State and the Fine Structure of the χ'b States

    NASA Astrophysics Data System (ADS)

    Narain, M.; Lovelock, D. M. J.; Heintz, U.; Lee-Franzini, J.; Schamberger, R. D.; Willins, J.; Yanagisawa, C.; Franzini, P.; Tuts, P. M.; Kanekal, S.; Wu, Q. W.

    1991-06-01

    Using the CUSB-II detector at the Cornell Electron Storage Ring, we have made precision measurements of the electric dipole transition rates from Υ'' toχ'b, which are in excellent agreement with theory. The fine-structure splitting is found to beM(χ'b2)-M(χ'b1=13.5+/-0.4+/-0.5 MeV and(χ'b1)-M(χ'b0)=23.2+/-0.7+/-0.7 MeV, leading to a ratioR=0.584+/-0.024+/-0.02. The fine structure measures the relative contributions of the spin-orbit interaction a=9.5+/-0.2+/-0.1 MeV and tensor interaction b=2.3+/-0.1+/-0.1 MeV. We also find that the long-range confining potential transforms as a Lorentz scalar.

  4. Astrophysically useful radiative transition parameters for the e 1Π- X 1Σ+ and 1Σ+- X 1Σ+ systems of zirconium oxide

    NASA Astrophysics Data System (ADS)

    Shanmugavel, R.; Sriramachandran, P.

    2011-04-01

    The zirconium oxide (ZrO) is well known for its astrophysical importance. The radiative transition parameters that include Franck-Condon (FC) factor, r-centroid, electronic transition moments, Einstein coefficient, band oscillator strengths, radiative life time and effective vibrational temperature have been estimated for e 1Π- X 1Σ+ and 1Σ+- X 1Σ+ band systems of 90ZrO molecule for the experimentally known vibrational levels using RKR potential energy curves. A reliable numerical integration method has been used to solve the radial Schrödinger equation for the vibrational wave functions of upper and lower electronic states based on the latest available spectroscopic data and known wavelengths. The estimated radiative transition parameters are tabulated. The effective vibrational temperatures of these band systems of 90ZrO molecule are found to be below 4200 K. Hence, the radiative transition parameters help us to ascertain the presence of 90ZrO molecule in the interstellar medium, S stars and sunspots.

  5. 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.

  6. E2→E1 transition and Rb(+) release induced by Na(+) in the Na(+)/K(+)-ATPase. Vanadate as a tool to investigate the interaction between Rb(+) and E2.

    PubMed

    Montes, Mónica R; Monti, José L E; Rossi, Rolando C

    2012-09-01

    This work presents a detailed kinetic study that shows the coupling between the E2→E1 transition and Rb(+) deocclusion stimulated by Na(+) in pig-kidney purified Na,K-ATPase. Using rapid mixing techniques, we measured in parallel experiments the decrease in concentration of occluded Rb(+) and the increase in eosin fluorescence (the formation of E1) as a function of time. The E2→E1 transition and Rb(+) deocclusion are described by the sum of two exponential functions with equal amplitudes, whose rate coefficients decreased with increasing [Rb(+)]. The rate coefficient values of the E2→E1 transition were very similar to those of Rb(+)-deocclusion, indicating that both processes are simultaneous. Our results suggest that, when ATP is absent, the mechanism of Na(+)-stimulated Rb(+) deocclusion would require the release of at least one Rb(+) ion through the extracellular access prior to the E2→E1 transition. Using vanadate to stabilize E2, we measured occluded Rb(+) in equilibrium conditions. Results show that, while Mg(2+) decreases the affinity for Rb(+), addition of vanadate offsets this effect, increasing the affinity for Rb(+). In transient experiments, we investigated the exchange of Rb(+) between the E2-vanadate complex and the medium. Results show that, in the absence of ATP, vanadate prevents the E2→E1 transition caused by Na(+) without significantly affecting the rate of Rb(+) deocclusion. On the other hand, we found the first evidence of a very low rate of Rb(+) occlusion in the enzyme-vanadate complex, suggesting that this complex would require a change to an open conformation in order to bind and occlude Rb(+).

  7. 76 FR 77302 - Federal Transit Administration

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  8. 75 FR 1632 - Public Housing Assessment System (PHAS): Asset Management Transition Year 2 Information

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  9. 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.

  10. Isomer-delayed γ -ray spectroscopy of A =159 -164 midshell nuclei and the variation of K -forbidden E 1 transition hindrance factors

    NASA Astrophysics Data System (ADS)

    Patel, Z.; Walker, P. M.; Podolyák, Zs.; Regan, P. H.; Berry, T. A.; Söderström, P.-A.; Watanabe, H.; Ideguchi, E.; Simpson, G. S.; Nishimura, S.; Wu, Q.; Xu, F. R.; Browne, F.; Doornenbal, P.; Lorusso, G.; Rice, S.; Sinclair, L.; Sumikama, T.; Wu, J.; Xu, Z. Y.; Aoi, N.; Baba, H.; Bello Garrote, F. L.; Benzoni, G.; Daido, R.; Dombrádi, Zs.; Fang, Y.; Fukuda, N.; Gey, G.; Go, S.; Gottardo, A.; Inabe, N.; Isobe, T.; Kameda, D.; Kobayashi, K.; Kobayashi, M.; Komatsubara, T.; Kojouharov, I.; Kubo, T.; Kurz, N.; Kuti, I.; Li, Z.; Matsushita, M.; Michimasa, S.; Moon, C.-B.; Nishibata, H.; Nishizuka, I.; Odahara, A.; Şahin, E.; Sakurai, H.; Schaffner, H.; Suzuki, H.; Takeda, H.; Tanaka, M.; Taprogge, J.; Vajta, Zs.; Yagi, A.; Yokoyama, R.

    2017-09-01

    Excited states have been studied in 159Sm, 161Sm, 162Sm (Z =62 ), 163Eu (Z =63 ), and 164Gd (Z =64 ), populated by isomeric decay following 238U projectile fission at RIBF, RIKEN. The isomer half-lives range from 50 ns to 2.6 μ s . In comparison with other published data, revised interpretations are proposed for 159Sm and 163Eu. The first data for excited states in 161Sm are presented, where a 2.6-μ s isomer is assigned a three-quasiparticle, Kπ=17 /2- structure. The interpretation is supported by multi-quasiparticle Nilsson-BCS calculations, including the blocking of pairing correlations. A consistent set of reduced E 1 hindrance factors is obtained. Limited evidence is also reported for isomeric decay in 163Sm, 164Eu, and 165Eu.

  11. Incrimination of Heterogeneous Nuclear Ribonucleoprotein E1 (hnRNP-E1) as a Candidate Sensor of Physiological Folate Deficiency*

    PubMed Central

    Tang, Ying-Sheng; Khan, Rehana A.; Zhang, Yonghua; Xiao, Suhong; Wang, Mu; Hansen, Deborah K.; Jayaram, Hiremagalur N.; Antony, Aśok C.

    2011-01-01

    The mechanism underlying the sensing of varying degrees of physiological folate deficiency, prior to adaptive optimization of cellular folate uptake through the translational up-regulation of folate receptors (FR) is unclear. Because homocysteine, which accumulates intracellularly during folate deficiency, stimulated interactions between heterogeneous nuclear ribonucleoprotein E1 (hnRNP-E1) and an 18-base FR-α mRNA cis-element that led to increased FR biosynthesis and net up-regulation of FR at cell surfaces, hnRNP-E1 was a plausible candidate sensor of folate deficiency. Accordingly, using purified components, we evaluated the physiological basis whereby l-homocysteine triggered these RNA-protein interactions to stimulate FR biosynthesis. l-Homocysteine induced a concentration-dependent increase in RNA-protein binding affinity throughout the range of physiological folate deficiency, which correlated with a proportionate increase in translation of FR in vitro and in cultured human cells. Targeted reduction of newly synthesized hnRNP-E1 proteins by siRNA to hnRNP-E1 mRNA reduced both constitutive and l-homocysteine-induced rates of FR biosynthesis. Furthermore, l-homocysteine covalently bound hnRNP-E1 via multiple protein-cysteine-S-S-homocysteine mixed disulfide bonds within K-homology domains known to interact with mRNA. These data suggest that a concentration-dependent, sequential disruption of critical cysteine-S-S-cysteine bonds by covalently bound l-homocysteine progressively unmasks an underlying RNA-binding pocket in hnRNP-E1 to optimize interaction with FR-α mRNA cis-element preparatory to FR up-regulation. Collectively, such data incriminate hnRNP-E1 as a physiologically relevant, sensitive, cellular sensor of folate deficiency. Because diverse mammalian and viral mRNAs also interact with this RNA-binding domain with functional consequences to their protein expression, homocysteinylated hnRNP-E1 also appears well positioned to orchestrate a novel

  12. 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

  13. Weak- and hyperfine-interaction-induced 1s2s 1S0 → 1s2 1S0 E1 transition rates of He-like ions

    NASA Astrophysics Data System (ADS)

    Laima, Radžiūtė; Erikas, Gaidamauskas; Gediminas, Gaigalas; Li, Ji-Guang; Dong, Chen-Zhong; Jönsson, Per

    2015-04-01

    Weak- and hyperfine-interaction-induced 1s2s 1S0 → 1s2 1S0 E1 transition rates for the isoelectronic sequence of He-like ions have been calculated using the multi-configuration Dirac-Hartree-Fock (MCDHF) and relativistic configuration interaction methods. The results should be helpful for the future experimental investigations of parity non-conservation effects. Project supported by the National Natural Science Foundation of China (Grant Nos. 11274254, 11147108, 10979007, U1331122, and U1332206) and in part by the National Basic Research Program of China (Grant No. 2013CB922200).

  14. 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.

  15. Breit-Pauli energy levels belonging to 2p 4, 2s2p 5, 2p 6, 2p 33ℓ configurations and all E1 transitions among these levels in Mg V

    NASA Astrophysics Data System (ADS)

    Deb, N. C.; Hibbert, A.

    2007-07-01

    We present accurate oscillator strengths, line strengths and radiative rates for 1073 E1 transitions among the 86 levels belonging to 2s 22p 4, 2s2p 5, 2p 6, and 2s 22p 3( 4S o, 2D o, 2P o)3ℓ configurations in Mg V. We have used 1s and 2s Hartree-Fock orbitals, re-optimized 2p on 2p 3( 2D o)3s 3D o and optimized 3s,3p,3d orbitals on real states. Sixteen additional orbitals up to 8d are optimized either as a correction to n = 3 physical orbitals or as a correlation orbital. A very large set of configurations including up to three electron promotions are used to account for all important correlation effects. All of the main five terms in the Breit-Pauli operator (except the orbit-orbit interaction) are included in order to account for the relativistic effects. Small adjustments to the diagonal elements of the Hamiltonian matrix are made to bring the calculated energies within a few cm -1 of the corresponding NIST recommended data wherever available. The calculated oscillator strengths, line strengths, and radiative rates for almost all of the E1 transitions show excellent agreement with the corresponding MCDF results of Fischer. The recent results of Bhatia et al. are found to be consistently higher by 20-45%. The accuracy of the present calculation is considered to be better than the NIST accuracy ratings for various transitions.

  16. Analysis of Low Excitation HDO Transitions toward the High-mass Star-forming Regions G34.26+0.15, W51e1/e2, and W49N

    NASA Astrophysics Data System (ADS)

    Kulczak-Jastrzȩbska, Magda

    2017-02-01

    We present observations of the ground state 10,1–00,0 rotational transition of HDO at 464.925 GHz and the 11,0–10,1 transition at 509.292 GHz, toward three high-mass star-forming regions: G34.26+0.15, W49N, and W51e1/e2, carried out with the Caltech Submillimeter Observatory. For the first time, the latter transition is observed from the ground. The spectra are modeled, together with observations of higher-energy HDO transitions, as well as submillimeter dust continuum fluxes from the literature, using a spherically symmetric radiative transfer model to derive the radial distribution of the HDO abundance in the target sources. The abundance profile is divided into an inner hot core region, with kinetic temperatures higher than 100 K, and a cold outer envelope with lower kinetic temperatures. The derived HDO abundance with respect to H2 is (0.3–3.7) × 10‑8 in the hot inner region (T > 100 K) and (7.0–10.0) × 10‑11 in the cold outer envelope. We also used two {{{H}}}218{{O}} fundamental transitions to constrain the H2O abundances in the outer envelopes. The HDO/H2O ratios in these cold regions are found to be (1.8–3.1) × 10‑3 and consequently are higher than in the hot inner regions of these sources.

  17. Weighted f-values, A-values, and line strengths for the E1 transitions among 3d 6, 3d 54s, and 3d 54p levels of Fe III

    NASA Astrophysics Data System (ADS)

    Deb, Narayan C.; Hibbert, Alan

    2009-03-01

    Weighted oscillator strengths, weighted radiative rates, and line strengths for all the E1 transitions between 285 fine-structure levels belonging to the 3d 6, 3d 54s, and 3d 54p configurations of Fe III are presented, in ascending order of wavelength. Calculations have been undertaken using the general configuration interaction (CI) code CIV3. The large configuration set is constructed by allowing single and double replacements from any of 3d 6, 3d 54s, 3d 54p, and 3d 54d configurations to nl orbitals with n⩽5,l⩽3 as well as 6p. Additional selective promotions from 3s and 3p subshells are also included in the CI expansions to incorporate the important correlation effects in the n=3 shell. Results of some strong transitions between levels of 3d 6, 3d 54s, and 3d 54p configurations are also presented and compared with other available calculations. It is found that large disagreements occur in many transitions among the existing calculations.

  18. 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.

  19. 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.

  20. 78 FR 46905 - Tobacco Transition Program; Final Assessment Procedures

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-02

    ...; ] DEPARTMENT OF AGRICULTURE Commodity Credit Corporation Tobacco Transition Program; Final Assessment... 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...

  1. 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 diverse...

  2. 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... planned series of workshops to analyze technology transitions from narrowband to broadband; from time... technological capabilities of wireless and wireline (copper, fiber and coax) technologies today and in...

  3. Determination of magic wavelengths for the 7 s 1/2 2S -7 p 3/2, 1/2 2P transitions in Fr

    NASA Astrophysics Data System (ADS)

    Singh, Sukhjit; Sahoo, B. K.; Arora, Bindiya

    2016-08-01

    Magic wavelengths (λmagic) for the 7 S1 /2-7 P1 /2 ,3 /2 transitions (D lines) in Fr were reported by Dammalapati et al. [U. Dammalapati, K. Harada, and Y. Sakemi, Phys. Rev. A 93, 043407 (2016), 10.1103/PhysRevA.93.043407]. These λmagic were determined by plotting dynamic polarizabilities (α ) of the involved states with the above transitions against a desired range of wavelengths. Electric dipole (E1) matrix elements listed in [J. E. Sansonetti, J. Phys. Chem. Ref. Data 36, 497 (2007), 10.1063/1.2719251], from the measured lifetimes of the 7 P1 /2 ,3 /2 states and from the calculations considering core-polarization effects in the relativistic Hartree-Fock (HFR) method, were used to determine α . However, contributions from core correlation effects and from the E1 matrix elements of the 7 P -7 S , 7 P -8 S , and 7 P -6 D transitions to α of the 7 P states were ignored. In this work, we demonstrate importance of these contributions and improve accuracies of α further by replacing the E1 matrix elements taken from the HFR method by the values obtained employing relativistic coupled-cluster theory. Our static α are found to be in excellent agreement with the other available theoretical results, whereas substituting the E1 matrix elements used by Dammalapati et al. gives very small α values for the 7 P states. Owing to this, we find disagreement in λmagic reported by Dammalapati et al. for linearly polarized light, especially at wavelengths close to the D lines and in the infrared region. As a consequence, a λmagic reported at 797.75 nm which was seen supporting a blue detuned trap in their work is now estimated at 771.03 nm and is supporting a red detuned trap. Also, none of our results match with the earlier results for circularly polarized light. Moreover, our static values of α will be very useful for guiding experiments to carry out their measurements.

  4. Translational upregulation of folate receptors is mediated by homocysteine via RNA-heterogeneous nuclear ribonucleoprotein E1 interactions

    PubMed Central

    Antony, Aśok C.; Tang, Ying-Sheng; Khan, Rehana A.; Biju, Mangatt P.; Xiao, Xiangli; Li, Qing-Jun; Sun, Xin-Lai; Jayaram, Hiremagalur N.; Stabler, Sally P.

    2004-01-01

    Cellular acquisition of folate is mediated by folate receptors (FRs) in many malignant and normal human cells. Although FRs are upregulated in folate deficiency and downregulated following folate repletion, the mechanistic basis for this relationship is unclear. Previously we demonstrated that interaction of an 18-base cis-element in the 5′-untranslated region of FR mRNA and a cystolic trans-factor (heterogeneous nuclear ribonucleoprotein E1 [hnRNP E1]) is critical for FR synthesis. However, the molecular mechanisms controlling this interaction, especially within the context of FR regulation and folate status, have remained obscure. Human cervical carcinoma cells exhibited progressively increasing upregulation of FRs after shifting of folate-replete cells to low-folate media, without a proportionate rise in FR mRNA or rise in hnRNP E1. Translational FR upregulation was accompanied by a progressive accumulation of the metabolite homocysteine within cultured cells, which stimulated interaction of the FR mRNA cis-element and hnRNP E1 as well as FR biosynthesis in a dose-dependent manner. Abrupt reversal of folate deficiency also led to a rapid parallel reduction in homocysteine and FR biosynthesis to levels observed in folate-replete cells. Collectively, these results suggest that homocysteine is the key modulator of translational upregulation of FRs and establishes the linkage between perturbed folate metabolism and coordinated upregulation of FRs. PMID:14722620

  5. 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. The...

  6. 76 FR 27168 - Airmen Transition to Experimental or Unfamiliar Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-10

    ... Federal Aviation Administration Airmen Transition to Experimental or Unfamiliar Airplanes AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of availability. SUMMARY: The Federal Aviation... experimental airplane, this AC should be used to develop the skills and knowledge necessary to safely...

  7. Transitions.

    ERIC Educational Resources Information Center

    Agnew, Jeanne L.; Choike, James R.

    1987-01-01

    Mathematical observations are made about some continuous curves, called transitions, encountered in well-known experiences. The transition parabola, the transition spiral, and the sidestep maneuver are presented. (MNS)

  8. 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, June...

  9. Multi-configuration Dirac-Hartree-Fock calculations of the transition rates of 2s22p2 - 2s2p3 and 2s2p3 - 2s22pnl (n ≥ 3) E1 transitions of N+

    NASA Astrophysics Data System (ADS)

    Shen, Xiaozhi; Liu, Juan; Zhou, Fuyang

    2016-10-01

    Wavefunctions were determined using the multi-configuration Dirac-Hartree-Fock method. The core-core, core-valence, valence correlation, Breit interaction and quantum electrodynamics effects, as well as some higher-order correlation effects, were considered to obtain accurate wavelengths (λ), oscillator strengths (gf) and transition rates (A) of 2s22p2 - 2s2p3, 2s2p3 - 2s22pnl (n ≥ 3) and 2s2p3 - 2s2p23s E1 transitions. The branching ratio of 2s2p3 5S^o_2 (namely Aλ2143.45/Aλ2139.68) based on the latest calculation of 2.462 ± 0.119 is recommended for the determination of a nebula's electron temperature and electron density. The largest calculated gf value of 2s2p3 - 2s22p4p is λ630.65, differing from that of λ1060.2 (i.e. 2s2p3 3P^o_2 - 2s22p4p 3S1) that was observed with the largest intensities in the Orion Nebula spectrum. In addition, the energy levels and the splittings of 2s2p3, the extremely difficult calculations of the rates of two-electron one-photon transitions as well as those of the very small intercombination A of 2s2p3 5S^o_2 were studied in detail. Because of the weak spin-orbit interaction, accurately calculating the levels 3P^o_{1,2,0} (or 3D^o_{3,2,1}) and their transition matrix elements is very sensitive to relativistic and electron correlation effects. A special case for this is when the transition operators synchronously applied to wavefunctions with regard to 2s2p3 3Po and 2s22pnl (n = 4) become extremely sensitive to some higher-order correlation effects.

  10. 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…

  11. 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)

  12. 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…

  13. 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.

  14. 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].

  15. Electrically controllable liquid crystal random lasers below the Fréedericksz transition threshold.

    PubMed

    Lee, Chia-Rong; Lin, Jia-De; Huang, Bo-Yuang; Lin, Shih-Hung; Mo, Ting-Shan; Huang, Shuan-Yu; Kuo, Chie-Tong; Yeh, Hui-Chen

    2011-01-31

    This investigation elucidates for the first time electrically controllable random lasers below the threshold voltage in dye-doped liquid crystal (DDLC) cells with and without adding an azo-dye. Experimental results show that the lasing intensities and the energy thresholds of the random lasers can be decreased and increased, respectively, by increasing the applied voltage below the Fréedericksz transition threshold. The below-threshold-electric-controllability of the random lasers is attributable to the effective decrease of the spatial fluctuation of the orientational order and thus of the dielectric tensor of LCs by increasing the electric-field-aligned order of LCs below the threshold, thereby increasing the diffusion constant and decreasing the scattering strength of the fluorescence photons in their recurrent multiple scattering. This can result in the decrease in the lasing intensity of the random lasers and the increase in their energy thresholds. Furthermore, the addition of an azo-dye in DDLC cell can induce the range of the working voltage below the threshold for the control of the random laser to reduce.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 76 FR 30997 - National Transit Database: Amendments to Urbanized Area Annual Reporting Manual

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-27

    ... Federal Transit Administration National Transit Database: Amendments to Urbanized Area Annual Reporting... Transit Database Urbanized Area Annual Reporting Manual. SUMMARY: This notice announces the adoption of certain amendments for the Federal Transit Administration's (FTA) 2011 National Transit Database...

  2. 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].

  3. 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

    ... Ridge National Laboratory Joe Diaz, Hilsborough Area Regional Transit Authority James M. Dougherty, Washington Metropolitan Area Transit Authority David Genova, Regional Transportation District Georgetta... Metropolitan Transportation District Pamela McCombe, Greater Cleveland Regional Transit Authority Alvin H...

  4. Atomic data from the Iron Project. LIII. Relativistic allowed and forbidden transition probabilities for Fe XVII

    NASA Astrophysics Data System (ADS)

    Nahar, Sultana N.; Eissner, Werner; Chen, Guo-Xin; Pradhan, Anil K.

    2003-09-01

    An extensive set of fine structure levels and corresponding transition probabilities for allowed and forbidden transitions in Fe XVII is presented. A total of 490 bound energy levels of Fe XVII of total angular momenta 0 <= J <= 7 of even and odd parities with 2 <= n<= 10, 0 <= l<= 8, 0 <= L<= 8, and singlet and triplet multiplicities, are obtained. They translate to over 2.6x 104 allowed (E1) transitions that are of dipole and intercombination type, and 2312 forbidden transitions that include electric quadrupole (E2), magnetic dipole (M1), electric octopole (E3), and magnetic quadrupole (M2) type representing the most detailed calculations to date for the ion. Oscillator strengths f, line strengths S, and coefficients A of spontaneous emission for the E1 type transitions are obtained in the relativistic Breit-Pauli R-matrix approximation. A-values for the forbidden transitions are obtained from atomic structure calculations using codes SUPERSTRUCTURE and GRASP. The energy levels are identified in spectroscopic notation with the help of a newly developed level identification algorithm. Nearly all 52 spectroscopically observed levels have been identified, their binding energies agreeing within 1% with our calculation. Computed transition probabilities are compared with other calculations and measurement. The effect of 2-body magnetic terms and other interactions is discussed. The present data set enhances by more than an order of magnitude the heretofore available data for transition probabilities of Fe XVII. Complete electronic data tables of energies and transition probabilities are only available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsweb.u-strasbg.fr/cgi-bin/qcat?J/A+A/408/789

  5. 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

    ... Federal Transit Administration Notice of Meeting of the Transit Rail Advisory Committee for Safety (TRACS) AGENCY: Federal Transit Administration, DOT. Action: Notice of meeting. SUMMARY: This notice announces a public meeting of the Transit Rail Advisory Committee for Safety (TRACS). TRACS is a Federal...

  6. 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...

  7. 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

    ... Federal Transit Administration Notice of Meeting of the Transit Rail Advisory Committee for Safety (TRACS) AGENCY: Federal Transit Administration, DOT. ACTION: Notice of meeting. SUMMARY: This notice announces a public meeting via teleconference of the Transit Rail Advisory Committee for Safety (TRACS). TRACS is...

  8. 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...

  9. 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...

  10. 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

    ... new transit safety requirements. DATES: Applications must be submitted no later than February 26, 2010... than 25 voting members representing key constituencies affected by rail transit safety requirements... affected by rail transit safety requirements. Nominees will also be evaluated based on the...

  11. 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 will...

  12. 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... Transitional Housing Assistance Program Grant for Victims of Domestic Violence, Dating Violence, Stalking, or... 300 Transitional Housing Assistance Program Grant for Victims of Domestic Violence, Dating Violence...

  13. 76 FR 19710 - Tobacco Transition Payment Program; Cigar and Cigarette Per Unit Assessments; Correction

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-08

    ...; ] DEPARTMENT OF AGRICULTURE Commodity Credit Corporation 7 CFR Part 1463 RIN 0560-AI12 Tobacco Transition... correction to the Request for Comments titled ``Tobacco Transition Payment Program; Cigar and Cigarette Per... calculation of assessments to fund the Tobacco Transition Payment Program (TTPP) as authorized by the Fair and...

  14. Two-dimensional Fröhlich interaction in transition-metal dichalcogenide monolayers: Theoretical modeling and first-principles calculations

    NASA Astrophysics Data System (ADS)

    Sohier, Thibault; Calandra, Matteo; Mauri, Francesco

    2016-08-01

    We perform ab initio calculations of the coupling between electrons and small-momentum polar-optical phonons in monolayer transition-metal dichalcogenides of the 2 H type: MoS2,MoSe2,MoTe2,WS2 , and WSe2. The polar-optical coupling with longitudinal optical phonons, or Fröhlich interaction, is fundamentally affected by the dimensionality of the system. In a plane-wave framework with periodic boundary conditions, the Fröhlich interaction is affected by the spurious interaction between the two-dimensional (2D) material and its periodic images. To overcome this difficulty, we perform density functional perturbation theory calculations with a truncated Coulomb interaction in the direction perpendicular to the plane of the 2D material. We show that the two-dimensional Fröhlich interaction is much stronger than assumed in previous ab initio studies. We provide analytical models depending on the effective charges and dielectric properties of the materials to interpret our ab initio calculations. Screening is shown to play a fundamental role in the phonon-momentum dependency of the polar-optical coupling, with a crossover between two regimes depending on the dielectric properties of the material relative to its environment. The Fröhlich interaction is screened by the dielectric environment in the limit of small phonon momenta and sharply decreases due to stronger screening by the monolayer at finite momenta. The small-momentum regime of the ab initio Fröhlich interaction is reproduced by a simple analytical model, for which we provide the necessary parameters. At larger momenta, however, direct ab initio calculations of electron-phonon interactions are necessary to capture band-specific effects. We compute and compare the carrier relaxation times associated with the scattering by both LO and A1 phonon modes. While both modes are capable of relaxing carriers on time scales under the picosecond at room temperature, their absolute importance and relative importance vary

  15. Expression of Acidothermus cellulolyticus endoglucanase E1 in transgenic tobacco: biochemical characteristics and physiological effects.

    PubMed

    Dai, Z; Hooker, B S; Anderson, D B; Thomas, S R

    2000-02-01

    The expression of the Acidothermus cellulolyticus endoglucanase E1 gene in transgenic tobacco (Nicotiana tabacum) was examined in this study, where E1 coding sequence was transcribed under the control of a leaf specific Rubisco small subunit promoter (tomato RbcS-3C). Targeting the E1 protein to the chloroplast was established using a chloroplast transit peptide of Rubisco small subunit protein (tomato RbcS-2A) and confirmed by immunocytochemistry. The E1 produced in transgenic tobacco plants was found to be biologically active, and to accumulate in leaves at levels of up to 1.35% of total soluble protein. Optimum temperature and pH for E1 enzyme activity in leaf extracts were 81 degrees C and 5.25, respectively. E1 activity remained constant on a gram fresh leaf weight basis, but dramatically increased on a total leaf soluble protein basis as leaves aged, or when leaf discs were dehydrated. E1 protein in old leaves, or after 5 h dehydration, was partially degraded although E1 activity remained constant. Transgenic plants exhibited normal growth and developmental characteristics with photosynthetic rates similar to those of untransformed SR1 tobacco plants. Results from these biochemical and physiological analyses suggest that the chloroplast is a suitable cellular compartment for accumulation of the hydrolytic E1 enzyme.

  16. 76 FR 60587 - Environmental Impact Statement; North Corridor Transit Project, Seattle (WA) Metropolitan Area...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-29

    ... urban area comprises one of the region's most productive markets for transit. The Regional Transit... centers located in the North Corridor and the other urban centers in the Central Puget Sound area; 2... gas emissions Chapter 70.235 RCW (Limiting Green House Gas Emissions) ] Potential EIS Alternatives The...

  17. 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 the...

  18. 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

    ... vehicle would be a low-floor diesel-electric hybrid bus with enhanced on-board passenger amenities. Diesel... of Fishers. Options to be considered include No-Build, Bus Rapid Transit (BRT) and Diesel Light Rail.... The No-Build alternative includes no changes to IndyGo bus service or other transit services...

  19. 78 FR 30951 - SBIR/STTR Phase I to Phase II Transition Benchmarks

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-23

    ... From the Federal Register Online via the Government Publishing Office SMALL BUSINESS ADMINISTRATION SBIR/STTR Phase I to Phase II Transition Benchmarks AGENCY: U.S. Small Business Administration. ACTION: Notice for Small Business Innovation Research Program Phase I to Phase II Transition...

  20. 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

    ... [Docket No. 100812348-0366-01] Best Practices for Transit, Transshipment, and Reexport of Items Subject to... 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...

  1. 76 FR 69119 - Commonwealth of the Northern Mariana Islands Transitional Worker Classification: Correction

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-08

    ... SECURITY 8 CFR Part 103 RIN 1615-AB76 Commonwealth of the Northern Mariana Islands Transitional Worker... inadvertently deleted in a September 7, 2011, final rule entitled Commonwealth of the Northern Mariana Islands... the final rule Commonwealth of the Northern Mariana Islands Transitional Worker Classification...

  2. 77 FR 63413 - Early Scoping Notification for the Alternatives Analysis of the Federal Way Transit Extension...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-16

    ... investment to follow Sound Move. This work included updating Sound Transit's Long-Range Plan and associated environmental review. After several years of Sound Transit system planning work, voters in 2008 authorized... development, a vision that promotes the well-being of people and communities, ensures economic vitality...

  3. 76 FR 71934 - Tobacco Transition Payment Program; Availability of Current Assessment Methods Determination...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-21

    ... Farm Service Agency Tobacco Transition Payment Program; Availability of Current Assessment Methods... and importer assessments that fund the Tobacco Transition Payment Program (TTPP). It is in response to.... v. Vilsack et al.-- involving the terms and construction of the Fair and Equitable Tobacco Reform...

  4. 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...

  5. 77 FR 19747 - Notice of Transportation Services' Transition from Paper to Electronic Fare Media

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-02

    ... transit benefits. TRANServe has shifted to electronic fare media in specific areas in New York, parts of... efficient mechanism for the qualified transportation fringe benefit. DATES: TRANServe will consider all.... SUPPLEMENTARY INFORMATION: Background TRANServe provides service to over 250,000 transit benefit participants...

  6. 72 FR 7872 - Pesticide Program Dialogue Committee: Azinphos-methyl Transition Issues Work Group, Spray Drift...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2007-02-21

    ... AGENCY Pesticide Program Dialogue Committee: Azinphos-methyl Transition Issues Work Group, Spray Drift Work Group, and Registration Review Implementation Work Group; Notice of Public Meetings AGENCY...) will hold public meetings for three PPDC Work Groups: the Azinphos-methyl (AZM) Transition Issues...

  7. 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

    ... Federal Transit Administration National Transit Database: Amendments to the Urbanized Area Annual...), DOT. ACTION: Notice of Proposed Amendments to the 2011 National Transit Database Urbanized Area Annual... to comment on changes to the Federal Transit Administration's (FTA) National Transit Database...

  8. 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

    ... Vehicle for Mobility applications support dynamic system operations and management, enable a convenient... Meeting and Webinar on Integrated Dynamic Transit Operations; Notice of Public Meeting AGENCY: Research.... Department of Transportation (USDOT) Intelligent Transportation System Joint Program Office (ITS JPO) will...

  9. 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...

  10. 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

    ...This notice proposes guidance in the form of a revised circular on the Federal Transit Administration's research, technical assistance, and training programs and seeks comment thereon. Proposed FTA Circular 6100.1D, ``Research, Technical Assistance, and Training Programs: Application Instructions and Program Management Guidelines,'' modifies FTA's existing FTA Circular 6100.1C, ``Transit Research and Technology Programs: Application Instructions and Program Management Guidelines'' to reflect current policy and new FTA programs, restructures the circular, and clarifies FTA's requirements and processes.

  11. Office treatment: intracavernous injections of prostaglandin E1 (PG E1) and improvement of spontaneous erections.

    PubMed

    Beretta, G; Marzotto, M; Zanollo, A; Re, B

    1991-01-01

    The Authors evaluated 48 patients with erectile dysfunctions, either psychogenic or neurologic or with vascular etiology. The experience confirms that PG E1 is able ti improve erection, mainly in case of psychological and vascular problems. The drug used is useful for the office treatment, since it has such a low incidence of side effects.

  12. 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

  13. Parity-nonconserving interaction-induced light shifts in the {7S}_{1/2}-{6D}_{3/2} transition of the ultracold {^{210}{Fr}} atoms to probe new physics beyond the standard model

    NASA Astrophysics Data System (ADS)

    Aoki, T.; Torii, Y.; Sahoo, B. K.; Das, B. P.; Harada, K.; Hayamizu, T.; Sakamoto, K.; Kawamura, H.; Inoue, T.; Uchiyama, A.; Ito, S.; Yoshioka, R.; Tanaka, K. S.; Itoh, M.; Hatakeyama, A.; Sakemi, Y.

    2017-04-01

    We present an experimental technique to measure light shifts due to the nuclear spin independent (NSI) parity-nonconserving (PNC) interaction in the 7S_{1/2}-6D_{3/2} transition in ultracold {^{210}Fr} atoms. The approach we propose is similar to the one by Fortson (Phys Rev Lett 70:2383, 10) to measure the PNC-induced light shift which arises from the interference of parity nonconserving electric dipole transition and electric quadrupole transition amplitudes. Its major advantage is that it can treat more than 10^4 ultracold {^{210}Fr} atoms to enhance the shot noise limit. A relativistic coupled-cluster method has been employed to calculate the electric dipole transition amplitudes arising from the PNC interaction. Based on these calculations, we have evaluated the PNC-induced light shifts for transitions between the hyperfine levels of the 7S_{1/2} and 6D_{3/2} states and suitable transitions are identified for carrying out PNC measurements. It is possible in principle to probe new physics beyond the standard model with our proposed experimental scheme.

  14. Many trained at E1 Salvador center.

    PubMed

    1970-02-01

    The Family Planning Association of E1 Salvador is conducting regular week-long courses in family planning for doctors, nurses, social workers and other interested people in El Salvador and the surrounding countries of Guatemala, Honduras, Nicaragua, Costa Rica and Panama. Twelve regional courses on population dynamics, the physiology of reproduction and family planning were held in the academic year 1968-69 at the Faculty of Medicine at the University of El Salvador. Because the demand for places far exceeds the capacity of the Association's training unit, careful selection of candidates is made through consultation with the national family planning associations. Most of those trained are doctors who are being specially equipped to carry out family planning work either as part of government maternal and child health centres or in Association clinics. Many places are also found for nurses and some social workers also attend in order to build up teams for effective clinic management. A few journalists and teachers have been among the trainees as well as groups of religious leaders including Roman Catholics. Lecturers are mainly university personnel drawn from a wide range of disciplines in order to relate family planning not only to health and medicine but also to socio-economic aspects and community welfare. The El Salvador Association, an IPPF member, gets financial support from the Population Council for the training programme but hopes eventually that responsibility for continuing the courses will be taken over by the Government, probably through the Ministry of Education. Another pace-setting activity of the Association has been its close contacts with industry, particulary through the efforts of its President, Mr. Lucio Burgos, General Manager of the El Salvador Power Company, who has gained the interest and support of business and union leaders. Not only do these groups help the work of the Association through fund-raising and public relations activities, but

  15. 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

    ...This document provides notice that U.S. Customs and Border Protection (``CBP'') has issued a final determination concerning the country of origin of the Transit Connect Electric Vehicle. Based upon the facts presented, CBP has concluded in the final determination that the United States is the country of origin of the vehicle for purposes of U.S. Government procurement.

  16. 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

    ...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 the Emergency Solutions Grants program. The......

  17. 77 FR 7095 - Transitional Program for Covered Business Method Patents-Definition of Technological Invention

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-10

    ... Patents-- Definition of Technological Invention AGENCY: United States Patent and Trademark Office... invention in a transitional post-grant review proceeding for covered business method patents. The provision..., Covered Business Method Patent Review Proposed Definition for Technological Invention.'' Comments may also...

  18. 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

    ... 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 County... NOI, would bring the North Red and Purple lines up to a state of good repair from the track structure...

  19. 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

    ... others those lessons learned from the participating sites. NIC also funded the development of the TJC... of the TJC model in learning sites. A related objective of the implementation evaluation is to... transition practice beyond the learning sites through two primary activities: (1) Development and...

  20. 76 FR 37175 - FY 2011 Discretionary Sustainability Funding Opportunity Transit Investments for Greenhouse Gas...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-24

    ... project; (2) Constructing or leasing clean fuel bus facilities or electrical recharging facilities and... With Discretionary Bus and Bus Facilities Program AGENCY: Federal Transit Administration (FTA), DOT... (TIGGER) program and Clean Fuels Grant program, augmented with Section 5309 Bus and Bus Facilities program...

  1. 76 FR 61135 - Waiver of Restriction on Assistance to the Transitional Federal Government of Somalia

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-03

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF STATE Waiver of Restriction on Assistance to the Transitional Federal Government of Somalia Pursuant to Section... determination shall be reported to the Congress, and published in the Federal Register. Dated: July 28,...

  2. 75 FR 26683 - Hospital and Outpatient Care for Veterans Released From Incarceration to Transitional Housing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-12

    ..., Medical devices, Medical research, Mental health programs, Nursing homes, Philippines, Reporting and... mental health issues are not addressed during the transitional period, upon release, many of these.... Mallik-Kane, K, and Visher, C.A., Health and prisoner re-entry: How physical, mental, and substance abuse...

  3. 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

    ... meetings are accessible to persons with disabilities. Any individual who requires special assistance or... transit infrastructure and providing access to persons with disabilities in the north lakefront and north... not have access for persons with disabilities; the volume of passengers, over 128,000 trips on an...

  4. 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

    ... applicable statutes and regulations. TRANServe's plan is a two-year initiative designed to be responsive to industry changes and technological advances. Over time, many State and local transit authorities are... system (vouchers) to an electronic fare media structure. Now that the Federal Register notification...

  5. 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 first...

  6. 77 FR 59543 - Homeless Emergency Assistance and Rapid Transition to Housing: Continuum of Care Program...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-28

    ... URBAN DEVELOPMENT 24 CFR Part 578 RIN 2506-AC29 Homeless Emergency Assistance and Rapid Transition to Housing: Continuum of Care Program: Extension of Public Comment Period AGENCY: Office of the Assistant Secretary for Community Planning and Development, HUD. ACTION: Interim rule; extension of comment period...

  7. 75 FR 24748 - Office of the Assistant Secretary for “Incarcerated Veterans Transition Program”

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-05

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF LABOR Veterans' Employment and Training Office of the Assistant Secretary for ``Incarcerated Veterans Transition Program'' AGENCY: Veterans' Employment and Training Service, Department of Labor. Announcement Type: New Notice of Availability of Funds...

  8. 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... agencies about ways for the acquisition community to transition to Secure Hash Algorithm SHA-256. SHA-256... for sign language interpretation or other auxiliary aids should be directed to Mr. Edward Loeb...

  9. 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

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; Inbound Transit of M/V TEAL, Savannah River... River to the Georgia Ports Authority, Garden City Terminal Container Berth 8 (CB8). This safety zone... necessary to protect life and property on the navigable waters of the Savannah River due to the hazards...

  10. 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

    .... The required electronic project proposal template as well as guidance on completing a proposal can be...: Solicitation of Project Proposals SUMMARY: The Federal Transit Administration (FTA) announces the availability... cooperation with FTA, will determine the final selection and funding of projects. Geographic diversity will be...

  11. 76 FR 62148 - Title VI; Proposed Circular, Environmental Justice; Proposed Circular

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-06

    ... Federal Transit Administration Title VI; Proposed Circular, Environmental Justice; Proposed Circular...; Proposed Circular'' and ``Environmental Justice; Proposed Circular.'' FOR FURTHER INFORMATION CONTACT: For... Circular'' (76 FR 60593) and ``Environmental Justice; Proposed Circular'' (76 FR 60590). Corrections The...

  12. Energies, E1, M1, and E2 transition rates, hyperfine structures, and Lande g{sub J} factors for states of the 2s{sup 2}2p{sup 2}, 2s2p{sup 3}, and 2p{sup 4} configurations in carbon-like ions between F IV and Ni XXIII

    SciTech Connect

    Joensson, P.; Rynkun, P.; Gaigalas, G.

    2011-11-15

    Energies, electric dipole, magnetic dipole, and electric quadrupole transition rates, hyperfine structures, and Lande g{sub J} factors from relativistic configuration interaction calculations are reported for the states of the (1s{sup 2})2s{sup 2}2p{sup 2}, 2s2p{sup 3}, and 2p{sup 4} configurations in all carbon-like ions between F IV and Ni XXIII. Valence, core-valence, and core-core correlation effects were accounted for through single/double-excitation-multireference expansions to increasing sets of active orbitals. The calculated energy levels generally agree within a few hundred cm{sup -1} with the experimentally compiled results, and the Babushkin (length), and Coulomb (velocity) forms of transition rates agree within less than 1% for a majority of the allowed transitions.

  13. 26 CFR 31.3231(e)-1 - Compensation.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 15 2013-04-01 2013-04-01 false Compensation. 31.3231(e)-1 Section 31.3231(e)-1... Retirement Tax Act (Chapter 22, Internal Revenue Code of 1954) General Provisions § 31.3231(e)-1 Compensation. (a) Definition—(1) The term compensation has the same meaning as the term wages in section...

  14. 26 CFR 31.3231(e)-1 - Compensation.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 15 2014-04-01 2014-04-01 false Compensation. 31.3231(e)-1 Section 31.3231(e)-1... Retirement Tax Act (Chapter 22, Internal Revenue Code of 1954) General Provisions § 31.3231(e)-1 Compensation. (a) Definition—(1) The term compensation has the same meaning as the term wages in section...

  15. 26 CFR 31.3231(e)-1 - Compensation.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 15 2012-04-01 2012-04-01 false Compensation. 31.3231(e)-1 Section 31.3231(e)-1... Retirement Tax Act (Chapter 22, Internal Revenue Code of 1954) General Provisions § 31.3231(e)-1 Compensation. (a) Definition—(1) The term compensation has the same meaning as the term wages in section...

  16. 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 § 1.514(e)-1...

  17. 26 CFR 1.514(e)-1 - Allocation rules.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 7 2011-04-01 2009-04-01 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 § 1.514(e)-1...

  18. Rsf-1, a chromatin remodelling protein, interacts with cyclin E1 and promotes tumour development.

    PubMed

    Sheu, Jim Jinn-Chyuan; Choi, Jung Hye; Guan, Bin; Tsai, Fuu-Jen; Hua, Chun-Hung; Lai, Ming-Tsung; Wang, Tian-Li; Shih, Ie-Ming

    2013-03-01

    Chromosome 11q13.5 containing RSF1 (HBXAP), a gene involved in chromatin remodelling, is amplified in several human cancers including ovarian carcinoma. Our previous studies demonstrated requirement of Rsf-1 for cell survival in cancer cells, which contributed to tumour progression; however, its role in tumourigenesis has not yet been elucidated. In this study, we co-immunoprecipitated proteins with Rsf-1 followed by nanoelectrospray mass spectrometry and identified cyclin E1, besides SNF2H, as one of the major Rsf-1 interacting proteins. Like RSF1, CCNE1 is frequently amplified in ovarian cancer, and both Rsf-1 and cyclin E1 were found co-up-regulated in ovarian cancer tissues. Ectopic expression of Rsf-1 and cyclin E1 in non-tumourigenic TP53(mut) RK3E cells led to an increase in cellular proliferation and tumour formation by activating cyclin E1-associated kinase (CDK2). Tumourigenesis was not detected if either cyclin E1 or Rsf-1 was expressed, or they were expressed in a TP53(wt) background. Domain mapping showed that cyclin E1 interacted with the first 441 amino acids of Rsf-1. Ectopic expression of this truncated domain significantly suppressed G1/S-phase transition, cellular proliferation, and tumour formation of RK3E-p53(R175H) /Rsf-1/cyclin E1 cells. The above findings suggest that Rsf-1 interacts and collaborates with cyclin E1 in neoplastic transformation and TP53 mutations are a prerequisite for tumour-promoting functions of the RSF/cyclin E1 complex.

  19. Transcription units of E1a, E1b and pIX regions of bovine adenovirus type 3.

    PubMed

    Zheng, B J; Graham, F L; Prevec, L

    1999-07-01

    The major mRNA species in the E1 region of the genome of bovine adenovirus type 3 (BAV3) have been defined by using a combination of PCR, 5' RACE, Northern analysis and DNA sequencing. Independent transcription initiation sites were identified for each of the E1a, E1b and protein IX (pIX) transcription units, but all mRNA species terminated at the same poly(A) addition site immediately downstream of the pIX open reading frame. Thus, the BAV3 E1 region, which consists of the E1a and E1b genes together with that for pIX, functions as a nested overlapping transcription unit. One major mRNA species encoding the E1a protein was found and two mRNAs encoding E1b species, the smaller of which encodes the E1b 17K protein alone and the larger encodes both 17K and 47K E1b proteins, were identified. One mRNA species encodes pIX. The E1a transcript, encoding the predicted 214 residue E1a protein, has four exons. The smaller E1b mRNA has two exons, the second of which corresponds to the last exon of E1a. No introns were detected in the larger E1b mRNA that encodes both the E1b 17K and 47K proteins nor in the mRNA encoding pIX. The relative times of appearance of the mRNAs from the E1-pIX gene region following infection of bovine cells with BAV3 was determined.

  20. Adenovirus E1A protein activates transcription of the E1A gene subsequent to transcription complex formation.

    PubMed Central

    Schaack, J; Logan, J; Vakalopoulou, E; Shenk, T

    1991-01-01

    The mechanism of transcriptional activation of the adenovirus E1A and E3 genes by E1A protein during infection was examined by using transcription-competition assays. Infection of HeLa cells with one virus led to inhibition of mRNA accumulation from a superinfecting virus. Synthesis of the E1A 289R protein by the first virus to infect reduced inhibition of transcription of the superinfecting virus, indicating that the E1A 289R protein was limiting for E1A-activated transcription. Infection with an E1A- virus, followed 6 h later by superinfection with a wild-type virus, led to preferential transcriptional activation of the E1A gene of the first virus, suggesting that a host transcription component(s) stably associated with the E1A promoter in the absence of E1A protein and that this complex was the substrate for transcriptional activation by E1A protein. The limiting host transcription component(s) bound to the E1A promoter to form a complex with a half-life greater than 24 h in the absence of E1A 289R protein, as demonstrated in a challenge assay with a large excess of superinfecting virus. In the presence of the E1A 289R protein, the E1A gene of the superinfecting virus was gradually activated with a reduction in E1A mRNA accumulation from the first virus. The kinetics of the activation suggest that this was due to an indirect effect rather than to destabilization of stable transcription complexes by the 289R protein. Images PMID:1825853

  1. 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

    ...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 Continuum of Care program, revises the Emergency Shelter Grants program and renames this program the Emergency Solutions Grants program, and creates the Rural Housing Stability Assistance program to replace the Rural Homelessness Grant program. The HEARTH Act also directs HUD to promulgate regulations for these new programs and processes. This proposed rule would provide for the establishment of regulations to implement the new Rural Housing Stability Assistance program. In addition to proposing the regulatory framework for the new Rural Housing Stability Assistance program, this rule also proposes to establish a definition for ``chronically homeless'' that includes a definition of ``homeless occasion'' that better targets persons with the longest histories of homelessness and the highest level of need.

  2. 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.

  3. 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.

  4. 78 FR 36298 - Notice of Intent to Prepare an Environmental Impact Statement for the Federal Way Transit...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-17

    ... long-range vision, goals, and objectives for transit service established by the Sound Transit Long-Range Plan for high-quality regional transit service connecting major activity centers in King, Pierce... Regional Transit Long-Range Plan. Implementing the project will help meet environmental and sustainability...

  5. Crossover from skin mode to proton-neutron mode in E1 excitations of neutron-rich nuclei

    NASA Astrophysics Data System (ADS)

    Nakada, H.; Inakura, T.; Sawai, H.

    2013-03-01

    The character of the low-energy E1 excitations is investigated by analyzing transition densities obtained from the RPA calculations in the doubly magic nuclei. We propose a decomposition method of the E1 excitations into the pn mode (i.e., oscillation between protons and neutrons) and the skin mode (i.e., oscillation of the neutron skin against the inner core) via the transition densities, by which their mixing is handled in a straightforward manner. Crossover behavior of the E1 excitations is found, from the skin mode at low energy to the pn mode at higher energy. The ratio of the skin-mode strength to the full strength turns out to be insensitive to the nuclides and to the effective interactions in the energy region of the crossover. Depending on the excitation energy, the observed low-energy E1 excitations are not necessarily dominated by the skin mode, as exemplified for 90Zr.

  6. 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.

  7. 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 D...

  8. 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...

  9. 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.

  10. 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...

  11. 77 FR 3454 - Department of Defense Task Force on the Care, Management, and Transition of Recovering Wounded...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-24

    ... Force on the Care, Management, and Transition of Recovering Wounded, Ill, and Injured Members of the... Committee meeting of the 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...

  12. 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

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

  13. 78 FR 38015 - Department of Defense Task Force on the Care, Management, and Transition of Recovering Wounded...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-25

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

  14. 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

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

  15. 76 FR 18930 - Medicare Programs: Changes to the End-Stage Renal Disease Prospective Payment System Transition...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-06

    ...: Changes to the End-Stage Renal Disease Prospective Payment System Transition Budget-Neutrality Adjustment...) transition budget-neutrality adjustment finalized in the CY 2011 ESRD Prospective Payment System (PPS) final... the transition budget-neutrality adjustment to reflect the actual election decision to receive...

  16. 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

    ... service from the eastern terminus of Norfolk's existing Light Rail Transit (LRT) system, ``The Tide,'' at... Light Rail Transit System Final EIS. This document looked at an 18-mile transit system connecting... relevant information that has been developed over the last several years since the 2009 Supplemental...

  17. 77 FR 21541 - Notice of Submission for OMB Review; Office of Innovation and Improvement; Transition to Teaching...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-10

    ... Notice of Submission for OMB Review; Office of Innovation and Improvement; Transition to Teaching Evaluation SUMMARY: The Transition to Teaching (TTT) grant program provides five- year grants to eligible... of Collection: Transition to Teaching Evaluation. OMB Control Number: 1855-0018. Type of...

  18. Structures of Human Cytochrome P-450 2E1

    PubMed Central

    Porubsky, Patrick R.; Meneely, Kathleen M.; Scott, Emily E.

    2008-01-01

    Human microsomal cytochrome P-450 2E1 (CYP2E1) monooxygenates >70 low molecular weight xenobiotic compounds, as well as much larger endogenous fatty acid signaling molecules such as arachidonic acid. In the process, CYP2E1 can generate toxic or carcinogenic compounds, as occurs with acetaminophen overdose, nitrosamines in cigarette smoke, and reactive oxygen species from uncoupled catalysis. Thus, the diverse roles that CYP2E1 has in normal physiology, toxicity, and drug metabolism are related to its ability to metabolize diverse classes of ligands, but the structural basis for this was previously unknown. Structures of human CYP2E1 have been solved to 2.2 Å for an indazole complex and 2.6 Å for a 4-methylpyrazole complex. Both inhibitors bind to the heme iron and hydrogen bond to Thr303 within the active site. Complementing its small molecular weight substrates, the hydrophobic CYP2E1 active site is the smallest yet observed for a human cytochrome P-450. The CYP2E1 active site also has two adjacent voids: one enclosed above the I helix and the other forming a channel to the protein surface. Minor repositioning of the Phe478 aromatic ring that separates the active site and access channel would allow the carboxylate of fatty acid substrates to interact with conserved 216QXXNN220 residues in the access channel while positioning the hydrocarbon terminus in the active site, consistent with experimentally observed ω-1 hydroxylation of saturated fatty acids. Thus, these structures provide insights into the ability of CYP2E1 to effectively bind and metabolize both small molecule substrates and fatty acids. PMID:18818195

  19. CYP2E1 hydroxylation of aniline involves negative cooperativity.

    PubMed

    Hartman, Jessica H; Knott, Katie; Miller, Grover P

    2014-02-01

    CYP2E1 plays a role in the metabolic activation and elimination of aniline, yet there are conflicting reports on its mechanism of action, and hence relevance, in aniline metabolism. Based on our work with similar compounds, we hypothesized that aniline binds two CYP2E1 sites during metabolism resulting in cooperative reaction kinetics and tested this hypothesis through rigorous in vitro studies. The kinetic profile for recombinant CYP2E1 demonstrated significant negative cooperativity based on a fit of data to the Hill equation (n=0.56). Mechanistically, the data were best explained through a two-binding site cooperative model in which aniline binds with high affinity (K(s)=30 μM) followed by a second weaker binding event (K(ss)=1100 uM) resulting in a threefold increase in the oxidation rate. Binding sites for aniline were confirmed by inhibition studies with 4-methylpyrazole. Inhibitor phenotyping experiments with human liver microsomes validated the central role for CYP2E1 in aniline hydroxylation and indicated minor roles for CYP2A6 and CYP2C9. Importantly, inhibition of minor metabolic pathways resulted in a kinetic profile for microsomal CYP2E1 that replicated the preferred mechanism and parameters observed with the recombinant enzyme. Scaled modeling of in vitro CYP2E1 metabolism of aniline to in vivo clearance, especially at low aniline levels, led to significant deviations from the traditional model based on non-cooperative, Michaelis-Menten kinetics. These findings provide a critical mechanistic perspective on the potential importance of CYP2E1 in the metabolic activation and elimination of aniline as well as the first experimental evidence of a negatively cooperative metabolic reaction catalyzed by CYP2E1.

  20. Therapeutic Strategies against Cyclin E1-Amplified Ovarian Cancers

    DTIC Science & Technology

    2016-10-01

    AWARD NUMBER: W81XWH-15-1-0566 TITLE: Therapeutic Strategies against Cyclin E1-Amplified Ovarian Cancers PRINCIPAL INVESTIGATOR: Dipanjan...SUBTITLE 5a. CONTRACT NUMBER Therapeutic Strategies against Cyclin E1-Amplified Ovarian Cancers 5b. GRANT NUMBER W81XWH-15-1-0566 5c. PROGRAM...resistance to platinum, management of CCNE1- amplified ovarian cancers is challenging. In this research, we evaluate three novel strategies against CCNE1

  1. Therapeutic Strategies against Cyclin E1-Amplified Ovarian Cancers

    DTIC Science & Technology

    2016-10-01

    strategy for targeting CCNE1 amplified tumors. In the next funding period, we plan to perform studies of miRNA mimics with additional PARP-inhibitors and...AWARD NUMBER: W81XWH-15-1-0564 TITLE: Therapeutic Strategies against Cyclin E1-Amplified Ovarian Cancers PRINCIPAL INVESTIGATOR: Panagiotis A...4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Therapeutic Strategies against Cyclin E1-Amplified Ovarian Cancers 5b. GRANT NUMBER W81XWH-15-1-0564 5c

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

    PubMed Central

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

    1994-01-01

    We 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. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 7 Figure 8 PMID:8037208

  3. Methylglyoxal induces oxidative stress and mitochondrial dysfunction in osteoblastic MC3T3-E1 cells.

    PubMed

    Suh, K S; Choi, E M; Rhee, S Y; Kim, Y S

    2014-02-01

    Methylglyoxal is a reactive dicarbonyl compound produced by glycolytic processing and identified as a precursor of advanced glycation end products. The elevated methylglyoxal levels in patients with diabetes are believed to contribute to diabetic complications, including bone defects. The objective of this study was to evaluate the effect of methylglyoxal on the function of osteoblastic MC3T3-E1 cells. The data indicated that methylglyoxal decreased osteoblast differentiation and induced osteoblast cytotoxicity. Pretreatment of MC3T3-E1 cells with aminoguanidine (a carbonyl scavenger), Trolox (an antioxidant), and cyclosporin A (a blocker of the mitochondrial permeability transition pore) prevented methylglyoxal-induced cytotoxicity in MC3T3-E1 cells. However, BAPTA/AM (an intracellular Ca(2+) chelator) and dantrolene (an inhibitor of endoplasmic reticulum Ca(2+) release) did not reverse the cytotoxic effect of methylglyoxal. Methylglyoxal increased the formation of intracellular reactive oxygen species, mitochondrial superoxide, and cardiolipin peroxidation in osteoblastic MC3T3-E1 cells. Methylglyoxal also decreased the mitochondrial membrane potential and intracellular ATP and nitric oxide levels, suggesting that carbonyl stress-induced loss of mitochondrial integrity contributes to the cytotoxicity of methylglyoxal. Furthermore, the results demonstrated that methylglyoxal induced protein adduct formation, inactivation of glyoxalase I, and activation of glyoxalase II. Aminoguanidine reversed all aforementioned effects of methylglyoxal. Taken together, these data support the notion that high methylglyoxal concentrations have detrimental effects on osteoblasts through a mechanism involving oxidative stress and mitochondrial dysfunction.

  4. 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

  5. 2E1 Ar(17+) decay and conventional radioactive sources to determine efficiency of semiconductor detectors.

    PubMed

    Lamour, Emily; Prigent, Christophe; Eberhardt, Benjamin; Rozet, Jean Pierre; Vernhet, Dominique

    2009-02-01

    Although reliable models may predict the detection efficiency of semiconductor detectors, measurements are needed to check the parameters supplied by the manufacturers, namely, the thicknesses of dead layer, beryllium window, and crystal active area. The efficiency of three silicon detectors has been precisely investigated in their entire photon energy range of detection. In the zero to a few keV range, we developed a new method based on the detection of the 2E1 decay of the metastable Ar(17+) 2s-->1s transition. Very good theoretical knowledge of the energetic distribution of the 2E1 decay mode enables precise characterization of the absorbing layers in front of the detectors. In the high-energy range (>10 keV), the detector crystal thickness plays a major role in the detection efficiency and has been determined using a (241)Am source.

  6. 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

    .... Environmental Finance topics expected to be discussed include: clean air technology; tribal environmental programs; transit-oriented development; energy efficiency; green infrastructure; and drinking water pricing...

  7. 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.

  8. 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

  9. Adenovirus type 12 E1B 55-kilodalton oncoprotein promotes p53-mediated apoptotic response of ovarian cancer to cisplatin.

    PubMed

    Wang, Junnai; Gao, Qinglei; Li, Qiang

    2015-08-01

    The tumor suppressor p53-mediated apoptotic response plays an important role in cisplatin resistant in ovarian cancer. The adenovirus (Ad) type 12 E1B 55-kDa protein binds to p53 and inactivates its transcriptional transactivation function. In this study, we test the hypothesis that Ad12 E1B 55-kDa oncoprotein promotes p53-mediated apoptotic response of ovarian cancer to cisplatin. First, we observed the upregulation protein level of p53 target genes in cisplatin-resistant or cisplatin-sensitive ovarian cancer by Western blotting. Second, after transfection of Ad12 E1b 55-kDa expression plasmid, the expressions of p53 target genes in A2780 cells were further enhanced. Co-IP experiment demonstrated Ad12 E1b 55 kDa associated with p53. MTT assay confirmed that the cell proliferation was enhanced after transfection, as well as the enhanced cell inhibitory rate in the presence of cisplatin. Using flow cytometry, transfection of Ad12 E1B 55-kDa protein induced apoptosis and promoted S-phase transition in proliferation. Finally, results showed that all these changes promoted by Ad12 E1b 55 kDa were attenuated by the exposure of specific inhibitor of p53 signaling, pifithrin-α. Taken together, we concluded that Ad E1B 55-kDa oncoprotein promotes p53-mediated apoptotic response of ovarian cancer to cisplatin.

  10. 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.... 10902 for Sonoma-Marin Area Rail Transit District (SMART), a Class III rail carrier, to acquire an approximately 11.25-mile line of railroad in Marin County, Cal., from Golden Gate Bridge, Highway,...

  11. 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

    ... Census B. Definitional Changes and New Definitions 1. Associated Transit Improvement 2. Bus Rapid Transit... (49 U.S.C. 5309) 3. Bus and Bus Facilities (49 U.S.C. 5309) 4. Job Access and Reverse Commute Program... (49 U.S.C. 5320) 7. Alternatives Analysis Program (49 U.S.C. 5339) 8. Over-the-Road Bus Accessibility...

  12. 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

    ... 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... Medical Care Case management. 11:45 a.m.-12:30 p.m. Lunch. 12:30-2 p.m. Task Force...

  13. 78 FR 59918 - Department of Defense Task Force on the Care, Management, and Transition of Recovering Wounded...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-30

    ... 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... organizations may submit written statements to the Department of Defense Task Force on the Care, Management,...

  14. 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 Care...

  15. 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..., 2011, from 8:30 a.m. to 5 p.m. CST, each day. ADDRESSES: St. Anthony Riverwalk Wyndham...

  16. 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

    ... Greenway Plaza (15,166). H- GAC 2005 and 2035 Person Trip Tables. US 90A/Southwest Rail Corridor Transit... defining the elements of the No Build Alternative. The No Build Alternative proposes no major transit or... outreach to community and civic groups; periodic meetings with various local organizations; a public...

  17. 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

  18. 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.

  19. 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.

  20. Atg8 transfer from Atg7 to Atg3: a distinctive E1-E2 architecture and mechanism in the autophagy pathway

    PubMed Central

    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.

    2011-01-01

    Summary 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 (Atg7NTD) recruits a unique “flexible region” from Atg3 (Atg3FR). The structure of an Atg7NTD-Atg3FR 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 cross-linking data allow modeling of a full-length, dimeric (Atg7∼Atg8-Atg3)2 complex. The model and biochemical data provide a rationale for Atg7 dimerization: Atg8 is transferred in trans from the catalytic Cys 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∼UBL-E2 architecture for enzymes mediating autophagy. PMID:22055190

  1. Atg8 transfer from Atg7 to Atg3: a distinctive E1-E2 architecture and mechanism in the autophagy pathway.

    PubMed

    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

    2011-11-04

    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(NTD)) recruits a unique "flexible region" from Atg3 (Atg3(FR)). The structure of an Atg7(NTD)-Atg3(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~Atg8-Atg3)(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~UBL-E2 architecture for enzymes mediating autophagy.

  2. 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...

  3. E1a induces the expression of epithelial characteristics

    PubMed Central

    1994-01-01

    Cells closely resembling epithelia constitute the first specific cell type in a mammalian embryo. Many other cell types emerge via epithelial- mesenchymal differentiation. The transcription factors and signal transduction pathways involved in this differentiation are being elucidated. I have previously reported (Frisch, 1991) that adenovirus E1a is a tumor suppressor gene in certain human cell lines. In the present report, I demonstrate that E1a expression caused diverse human tumor cells (rhabdomyosarcoma, fibrosarcoma, melanoma, osteosarcoma) and fibroblasts to assume at least two of the following epithelial characteristics: (a) epithelioid morphology; (b) epithelial-type intercellular adhesion proteins localized to newly formed junctional complexes; (c) keratin-containing intermediate filaments; and (d) down- regulation of non-epithelial genes. E1a thus appeared to partially convert diverse human tumor cells into an epithelial phenotype. This provides a new system for molecular analysis of epithelial-mesenchymal interconversions. This effect may also contribute to E1a's tumor suppression activity, possibly through sensitization to anoikis (Frisch, S.M., and H. Francis, 1994. J. Cell Biol. 124:619-626). PMID:7525602

  4. 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...

  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. 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

    ... knowledge base with professionals who have done academic research in the safety field. DATES: Applications... research on the emerging trends or issues related to rail transit safety. The nominees will be...

  7. Fructose feeding in the suckling-weaning transition in rats: effects on hyperlipidemia in adulthood.

    PubMed

    Bell, R C; Hoedl, A; Turchinsky, J

    2003-02-01

    The sucking-weaning transition is characterized by high rates of growth and development and may be a sensitive period during which dietary intake could program metabolism to increase the risk of cardiovascular disease and diabetes in adulthood. Intake of a high fructose (FR) diet is known to induce hypertriglyceridemia and insulin resistance in rats when they are consuming this diet. We examined whether a FR diet fed early in life produces detrimental changes in lipid and glucose metabolism that persist to adulthood. Weanling rats were fed 65% FR (wt/wt), a purified control diet (CNTL) or standard chow (CHOW) for 5 weeks. Beyond 9 weeks of age, all rats were fed CHOW. During FR feeding, plasma triglycerides (TG) were significantly elevated in the FR group (FR = 217 +/- 20; CNTL = 163 +/- 17; chow = 156 +/- 10). At 21 wks of age, TG's were similar in rats fed FR or CNTL versus CHOW at weaning (p > 0.87). Hepatic fatty acid synthase (FAS) activity was elevated in FR and CNTL groups vs. CHOW (65 +/- 7, 72 +/- 6 vs. 48 +/- 4 nmol NADPH/mg protein/min, p < 0.01). There were no differences in indices of glucose homeostasis at 21 weeks of age. Early exposure to a diet high in simple sugars (FR or CNTL) and/or low in fiber during the suckling-weaning transition may contribute to modest dyslipidemia later in life. Together, changes observed in this study may increase the risk of cardiovascular disease in adulthood.

  8. The harlequin color change and association with prostaglandin E1.

    PubMed

    Rao, Jaggi; Campbell, Morag E; Krol, Alfons

    2004-01-01

    The harlequin color change is an unusual cutaneous phenomenon observed in newborn infants as transient, benign episodes of a sharply demarcated erythema on half of the infant, with simultaneous contralateral blanching. In this report, two newborns with congenital heart anomalies demonstrated the harlequin color change, one whose skin findings showed a course related to the dose of systemic prostaglandin E1, suggesting a possible association. The benign, self-limited nature of the color change mandates that prostaglandin E1 not be discontinued for this reason. The entity is likely more common than the paucity of reports in the world literature suggests, and all physicians should recognize its graphic appearance to avoid unnecessary exposure to agents in an effort to treat it.

  9. Discovery and Classification of DES15E1iuh

    NASA Astrophysics Data System (ADS)

    Smith, M.; Sullivan, M.; Childress, M.; D'Andrea, C.; Lewis, G. F.; Mould, J.; Lidman, C.; Tucker, B. E.; Sharp, R.; Yuan, F.; Martini, P.; Brown, P. J.; Krisciunas, K.; Suntzeff, N.; Nichol, R.; Papadopoulos, A.; Maartens, R.; Gupta, R.; Kovacs, E.; Kuhlmann, S.; Spinka, H.; Ahn, E.; Finley, D. A.; Frieman, J.; Marriner, J.; Wester, W.; Aldering, G.; Kim, A. G.; Thomas, R. C.; Barbary, K.; Bloom, J. S.; Goldstein, D.; Nugent, P.; Perlmutter, S.; Foley, R. J.; Casas, R.; Castander, F. J.; Desai, S.; Paech, K.; Smith, R. C.; Schubnell, M.; Kessler, R.; Lasker, J.; Scolnic, D.; Brout, D. J.; Gladney, L.; Sako, M.; Wolf, R. C.

    2015-10-01

    We report optical spectroscopy of DES15E1iuh discovered by the Dark Energy Survey. We obtained spectra using the X-SHOOTER instrument (wavelength range 380-950nm) on the Very Large Telescope (VLT) of the European Southern Observatory (ESO) and the AAOmega Spectrograph (Saunders et al. 2004, SPIE, 5492, 389; wavelength range 370-885nm) and the 2dF fibre positioner at the Anglo-Australian Telescope (AAT).

  10. 77 FR 55473 - Agency Information Collection Activities; Renewal of a Currently Approved Collection; Comment...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-10

    ..., Implementation of Basel III, Minimum Regulatory Capital Ratios, Capital Adequacy, Transition Provisions, and...) make certain public disclosures regarding their capital ratios, their components, and information on... Capital Ratios, Capital Adequacy, Transition Provisions, and Prompt Corrective Action (77 FR...

  11. 77 FR 56632 - Privacy Act of 1974; System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-13

    ... duty personnel grades Airman Basic (E-1) through Chief Master Sergeant (E-9). Air National Guard and Air Force Reserve personnel grades Staff Sergeant (E-5) through Chief Master Sergeant (E- 9... Guard personnel grades airman basic E-1 through general O-10.'' * * * * * [FR Doc. 2012-22580 Filed...

  12. 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.

  13. A simple method for the simultaneous detection of E1A and E1B in adenovirus stocks.

    PubMed

    Suzuki, Erika; Murata, Takehide; Watanabe, Sanae; Kujime, Yukari; Hirose, Megumi; Pan, Jianzhi; Yamazaki, Takahito; Ugai, Hideyo; Yokoyama, Kazunari K

    2004-01-01

    Recombinant adenoviral vectors have been developed for use as therapeutic agents and for the introduction of exogenous genes into living cells. However, the occurrence of replication-competent adenoviruses (RCA) in adenovirus stocks produced in 293 cells remains a major problem in terms of the safe use of such vectors. To overcome the problems associated with the occurrence of RCA, we have established a simple method for the simultaneous detection of amplified E1A and E1B from RCA that might contaminate adenoviral stocks. The products amplified by polymerase chain reaction (PCR) were fractionated by regular electrophoresis on agarose gels and visualized by staining with ethidium bromide. This method is rapid and inexpensive for detection of RCA in the preparation of adenoviruses.

  14. 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

    ... period of 60 months to the University of North Carolina at Charlotte to carry out the National Secondary... educational agencies (LEAs) to advance implementation of effective transition planning and services. NSTTAC's... changes being made to the Elementary and Secondary Education Act (ESEA) during the process...

  15. 75 FR 3962 - Notice of Availability of a Record of Decision (ROD) for the Proposed Bay Area Rapid Transit...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-25

    ... Area Rapid Transit (BART) Connector Project at Oakland International Airport (OAK), Oakland, Alameda... for the proposed construction and operation of the proposed BART connector project at OAK. The ROD evaluated the proposed BART-OAK connector project at OAK, Oakland, Alameda County, California. SUPPLEMENTARY...

  16. 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

    ... Hospital to Home'' Authority: 15 U.S.C. 3719. AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice. SUMMARY: The ``Ensuring Safe Transitions from Hospital to Home... five patients discharged from a hospital will be readmitted within 30 days. A large proportion of...

  17. 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

    ...: Mail Delivery service through Wounded Warrior Task Force, Hoffman Building II, 200 Stoval St... policies and programs relating to the care, management and transition of recovering service members and... support programs provided by the Military Services and the DoD. In addition, the Task Force will...

  18. 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

    ... 1:00 p.m.-3:00 p.m. Defense Centers of Excellence for Psychological Health and Traumatic Brain... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary Department of Defense Task Force on the Care, Management, and Transition...

  19. 77 FR 75150 - Department of Defense Task Force on the Care, Management, and Transition of Recovering Wounded...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-19

    .... Break 2:45 p.m.-4:45 p.m. Defense Centers of Health on Psychological Health and Traumatic Brain Injury... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary Department of Defense Task Force on the Care, Management, and Transition...

  20. 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

    ... COMMISSION Draft Regulatory Guide, DG-1216,''Plant-Specific Applicability of Transition Break Size Specified in 10 CFR 50.46a.'' Issuance, Availability; Extension of Comment Period AGENCY: Nuclear Regulatory Commission. ACTION: Extension of comment period. FOR FURTHER INFORMATION CONTACT: Robert Tregoning, U.S...

  1. 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, and...

  2. 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

    .... SUPPLEMENTARY INFORMATION: A. Background Section 716 of the Dodd-Frank Wall Street Reform and Consumer... Office of the Comptroller of the Currency Transition Period Under Section 716 of the Dodd-Frank Wall Street Reform and Consumer Protection Act AGENCY: Office of the Comptroller of the Currency,...

  3. A large scale virtual screen of DprE1.

    PubMed

    Wilsey, Claire; Gurka, Jessica; Toth, David; Franco, Jimmy

    2013-12-01

    Tuberculosis continues to plague the world with the World Health Organization estimating that about one third of the world's population is infected. Due to the emergence of MDR and XDR strains of TB, the need for novel therapeutics has become increasing urgent. Herein we report the results of a virtual screen of 4.1 million compounds against a promising drug target, DrpE1. The virtual compounds were obtained from the Zinc docking site and screened using the molecular docking program, AutoDock Vina. The computational hits have led to the identification of several promising lead compounds.

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

    NASA Image and Video Library

    2010-03-30

    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.

  5. 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.

  6. Dissecting the roles of E1A and E1B in adenoviral replication and RCAd-enhanced RDAd transduction efficacy on tumor cells

    PubMed Central

    Wei, Fang; Wang, Huiping; Chen, Xiafang; Li, Chuanyuan; Huang, Qian

    2014-01-01

    Oncolytic viruses have recently received widespread attention for their potential in innovative cancer therapy. Many telomerase promoter-regulated oncolytic adenoviral vectors retain E1A and E1B. However, the functions of E1A and E1B proteins in the oncolytic role of replication-competent adenovirus (RCAd) and RCAd enhanced transduction of replication defective adenoviruses (RDAd) have not been addressed well. In this study, we constructed viruses expressing E1A alone, E1A plus E1B-19 kDa, and E1A plus E1B-19 kDa/55 kDa. We then tested their roles in oncolysis and replication of RCAd as well as their roles in RCAd enhanced transfection rate and transgene expression of RDAd in various cancer cells in vitro and in xenografted human NCI-H460 tumors in nude mice. We demonstrated that RCAds expressing E1A alone and plus E1B-19 kDa exhibited an obvious ability in replication and oncolytic effects as well as enhanced RDAd replication and transgene expression, with the former showed more effective oncolysis, while the latter exhibited superior viral replication and transgene promotion activity. However, RCAd expressing both E1A and E1B-19 kDa/55 kDa was clearly worst in all these abilities. The effects of E1A and E1B observed through using RCAd were further validated by using plasmids expressing E1A alone, E1A plus E1B-19 kDa, and E1A plus E1B-19 kDa/55 kDa proteins. Our study provided evidence that E1A was essential for inducing replication and oncolytic effects of RCAd as well as RCAd enhanced RDAd transduction, and expression of E1B-19 kDa other than E1B-55 kDa could promote these effects. E1B-55 kDa is not necessary for the oncolytic effects of adenoviruses and somehow inhibits RCAd-mediated RDAd replication and transgene expression. PMID:25019940

  7. Population gradients and photometric metallicities in early- and transition-type dwarf galaxies: Clues from the Sculptor group

    NASA Astrophysics Data System (ADS)

    Lianou, S.; Grebel, E. K.; Da Costa, G. S.; Rejkuba, M.; Jerjen, H.; Koch, A.

    2013-02-01

    Aims: We focus on the resolved stellar populations of one early-type and four transition-type dwarf galaxies in the Sculptor group, with the aim to examine the potential presence of population gradients and place constraints on their mean metallicities. Methods: We use deep Hubble Space Telescope images to construct color-magnitude diagrams, from which we select stellar populations that trace different evolutionary phases in order to constrain their range of ages and metallicities, as well as to examine their spatial distribution. In addition, we use the resolved stars in the red giant branch in order to derive photometric metallicities. Results: All studied dwarfs contain intermediate-age stars with ages of ~1 Gyr and older as traced by the luminous asymptotic giant branch and red clump stars, while the transition-type dwarfs contain also stars younger than ~1 Gyr as traced by a young main sequence and vertical red clump stars. Moreover, the spatial distribution of the stars that trace different evolutionary phases shows a population gradient in all transition-type dwarfs. The derived error-weighted mean metallicities, assuming purely old stellar populations, range from -1.5 dex for ESO294-G010 to -1.9 dex for Scl-dE1, and should be considered as lower limits to their true metallicities. Assuming intermediate-age stellar populations to dominate the dwarfs, we derive upper limits for the metallicities that are 0.3 to 0.2 dex higher than the metallicities derived assuming purely old populations. We discuss how photometric metallicity gradients are affected by the age-metallicity degeneracy, which prevents strong conclusions regarding their actual presence. Finally, the transition-type dwarfs lie beyond the virial radius of their closest bright galaxy, as also observed for the Local Group transition-type dwarfs. Scl-dE1 is the only dwarf spheroidal in our sample and is an outlier in a potential morphology-distance relation, similar as the two isolated dwarf

  8. 76 FR 75942 - Qualification of Drivers; Exemption Applications; Vision

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-05

    ... 10471; 67 FR 19798; 68 FR 54775;68 FR 64944; 68 FR 69434; 69 FR 19611; 70 FR 30999; 70 FR 46567; 70 FR 48797; 70 FR 53412; 70 FR 57353; 70 FR 61493; 70 FR 67776; 70 FR 72689; 70 FR 74102; 72 FR 39879; 72 FR... on January 17, 2008 (73 FR 3316), or you may visit http://edocket.access.gpo.gov/2008/pdf/E8-785.pdf...

  9. 76 FR 34133 - Qualification of Drivers; Exemption Applications; Vision

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-10

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  10. 76 FR 55467 - Qualification of Drivers; Exemption Applications; Vision

    Federal Register 2010, 2011, 2012, 2013, 2014

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  11. 78 FR 26106 - Qualification of Drivers; Exemption Applications; Vision

    Federal Register 2010, 2011, 2012, 2013, 2014

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  12. Is Comet C/1853 E1 (Secchi) extrasolar?

    NASA Astrophysics Data System (ADS)

    Branham, R. L., Jr.

    2012-02-01

    Comet C/1853 E1 (Secchi) has a hyperbolic orbit with eccentricity 1.01060 and perihelion outside of the Earth's orbit. Integrating the orbit with barycentric coordinates backwards to 50 000 AU, the approximate edge of the Oort cloud, shows that the orbit remains hyperbolic. This is still true even if plutoids additional to Pluto are included in the integration. Nor does including Galactic tidal and disc effects and possible nongravitational forces change the orbit to a high eccentricity ellipse. Although certain factors, such as unknown massive plutoids, gravitational effects by interstellar gas clouds, or unmodelled nongravitational forces operating on the comet, could change this situation, the tentative conclusion that the origin of this comet is extrasolar remains the one most consistent with the observations.

  13. Temperature regulation and prostaglandin E1 fever in scorpions.

    PubMed Central

    Cabanac, M; Le Guelte, L

    1980-01-01

    1. Scorpions Buthus occitanus and Androctonus australis were placed in a temperature gradient where they could select their thermopreferendum. Intrathoracic temperature was recorded continuously. 2. Both species selected 24.8 +/- 1.0 degrees C as their preferred body temperature. No nycthemeral cycle of preference was observed in the experimental conditions. Saline injection did not modify this thermopreferendum. 3. Prostaglandin E1 (PGE1) produced a fever. Duration and magnitude of fevers were related to PGE1 doses in a bell-shaped curve. The longest and highest fevers were obtained with 4 microgram . g-1 PGE1. 4. These results show that there is an ability to produce fever and, thus, indirectly, that there is a set point in body temperature regulation in arthropods, among the oldest known terrestrial animals. PMID:7431238

  14. Photoneutron studies of E1, M1, and E2 excitations in /sup 13/C

    SciTech Connect

    Holt, R.J.; Laszewski, R.M.; Jackson, H.E.; Monahan, J.E.; Specht, J.R.

    1980-05-01

    The angular distribution for the /sup 13/C(..gamma..,n/sub 0/)/sup 12/C reaction was observed in the energy region 6.5 to 9.3 MeV and at angles of 90/sup 0/ and 135/sup 0/. The photoneutron measurements were analyzed in terms of a multilevel R-matrix formalism. The /sup 12/C(n,n)/sup 12/C reaction channel was explicitly included in this analysis. The effects of potential capture were directly observed in the photoneutron spectra. The ground-state radiative widths for resonances in this energy region were deduced from the R-matrix interpretation of the results. The ground-state transition probabilities for E1 excitations at 7.69 and 8.19 MeV were found to be in good agreement with the predictions of the weak-coupling model.

  15. Toroidal, compressive, and E 1 properties of low-energy dipole modes in 10Be

    NASA Astrophysics Data System (ADS)

    Kanada-En'yo, Yoshiko; Shikata, Yuki

    2017-06-01

    We studied dipole excitations in 10Be based on an extended version of the antisymmetrized molecular dynamics, which can describe 1p-1h excitations and large amplitude cluster modes. Toroidal and compressive dipole operators are found to be good proves to separate the low-energy and high-energy parts of the isoscalar dipole excitations, respectively. Two low-energy 1- states, the toroidal dominant 11- state at E ˜8 MeV and the E 1 dominant 12- state at E ˜16 MeV, were obtained. By analysis of transition current densities, the 11- state is understood as a toroidal dipole mode with exotic toroidal neutron flow caused by rotation of a deformed 6He cluster, whereas the 12- state is regarded as a neutron-skin oscillation mode, which are characterized by surface neutron flow with inner isoscalar flow caused by the surface neutron oscillation against the 2 α core.

  16. Atomic data from the Iron Project. XLIV. Transition probabilities and line ratios for Fe VI with fluorescent excitation in planetary nebulae

    NASA Astrophysics Data System (ADS)

    Chen, Guo Xin; Pradhan, Anil K.

    2000-11-01

    Relativistic atomic structure calculations for electric dipole (E1), electric quadrupole (E2) and magnetic dipole (M1) transition probabilities among the first 80 fine-structure levels of Fe VI, dominated by configurations 3d3, 3d24s, and 3d24p, are carried out using the Breit-Pauli version of the code SUPERSTRUCTURE. Experimental energies are used to improve the accuracy of these transition probabilities. Employing the 80-level collision-radiative (CR) model with these dipole and forbidden transition probabilities, and Iron Project R-matrix collisional data, we present a number of [Fe VI] line ratios applicable to spectral diagnostics of photoionized H II regions. It is shown that continuum fluorescent excitation needs to be considered in CR models in order to interpret the observed line ratios of optical [Fe VI] lines in planetary nebulae NGC 6741, IC 351, and NGC 7662. The analysis leads to parametrization of line ratios as function of, and as constraints on, the electron density and temperature, as well as the effective radiation temperature of the central source and a geometrical dilution factor. The spectral diagnostics may also help ascertain observational uncertainties. The method may be generally applicable to other objects with intensive background radiation fields, such as novae and active galactic nuclei. The extensive new Iron Project radiative and collisional calculations enable a consistent analysis of many line ratios for the complex iron ions. The complete tables of transition probabilities are only available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsweb.u-strasbg.fr/Abstract.html.

  17. Tumorigenicity and adenovirus-transformed cells: Collagen interaction and cell surface laminin are controlled by the serotype origin of the E1A and E1B genes

    SciTech Connect

    Bober, F.J.; Birk, D.E.; Raska, K. Jr. ); Shenk, T. )

    1988-02-01

    A library of cells transformed with recombinant adenoviruses was used to study tumorigenicity and interaction with extracellular matrix. Cells expressing the complete E1 region of highly oncogenic adenovirus type 12 (Ad12) are tumorigenic, adhere preferentially to type IV collagen, and express cell surface laminin. Weakly tumorigenic cells, which express the E1A oncogene of Ad12 and the E1B genes of Ad5, also attach preferentially to type IV collagen but do not contain laminin on their surface. Cells which express the E1A oncogene of Ad5 and the E1B genes of Ad12 are nontumorigenic and do not preferentially attach to type IV versus type I collagen but have laminin on their surface. There is no significant difference in the amounts of laminin secreted into the culture medium among cells expressing the E1B genes of Ad5 or Ad12. In vitro assays show that cells which express the E1B genes of Ad12, irrespective of the origin of the E1A genes, can bind three times more exogenously added {sup 125}I-laminin than cells expressing the E1B genes of nononcogenic Ad5. The interaction of adenovirus-transformed cells with collagen is controlled by the serotype origin of the E1A oncogene, whereas cell surface laminin is controlled by the serotype origin of the E1B genes.

  18. 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.

  19. 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.

  20. 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.

  1. The Role of Polyunsaturated ω-3 Fatty Acid Eicosapentaenoic Acid–Derived Resolvin E1 (RvE1) in Bone Preservation

    PubMed Central

    Gyurko, Robert; Van Dyke, Thomas E.

    2014-01-01

    Resolvin E1 (RvE1) is a recently discovered lipid-derived mediator that is endogenously synthesized from the polyunsaturated fatty acid eicosapentaenoic acid. RvE1 is locally generated in response to inflammation where it enhances the resolution phase of inflammation by diminishing neutrophil chemotaxis and by enhancing nonphlogistic macrophage-directed clearance of apoptotic neutrophils. RvE1 was also found to be effective in preventing and restoring bone loss in the inflammatory bone disease periodontitis. This review examines experimental evidence on RvE1's actions in bone. Current data indicate that in addition to anti-inflammatory actions, RvE1 also directly acts on bone cells and promotes bone preservation. PMID:24941160

  2. 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

  3. Conformational anti-cytochrome P4502E1 (CYP2E1) auto-antibodies contribute to necro-inflammatory injury in chronic hepatitis C.

    PubMed

    Sutti, S; Vidali, M; Mombello, C; Sartori, M; Albano, E

    2010-10-01

    Circulating auto-antibodies against cytochrome P4502E1 (CYP2E1) have been observed in a significant fraction of patients with chronic hepatitis C (CHC). This study investigated the clinical significance of these auto-antibodies in relation to their antigen specificity. The presence of anti-CYP2E1 IgG was investigated in 137 consecutive patients with biopsy-proven CHC. Anti-CYP2E1 IgG above control threshold levels was detected in 52 (38%) subjects. By combined immunoprecipitation and western blotting, we observed that among anti-CYP2E1 IgG-positive sera, 23 (44%) were unreactive towards denaturated CYP2E1, indicating a prevalent recognition of conformational CYP2E1 antigens. Conformational anti-CYP2E1 auto-antibodies were unrelated to circulating gamma-globulins, alcohol intake or infection by specific HCV genotypes. The presence of anti-CYP2E1 auto-antibodies was associated with an 11-fold (OR 10.9 95%CI 1.4-86.6 P = 0.008) increased prevalence of necro-inflammatory grading ≥ 4 (Ishack's criteria) and 4-fold (OR 4.0; 95%CI 1.3-11-7: P = 0.014) increased prevalence of fibrosis staging ≥ 2, respectively. Multivariate analysis confirmed conformational anti-CYP2E1 IgG (P = 0.005) and age (P = 0.033) as independent predictors of necro-inflammatory grading ≥ 4. The development of anti-CYP2E1 auto-antibodies targeting conformational CYP2E1 epitopes is associated with more severe liver damage in CHC.

  4. 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…

  5. 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

  6. 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.

  7. 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

  8. A plasma β transition within a propagating flux rope

    SciTech Connect

    Savani, N. P.; Vourlidas, A.; Linton, M. G.; Shiota, D.; Kusano, K.; Lugaz, N.; Rouillard, A. P.

    2013-12-20

    We present a 2.5 dimensional magnetohydrodynamic simulation of a magnetic flux rope (FR) propagating in the heliosphere and investigate the cause of the observed sharp plasma β transition. Specifically, we consider a strong internal magnetic field and an explosive fast start, such that the plasma β is significantly lower in the FR than in the sheath region that is formed ahead. This leads to an unusual FR morphology in the first stage of propagation, while the more traditional view (e.g., from space weather simulations like Enlil) of a pancake-shaped FR is observed as it approaches 1 AU. We investigate how an equipartition line, defined by a magnetic Weber number, surrounding a core region of a propagating FR, can demarcate a boundary layer where there is a sharp transition in the plasma β. The substructure affects the distribution of toroidal flux, with the majority of the flux remaining in a small core region that maintains a quasi-cylindrical structure. We quantitatively investigate a locus of points where the kinetic energy density of the relative inflow field is equal to the energy density of the transverse magnetic field (i.e., effective tension force). The simulation provides compelling evidence that at all heliocentric distances the distribution of toroidal magnetic flux away from the FR axis is not linear, with 80% of the toroidal flux occurring within 40% of the distance from the FR axis. Thus, our simulation displays evidence that the competing ideas of a pancaking structure observed remotely can coexist with a quasi-cylindrical magnetic structure seen in situ.

  9. E1-E2 interactions in ubiquitin and Nedd8 ligation pathways.

    PubMed

    Tokgöz, Zeynep; Siepmann, Thomas J; Streich, Frederick; Kumar, Brajesh; Klein, Jennifer M; Haas, Arthur L

    2012-01-02

    Initial rates of E1-catalyzed E2 transthiolation have been used as a reporter function to probe the mechanism of 125I-ubiquitin transfer between activation and ligation half-reactions of ubiquitin conjugation. A functional survey of 11 representative human E2 paralogs reveals similar Km for binding to human Uba1 ternary complex (Km(ave)=121±72 nm) and kcat for ubiquitin transfer (kcat(ave)=4.0±1.2 s(-1)), suggesting that they possess a conserved binding site and transition state geometry and that they compete for charging through differences in intracellular concentration. Sequence analysis and mutagenesis localize this binding motif to three basic residues within Helix 1 of the E2 core domain, confirmed by transthiolation kinetics. Partial conservation of the motif among E2 paralogs not recognized by Uba1 suggests that another factor(s) account for the absolute specificity of cognate E2 binding. Truncation of the Uba1 carboxyl-terminal β-grasp domain reduces cognate Ubc2b binding by 31-fold and kcat by 3.5×10(4)-fold, indicating contributions to E2 binding and transition state stabilization. Truncation of the paralogous domain from the Nedd8 activating enzyme has negligible effect on cognate Ubc12 transthiolation but abrogates E2 specificity toward non-cognate carrier proteins. Exchange of the β-grasp domains between ubiquitin and Nedd8 activating enzymes fails to reverse the effect of truncation. Thus, the conserved Helix 1 binding motif and the β-grasp domain direct general E2 binding, whereas the latter additionally serves as a specificity filter to exclude charging of non-cognate E2 paralogs in order to maintain the fidelity of downstream signaling.

  10. Sensitivity, changeover responses, and choice in transition.

    PubMed

    Jiménez, Angel A; Aparicio, Carlos F

    2009-09-01

    Studies of choice in steady state have shown that sensitivity to reinforcement increases with increasing fixed-ratio changeover (FR CO) requirements. We assessed the generality of this finding with choice in transition. Food deliveries were programmed according to concurrent variable-interval (VI) schedules. Seven different VI pairs arranged ratios of food deliveries (left/right) of 27:1, 9:1, 3:1, 1:1, 1:3, 1:9, and 1:27 at a constant overall rate across components. Within sessions, all seven ratios were presented in random order. Each component lasted for 10 food deliveries; components were separated by 60-s blackouts. A changeover lever required 1, 2, 4, 8, 16, 32, and 64 responses to alternate between two main levers. Redeterminations to all FR COs, but 64 responses, were obtained in descending order. Choice adjusted rapidly to rapid changes in the reinforcer ratio, tracking the lever associated with the highest probability of reinforcer. Sensitivity to reinforcement increased with increasing FR CO, replicating the negatively accelerated function found in our earlier study. With successive reinforcers in components, however, sensitivity reached asymptote values sooner with the largest (8, 16, and 32 responses), than with the smallest (1, 2, and 4 responses), FR CO requirements.

  11. High temperature x-ray diffraction studies on antiferroelectric and ferroelectric phase transitions in (Pb1-xBax)ZrO3 (x=0.05,0.10)

    NASA Astrophysics Data System (ADS)

    Pokharel, Bhadra P.; Pandey, Dhananjai

    2001-09-01

    We have carried out high temperature x-ray diffraction studies on (Pb1-xBax)ZrO3(PBZ) to correlate the large thermal hysteresis (˜100 °C for x=0.05) and irreversibility (for x=0.10) of the antiferroelectric (AFE)-ferroelectric (FE) phase transition observed in dielectric measurements with structural changes. It is shown that for both the compositions, the sequence of phase transitions during heating is orthorhombic antiferroelectric (AO) to rhombohedral ferroelectric (FR) and then to cubic paraelectric (PC). The wide phase coexistence region (˜80 °C for x=0.05 and ˜160 °C for x=0.10) and the arrest of the FR to AO transition for x=0.10 during cooling strongly indicate first order character of the AO-FR transition. It is shown that the transformation strains associated with the AO to FR transition increases with Ba2+ concentration from a value of 0.6% for x=0 to 0.9% for 0.10. Similarities of the AO-FR transition in PBZ with nonthermoelastic martensitic transformations are pointed out. The FR to PC transition is also shown to be first order but with a small thermal hysteresis (˜10 °C) and a small discontinuous change in the cell volume (˜0.5%).

  12. Identification of a Nuclear Export Signal Sequence for Bovine Papillomavirus E1 Protein

    PubMed Central

    Rosas-Acosta, Germán; Wilson, Van G.

    2008-01-01

    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 the 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 pulldown assays. 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 wildtype E1, yet was defective for viral origin replication, implying that nucleocytoplasmic shuttling may be required to maintain E1 in a replication competent state. PMID:18201744

  13. 26 CFR 1.263(e)-1 - Expenditures in connection with certain railroad rolling stock.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 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 § 1.263(e)-1... section 263(e), for any taxable year beginning after December 31, 1969, a taxpayer may elect to...

  14. Novel mechanism of JNK pathway activation by adenoviral E1A.

    PubMed

    Romanov, Vasily S; Brichkina, Anna I; Morrison, Helen; Pospelova, Tatiana V; Pospelov, Valery A; Herrlich, Peter

    2014-04-30

    The adenoviral oncoprotein E1A influences cellular regulation by interacting with a number of cellular proteins. In collaboration with complementary oncogenes, E1A fully transforms primary cells. As part of this action, E1A inhibits transcription of c-Jun:Fos target genes while promoting that of c-Jun:ATF2-dependent genes including jun. Both c-Jun and ATF2 are hyperphosphorylated in response to E1A. In the current study, E1A was fused with the ligand binding domain of the estrogen receptor (E1A-ER) to monitor the immediate effect of E1A activation. With this approach we now show that E1A activates c-Jun N-terminal kinase (JNK), the upstream kinases MKK4 and MKK7, as well as the small GTPase Rac1. Activation of the JNK pathway requires the N-terminal domain of E1A, and, importantly, is independent of transcription. In addition, it requires the presence of ERM proteins. Downregulation of signaling components upstream of JNK inhibits E1A-dependent JNK/c-Jun activation. Taking these findings together, we show that E1A activates the JNK/c-Jun signaling pathway upstream of Rac1 in a transcription-independent manner, demonstrating a novel mechanism of E1A action.

  15. 17 CFR 270.30e-1 - Reports to stockholders of management companies.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... management companies. 270.30e-1 Section 270.30e-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.30e-1 Reports to stockholders of management companies. (a) Every registered management company shall transmit to...

  16. 40 CFR Figure E-1 to Subpart E of... - Designation Testing Checklist

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 6 2014-07-01 2014-07-01 false Designation Testing Checklist E Figure E-1 to Subpart E of Part 53 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Equivalent Methods for PM 2.5 or PM 10-2.5 Pt. 53, Subpt. E, Fig. E-1 Figure E-1 to Subpart E of Part 53...

  17. 40 CFR Figure E-1 to Subpart E of... - Designation Testing Checklist

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 6 2012-07-01 2012-07-01 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 53...

  18. 40 CFR Figure E-1 to Subpart E of... - Designation Testing Checklist

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 6 2013-07-01 2013-07-01 false Designation Testing Checklist E Figure E-1 to Subpart E of Part 53 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Equivalent Methods for PM 2.5 or PM 10-2,5 Pt. 53, Subpt. E, Fig. E-1 Figure E-1 to Subpart E of Part 53...

  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, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 5 2011-07-01 2011-07-01 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 53...

  1. 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 meet...

  2. 26 CFR 301.6229(e)-1 - Information with respect to unidentified partner.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ....6229(e)-1 Information with respect to unidentified partner. (a) In general. A partner who is not properly identified on the partnership return (including an indirect partner) remains an unidentified... partner. 301.6229(e)-1 Section 301.6229(e)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF...

  3. 26 CFR 301.6229(e)-1 - Information with respect to unidentified partner.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ....6229(e)-1 Information with respect to unidentified partner. (a) In general. A partner who is not properly identified on the partnership return (including an indirect partner) remains an unidentified... partner. 301.6229(e)-1 Section 301.6229(e)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF...

  4. Facile synthesis of covalent probes to capture enzymatic intermediates during E1 enzyme catalysis.

    PubMed

    An, Heeseon; Statsyuk, Alexander V

    2016-02-11

    We report a facile synthetic strategy to prepare UBL-AMP electrophilic probes that form a covalent bond with the catalytic cysteine of cognate E1s, mimicking the tetrahedral intermediate of the E1-UBL-AMP complex. These probes enable the structural and biochemical study of both canonical- and non-canonical E1s.

  5. 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...

  6. 26 CFR 1.691(e)-1 - Installment obligations transmitted at death when prior law applied.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... when prior law applied. 1.691(e)-1 Section 1.691(e)-1 Internal Revenue INTERNAL REVENUE SERVICE... Decedents § 1.691(e)-1 Installment obligations transmitted at death when prior law applied. (a) In general—(1) Application of prior law. Under section 44(d) of the Internal Revenue Code of 1939 and...

  7. 26 CFR 1.691(e)-1 - Installment obligations transmitted at death when prior law applied.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... when prior law applied. 1.691(e)-1 Section 1.691(e)-1 Internal Revenue INTERNAL REVENUE SERVICE... Decedents § 1.691(e)-1 Installment obligations transmitted at death when prior law applied. (a) In general—(1) Application of prior law. Under section 44(d) of the Internal Revenue Code of 1939 and...

  8. 26 CFR 1.691(e)-1 - Installment obligations transmitted at death when prior law applied.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... when prior law applied. 1.691(e)-1 Section 1.691(e)-1 Internal Revenue INTERNAL REVENUE SERVICE....691(e)-1 Installment obligations transmitted at death when prior law applied. (a) In general—(1) Application of prior law. Under section 44(d) of the Internal Revenue Code of 1939 and corresponding...

  9. 26 CFR 1.691(e)-1 - Installment obligations transmitted at death when prior law applied.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... when prior law applied. 1.691(e)-1 Section 1.691(e)-1 Internal Revenue INTERNAL REVENUE SERVICE... Decedents § 1.691(e)-1 Installment obligations transmitted at death when prior law applied. (a) In general—(1) Application of prior law. Under section 44(d) of the Internal Revenue Code of 1939 and...

  10. 26 CFR 1.691(e)-1 - Installment obligations transmitted at death when prior law applied.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... when prior law applied. 1.691(e)-1 Section 1.691(e)-1 Internal Revenue INTERNAL REVENUE SERVICE... Decedents § 1.691(e)-1 Installment obligations transmitted at death when prior law applied. (a) In general—(1) Application of prior law. Under section 44(d) of the Internal Revenue Code of 1939 and...

  11. 76 FR 15360 - Qualification of Drivers; Exemption Applications; Vision

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-21

    ...; 68 FR 13360; 68 FR 15037; 69 FR 52741; 70 FR 12265; 70 FR 14747; 70 FR 16887; 70 FR 2701; 70 FR 7545... Federal Register on January 17, 2008 (73 FR 3316), or you may visit http://edocket.access.gpo.gov/2008/pdf... exemption from the vision requirements (63 FR 66226; 64 FR 16517; 65 FR 20245; 65 FR 57230; 65 FR 66286; 65...

  12. [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.

  13. UV-crosslinking of E1 small nucleolar RNA to proteins in frog oocytes.

    PubMed

    Smith, James L; Walton, Andrew H; Eliceiri, George L

    2005-04-01

    E1/U17 small nucleolar RNA (snoRNA) is a box H/ACA snoRNA. To detect protein bands that UV-crosslink to E1 RNA primarily at uridines, frog oocytes were injected with [alpha-32P]UTP-labeled E1 RNA and incubated, isolated nuclei were UV irradiated, and nuclear contents were digested with RNase A. Wild-type E1 RNA specifically UV-crosslinked to several protein bands. To identify E1 RNA sites involved in these interactions, we tested 21 E1 RNA mutants, each consisting of substitutions in a conserved sequence or structure. UV-crosslinking of different protein bands to E1 RNA depended on one of the following sets of conserved E1 RNA segments: two 5' end RNA sites; five 5' half RNA sites; two 3' half RNA sites; or 14 sites located throughout E1 RNA. Of these conserved E1 RNA sites, UV-crosslinking apparently depended on sequences at 11 sites, and structures at 2 sites. Gel electrophoresis with and without RNA competition detected protein bands that are not common to all of the box H/ACA snoRNAs. 2004 Wiley-Liss, Inc.

  14. 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.

  15. Work transitions.

    PubMed

    Fouad, Nadya A; Bynner, John

    2008-01-01

    Individuals make choices in, and adjust to, a world of work that is often a moving target. Because work is so central to human functioning, and transitions in and out of work can have major mental health repercussions, the authors argue that applied psychologists in health services need to understand those transitions. This article focuses on the different types of transition throughout a person's working life and the resources needed at different stages to ensure the success of these transitions. The authors start by examining the roles of capability and adaptability in supporting and facilitating adjustment to work transitions and their relation to identity development. They then examine the role of social and institutional contexts in shaping work transitions and their outcomes. The authors focus on voluntary versus involuntary transitions and then broaden the lens in discussing the policy implications of research on work transitions.

  16. The Role of CYP2E1 in the Drug Metabolism or Bioactivation in the Brain.

    PubMed

    García-Suástegui, W A; Ramos-Chávez, L A; Rubio-Osornio, M; Calvillo-Velasco, M; Atzin-Méndez, J A; Guevara, J; Silva-Adaya, D

    2017-01-01

    Organisms have metabolic pathways that are responsible for removing toxic agents. We always associate the liver as the major organ responsible for detoxification of the body; however this process occurs in many tissues. In the same way, as in the liver, the brain expresses metabolic pathways associated with the elimination of xenobiotics. Besides the detoxifying role of CYP2E1 for compounds such as electrophilic agents, reactive oxygen species, free radical products, and the bioactivation of xenobiotics, CYP2E1 is also related in several diseases and pathophysiological conditions. In this review, we describe the presence of phase I monooxygenase CYP2E1 in regions of the brain. We also explore the conditions where protein, mRNA, and the activity of CYP2E1 are induced. Finally, we describe the relation of CYP2E1 in brain disorders, including the behavioral relations for alcohol consumption via CYP2E1 metabolism.

  17. The Role of CYP2E1 in the Drug Metabolism or Bioactivation in the Brain

    PubMed Central

    García-Suástegui, W. A.; Ramos-Chávez, L. A.; Rubio-Osornio, M.; Calvillo-Velasco, M.; Atzin-Méndez, J. A.; Guevara, J.

    2017-01-01

    Organisms have metabolic pathways that are responsible for removing toxic agents. We always associate the liver as the major organ responsible for detoxification of the body; however this process occurs in many tissues. In the same way, as in the liver, the brain expresses metabolic pathways associated with the elimination of xenobiotics. Besides the detoxifying role of CYP2E1 for compounds such as electrophilic agents, reactive oxygen species, free radical products, and the bioactivation of xenobiotics, CYP2E1 is also related in several diseases and pathophysiological conditions. In this review, we describe the presence of phase I monooxygenase CYP2E1 in regions of the brain. We also explore the conditions where protein, mRNA, and the activity of CYP2E1 are induced. Finally, we describe the relation of CYP2E1 in brain disorders, including the behavioral relations for alcohol consumption via CYP2E1 metabolism. PMID:28163821

  18. 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 amount...

  19. [Transgenic plant regeneration of tobacco (Nicotiana tabacum) haboring mammalian cyp2e1 gene].

    PubMed

    Li, Peihan; Xiang, Taihe; Xie, Jun; Feng, Ting; Lu, Wenyi

    2012-10-01

    CYP2E1 enzyme encoded by cyp2e1 gene plays an important role in metabolism of heterogeneous organics in mammalian liver cells. The transgenic plant with cyp2e1 can metabolize various low molecular weight organic pollutants. However, it is unclear the mechanism of expression control of cyp2e1 in transgenic plant. In this study, plasmid pSLD50-6 with cyp2e1 and pKH200 with gus as control were transformed into Agrobacterium tumefaciens GV3101 separately. Then, the cyp2e1 or gus genes were transferred into tobacco (Nicotiana tabacum) and the transgenic plants were regenerated via Agrobacterium tumefaciens method. Real-time quantitative PCR (qRT-PCR) was used to analyze the cyp2e1 gene expression. The expression of cyp2e1 in transgenic tobacco with cyp2e1 decreased obviously treated by ethyl alcohol and reduced slightly by benzene and toluene, while it enhanced by acetone, formaldehyde and oxygen deficit in different levels. In addition, the gene expression of NADPH-P450 oxidoreductase and cytochrome b5 enzyme in the transgenic tobacco with cyp2e1 were increased significantly treated by benzene, which showed that NADPH-P450 oxidoreductase and cytochrome b5 enzyme in transgenic tobacco have relation with CYP2E1 detoxication process. It suggested that the NADPH-P450 oxidoreductase and cytochrome b5 enzyme in transgenic plant formed the requirement in mammalian and participated in the electron transport chain of CYP2E1 enzyme catalytic process.

  20. CYP2E1-dependent hepatotoxicity and oxidative damage after ethanol administration in human primary hepatocytes

    PubMed Central

    Liu, Lie-Gang; Yan, Hong; Yao, Ping; Zhang, Wen; Zou, Li-Jun; Song, Fang-Fang; Li, Ke; Sun, Xiu-Fa

    2005-01-01

    AIM: To observe the relationship between ethanol-induced oxidative damage in human primary cultured hepatocytes and cytochrome P450 2E1 (CYP2E1) activity, in order to address if inhibition of CYP2E1 could attenuate ethanol-induced cellular damage. METHODS: The dose-dependent (25-100 mmol/L) and time-dependent (0-24 h) exposures of primary human cultured hepatocytes to ethanol were carried out. CYP2E1 activity and protein expression were detected by spectrophotometer and Western blot analysis respectively. Hepatotoxicity was investigated by determination of lactate dehydrogenase (LDH) and aspartate transaminase (AST) level in hepatocyte culture supernatants, as well as the intracellular formation of malondialdehyde (MDA). RESULTS: A dose-and time-dependent response between ethanol exposure and CYP2E1 activity in human hepatocytes was demonstrated. Moreover, there was a time-dependent increase of CYP2E1 protein after 100 mmol/L ethanol exposure. Meanwhile, ethanol exposure of hepatocytes caused a time-dependent increase of cellular MDA level, LDH, and AST activities in supernatants. Furthermore, the inhibitor of CYP2E1, diallyl sulfide (DAS) could partly attenuate the increases of MDA, LDH, and AST in human hepatocytes. CONCLUSION: A positive relationship between ethanol-induced oxidative damage in human primary cultured hepatocytes and CYP2E1 activity was exhibited, and the inhibition of CYP2E1 could partly attenuate ethanol-induced oxidative damage. PMID:16052683

  1. Methodology to assay CYP2E1 mixed function oxidase catalytic activity and its induction

    PubMed Central

    Cederbaum, Arthur I.

    2014-01-01

    The cytochrome P450 mixed function oxidase enzymes are the major catalysts involved in drug metabolism. There are many forms of P450. CYP2E1 metabolizes many toxicologically important compounds including ethanol and is active in generating reactive oxygen species. Since several of the contributions in the common theme series “Role of CYP2E1 and Oxidative/Nitrosative Stress in the Hepatotoxic Actions of Alcohol” discuss CYP2E1, this methodology review describes assays on how CYP2E1 catalytic activity and its induction by ethanol and other inducers can be measured using substrate probes such as the oxidation of para-nitrophenol to para-nitrocatechol and the oxidation of ethanol to acetaldehyde. Approaches to validate that a particular reaction e.g. oxidation of a drug or toxin is catalyzed by CYP2E1 or that induction of that reaction is due to induction of CYP2E1 are important and specific examples using inhibitors of CYP2E1, anti-CYP2E1 IgG or CYP2E1 knockout and knockin mice will be discussed. PMID:25454746

  2. 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.

  3. 78 FR 33889 - Notice of Request for Revisions of an Information Collection

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-05

    ...] [FR Doc No: 2013-13303] DEPARTMENT OF TRANSPORTATION Federal Transit Administration [FTA Docket No. 2013-0028] Notice of Request for Revisions of an Information Collection AGENCY: Federal Transit... Act of 1995, this notice announces the intention of the Federal Transit Administration (FTA)...

  4. [How should we treat intestinal ischemia?--II: Effects of pentoxifylline, glucagon and prostaglandin E1].

    PubMed

    Sakio, H; Tanaka, Y; Ueno, K; Oishi, S; Ohtsu, S; Okuda, C

    1995-02-01

    It is important to repair or ameliorate the intestinal ischemia in critically ill patients. Recent study of our suggests the superiority of dobutamine, but not dopamine, in improving the intestinal oxygenation. In this study we examined the effects of pentoxifylline (PF), glucagon (GL) and prostaglandin E1 (PGE1) during reduced blood flow of the superior mesenteric artery (SMA) in 20 anesthetized dogs. As an index of the intestinal oxygenation, tonometrically measured intestinal intramural pH (pHi) was used. A tonometer was inserted into the midjejunum through enterotomy. The SMA blood flow was measured by a transit-time flow meter. A vascular screw clamp for blood flow reduction was placed around the origin of the SMA, proximal to the flow probe. The SMA blood flow was adjusted to 70% of baseline for three hours. After two hours of decreased blood flow, pHi dropped significantly from baseline. Then, either PF (20 mg.kg-1.min-1 over 10 min, followed by 0.1 mg.kg-1.min-1), GL (1 microgram.kg-1.min-1) or PGE1 (0.05 and 0.5 microgram.kg-1.min-1) was infused intravenously for one hour. With infusions of GL and large dose of PGE1, pHi tended to decrease further, although GL increased the cardiac output. Small dose of PGE1 had no significant effect on pHi. PF treatment showed beneficial effects not only on the cardiac output and the SMA blood flow, but also on pHi. We conclude that PF therapy may restore the intestinal microvascular blood flow. Further study of the effects of PF on tissue oxygenation and blood rheology is warranted.

  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. Venus Transit

    NASA Image and Video Library

    2012-06-05

    It appeared that New Yorkers were not going to be able to see the transit of the planet Venus across the Sun, but just before the transit was over the sun broke through the clouds and Yvette Lee Kang was able to catch a glimpse of the transit on Tuesday, June 5, 2012 in New York. A transit of Venus occurs when the planet passes directly between the sun and earth. This alignment is rare, coming in pairs that are eight years apart but separated by over a century. The next Venus transit will be in December 2117. Photo Credit: (NASA/Bill Ingalls)

  7. Venus Transit

    NASA Image and Video Library

    2012-06-05

    It appeared that New Yorkers were not going to be able to see the transit of the planet Venus across the Sun, but just before the transit was over the sun broke through the clouds and Liz Heller and Andriel Mesznik were able to catch a glimpse of the transit on Tuesday, June 5, 2012 in New York. A transit of Venus occurs when the planet passes directly between the sun and earth. This alignment is rare, coming in pairs that are eight years apart but separated by over a century. The next Venus transit will be in December 2117. Photo Credit: (NASA/Bill Ingalls)

  8. A systematic evaluation of microRNAs in regulating human hepatic CYP2E1.

    PubMed

    Wang, Yong; Yu, Dianke; Tolleson, William H; Yu, Li-Rong; Green, Bridgett; Zeng, Linjuan; Chen, Yinting; Chen, Si; Ren, Zhen; Guo, Lei; Tong, Weida; Guan, Huaijin; Ning, Baitang

    2017-08-15

    Cytochrome P450 2E1 (CYP2E1) is an important drug metabolizing enzyme for processing numerous xenobiotics in the liver, including acetaminophen and ethanol. Previous studies have shown that microRNAs (miRNAs) can suppress CYP2E1 expression by binding to the 3'-untranslated region (3'-UTR) of its transcript. However, a systematic analysis of CYP2E1 regulation by miRNAs has not been described. Here, we applied in silico, in vivo, and in vitro approaches to investigate miRNAs involved in the regulation of CYP2E1. Initially, potential miRNA binding sites in the CYP2E1 mRNA transcript were identified and screened using in silico methods. Next, inverse correlations were found in human liver samples between the expression of CYP2E1 mRNA and the levels of two miRNA species, hsa-miR-214-3p and hsa-miR-942-5p. In a HepG2-derived CYP2E1 over-expression cell model, hsa-miR-214-3p exhibited strong suppression of CYP2E1 expression by targeting the coding region of its mRNA transcript, but hsa-miR-942-5p did not inhibit CYP2E1 levels. Electrophoretic mobility shift assays confirmed that hsa-miR-214-3p recruited other cellular protein factors to form stable complexes with specific sequences present in the CYP2E1 mRNA open reading frame. Transfection of HepaRG cells with hsa-miR-214-3p mimics inhibited expression of the endogenous CYP2E1 gene. Further, hsa-miR-214-3p mimics partially blocked ethanol-dependent increases in CYP2E1 mRNA and protein levels in HepG2 cells and they reduced the release of alanine aminotransferase from CYP2E1-overexpressing HepG2 cells exposed to acetaminophen. These results substantiate the suppressing effect of hsa-miR-214-3p on CYP2E1 expression. Published by Elsevier Inc.

  9. Co-activator candidate interactions for orphan nuclear receptor NR2E1.

    PubMed

    Corso-Díaz, Ximena; de Leeuw, Charles N; Alonso, Vivian; Melchers, Diana; Wong, Bibiana K Y; Houtman, René; Simpson, Elizabeth M

    2016-10-26

    NR2E1 (Tlx) is an orphan nuclear receptor that regulates the maintenance and self-renewal of neural stem cells, and promotes tumourigenesis. Nr2e1-null mice exhibit reduced cortical and limbic structures and pronounced retinal dystrophy. NR2E1 functions mainly as a repressor of gene transcription in association with the co-repressors atrophin-1, LSD1, HDAC and BCL11A. Recent evidence suggests that NR2E1 also acts as an activator of gene transcription. However, co-activator complexes that interact with NR2E1 have not yet been identified. In order to find potential novel co-regulators for NR2E1, we used a microarray assay for real-time analysis of co-regulator-nuclear receptor interaction (MARCoNI) that contains peptides representing interaction motifs from potential co-regulatory proteins, including known co-activator nuclear receptor box sequences (LxxLL motif). We found that NR2E1 binds strongly to an atrophin-1 peptide (Atro box) used as positive control and to 19 other peptides that constitute candidate NR2E1 partners. Two of these proteins, p300 and androgen receptor (AR), were further validated by reciprocal pull-down assays. The specificity of NR2E1 binding to peptides in the array was evaluated using two single amino acid variants, R274G and R276Q, which disrupted the majority of the binding interactions observed with wild-type NR2E1. The decreased binding affinity of these variants to co-regulators was further validated by pull-down assays using atrophin1 as bait. Despite the high conservation of arginine 274 in vertebrates, its reduced interactions with co-regulators were not significant in vivo as determined by retinal phenotype analysis in single-copy Nr2e1-null mice carrying the variant R274G. We showed that MARCoNI is a specific assay to test interactions of NR2E1 with candidate co-regulators. In this way, we unveiled 19 potential co-regulator partners for NR2E1, including eight co-activators. All the candidates here identified need to be further

  10. Expression of constitutive and inducible cytochrome P450 2E1 in rat brain.

    PubMed

    Yadav, Sanjay; Dhawan, Alok; Singh, Ram L; Seth, Prahlad K; Parmar, Devendra

    2006-06-01

    Studies initiated to investigate the expression of cytochrome P450 2E1 (CYP2E1) in rat brain demonstrated low but detectable protein and mRNA expression in control rat brain. Though mRNA and protein expression of CYP2E1 in brain was several fold lower as compared to liver, relatively high activity of N-nitrosodimethylamine demethylase (NDMA-d) was observed in control rat brain microsomes. Like liver, pretreatment with CYP2E1 inducers such as ethanol or pyrazole or acetone significantly increased the activity of brain microsomal NDMA-d. Kinetic studies also showed an increase in the Vmax and affinity (Km) of the substrate towards the brain enzyme due to increased expression of CYP2E1 in microsomes of brain isolated from ethanol pretreated rats. In vitro studies using organic inhibitors, specific for CYP2E1 and anti-CYP2E1 significantly inhibited the brain NDMA-d activity indicating that like liver, NDMA-d activity in rat brain is catalyzed by CYP2E1. Olfactory lobes exhibited the highest CYP2E1 expression and catalytic activity in control rats. Furthermore, several fold increase in the mRNA expression and activity of CYP2E1 in cerebellum and hippocampus while a relatively small increase in the olfactory lobes and no significant change in other brain regions following ethanol pretreatment have indicated that CYP2E1 induction maybe involved in selective sensitivity of these brain areas to ethanol induced free radical damage and neuronal degeneration.

  11. Functional characterization and tissue expression of marmoset cytochrome P450 2E1.

    PubMed

    Uehara, Shotaro; Uno, Yasuhiro; Tomioka, Etsuko; Inoue, Takashi; Sasaki, Erika; Yamazaki, Hiroshi

    2017-09-01

    Common marmosets (Callithrix jacchus) have attracted increasing attention as a useful small non-human primate model in preclinical research. However, studies on marmoset cytochrome P450 (P450) 2E enzyme have scarcely been conducted. In this study, the full-length cDNA encoding P450 2E1 enzyme was isolated from marmoset livers by reverse transcription (RT)-polymerase chain reaction (PCR). Marmoset P450 2E1 amino acid sequences were highly identical (>88%) to those of cynomolgus monkey and human P450 2E1 enzymes. Phylogenetic analysis indicated a close evolutionary relationship among marmoset, cynomolgus monkey, and human P450 2E1 enzymes. The tissue expression pattern analyzed by real-time RT-PCR and immunoblotting demonstrated that marmoset P450 2E1 mRNA and proteins were predominantly expressed in livers. Marmoset P450 2E1 enzyme heterologously expressed in Escherichia coli catalyzed the hydroxylation of p-nitrophenol, chlorzoxazone, and theophylline, similar to cynomolgus monkey and human P450 2E1 enzymes. By kinetic analyses, those P450 2E1 enzymes catalyzed p-nitrophenol hydroxylation with similar affinities and relatively high intrinsic clearance efficiencies. These results indicated that tissue distribution and enzyme-substrate specificity of marmoset P450 2E1 were similar to cynomolgus monkey and human P450 2E1 enzymes, suggesting that marmosets are a suitable primate model for P450 2E1-dependent drug and xenobiotic metabolism. Copyright © 2017 John Wiley & Sons, Ltd.

  12. 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

  13. 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...

  14. 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...

  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, 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...

  18. 11 CFR 101.1 - Candidate designations (2 U.S.C. 432(e)(1)).

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 11 Federal Elections 1 2010-01-01 2010-01-01 false Candidate designations (2 U.S.C. 432(e)(1)). 101.1 Section 101.1 Federal Elections FEDERAL ELECTION COMMISSION GENERAL CANDIDATE STATUS AND DESIGNATIONS (2 U.S.C. 432(e)) § 101.1 Candidate designations (2 U.S.C. 432(e)(1)). (a) Principal...

  19. Transcription control region within the protein-coding portion of adenovirus E1A genes.

    PubMed Central

    Osborne, T F; Arvidson, D N; Tyau, E S; Dunsworth-Browne, M; Berk, A J

    1984-01-01

    A single-base deletion within the protein-coding region of the adenovirus type 5 early region 1A (E1A) genes, 399 bases downstream from the transcription start site, depresses transcription to 2% of the wild-type rate. Complementation studies demonstrated that this was due to two effects of the mutation: first, inactivation of an E1A protein, causing a reduction by a factor of 5; second, a defect which acts in cis to depress E1A mRNA and nuclear RNA concentrations by a factor of 10. A larger deletion within the protein-coding region of E1A which overlaps the single-base deletion produces the same phenotype. In contrast, a linker insertion which results in a similar truncated E1A protein does not produce the cis-acting defect in E1A transcription. These results demonstrate that a critical cis-acting transcription control region occurs within the protein coding sequence in adenovirus type 5 E1A. The single-base deletion occurs in a sequence which shows extensive homology with a sequence from the enhancer regions of simian virus 40 and polyomavirus. This region is not required for E1A transcription during the late phase of infection. Images PMID:6334230

  20. 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. © 2015 Sawada et al.

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

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 15 2013-04-01 2013-04-01 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...

  2. 26 CFR 31.3121(e)-1 - State, United States, and citizen.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 15 2012-04-01 2012-04-01 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...

  3. 26 CFR 31.3121(e)-1 - State, United States, and citizen.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 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...

  4. [Association of CYP2E1 of PON2311 polymorphisms in neonates with preterm].

    PubMed

    Liang, Hong-Ye; Wu, Bai-Yan; Chen, Da-Fang; Yang, Fan; Hu, Hai-Yan; Chen, Li; Xu, Xi-Ping

    2002-10-01

    The objective is to investigate whether Rsa I polymorphism in the 5'-flanking region of CYP2E1 and PON2311 polymorphism in neonates are associated with preterm. Using standard questionnaires, 194 singleton live born mother-neonate pairs (including preterm cases and term controls) were investigated by the trained field workers with cross-sectional survey at the hospitals in Anqing, Anhui Province, China. Epidemiological and clinical data and blood samples were obtained from 194 mother-neonate pairs. CYP2E1 homozygous wild-type (cut/cut) is not associated with a shortened gestation among neonates, compared with CYP2E1 homozygous mutant-type (uncut/uncut)/CYP2E1 heterozygote (cut/uncut) before and after adjustment confounders. However, PON2 Ser311Ser homozygote is significantly associated with a shortened gestation among neonates. When Rsa I polymorphism in the 5'-flanking region of CYP2E1 and PON2311 polymorphism were considered jointly, a significant shortened gestation was observed among neonates with the combined genotype of CYP2E1 homozygous wild-type and PON2 Ser311Ser homozygote. In conclusion, Rsa I polymorphism in the 5'-flanking region of CYP2E1 in neonates is not associated with preterm, however, PON2311 polymorphism in neonates is significantly associated with preterm. Furthermore, the gene interaction between Rsa I polymorphism in the 5'-flanking region of CYP2E1 and PON2311 polymorphism in neonates is significantly associated with preterm.

  5. 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 § 1...

  6. 42 CFR 52e.1 - To what programs do these regulations apply?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 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 do... the prevention and control of heart, blood vessel, lung, and blood diseases, with...

  7. 42 CFR 52e.1 - To what programs do these regulations apply?

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 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 do... the prevention and control of heart, blood vessel, lung, and blood diseases, with...

  8. 42 CFR 52e.1 - To what programs do these regulations apply?

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 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 do... the prevention and control of heart, blood vessel, lung, and blood diseases, with...

  9. 42 CFR 52e.1 - To what programs do these regulations apply?

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 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 do... the prevention and control of heart, blood vessel, lung, and blood diseases, with...

  10. E1A RNA transcripts amplify adenovirus-mediated tumor reduction.

    PubMed

    Dion, L D; Goldsmith, K T; Strong, T V; Bilbao, G; Curiel, D T; Garver, R I

    1996-11-01

    Previous work by this group has established that E1-defective, recombinant adenoviruses can be replication-enabled by the codelivery of a plasmid encoding the deleted E1 functions, a strategy now designated conditional replication-enablement system for adenovirus (CRESA). In the studies reported here, the original replication-enabling plasmid was replaced by two separate plasmids that encoded the necessary E1A and E1B functions, respectively. An RNA transcript encoding the requisite E1A functions was shown to substitute functionally for the E1A plasmid without significant loss of new adenovirus production in in vitro experiments. No replication competent adenovirus was detectable in the cells treated with the plasmids, or the RNA and plasmid combinations. Subcutaneous human tumor nodules containing a fraction of cells cotransduced with the replication-enabling RNA + DNA and an adenovirus containing a herpes simplex virus thymidine kinase (HSVtk) expression cassette were reduced to a greater extent than control nodules containing the same fraction of cells cotransduced with the virus and an irrelevant plasmid. These experiments show that an E1-defective adenovirus can be conditionally replication-enabled by an RNA transcript encoding the required E1 functions, and that the replication-enablement is sufficient to produce an augmentation of an adenovirus-mediated therapeutic effect in vivo.

  11. E1a is an exogenous in vivo tumour suppressor.

    PubMed

    Cimas, Francisco J; Callejas-Valera, Juan L; García-Olmo, Dolores C; Hernández-Losa, Javier; Melgar-Rojas, Pedro; Ruiz-Hidalgo, María J; Pascual-Serra, Raquel; Ortega-Muelas, Marta; Roche, Olga; Marcos, Pilar; Garcia-Gil, Elena; Fernandez-Aroca, Diego M; Ramón Y Cajal, Santiago; Gutkind, J Silvio; Sanchez-Prieto, Ricardo

    2017-07-28

    The E1a gene from adenovirus has become a major tool in cancer research. Since the discovery of E1a, it has been proposed to be an oncogene, becoming a key element in the model of cooperation between oncogenes. However, E1a's in vivo behaviour is consistent with a tumour suppressor gene, due to the block/delay observed in different xenograft models. To clarify this interesting controversy, we have evaluated the effect of the E1a 13s isoform from adenovirus 5 in vivo. Initially, a conventional xenograft approach was performed using previously unreported HCT116 and B16-F10 cells, showing a clear anti-tumour effect regardless of the mouse's immunological background (immunosuppressed/immunocompetent). Next, we engineered a transgenic mouse model in which inducible E1a 13s expression was under the control of cytokeratin 5 to avoid side effects during embryonic development. Our results show that E1a is able to block chemical skin carcinogenesis, showing an anti-tumour effect. The present report demonstrates the in vivo anti-tumour effect of E1a, showing that the in vitro oncogenic role of E1a cannot be extrapolated in vivo, supporting its future use in gene therapy approaches. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Ethanol-inducible cytochrome P4502E1: regulation, enzymology and molecular biology.

    PubMed

    Ingelman-Sundberg, M; Ronis, M J; Lindros, K O; Eliasson, E; Zhukov, A

    1994-01-01

    Cytochrome P450 2E1 (CYP2E1) is constitutively expressed in liver and many other tissues. CYP2E1 is effectively induced in the liver by a diverse set of chemicals having various structures. The enzyme constitutes the only P450 form that is strongly induced by ethanol. CYP2E1 metabolizes a wide array of chemicals with different structures, in particular small and hydrophobic compounds, including potential carcinogens. In addition, CYP2E1 has a unique capacity to reduce dioxygen to reactive oxy radicals that might initiate membranous lipid peroxidation, yielding products, mainly aldehydes, which activate immune cells for cytokine production and Ito cells for collagen formation. CYP2E1 mediated formation of reactive lipid peroxidation products and alpha-hydroxyethyl radicals gives rise to protein adduct formation, some of which can cause autoimmune reactions. The regulation of CYP2E1 is unusually complicated and is exerted at several different cellular levels. CYP2E1 has received much attention, mainly because of its putative importance in the activation of chemicals to cytotoxic or carcinogenic products and its potential role in ethanol-induced hepatotoxicity.

  13. 78 FR 67452 - Qualification of Drivers; Exemption Applications; Vision

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-12

    ... 69434; 69 FR 19611; 70 FR 48797; 70 FR 53412; 70 FR 57353; 70 FR 61493; 70 FR 67776; 70 FR 72689; 70 FR... January 17, 2008 (73 FR 3316). FOR FURTHER INFORMATION CONTACT: Elaine M. Papp, Chief, Medical Programs... applicants has satisfied the entry conditions for obtaining an exemption from the vision requirements (64 FR...

  14. 76 FR 25762 - Qualification of Drivers; Exemption Applications; Vision

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-05

    ... 62741; 70 FR 2701; 70 FR 7545; 70 FR 12265; 70 FR 14747; 70 FR 17504; 70 FR 30997; 70 FR 16886; 70 FR... Federal Register on January 17, 2008 (73 FR 3316), or you may visit http://edocket.access.gpo.gov/2008/pdf... applicants has satisfied the entry conditions for obtaining an exemption from the vision requirements (65 FR...

  15. 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

  16. Distinct features of cap binding by eIF4E1b proteins.

    PubMed

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

    2015-01-30

    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 m(7)GTP-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 N(7) 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 N(7) 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. Copyright © 2014. Published by Elsevier Ltd.

  17. 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

  18. Planar Organization of Multiciliated Ependymal (E1) Cells in the Brain Ventricular Epithelium.

    PubMed

    Ohata, Shinya; Alvarez-Buylla, Arturo

    2016-08-01

    Cerebrospinal fluid (CSF) continuously flows through the cerebral ventricles, a process essential for brain homeostasis. Multiciliated ependymal (E1) cells line the walls of the ventricles and contribute importantly to CSF flow through ciliary beating. Key to this function is the rotational and translational planar cell polarity (PCP) of E1 cells. Defects in the PCP of E1 cells can result in abnormal CSF accumulation and hydrocephalus. Here, we integrate recent data on the roles of early CSF flow in the embryonic ventricles, PCP regulators (e.g., Vangl2 and Dishevelled), and cytoskeletal networks in the establishment, refinement, and maintenance of E1 cells' PCP. The planar organization mechanisms of E1 cells could explain how CSF flow contributes to brain function and may help in the diagnosis and prevention of hydrocephalus.

  19. Bovine Papillomavirus Replicative Helicase E1 Is a Target of the Ubiquitin Ligase APC

    PubMed Central

    Mechali, Francisca; Hsu, Chiung-Yueh; Castro, Anna; Lorca, Thierry; Bonne-Andrea, Catherine

    2004-01-01

    The papillomavirus E1 replicative helicase is essential for replication and maintenance of extrachromosomal viral genomes in infected cells. We previously found that the bovine papillomavirus E1 protein is a substrate of the ubiquitin-dependent proteolytic pathway. Here we show that E1 is targeted for degradation by the anaphase-promoting complex (APC). Inhibition of APC activity by the specific inhibitor Emi1 or point mutations in the D-box and KEN-box motifs of E1 stabilize the protein and increase viral DNA replication in both a cell-free system and in living cells. These findings involve APC as the ubiquitin ligase that controls E1 levels to maintain a constant low copy number of the viral genome during latent infection. PMID:14963168

  20. Hedgehog Pathway Antagonist 5E1 Binds Hedgehog at the Pseudo-active Site

    PubMed Central

    Maun, Henry R.; Wen, Xiaohui; Lingel, Andreas; de Sauvage, Frederic J.; Lazarus, Robert A.; Scales, Suzie J.; Hymowitz, Sarah G.

    2010-01-01

    Proper hedgehog (Hh) signaling is crucial for embryogenesis and tissue regeneration. Dysregulation of this pathway is associated with several types of cancer. The monoclonal antibody 5E1 is a Hh pathway inhibitor that has been extensively used to elucidate vertebrate Hh biology due to its ability to block binding of the three mammalian Hh homologs to the receptor, Patched1 (Ptc1). Here, we engineered a murine:human chimeric 5E1 (ch5E1) with similar Hh-binding properties to the original murine antibody. Using biochemical, biophysical, and x-ray crystallographic studies, we show that, like the regulatory receptors Cdon and Hedgehog-interacting protein (Hhip), ch5E1 binding to Sonic hedgehog (Shh) is enhanced by calcium ions. In the presence of calcium and zinc ions, the ch5E1 binding affinity increases 10–20-fold to tighter than 1 nm primarily because of a decrease in the dissociation rate. The co-crystal structure of Shh bound to the Fab fragment of ch5E1 reveals that 5E1 binds at the pseudo-active site groove of Shh with an epitope that largely overlaps with the binding site of its natural receptor antagonist Hhip. Unlike Hhip, the side chains of 5E1 do not directly coordinate the Zn2+ cation in the pseudo-active site, despite the modest zinc-dependent increase in 5E1 affinity for Shh. Furthermore, to our knowledge, the ch5E1 Fab-Shh complex represents the first structure of an inhibitor antibody bound to a metalloprotease fold. PMID:20504762

  1. 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.

  2. 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

  3. 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.

  4. Regulation of the 26S proteasome by adenovirus E1A

    PubMed Central

    Turnell, Andrew S.; Grand, Roger J.A.; Gorbea, Carlos; Zhang, Xian; Wang, Wenlan; Mymryk, Joe S.; Gallimore, Phillip H.

    2000-01-01

    We have identified the N-terminus of adenovirus early region 1A (AdE1A) as a region that can regulate the 26S proteasome. Specifically, in vitro and in vivo co-precipitation studies have revealed that the 19S regulatory components of the proteasome, Sug1 (S8) and S4, bind through amino acids (aa) 4–25 of Ad5 E1A. In vivo expression of wild-type (wt) AdE1A, in contrast to the N-terminal AdE1A mutant that does not bind the proteasome, reduces ATPase activity associated with anti-S4 immunoprecipitates relative to mock-infected cells. This reduction in ATPase activity correlates positively with the ability of wt AdE1A, but not the N-terminal deletion mutant, to significantly reduce the ability of HPV16 E6 to target p53 for ubiquitin-mediated proteasomal degradation. AdE1A/proteasomal complexes are present in both the cytoplasm and the nucleus, suggesting that AdE1A interferes with both nuclear and cytoplasmic proteasomal degradation. We have also demonstrated that wt AdE1A and the N-terminal AdE1A deletion mutant are substrates for proteasomal-mediated degradation. AdE1A degradation is not, however, mediated through ubiquitylation, but is regulated through phosphorylation of residues within a C-terminal PEST region (aa 224–238). PMID:10970867

  5. Induction and recovery time course of rat brain CYP2E1 after nicotine treatment.

    PubMed

    Joshi, Meenal; Tyndale, Rachel F

    2006-04-01

    CYP2E1, the primary ethanol-metabolizing cytochrome P450, metabolizes endogenous substrates (e.g., arachidonic acid) and drugs (e.g., acetaminophen, chlorzoxazone) and bioactivates procarcinogens (e.g., tobacco-specific nitrosamines) and toxins (e.g., carbon tetrachloride). Nicotine from tobacco smoke may contribute to the enhanced hepatic CYP2E1 activity in smokers. We have previously shown that chronic nicotine treatment can increase CYP2E1 in rat liver and brain. In this study, induction of brain CYP2E1 was assessed after a single acute or a 7-day chronic treatment with saline or nicotine (1 mg/kg s.c.), with sacrifice performed at various times after the last injection. Chronic 7-day nicotine treatment showed the highest levels of CYP2E1 12 h after the last injection in frontal cortex (1.4-fold, p < 0.05) versus 8 h in hippocampus (1.8-fold, p < 0.01) and cerebellum (1.4-fold, p < 0.05), returning to basal levels by 24 h. In contrast, acute nicotine treatment did not induce CYP2E1 in frontal cortex and hippocampus but increased CYP2E1 in cerebellum 8 h after treatment (1.6-fold, p < 0.01). Brain CYP2E1 mRNA levels did not increase after chronic nicotine treatment, suggesting nontranscriptional regulation. Thus, humans exposed to nicotine may have altered CYP2E1-mediated metabolism of centrally acting drugs and toxins as well as altered toxicity because of oxidative stress caused by CYP2E1. Those affected may include current and passive smokers and people that may be treated with nicotine such as smokers and, potentially, patients with Alzheimer's, Parkinson's disease, or ulcerative colitis.

  6. An automated exploration of the isomerization and dissociation pathways of (E)-1,2-dichloroethene cations and anions

    NASA Astrophysics Data System (ADS)

    Kishimoto, Naoki; Nishi, Yuito

    2017-04-01

    Isomerization and dissociation pathways after the photoionization or electron attachment of (E)-1,2-dichloroethene were calculated with an automated exploration method utilizing a scaled hypersphere search of the anharmonic downward distortion following algorithm at the UB3LYP/6-311G(2d,d,p) level of theory. The potential energies of transition states and dissociation channels were calculated by a composite method ((RO)CBS-QB3) and compared with the breakdown diagrams and electron attachment spectra observed in previous spectroscopic studies. The results of single point calculations with several DFT and post-SCF methods are compared using the root mean square deviations from the (RO)CBS-QB3 energies for six states of anionic dichloroethene.

  7. Copy number and haplotype variation at the VRN-A1 and central FR-A2 loci are associated with frost tolerance in hexaploid wheat

    USDA-ARS?s Scientific Manuscript database

    Frost tolerance is a key trait to ensure winter wheat survival. Natural variation for this trait is mainly associated with allelic differences at the VERNALIZATION 1 (VRN1) and FROST RESISTANCE 2 (FR2) loci. VRN1 regulates the transition between vegetative and reproductive stages and FR2, a locus in...

  8. 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

  9. E1-Mediated Recruitment of a UAF1-USP Deubiquitinase Complex Facilitates Human Papillomavirus DNA Replication

    PubMed Central

    Lehoux, Michaël; Gagnon, David

    2014-01-01

    ABSTRACT The human papillomavirus (HPV) E1 helicase promotes viral DNA replication through its DNA unwinding activity and association with host factors. The E1 proteins from anogenital HPV types interact with the cellular WD repeat-containing factor UAF1 (formerly known as p80). Specific amino acid substitutions in E1 that impair this interaction inhibit maintenance of the viral episome in immortalized keratinocytes and reduce viral DNA replication by up to 70% in transient assays. In this study, we determined by affinity purification of UAF1 that it interacts with three deubiquitinating enzymes in C33A cervical carcinoma cells: USP1, a nuclear protein, and the two cytoplasmic enzymes USP12 and USP46. Coimmunoprecipitation experiments indicated that E1 assembles into a ternary complex with UAF1 and any one of these three USPs. Moreover, expression of E1 leads to a redistribution of USP12 and USP46 from the cytoplasm to the nucleus. Chromatin immunoprecipitation studies further revealed that E1 recruits these threes USPs to the viral origin in association with UAF1. The function of USP1, USP12, and USP46 in viral DNA replication was investigated by overproduction of catalytically inactive versions of these enzymes in transient assays. All three dominant negative USPs reduced HPV31 DNA replication by up to 60%, an effect that was specific, as it was not observed in assays performed with a truncated E1 lacking the UAF1-binding domain or with bovine papillomavirus 1 E1, which does not bind UAF1. These results highlight the importance of the USP1, USP12, and USP46 deubiquitinating enzymes in anogenital HPV DNA replication. IMPORTANCE Human papillomaviruses are small DNA tumor viruses that induce benign and malignant lesions of the skin and mucosa. HPV types that infect the anogenital tract are the etiological agents of cervical cancer, the majority of anal cancers, and a growing proportion of head-and-neck cancers. Replication of the HPV genome requires the viral

  10. Adenovirus E1A specifically blocks SWI/SNF-dependent transcriptional activation.

    PubMed Central

    Miller, M E; Cairns, B R; Levinson, R S; Yamamoto, K R; Engel, D A; Smith, M M

    1996-01-01

    Expression of the adenovirus E1A243 oncoprotein in Saccharomyces cerevisiae produces a slow-growth phenotype with accumulation of cells in the G1 phase of the cell cycle. This effect is due to the N-terminal and CR1 domains of E1A243, which in rodent cells are involved in triggering cellular transformation and also in binding to the cellular transcriptional coactivator p300. A genetic screen was undertaken to identify genes required for the function of E1A243 in S. cerevisiae. This screen identified SNF12, a gene encoding the 73-kDa subunit of the SWI/SNF transcriptional regulatory complex. Mutation of genes encoding known members of the SWI/SNF complex also led to loss of E1A function, suggesting that the SWI/SNF complex is a target of E1A243. Moreover, expression of E1A in wild-type cells specifically blocked transcriptional activation of the INO1 and SUC2 genes, whose activation pathways are distinct but have a common requirement for the SWI/SNF complex. These data demonstrate a specific functional interaction between E1A and the SWI/SNF complex and suggest that a similar interaction takes place in rodent and human cells. PMID:8816487

  11. Resolvin E1 Inhibits Substance P-Induced Potentiation of TRPV1 in Primary Sensory Neurons

    PubMed Central

    Jo, Youn Yi; Lee, Ji Yeon

    2016-01-01

    The neuropeptide substance P (SP) is expressed in primary sensory neurons and is commonly regarded as a “pain” neurotransmitter. Upon peripheral inflammation, SP activates the neurokinin-1 (NK-1) receptor and potentiates activity of transient receptor potential vanilloid subtype 1 (TRPV1), which is coexpressed by nociceptive neurons. Therefore, SP functions as an important neurotransmitter involved in the hypersensitization of inflammatory pain. Resolvin E1 (RvE1), derived from omega-3 polyunsaturated fatty acids, inhibits TRPV1 activity via activation of the chemerin 23 receptor (ChemR23)—an RvE1 receptor located in dorsal root ganglion neurons—and therefore exerts an inhibitory effect on inflammatory pain. We demonstrate here that RvE1 regulates the SP-induced potentiation of TRPV1 via G-protein coupled receptor (GPCR) on peripheral nociceptive neurons. SP-induced potentiation of TRPV1 inhibited by RvE1 was blocked by the Gαi-coupled GPCR inhibitor pertussis toxin and the G-protein inhibitor GDPβ-S. These results indicate that a low concentration of RvE1 strongly inhibits the potentiation of TRPV1, induced by the SP-mediated activation of NK-1, via a GPCR signaling pathway activated by ChemR23 in nociceptive neurons. RvE1 might represent a new therapeutic target for the treatment of inflammatory pain as a prospective endogenous inhibitor that strongly inhibits TRPV1 activity associated with peripheral inflammation. PMID:27738388

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

    PubMed

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

    2013-08-01

    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.

  13. E1A dependent up-regulation of c-jun/AP-1 activity.

    PubMed Central

    Kitabayashi, I; Chiu, R; Gachelin, G; Yokoyama, K

    1991-01-01

    E1A, the early region 1A transcription unit of human adenovirus, exhibits multiple functions that regulate the expression of some cellular genes and promote cell growth and division. We found that E1A stimulated c-jun gene expression at least fifty-fold in rat 3Y1 cells in a serum-independent manner, concomitantly with E1A down-regulation of jun B expression. The E1A-dependent induction of c-jun transcription resulted in increase amount of cJun/AP1. This induction was mediated by the enhancement of the binding activity of the transcription factor cJun/AP1 to an AP1 binding site in the c-jun promoter. Additionally, this induction can be repressed by introducing junB into the cells. Taken collectively, these results suggest that the differential expression of two closely related proteins greatly expands their cellular regulation. Induction of c-jun expression by E1A as well as c-jun autoregulation may amplify the action of E1A during adenovirus infection. Therefore, some of the biological effects of E1A may include mediating the constitutive activation of c-jun, which is important in transcriptional regulation and oncogenic transformation. Images PMID:1826351

  14. Long-Term Prostaglandin E1 Infusion for Newborns with Critical Congenital Heart Disease.

    PubMed

    Aykanat, Alper; Yavuz, Taner; Özalkaya, Elif; Topçuoğlu, Sevilay; Ovalı, Fahri; Karatekin, Güner

    2016-01-01

    Prostaglandin E1 is crucial for keeping the patent ductus arteriosus in critical congenital heart disease for the survival and palliation of particularly prematurely born babies until a cardiosurgical intervention is available. In this study, the side effects of prostaglandin E1 in newborns with critical congenital heart disease and clinical outcomes were evaluated. Thirty-five newborns diagnosed with critical congenital heart disease were treated with prostaglandin E1 between January 2012 and September 2014 at our hospital. Patient charts were examined for prostaglandin E1 side effects (metabolic, gastric outlet obstruction, apnea), clinical status, and prognosis. Acquired data were analyzed in the SPSS 20.0 program. Patients with birth weight under 2500 g needed more days of prostaglandin E1 infusion than ones with birthweight over 2500 g (P = 0.016). The ratio of patients with birth weight under 2500 g who received prostaglandin E1 longer than 7 days was higher than the patients with birth weight over 2500 g (P = 0.02). Eighteen side effects were encountered in 11 of 35 patients (31%). Of these side effects, 1 patient had 4, 4 patients had 2, and 6 patients had only 1 side effect. Discontinuation of the therapy was never needed. Prostaglandin E1 is an accepted therapy modality for survival and outcome in critical congenital heart disease in particularly low-birth-weight babies until a surgical intervention is available. Side effects are not less encountered but are almost always manageable, and discontinuation is not needed.

  15. Isotope shifts in francium isotopes Fr-213206 and 221Fr

    NASA Astrophysics Data System (ADS)

    Collister, R.; Gwinner, G.; Tandecki, M.; Behr, J. A.; Pearson, M. R.; Zhang, J.; Orozco, L. A.; Aubin, S.; Gomez, E.; FrPNC Collaboration

    2014-11-01

    We present the isotope shifts of the 7 s1 /2 to 7 p1 /2 transition for francium isotopes 206 -213Fr with reference to 221Fr collected from two experimental periods. The shifts are measured on a sample of atoms prepared within a magneto-optical trap by a fast sweep of radio-frequency sidebands applied to a carrier laser. King plot analysis, which includes literature values for 7 s1 /2 to 7 p3 /2 isotope shifts, provides a field shift constant ratio of 1.0520(10) and a difference between the specific mass shift constants of 170(100) GHz amu between the D1 and D2 transitions, of sufficient precision to differentiate between ab initio calculations.

  16. Systematic exploration of ubiquitin sequence, E1 activation efficiency, and experimental fitness in yeast

    PubMed Central

    Roscoe, Benjamin P.; Bolon, Daniel N. A.

    2014-01-01

    The complexity of biological interaction networks poses a challenge to understanding the function of individual connections in the overall network. To address this challenge, we developed a high throughput reverse engineering strategy to analyze how thousands of specific perturbations (encompassing all point mutations in a central gene) impact both a specific edge (interaction to a directly connected node) as well as overall network function. We analyzed the effects of ubiquitin mutations on activation by the E1 enzyme and compared these to effects on yeast growth rate. Using this approach, we delineated ubiquitin mutations that selectively impacted the ubiquitin-E1 edge. We find that the elasticity function relating the efficiency of ubiquitin-E1 interaction to growth rate is non-linear and that a greater than 50-fold decrease in E1 activation efficiency is required to reduce growth rate by two fold. Despite the robustness of fitness to decreases in E1 activation efficiency, the effects of most ubiquitin mutations on E1 activation paralleled the effects on growth rate. Our observations indicate that most ubiquitin mutations that disrupt E1 activation also disrupt other functions. The structurally characterized ubiquitin-E1 interface encompasses the interfaces of ubiquitin with most other known binding partners, and we propose that this enables E1 in wild-type cells to selectively activate ubiquitin protein molecules capable of binding to other partners from the cytoplasmic pool of ubiquitin protein that will include molecules with chemical damage and/or errors from transcription and translation. PMID:24862281

  17. Functional Mapping of the Human Papillomavirus Type 16 E1 Cistron▿

    PubMed Central

    Lace, Michael J.; Anson, James R.; Turek, Lubomir P.; Haugen, Thomas H.

    2008-01-01

    Replication of the double-stranded, circular human papillomavirus (HPV) genomes requires the viral DNA replicase E1. Here, we report an initial characterization of the E1 cistron of HPV type 16 (HPV-16), the most common oncogenic mucosal HPV type found in cervical and some head and neck cancers. The first step in HPV DNA replication is an initial burst of plasmid viral DNA amplification. Complementation assays between HPV-16 genomes carrying mutations in the early genes confirmed that the expression of E1 was necessary for initial HPV-16 plasmid synthesis. The major early HPV-16 promoter, P97, was dispensable for E1 production in the initial amplification because cis mutations inactivating P97 did not affect the trans complementation of E1− mutants. In contrast, E1 expression was abolished by cis mutations in the splice donor site at nucleotide (nt) 226, the splice acceptor site at nt 409, or a TATAA box at nt 7890. The mapping of 5′ mRNA ends using rapid amplification of cDNA ends defined a promoter with a transcription start site at HPV-16 nt 14, P14. P14-initiated mRNA levels were low and required intact TATAA (7890). E1 expression required the HPV-16 keratinocyte-dependent enhancer, since cis mutations in its AP-2 and TEF-1 motifs abolished the ability of the mutant genomes to complement E1− genomes, and it was further modulated by origin-proximal and -distal binding sites for the viral E2 gene products. We conclude that P14-initiated E1 expression is critical for and limiting in the initial amplification of the HPV-16 genome. PMID:18753208

  18. 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.

  19. Functional mapping of the human papillomavirus type 16 E1 cistron.

    PubMed

    Lace, Michael J; Anson, James R; Turek, Lubomir P; Haugen, Thomas H

    2008-11-01

    Replication of the double-stranded, circular human papillomavirus (HPV) genomes requires the viral DNA replicase E1. Here, we report an initial characterization of the E1 cistron of HPV type 16 (HPV-16), the most common oncogenic mucosal HPV type found in cervical and some head and neck cancers. The first step in HPV DNA replication is an initial burst of plasmid viral DNA amplification. Complementation assays between HPV-16 genomes carrying mutations in the early genes confirmed that the expression of E1 was necessary for initial HPV-16 plasmid synthesis. The major early HPV-16 promoter, P97, was dispensable for E1 production in the initial amplification because cis mutations inactivating P97 did not affect the trans complementation of E1- mutants. In contrast, E1 expression was abolished by cis mutations in the splice donor site at nucleotide (nt) 226, the splice acceptor site at nt 409, or a TATAA box at nt 7890. The mapping of 5' mRNA ends using rapid amplification of cDNA ends defined a promoter with a transcription start site at HPV-16 nt 14, P14. P14-initiated mRNA levels were low and required intact TATAA (7890). E1 expression required the HPV-16 keratinocyte-dependent enhancer, since cis mutations in its AP-2 and TEF-1 motifs abolished the ability of the mutant genomes to complement E1- genomes, and it was further modulated by origin-proximal and -distal binding sites for the viral E2 gene products. We conclude that P14-initiated E1 expression is critical for and limiting in the initial amplification of the HPV-16 genome.

  20. Antisense inhibition of mitochondrial pyruvate dehydrogenase E1alpha subunit in anther tapetum causes male sterility.

    PubMed

    Yui, Rika; Iketani, Satoru; Mikami, Tetsuo; Kubo, Tomohiko

    2003-04-01

    We hypothesized that cytoplasmic male sterility (CMS) in sugar beet may be the consequence of mitochondrial dysfunctions affecting normal anther development. To test the hypothesis, we attempted to mimic the sugar beet CMS phenotype by inhibiting the expression of mitochondrial pyruvate dehydrogenase (PDH), which is essential for the operation of the tricarboxylic acid (TCA) cycle. Screening with a cDNA library of sugar beet flower buds allowed the identification of two PDH E1alpha subunit genes (bvPDH_E1alpha-1 and bvPDH_E1alpha-2). bvPDH_E1alpha-1 was found to be highly expressed in tap roots, whereas bvPDH_E1alpha-2 was expressed most abundantly in flower buds. Green fluorescent protein (GFP) fusion of bvPDH_E1alpha revealed mitochondrial targeting properties. A 300-bp bvPDH_E1alpha-1 cDNA sequence (from +620 to +926) was connected to a tapetum-specific promoter in the antisense orientation and then introduced into tobacco. Antisense expression of bvPDH_E1alpha-1 resulted in conspicuously decreased endogenous bvPDH_E1alpha-1 transcripts and male sterility. The tapetum in the male-sterile anthers showed swelling or abnormal vacuolation. It is also worth noting that in the sterile anthers, cell organelles, such as elaioplasts, tapetosomes and orbicules were poorly formed and microspores exhibited aberrant exine development. These features are shared by sugar beet CMS. The results thus clearly indicate that inhibition of PDH activity in anther tapetum is sufficient to cause male sterility, a phenocopy of the sugar beet CMS.

  1. Absence of NR2E1 mutations in patients with aniridia

    PubMed Central

    Corso-Díaz, Ximena; Borrie, Adrienne E.; Bonaguro, Russell; Schuetz, Johanna M.; Rosenberg, Thomas; Jensen, Hanne; Brooks, Brian P.; MacDonald, Ian M.; Pasutto, Francesca; Walter, Michael A.; Grønskov, Karen; Brooks-Wilson, Angela

    2012-01-01

    Purpose Nuclear receptor 2E1 (NR2E1) is a transcription factor with many roles during eye development and thus may be responsible for the occurrence of certain congenital eye disorders in humans. To test this hypothesis, we screened NR2E1 for candidate mutations in patients with aniridia and other congenital ocular malformations (anterior segment dysgenesis, congenital optic nerve malformation, and microphthalmia). Methods The NR2E1 coding region, 5′ and 3′ untranslated regions (UTRs), exon flanking regions including consensus splice sites, and six evolutionarily conserved non-coding candidate regulatory regions were analyzed by sequencing 58 probands with aniridia of whom 42 were negative for PAX6 mutations. Nineteen probands with anterior segment dysgenesis, one proband with optic nerve malformation, and two probands with microphthalmia were also sequenced. The control population comprised 376 healthy individuals. All sequences were analyzed against the GenBank sequence AL078596.8 for NR2E1. In addition, the coding region and flanking intronic sequences of FOXE3, FOXC1, PITX2, CYP1B1, PAX6, and B3GALTL were sequenced in one patient and his relatives. Results Sequencing analysis showed 17 NR2E1 variants including two novel rare non-coding variants (g.-1507G>A, g.14258C>T), and one novel rare coding variant (p.Arg274Gly). The latter was present in a male diagnosed with Peters’ anomaly who subsequently was found to have a known causative mutation for Peters’ plus syndrome in B3GALTL (c.660+1G>A). In addition, the NR2E1 novel rare variant Arg274Gly was present in the unaffected mother of the patient but absent in 746 control chromosomes. Conclusions We eliminated a major role for NR2E1 regulatory and coding mutations in aniridia and found a novel rare coding variant in NR2E1. In addition, we found no coding region variation in the control population for NR2E1, which further supports its previously reported high level of conservation and low genetic diversity

  2. Suppression of mutations in two Saccharomyces cerevisiae genes by the adenovirus E1A protein.

    PubMed Central

    Zieler, H A; Walberg, M; Berg, P

    1995-01-01

    The protein products of the adenoviral E1A gene are implicated in a variety of transcriptional and cell cycle events, involving interactions with several proteins present in human cells, including parts of the transcriptional machinery and negative regulators of cell division such as the Rb gene product and p107. To determine if there are functional homologs of E1A in Saccharomyces cerevisiae, we have developed a genetic screen for mutants that depend on E1A for growth. The screen is based on a colony color sectoring assay which allows the identification of mutants dependent on the maintenance and expression of an E1A-containing plasmid. Using this screen, we have isolated five mutants that depend on expression of the 12S or 13S cDNA of E1A for growth. A plasmid shuffle assay confirms that the plasmid-dependent phenotype is due to the presence of either the 12S or the 13S E1A cDNA and that both forms of E1A rescue growth of all mutants equally well. The five mutants fall into two classes that were named web1 and web2 (for "wants E1A badly"). Plasmid shuffle assays with mutant forms of E1A show that conserved region 1 (CR1) is required for rescue of the growth of the web1 and web2 E1A-dependent yeast mutants, while the N-terminal 22 amino acids are only partially required; conserved region 2 (CR2) and the C terminus are dispensable. The phenotypes of mutants in both the web1 and the web2 groups are due to a single gene defect, and the yeast genes that fully complement the mutant phenotypes of both groups were cloned. The WEB1 gene sequence encodes a 1,273-amino-acid protein that is identical to SEC31, a protein involved in the budding of transport vesicles from the endoplasmic reticulum. The WEB2 gene encodes a 1,522-amino-acid protein with homology to nucleic acid-dependent ATPases. Deletion of either WEB1 or WEB2 is lethal. Expression of E1A is not able to rescue the lethality of either the web1 or the web2 null allele, implying allele-specific mutations that lead

  3. Limited temperature-sensitive transactivation by mutant adenovirus type 2 E1a proteins.

    PubMed Central

    Fahnestock, M L; Lewis, J B

    1989-01-01

    A series of linker-scanning and deletion mutations was generated in the transactivating domain of the larger, 289-amino-acid-residue E1a protein of adenovirus type 2. Mutant genes were recombined into virus to assay the ability of the variant E1a proteins to activate expression of an E1a-dependent viral gene during infection. Results of assays performed at 32, 37, and 40 degrees C indicated that at least 2 of the 10 mutants tested showed limited temperature sensitivity for transactivation. Images PMID:2523001

  4. Identification of a functional splice variant of 14-3-3E1 in rainbow trout.

    PubMed

    Wanna, Warapond; Rexroad, Caird E; Yao, Jianbo

    2010-02-01

    The 14-3-3 protein family is a family of regulatory proteins involved in diverse cellular processes. The presence of 14-3-3 isoforms and the diversity of cellular processes regulated by 14-3-3 isoforms suggest functional specificity of the isoforms. In this study, we report the identification and characterization of a new isoform of the rainbow trout 14-3-3E1 gene generated by alternative splicing. The new isoform contains an insertion of 48 nucleotides (from intron 5) in the coding region of 14-3-3E1 which results in the introduction of a premature stop codon between exon 5 and exon 6. Thus, the alternatively spliced form of 14-3-3E1 (14-3-3E1DeltaC17) lacks 17 amino acid residues at the C terminus encoded by the last exon (exon 6). Reverse-transcription polymerase chain reaction analysis revealed that the wild-type 14-3-3E1 (14-3-3E1wt) is ubiquitously expressed, while 14-3-3E1DeltaC17 shows tissue-specific as well as stage-specific expression during ovarian development and early embryogenesis. Analysis by yeast two-hybrid system demonstrated that 14-3-3E1Delta17 interacts with a number of proteins including ATP synthase, ankyrin repeat domain 13b, cytochrome c subunit VIa, cytochrome c subunit VIb, 60S ribosomal protein L34, solute carrier family 17 member 6 (SLC17A6), troponin I, and an unknown protein. Although all of these proteins except for SLC17A6 also interact with 14-3-3E1wt, 14-3-3E1Delta17 appears to have higher binding affinity with these proteins than 14-3-3E1wt. These findings suggest that alternative splicing affects the function and tissue-specific expression of 14-3-3E1.

  5. Transitional Care

    ERIC Educational Resources Information Center

    Naylor, Mary; Keating, Stacen A.

    2008-01-01

    Transitional care encompasses a broad range of services and environments designed to promote the safe and timely passage of patients between levels of health care and across care settings. High-quality transitional care is especially important for older adults with multiple chronic conditions and complex therapeutic regimens, as well as for their…

  6. Transitional Care

    ERIC Educational Resources Information Center

    Naylor, Mary; Keating, Stacen A.

    2008-01-01

    Transitional care encompasses a broad range of services and environments designed to promote the safe and timely passage of patients between levels of health care and across care settings. High-quality transitional care is especially important for older adults with multiple chronic conditions and complex therapeutic regimens, as well as for their…

  7. TEM-E1: a novel beta-lactamase conferring resistance to ceftazidime.

    PubMed

    Payne, D J; Marriott, M S; Amyes, S G

    1989-05-01

    A novel beta-lactamase, conferring resistance to ceftazidime, has been identified to be encoded by a 31 kb plasmid (pUK720) in a clinical E. coli strain isolated in Belgium. The beta-lactamase, new designated TEM-E1, has a pI of approximately 5.4 and lies in between the iso-electric focused bands of the beta-lactamases TEM-1 and TEM-7. The TEM-E1 beta-lactamase has a similar molecular weight of 22,000 to the TEM-1 and it is also inhibited by clavulanic acid. However, the TEM-E1 enzyme differs from TEM-1 by its low rates and efficiency of hydrolysis for ceftazidime and cefotaxime, TEM-E1 has similar efficiency of hydrolysis values for ceftazidime and cefotaxime, but only confers resistance to ceftazidime.

  8. The C-terminal region of E1A: a molecular tool for cellular cartography.

    PubMed

    Yousef, Ahmed F; Fonseca, Gregory J; Cohen, Michael J; Mymryk, Joe S

    2012-04-01

    The adenovirus E1A proteins function via protein-protein interactions. By making many connections with the cellular protein network, individual modules of this virally encoded hub reprogram numerous aspects of cell function and behavior. Although many of these interactions have been thoroughly studied, those mediated by the C-terminal region of E1A are less well understood. This review focuses on how this region of E1A affects cell cycle progression, apoptosis, senescence, transformation, and conversion of cells to an epithelial state through interactions with CTBP1/2, DYRK1A/B, FOXK1/2, and importin-α. Furthermore, novel potential pathways that the C-terminus of E1A influences through these connections with the cellular interaction network are discussed.

  9. 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

  10. 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.

  11. Anomalous behaviors of E1/E2 deep level defects in 6H silicon carbide

    NASA Astrophysics Data System (ADS)

    Chen, X. D.; Ling, C. C.; Gong, M.; Fung, S.; Beling, C. D.; Brauer, G.; Anwand, W.; Skorupa, W.

    2005-01-01

    Deep level defects E1/E2 were observed in He-implanted, 0.3 and 1.7MeV electron-irradiated n-type 6H-SiC. Similar to others' results, the behaviors of E1 and E2 (like the peak intensity ratio, the annealing behaviors or the introduction rates) often varied from sample to sample. This anomalous result is not expected of E1/E2 being usually considered arising from the same defect located at the cubic and hexagonal sites respectively. The present study shows that this anomaly is due to another DLTS peak overlapping with the E1/E2. The activation energy and the capture cross section of this defect are EC-0.31eV and σ ˜8×10-14cm2, respectively.

  12. 26 CFR 1.1397E-1 - Qualified zone academy bonds.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... TAX (CONTINUED) INCOME TAXES Empowerment Zone Employment Credit § 1.1397E-1 Qualified zone academy...), (iii), (iv) or (v). Services of employees of the eligible local education agency do not constitute...

  13. [Prostaglandin E1 in the treatment of chronic ischemia of the extremities].

    PubMed

    Kowal-Gierczak, B; Kurzawska-Mielecka, M; Czarnacki, M

    1990-11-01

    The authors observed the effect of prostaglandin E1 (Prostavasine) on the blood flow in the lower extremities in 25 patients with chronic ischemia caused by thrombo-angitis obliterans and arteriosclerosis obliterans (clinical stage III and IV). The blood flow in the lower extremities and the effects of prostaglandin E1 were assessed by means of rheo-angiographic and Doppler-testing investigations. The parameters A (amplitude), S (area) and WOT (index) of rheo-angiographic curves showed significant increased. No significant changes were found in the determined Doppler's indexes. The observed differences of values the parameters of rheo-angiographic curves suggests that prostaglandin E1 evident improvement the tissue blood flow in patients with critical ischemia of the lower extremities. The authors found that prostaglandin E1 was without any significant effect dilating the great vessels, but an evident improvement was observed in rheo-angiographic records which reflect rather the blood flow values in the small vessels.

  14. Mitochondrial dysfunction by gamma-irradiation accompanies the induction of cytochrome P450 2E1 (CYP2E1) in rat liver.

    PubMed

    Chung, H C; Kim, S H; Lee, M G; Cho, C K; Kim, T H; Lee, D H; Kim, S G

    2001-03-21

    Multiple biological effects are induced by ionizing radiation through dysfunction of cellular organelles, direct interaction with nucleic acids and production of free radical species. The expression of cytochrome P450s was assessed in the livers of 60Co gamma-irradiated rats. Three gray (G) of gamma-irradiation caused CYP2E1 induction with a 3.6-fold increase in the mRNA at 24 h, whereas the expression of CYP1A2 and CYP3A was not changed. Pharmacokinetics of chlorzoxazone, a specific substrate of CYP2E1, was studied in 3 G-irradiated rats. The area under the plasma concentration-time curve from time zero to infinity of 6-hydroxychlorzoxazone and the amount of 6-hydroxychlorzoxazone excreted in 8 h urine were both significantly greater than those in control rats. Hepatic CYP2E1 was not induced in rats exposed to 0.5-1 G of gamma-rays. Rats irradiated at 6-9 G accumulated doses of gamma-rays exhibited smaller increases in the mRNA due to liver injury than those irradiated at a single dose of 3 G gamma-rays. The plasma glucose and insulin levels were not altered in rats with 3 G of gamma-irradiation. As the exposure level of gamma-irradiation increased, the activity of hepatic aconitase, a key enzyme in energy metabolism in mitochondria, was 30-90% decreased. The amount of mitochondrial DNA per gram of wet liver was 50% decreased in rats exposed to 3 G of gamma-rays. These results demonstrated that gamma-ray irradiation at the exposure level inducing organelle dysfunction induced CYP2E1 in the liver, which might be associated with mitochondrial damage, but not with alterations in glucose or insulin levels.

  15. Evolution of the ubiquitin-activating enzyme Uba1 (E1)

    NASA Astrophysics Data System (ADS)

    Allan, Douglas C.; Phillips, J. C.

    2017-10-01

    Ubiquitin tags diseased proteins and initiates an enzyme conjugation cascade, which has three stages. The first-stage enzyme Uba1 (E1) has evolved only modestly from slime mold to humans, and is > 14 times larger than Ub. Here we use critical point thermodynamic scaling theory to connect Uba1 (E1) evolution from yeast and slime mold to fruit flies and humans to subtle changes in its amino acid sequences.

  16. The E1-E2 center in gallium arsenide is the divacancy.

    PubMed

    Schultz, Peter A

    2015-02-25

    Based on defect energy levels computed from first-principles calculations, it is shown the E1-E2 center in irradiated GaAs cannot be due to an isolated arsenic vacancy. The only simple intrinsic defect with levels compatible with E1 and E2 is the divacancy. The arsenic monovacancy is reassigned to the E3 center in irradiated GaAs. These new assignments are shown to reconcile a number of seemingly contradictory experimental observations.

  17. E1A-responsive elements for repression of rat fibronectin gene transcription.

    PubMed Central

    Nakajima, T; Nakamura, T; Tsunoda, S; Nakada, S; Oda, K

    1992-01-01

    The level of fibronectin (FN) gene transcription in resting rat 3Y1 cells is very high but decreases steeply after growth stimulation by serum or by the induction of E1A expression. To study the mechanism of this E1A-mediated down-regulation, the 5' flanking regions of the FN gene with various deletions and substitutions were fused to the Escherichia coli chloramphenicol acetyltransferase (CAT) gene and introduced into resting 3Y1 cells with E1A expression plasmids. The results indicate that the G10 stretch located from nucleotide position -239 to -230 and two GC boxes from position -105 to -95 and position -54 to -44 are the primary E1A-responsive elements for repression of the FN gene. Two GC boxes also contain a G10 stretch that is interrupted by the presence of an internal C residue. These sequences overlap with the Sp1 motif GGGCGG. Substitution of the sequence GGGG with ATCC or CTTA in these G-rich sequences, leaving the Sp1 motif intact, completely abolished the E1A sensitivity of the promoter. Analysis of the E1A domains by using various E1A deletion mutants indicated that the domain for binding to the retinoblastoma susceptibility gene product (RB) is essential for efficient repression. These results suggest that the gene encoding a negative factor(s) binding to the three G-rich sequences in the FN promoter is repressed by RB in resting 3Y1 cells and derepressed by expression of E1A. PMID:1534144

  18. Trans-complementable copy-number mutants of plasmid ColE1.

    PubMed

    Twigg, A J; Sherratt, D

    1980-01-10

    Plasmid ColE1, like many other small non-conjugative plasmids, is present in multiple copies (about 15 per chromsome equivalent) in Escherichia coli cells. Because of their high copy number, the replication of such plasmids has been described as 'relaxed', even though there is good evidence that it is strictly controlled: ColE1 derivatives have characteristic but different copy numbers and ColE1 copy-number mutants have been characterised. No plasmid-specified protein is essential for the replication of ColE1 and related plasmids, as extensive replication can occur in chloramphenicol-treated cells, in plasmid-free chloramphenicol-treated cells transfected with a hybrid ColE1/phage replicon and in vitro in extracts derived from plasmid-free cells. Nevertheless, it is possible that a plasmid-specified protein is involved in ColE1 replication control in viable cells. Here we show that deletion of a given non-essential region from ColE1-like plasmids results in a raised copy number. Such plasmids are stably maintained and have their copy number returned to normal when a complementing plasmid is present in the same cell, indicating that a plasmid-specified diffusible gene product regulates the plasmid content of ColE1-containing cells. Deletion of the equivalent region from the cloning vector pBR322 gives a derivative which has a raised copy number and which has also lost its origin for conjugal transfer; unlike pBR322, it cannot be mobilised.

  19. Impact of resolvin E1 on murine neutrophil phagocytosis in type 2 diabetes.

    PubMed

    Herrera, Bruno S; Hasturk, Hatice; Kantarci, Alpdogan; Freire, Marcelo O; Nguyen, Olivia; Kansal, Shevali; Van Dyke, Thomas E

    2015-02-01

    Diabetic complications involve inflammation-mediated microvascular and macrovascular damage, disruption of lipid metabolism, glycosylation of proteins, and abnormalities of neutrophil-mediated events. Resolution of inflamed tissues to health and homeostasis is an active process mediated by endogenous lipid agonists, including lipoxins and resolvins. This proresolution system appears to be compromised in type 2 diabetes (T2D). The goal of this study was to investigate unresolved inflammation in T2D. Wild-type (WT) and genetically engineered mice, including T2D mice (db/db), transgenic mice overexpressing the human resolvin E1 (RvE1) receptor (ERV1), and a newly bred strain of db/ERV1 mice, were used to determine the impact of RvE1 on the phagocytosis of Porphyromonas gingivalis in T2D. Neutrophils were isolated and incubated with fluorescein isothiocyanate-labeled P. gingivalis, and phagocytosis was measured in a fluorochrome-based assay by flow cytometry. Mitogen-activated protein kinase (MAPK) (p42 and p44) and Akt (Thr308 and Ser473) phosphorylation was analyzed by Western blotting. The mouse dorsal air pouch model was used to evaluate the in vivo impact of RvE1. Results revealed that RvE1 increased the neutrophil phagocytosis of P. gingivalis in WT animals but had no impact in db/db animals. In ERV1-transgenic and ERV1-transgenic diabetic mice, phagocytosis was significantly increased. RvE1 decreased Akt and MAPK phosphorylation in the transgenic animals. In vivo dorsal air pouch studies revealed that RvE1 decreases neutrophil influx into the pouch and increases neutrophil phagocytosis of P. gingivalis in the transgenic animals; cutaneous fat deposition was reduced, as was macrophage infiltration. The results suggest that RvE1 rescues impaired neutrophil phagocytosis in obese T2D mice overexpressing ERV1.

  20. 11 CFR 300.60 - Scope (2 U.S.C. 441i(e)(1)).

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 11 Federal Elections 1 2013-01-01 2012-01-01 true Scope (2 U.S.C. 441i(e)(1)). 300.60 Section 300.60 Federal Elections FEDERAL ELECTION COMMISSION BIPARTISAN CAMPAIGN REFORM ACT OF 2002-(BCRA) REGULATIONS NON-FEDERAL FUNDS Federal Candidates and Officeholders § 300.60 Scope (2 U.S.C. 441i(e)(1)). This...

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

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 11 Federal Elections 1 2012-01-01 2012-01-01 false Scope (2 U.S.C. 441i(e)(1)). 300.60 Section 300.60 Federal Elections FEDERAL ELECTION COMMISSION BIPARTISAN CAMPAIGN REFORM ACT OF 2002-(BCRA) REGULATIONS NON-FEDERAL FUNDS Federal Candidates and Officeholders § 300.60 Scope (2 U.S.C. 441i(e)(1)). This...

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

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 11 Federal Elections 1 2014-01-01 2014-01-01 false Scope (2 U.S.C. 441i(e)(1)). 300.60 Section 300.60 Federal Elections FEDERAL ELECTION COMMISSION BIPARTISAN CAMPAIGN REFORM ACT OF 2002-(BCRA) REGULATIONS NON-FEDERAL FUNDS Federal Candidates and Officeholders § 300.60 Scope (2 U.S.C. 441i(e)(1)). This...

  3. Structure-function analysis of hepatitis C virus envelope glycoproteins E1 and E2.

    PubMed

    Nayak, Aparajita; Pattabiraman, Nagarajan; Fadra, Numrah; Goldman, Radoslav; Kosakovsky Pond, Sergei L; Mazumder, Raja

    2015-01-01

    Hepatitis C virus (HCV) is the leading cause of chronic liver disease in humans. The envelope proteins of HCV are potential candidates for vaccine development. The absence of three-dimensional (3D) structures for the functional domain of HCV envelope proteins [E1.E2] monomer complex has hindered overall understanding of the virus infection, and also structure-based drug design initiatives. In this study, we report a 3D model containing both E1 and E2 proteins of HCV using the recently published structure of the core domain of HCV E2 and the functional part of E1, and investigate immunogenic implications of the model. HCV [E1.E2] molecule is modeled by using aa205-319 of E1 to aa421-716 of E2. Published experimental data were used to further refine the [E1.E2] model. Based on the model, we predict 77 exposed residues and several antigenic sites within the [E1.E2] that could serve as vaccine epitopes. This study identifies eight peptides which have antigenic propensity and have two or more sequentially exposed amino acids and 12 singular sites are under negative selection pressure that can serve as vaccine or therapeutic targets. Our special interest is 285FLVGQLFTFSPRRHW299 which has five negatively selected sites (L286, V287, G288, T292, and G303) with three of them sequential and four amino acids exposed (F285, L286, T292, and R296). This peptide in the E1 protein maps to dengue envelope vaccine target identified previously by our group. Our model provides for the first time an overall view of both the HCV envelope proteins thereby allowing researchers explore structure-based drug design approaches.

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

    PubMed

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

    2017-02-06

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

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

    PubMed Central

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

    2017-01-01

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

  6. 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.

  7. CYP2E1 potentiates binge alcohol-induced gut leakiness, steatohepatitis and apoptosis

    PubMed Central

    Abdelmegeed, Mohamed A.; Banerjee, Atrayee; Jang, Sehwan; Yoo, Seong-Ho; Yun, Jun-Won; Gonzalez, Frank J.; Keshavarzian, Ali; Song, Byoung-Joon

    2013-01-01

    Ethanol-inducible cytochrome P450 2E1 (CYP2E1) contributes to increased oxidative stress and steatosis in chronic alcohol-exposure models. However, its role in binge ethanol-induced gut leakiness and hepatic injury is unclear. This study was aimed to investigate the role of CYP2E1 in binge alcohol-induced gut leakiness and the mechanisms of steatohepatitis. Female wild-type (WT) and Cyp2e1-null mice were treated with three doses of binge ethanol (WT-EtOH or Cyp2e1-null-EtOH) (6 g/kg oral gavage at 12-h intervals) or dextrose (negative control). Intestinal histology of only WT-EtOH exhibited epithelial alteration and blebbing of lamina propria while liver histology obtained at 6 h after the last ethanol dose showed elevated steatosis with scattered inflammatory foci. These were accompanied by increased levels of serum endotoxin, hepatic enterobacteria and triglycerides. All these changes including the intestinal histology and hepatic apoptosis, determined by TUNEL assay, were significantly reversed when WT-EtOH mice were treated with the specific inhibitor of CYP2E1 chlormethiazole and the antioxidant N-acetyl-cysteine, both of which suppressed the oxidative markers including intestinal CYP2E1. WT-EtOH also exhibited elevated amounts of serum TNF-α, hepatic cytokines, CYP2E1 and lipid peroxidation with decreased levels of mitochondrial superoxide dismutase and suppressed aldehyde dehydrogenase 2 activity. Increased hepatocyte apoptosis with elevated levels of pro-apoptotic proteins and decreased levels of active (phosphorylated) p-AKT, p-AMPK and peroxisome proliferator-activated receptor-alpha (PPAR-α), all of which are involved in fat metabolism and inflammation, were observed in WT-EtOH. These changes were significantly attenuated in the corresponding Cyp2e1-null-EtOH mice. These data indicate that both intestinal and hepatic CYP2E1 induced by binge alcohol seem critical in the binge alcohol-mediated increased nitroxidative stress, gut leakage, endotoxemia, and

  8. CYP2E1 potentiates binge alcohol-induced gut leakiness, steatohepatitis, and apoptosis.

    PubMed

    Abdelmegeed, Mohamed A; Banerjee, Atrayee; Jang, Sehwan; Yoo, Seong-Ho; Yun, Jun-Won; Gonzalez, Frank J; Keshavarzian, Ali; Song, Byoung-Joon

    2013-12-01

    Ethanol-inducible cytochrome P450 2E1 (CYP2E1) contributes to increased oxidative stress and steatosis in chronic alcohol-exposure models. However, its role in binge ethanol-induced gut leakiness and hepatic injury is unclear. This study was aimed at investigating the role of CYP2E1 in binge alcohol-induced gut leakiness and the mechanisms of steatohepatitis. Female wild-type (WT) and Cyp2e1-null mice were treated with three doses of binge ethanol (WT-EtOH or Cyp2e1-null-EtOH) (6g/kg oral gavage at 12-h intervals) or dextrose (negative control). Intestinal histology of only WT-EtOH exhibited epithelial alteration and blebbing of lamina propria, and liver histology obtained at 6h after the last ethanol dose showed elevated steatosis with scattered inflammatory foci. These were accompanied by increased levels of serum endotoxin, hepatic enterobacteria, and triglycerides. All these changes, including the intestinal histology and hepatic apoptosis, determined by TUNEL assay, were significantly reversed when WT-EtOH mice were treated with the specific inhibitor of CYP2E1 chlormethiazole and the antioxidant N-acetylcysteine, both of which suppressed oxidative markers including intestinal CYP2E1. WT-EtOH also exhibited elevated amounts of serum TNF-α, hepatic cytokines, CYP2E1, and lipid peroxidation, with decreased levels of mitochondrial superoxide dismutase and suppressed aldehyde dehydrogenase 2 activity. Increased hepatocyte apoptosis with elevated levels of proapoptotic proteins and decreased levels of active (phosphorylated) p-AKT, p-AMPK, and peroxisome proliferator-activated receptor-α, all of which are involved in fat metabolism and inflammation, were observed in WT-EtOH. These changes were significantly attenuated in the corresponding Cyp2e1-null-EtOH mice. These data indicate that both intestinal and hepatic CYP2E1 induced by binge alcohol seems critical in binge alcohol-mediated increased nitroxidative stress, gut leakage, and endotoxemia; altered fat

  9. 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

  10. Geological Transition

    NASA Image and Video Library

    2014-09-11

    This image, taken by NASA Mars Reconnaissance Orbiter, shows the transition between the Murray Formation, in which layers are poorly expressed and difficult to trace from orbit, and the hematite ridge, which is made up of continuous layers.

  11. 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

  12. CYP2E1-dependent elevation of serum cholesterol, triglycerides, and hepatic bile acids by isoniazid.

    PubMed

    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. Published by Elsevier Inc.

  13. Cytochrome P450-2E1 promotes fast food-mediated hepatic fibrosis.

    PubMed

    Abdelmegeed, Mohamed A; Choi, Youngshim; Godlewski, Grzegorz; Ha, Seung-Kwon; Banerjee, Atrayee; Jang, Sehwan; Song, Byoung-Joon

    2017-01-04

    Cytochrome P450-2E1 (CYP2E1) increases oxidative stress. High hepatic cholesterol causes non-alcoholic steatohepatitis (NASH) and fibrosis. Thus, we aimed to study the role of CYP2E1 in promoting liver fibrosis by high cholesterol-containing fast-food (FF). Male wild-type (WT) and Cyp2e1-null mice were fed standard chow or FF for 2, 12, and 24 weeks. Various parameters of liver fibrosis and potential mechanisms such as oxidative and endoplasmic reticulum (ER) stress, inflammation, and insulin resistance (IR) were studied. Indirect calorimetry was also used to determine metabolic parameters. Liver histology showed that only WT fed FF (WT-FF) developed NASH and fibrosis. Hepatic levels of fibrosis protein markers were significantly increased in WT-FF. The nitroxidative stress marker iNOS, but not CYP2E1, was significantly elevated only in FF-fed WT. Serum endotoxin, TLR-4 levels, and inflammatory markers were highest in WT-FF. FAS, PPAR-α, PPAR-γ, and CB1-R were markedly altered in WT-FF. Electron microscopy and immunoblot analyses showed significantly higher levels of ER stress in FF-fed WT. Indirect calorimetry showed that Cyp2e1-null-mice fed FF exhibited consistently higher total energy expenditure (TEE) than their corresponding WT. These results demonstrate that CYP2E1 is important in fast food-mediated liver fibrosis by promoting nitroxidative and ER stress, endotoxemia, inflammation, IR, and low TEE.

  14. Mutation in E1, the ubiquitin activating enzyme, reduces Drosophila lifespan and results in motor impairment.

    PubMed

    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.

  15. Neutrophil Resolvin E1 Receptor Expression and Function in Type 2 Diabetes.

    PubMed

    Freire, Marcelo O; Dalli, Jesmond; Serhan, Charles N; Van Dyke, Thomas E

    2017-01-15

    Unresolved inflammation is key in linking metabolic dysregulation and the immune system in type 2 diabetes. Successful regulation of acute inflammation requires biosynthesis of specialized proresolving lipid mediators, such as E-series resolvin (RvE) 1, and activation of cognate G protein-coupled receptors. RvE1 binds to leukotriene B4 (BLT-1) on neutrophils and to ERV-1/ChemR23 on monocyte/macrophages. We show novel actions of RvE1 and expression patterns of neutrophil receptors in type 2 diabetes. Neutrophils from healthy subjects express functional BLT-1, low levels of minimally functional ERV-1, and inversed coexpression when compared to neutrophils from type 2 diabetes subjects. Stimulation with TNF-α or LPS increased the expression of ERV-1 by healthy and diabetic neutrophils. RvE1 counteracted LPS and TNF-α induction of ERV-1 overexpression and endogenous diabetic overexpression, activating phagocytosis and resolution signals. Functional ERV-1 was determined by phosphorylation of the signaling protein ribosomal S6. Receptor-antagonism experiments revealed that the increase in phosphorylation of ribosomal S6 was mediated by BLT-1 in healthy subject neutrophils and by ERV-1 in diabetes. Metabololipidomics reveal a proinflammatory profile in diabetic serum. Cell phagocytosis is impaired in type 2 diabetes and requires RvE1 for activation. The dose of RvE1 required to activate resolution signals in type 2 diabetic neutrophils was significantly higher than in healthy controls. RvE1 rescues the dysregulation seen on neutrophil receptor profile and, following a therapeutic dosage, activates phagocytosis and resolution signals in type 2 diabetes. These findings reveal the importance of resolution receptors in health, disease, and dysregulation of inflammation in type 2 diabetes.

  16. Multifactorial Comparative Proteomic Study of Cytochrome P450 2E1 Function in Chronic Alcohol Administration

    PubMed Central

    Wang, Yuan; Kou, Yan; Wang, Xiaodong; Cederbaum, Arthur; Wang, Rong

    2014-01-01

    With the use of iTRAQ technique, a multifactorial comparative proteomic study can be performed. In this study, to obtain an overview of ethanol, CYP2E1 and gender effects on liver injury and gain more insight into the underlying molecular mechanism, mouse liver proteomes were quantitatively analyzed using iTRAQ under eight conditions including mice of different genders, wild type versus CYP2E1 knockout, and normal versus alcohol diet. A series of statistical and bioinformatic analyses were explored to simplify and clarify multifactorial comparative proteomic data. First, with the Principle Component analysis, six proteins, CYP2E1, FAM25, CA3, BHMT, HIBADH and ECHS1, involved in oxidation reduction, energy and lipid metabolism and amino acid metabolism, were identified as the most differentially expressed gene products across all of the experimental conditions of our chronic alcoholism model. Second, hierarchical clustering analysis showed CYP2E1 knockout played a primary role in the overall differential protein expression compared with ethanol and gender factors. Furthermore, pair-wise multiple comparisons have revealed that the only significant expression difference lied in wild-type and CYP2E1 knockout mice both treated with ethanol. Third, K-mean clustering analysis indicated that the CYP2E1 knockout had the reverse effect on ethanol induced oxidative stress and lipid oxidation. More importantly, IPA analysis of proteomic data inferred that the gene expressions of two upstream regulators, NRF2 and PPARα, regulated by chronic alcohol feeding and CYP2E1 knockout, are involved in ethanol induced oxidative stress and lipid oxidation. The present study provides an effectively comprehensive data analysis strategy to compare multiple biological factors, contributing to biochemical effects of alcohol on the liver. The mass spectrometry proteomics data have been deposited to the ProteomeXchange with data set identifier of PXD000635. PMID:24658151

  17. In vivo and in vitro characterization of CYP2E1 activity in Japanese and Caucasians.

    PubMed

    Kim, R B; Yamazaki, H; Chiba, K; O'Shea, D; Mimura, M; Guengerich, F P; Ishizaki, T; Shimada, T; Wilkinson, G R

    1996-10-01

    Chlorzoxazone's disposition after oral administration was determined in 20 young healthy Caucasian men and a similar group of Japanese men. The drug's plasma concentrations were significantly higher and its rate of elimination slower in Japanese compared to Caucasian men. Accordingly, chlorzoxazone's oral clearance was smaller (40%) in Japanese men and a similar difference (30%) was still apparent after normalizing for body weight (3.74 +/- 1.23 versus 5.05 +/- 1.41 ml.min-1.kg-1, P < .05). This slower elimination was associated with a reduced (fractional) clearance by 6-hydroxylation (2.34 +/- 1.04 ml.min-1.kg-1 versus 3.23 +/- 1.10, P < .05). Because such metabolism is mediated by cytochrome P4502E1 (CYP2E1), these findings suggest a lower level of the enzyme's catalytic activity in Japanese men. This was confirmed by in vitro studies with microsomes prepared from livers of individuals representative of the two racial groups. CYP2E1 levels were lower (61% P < .002) and CYP2E1-mediated chlorzoxazone 6-hydroxylase (22%, P < .001) and aniline 4-hydroylase (35%, P < .0001) activities were reduced in Japanese preparations compared to those from Caucasians. No relationships were found between measures of CYP2E1 activity, both in vivo and in vitro, and genomic polymorphisms in the CYP2E1 gene identified by Rsal/Pstl and Dral restriction fragment length polymorphisms. Collectively, these data show an interracial difference in CYP2E1 activity. Because this enzyme is importantly involved in the activation of environmental procarcinogens, such a difference may account, in part, for the lower rate of some cancers, e.g., lung cancer, in Japanese compared to Caucasians men.

  18. Cytochrome P450-2E1 promotes fast food-mediated hepatic fibrosis

    PubMed Central

    Abdelmegeed, Mohamed A.; Choi, Youngshim; Godlewski, Grzegorz; Ha, Seung-Kwon; Banerjee, Atrayee; Jang, Sehwan; Song, Byoung-Joon

    2017-01-01

    Cytochrome P450-2E1 (CYP2E1) increases oxidative stress. High hepatic cholesterol causes non-alcoholic steatohepatitis (NASH) and fibrosis. Thus, we aimed to study the role of CYP2E1 in promoting liver fibrosis by high cholesterol-containing fast-food (FF). Male wild-type (WT) and Cyp2e1-null mice were fed standard chow or FF for 2, 12, and 24 weeks. Various parameters of liver fibrosis and potential mechanisms such as oxidative and endoplasmic reticulum (ER) stress, inflammation, and insulin resistance (IR) were studied. Indirect calorimetry was also used to determine metabolic parameters. Liver histology showed that only WT fed FF (WT-FF) developed NASH and fibrosis. Hepatic levels of fibrosis protein markers were significantly increased in WT-FF. The nitroxidative stress marker iNOS, but not CYP2E1, was significantly elevated only in FF-fed WT. Serum endotoxin, TLR-4 levels, and inflammatory markers were highest in WT-FF. FAS, PPAR-α, PPAR-γ, and CB1-R were markedly altered in WT-FF. Electron microscopy and immunoblot analyses showed significantly higher levels of ER stress in FF-fed WT. Indirect calorimetry showed that Cyp2e1-null-mice fed FF exhibited consistently higher total energy expenditure (TEE) than their corresponding WT. These results demonstrate that CYP2E1 is important in fast food-mediated liver fibrosis by promoting nitroxidative and ER stress, endotoxemia, inflammation, IR, and low TEE. PMID:28051126

  19. Adenovirus E1B 19-Kilodalton Protein Modulates Innate Immunity through Apoptotic Mimicry

    PubMed Central

    Grigera, Fernando; Ucker, David S.; Cook, James L.

    2014-01-01

    ABSTRACT Cells that undergo apoptosis in response to chemical or physical stimuli repress inflammatory reactions, but cells that undergo nonapoptotic death in response to such stimuli lack this activity. Whether cells dying from viral infection exhibit a cell death-type modulatory effect on inflammatory reactions is unknown. We compared the effects on macrophage inflammatory responses of cells dying an apoptotic or a nonapoptotic death as a result of adenoviral infection. The results were exactly opposite to the predictions from the conventional paradigm. Cells dying by apoptosis induced by infection with an adenovirus type 5 (Ad5) E1B 19-kilodalton (E1B 19K) gene deletion mutant did not repress macrophage NF-κB activation or cytokine responses to proinflammatory stimuli, whereas cells dying a nonapoptotic death from infection with E1B 19K-competent, wild-type Ad5 repressed these macrophage inflammatory responses as well as cells undergoing classical apoptosis in response to chemical injury. The immunorepressive, E1B 19K-related cell death activity depended upon direct contact of the virally infected corpses with responder macrophages. Replacement of the viral E1B 19K gene with the mammalian Bcl-2 gene in cis restored the nonapoptotic, immunorepressive cell death activity of virally infected cells. These results define a novel function of the antiapoptotic, adenoviral E1B 19K protein that may limit local host innate immune inflammation during accumulation of virally infected cells at sites of infection and suggest that E1B 19K-deleted, replicating adenoviral vectors might induce greater inflammatory responses to virally infected cells than E1B 19K-positive vectors, because of the net effect of their loss-of-function mutation. IMPORTANCE We observed that cells dying a nonapoptotic cell death induced by adenovirus infection repressed macrophage proinflammatory responses while cells dying by apoptosis induced by infection with an E1B 19K deletion mutant virus did not

  20. Polymorphisms of E1 and GIGANTEA in wild populations of Lotus japonicus.

    PubMed

    Wakabayashi, Tomomi; Oh, Hana; Kawaguchi, Masayoshi; Harada, Kyuya; Sato, Shusei; Ikeda, Hajime; Setoguchi, Hiroaki; Hiroaki, Setoguchi

    2014-11-01

    In plants, timing of flowering is an essential factor that controls the survival rates of descendants. The circadian clock genes E1 and GIGANTEA (GI) play a central role in transmitting signals to flowering locus T (FT) in leguminous plants. Lotus japonicus is a wild Japanese species that ranges from northern Hokkaido to the southern Ryukyus and exhibits a wide range in terms of the time between seeding and first flowering. In this study, we first identified LjGI and analyzed polymorphisms of LjE1 and LjGI among wild populations covering the entire distribution range of this species in Japan. LjGI had a coding sequence (CDS) length of 3495 bp and included 14 exons. The homologies of DNA and amino acid sequences between LjGI and GmGI were 89 and 88% (positive rate was 92%), respectively. LjE1 harbored five nucleic acid changes in a 552 bp CDS, all of which were nonsynonymous; four of the changes were located in the core function area. LjE1 alleles exhibited partial north-south differentiation and non-neutrality. In contrast, the LjGI harbored one synonymous and one nonsynonymous change. Thus, our study suggests that LjE1 may be involved in the control of flowering times, whereas LjGI may be under strong purifying selection.

  1. Olive cultivar origin is a major cause of polymorphism for Ole e 1 pollen allergen

    PubMed Central

    Hamman-Khalifa, AbdelMounim; Castro, Antonio Jesús; Jiménez-López, José Carlos; Rodríguez-García, María Isabel; Alché, Juan de Dios

    2008-01-01

    Background Pollens from different olive (Olea europaea L.) cultivars have been shown to differ significantly in their content in Ole e 1 and in their overall allergenicity. This allergen is, in addition, characterized by a high degree of polymorphism in its sequence. The purpose of this study is to evaluate the putative presence of divergences in Ole e 1 sequences from different olive cultivars. Results RNA from pollen individually collected from 10 olive cultivars was used to amplify Ole e 1 sequences by RT-PCR, and the sequences were analyzed by using different bioinformatics tools. Numerous nucleotide substitutions were detected throughout the sequences, many of which resulted in amino acid substitutions in the deduced protein sequences. In most cases variability within a single variety was much lower than among varieties. Key amino acid changes in comparison with "canonical" sequences previously described in the literature included: a) the substitution of C19-relevant to the disulphide bond structure of the protein-, b) the presence of an additional N-glycosylation motif, and c) point substitutions affecting regions of Ole e 1 already described like relevant for the immunogenicity/allergenicity of the protein. Conclusion Varietal origin of olive pollen is a major factor determining the diversity of Ole e 1 variants. We consider this information of capital importance for the optimal design of efficient and safe allergen formulations, and useful for the genetic engineering of modified forms of the allergen among other applications. PMID:18218146

  2. 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.

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

    PubMed

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

    2013-09-01

    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.

  4. Active site remodelling accompanies thioester bond formation in the SUMO E1.

    PubMed

    Olsen, Shaun K; Capili, Allan D; Lu, Xuequan; Tan, Derek S; Lima, Christopher D

    2010-02-18

    E1 enzymes activate ubiquitin (Ub) and ubiquitin-like (Ubl) proteins in two steps by carboxy-terminal adenylation and thioester bond formation to a conserved catalytic cysteine in the E1 Cys domain. The structural basis for these intermediates remains unknown. Here we report crystal structures for human SUMO E1 in complex with SUMO adenylate and tetrahedral intermediate analogues at 2.45 and 2.6 A, respectively. These structures show that side chain contacts to ATP.Mg are released after adenylation to facilitate a 130 degree rotation of the Cys domain during thioester bond formation that is accompanied by remodelling of key structural elements including the helix that contains the E1 catalytic cysteine, the crossover and re-entry loops, and refolding of two helices that are required for adenylation. These changes displace side chains required for adenylation with side chains required for thioester bond formation. Mutational and biochemical analyses indicate these mechanisms are conserved in other E1s.

  5. Active site remodelling accompanies thioester bond formation in the SUMO E1

    SciTech Connect

    Olsen, Shaun K.; Capili, Allan D.; Lu, Xuequan; Tan, Derek S.; Lima, Christopher D.

    2010-03-30

    E1 enzymes activate ubiquitin (Ub) and ubiquitin-like (Ubl) proteins in two steps by carboxy-terminal adenylation and thioester bond formation to a conserved catalytic cysteine in the E1 Cys domain. The structural basis for these intermediates remains unknown. Here we report crystal structures for human SUMO E1 in complex with SUMO adenylate and tetrahedral intermediate analogues at 2.45 and 2.6 {angstrom}, respectively. These structures show that side chain contacts to ATP-Mg are released after adenylation to facilitate a 130 degree rotation of the Cys domain during thioester bond formation that is accompanied by remodelling of key structural elements including the helix that contains the E1 catalytic cysteine, the crossover and re-entry loops, and refolding of two helices that are required for adenylation. These changes displace side chains required for adenylation with side chains required for thioester bond formation. Mutational and biochemical analyses indicate these mechanisms are conserved in other E1s.

  6. Silencing E1A mRNA by RNA interference inhibits adenovirus replication.

    PubMed

    Chung, Y-S; Kim, M-K; Lee, W-J; Kang, C

    2007-01-01

    The adenovirus family contains 51 human serotypes, and most human adenoviruses cause widespread respiratory tract infections. Adenovirus infections can result in severe complications in some cases, such as in adenovirus type 11 infection in immunocompromised patients. However, effective treatment methods for adenovirus infections are currently unavailable. This prompted the search for antiviral agents effective against adenovirus infections. In the present study, adenovirus E1A was targeted by RNA interference (RNAi) using synthetic small interfering RNAs (siRNAs) in an attempt to inhibit viral replication, since adenovirus E1A proteins are known to be involved in the transcriptional activation of the viral and cellular genes necessary for controlling the cell cycle and viral replication. The results indicated that the siRNAs effectively reduced the amount of adenovirus E1A mRNA and the levels of replicative intermediates. Additionally, siRNA-mediated gene silencing inhibited adenovirus replication by suppressing the E1A mRNA. These results suggest that the RNAi-mediated targeting of adenovirus E1A may have a potentially therapeutic effect in controlling adenovirus infections.

  7. Cross-Inhibition of Chikungunya Virus Fusion and Infection by Alphavirus E1 Domain III Proteins

    PubMed Central

    Sánchez-San Martín, Claudia; Nanda, Soumya; Zheng, Yan; Fields, Whitney

    2013-01-01

    Alphaviruses are small enveloped RNA viruses that include important emerging human pathogens, such as chikungunya virus (CHIKV). These viruses infect cells via a low-pH-triggered membrane fusion reaction, making this step a potential target for antiviral therapies. The E1 fusion protein inserts into the target membrane, trimerizes, and refolds to a hairpin-like conformation in which the combination of E1 domain III (DIII) and the stem region (DIII-stem) pack against a core trimer composed of E1 domains I and II (DI/II). Addition of exogenous DIII proteins from Semliki Forest virus (SFV) has been shown to inhibit E1 hairpin formation and SFV fusion and infection. Here we produced and characterized DIII and DI/II proteins from CHIKV and SFV. Unlike SFV DIII, both core trimer binding and fusion inhibition by CHIKV DIII required the stem region. CHIKV DIII-stem and SFV DIII-stem showed efficient cross-inhibition of SFV, Sindbis virus, and CHIKV infections. We developed a fluorescence anisotropy-based assay for the binding of SFV DIII-stem to the core trimer and used it to demonstrate the relatively high affinity of this interaction (Kd [dissociation constant], ∼85 nM) and the importance of the stem region. Together, our results support the conserved nature of the key contacts of DIII-stem in the alphavirus E1 homotrimer and describe a sensitive and quantitative in vitro assay for this step in fusion protein refolding. PMID:23637415

  8. 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.

  9. 2-Carboxyquinoxalines kill mycobacterium tuberculosis through noncovalent inhibition of DprE1.

    PubMed

    Neres, João; Hartkoorn, Ruben C; Chiarelli, Laurent R; Gadupudi, Ramakrishna; Pasca, Maria Rosalia; Mori, Giorgia; Venturelli, Alberto; Savina, Svetlana; Makarov, Vadim; Kolly, Gaelle S; Molteni, Elisabetta; Binda, Claudia; Dhar, Neeraj; Ferrari, Stefania; Brodin, Priscille; Delorme, Vincent; Landry, Valérie; de Jesus Lopes Ribeiro, Ana Luisa; Farina, Davide; Saxena, Puneet; Pojer, Florence; Carta, Antonio; Luciani, Rosaria; Porta, Alessio; Zanoni, Giuseppe; De Rossi, Edda; Costi, Maria Paola; Riccardi, Giovanna; Cole, Stewart T

    2015-03-20

    Phenotypic screening of a quinoxaline library against replicating Mycobacterium tuberculosis led to the identification of lead compound Ty38c (3-((4-methoxybenzyl)amino)-6-(trifluoromethyl)quinoxaline-2-carboxylic acid). With an MIC99 and MBC of 3.1 μM, Ty38c is bactericidal and active against intracellular bacteria. To investigate its mechanism of action, we isolated mutants resistant to Ty38c and sequenced their genomes. Mutations were found in rv3405c, coding for the transcriptional repressor of the divergently expressed rv3406 gene. Biochemical studies clearly showed that Rv3406 decarboxylates Ty38c into its inactive keto metabolite. The actual target was then identified by isolating Ty38c-resistant mutants of an M. tuberculosis strain lacking rv3406. Here, mutations were found in dprE1, encoding the decaprenylphosphoryl-d-ribose oxidase DprE1, essential for biogenesis of the mycobacterial cell wall. Genetics, biochemical validation, and X-ray crystallography revealed Ty38c to be a noncovalent, noncompetitive DprE1 inhibitor. Structure-activity relationship studies generated a family of DprE1 inhibitors with a range of IC50's and bactericidal activity. Co-crystal structures of DprE1 in complex with eight different quinoxaline analogs provided a high-resolution interaction map of the active site of this extremely vulnerable target in M. tuberculosis.

  10. Equilibrium melting of plasmid ColE1 DNA: electron-microscopic visualization.

    PubMed Central

    Borovik, A S; Kalambet, Y A; Lyubchenko, Y L; Shitov, V T; Golovanov, E I

    1980-01-01

    The fine structure of the melting curve for the linear colE1 DNA has been obtained. To find the ColE1 DNA regions corresponding to peaks in the melting curve's fine structure, we fixed the melted DNA regions with glyoxal /12/. Electron-microscopic denaturation maps were obtained for nine temperature points within the melting range. Thereby the whole process of colE1 DNA melting was reconstructed in detail. Spectrophotometric and electron microscopic data were used for mapping the distribution of Gc-pairs over the DNA molecule. The most AT-rich DNA regions (28 and 37% of GC-pairs), 380 and 660 bp long resp., are located on both sides of the site of ColE1 DNA's cleavage by EcoR1 endonuclease. The equilibrium denaturation maps are compared with maps obtained by the method of Inman /20/ for eight points of the kinetic curve of ColE1 DNA unwinding by formaldehyde. Images PMID:6253910

  11. Prevalence of ColE1-like plasmids and kanamycin resistance genes in Salmonella enterica serovars.

    PubMed

    Chen, Chin-Yi; Lindsey, Rebecca L; Strobaugh, Terence P; Frye, Jonathan G; Meinersmann, Richard J

    2010-10-01

    Multi-antimicrobial-resistant Salmonella enterica strains frequently carry resistance genes on plasmids. Recent studies focus heavily on large conjugative plasmids, and the role that small plasmids play in resistance gene transfer is largely unknown. To expand our previous studies in assessing the prevalence of the isolates harboring ColE1-like plasmids carrying the aph gene responsible for kanamycin resistance (Kan(r)) phenotypes, 102 Kan(r) Salmonella isolates collected through the National Antimicrobial Resistance Monitoring System (NARMS) in 2005 were screened by PCR using ColE1 primer sets. Thirty isolates were found to be positive for ColE1-like replicon. Plasmids from 23 isolates were able to propagate in Escherichia coli and were subjected to further characterization. Restriction mapping revealed three major plasmid groups found in three or more isolates, with each group consisting of two to three subtypes. The aph genes from the Kan(r) Salmonella isolates were amplified by PCR, sequenced, and showed four different aph(3')-I genes. The distribution of the ColE1 plasmid groups in association with the aph gene, Salmonella serovar, and isolate source demonstrated a strong linkage of the plasmid with S. enterica serovar Typhimurium DT104. Due to their high copy number and mobility, the ColE1-like plasmids may play a critical role in transmission of antibiotic resistance genes among enteric pathogens, and these findings warrant a close monitoring of this plasmid incompatibility group.

  12. 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

  13. 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

  14. Nature of Col E1 Plasmid Replication in Escherichia coli in the Presence of Chloramphenicol

    PubMed Central

    Clewell, Don B.

    1972-01-01

    The colicinogenic factor E1 (Col E1) in Escherichia coli continues to replicate by a semiconservative mechanism in the presence of chloramphenicol (CAP) for 10 to 15 hr, long after chromosomal deoxyribonucleic acid (DNA) synthesis has terminated. Following CAP addition, the rate of synthesis of plasmid DNA gradually increases to an extent dependent on the medium employed. Within 2 to 4 hr after the addition of CAP, replication in a glucose-Casamino Acids medium approaches a maximum rate representing approximately eight times an average rate which would be required for a net doubling of DNA per cell in one generation. The number of copies of Col E1 DNA molecules that accumulate under these conditions approaches about 3,000 copies per cell, representing a 125-fold increase over the normal level of 24 copies per cell. The system is particularly convenient for studying the mechanism of DNA replication. Images PMID:4336693

  15. 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.

  16. E1 and M1 γ-strength functions in 144Nd

    DOE PAGES

    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.

  17. Calcification of MC3T3-E1 cells on titanium and zirconium.

    PubMed

    Umezawa, Takayuki; Chen, Peng; Tsutsumi, Yusuke; Doi, Hisashi; Ashida, Maki; Suzuki, Shoichi; Moriyama, Keiji; Hanawa, Takao

    2015-01-01

    To confirm similarity of hard tissue compatibility between titanium and zirconium, calcification of MC3T3-E1 cells on titanium and zirconium was evaluated in this study. Mirror-polished titanium (Ti) and zirconium (Zr) disks and zirconium-sputter deposited titanium (Zr/Ti) were employed in this study. The surface of specimens were characterized using scanning electron microscopy and X-ray diffraction. Then, the cellular proliferation, differentiation and calcification of MC3T3-E1 cells on specimens were investigated. The surface of Zr/Ti was much smoother and cleaner than those of Ti and Zr. The proliferation of the cell was the same among three specimens, while the differentiation and calcification on Zr/Ti were faster than those on Ti and Zr. Therefore, Ti and Zr showed the identical hard tissue compatibility according to the evaluation with MC3T3-E1 cells. Sputter deposition may improve cytocompatibility.

  18. Processing of plasmid DNA with ColE1-like replication origin.

    PubMed

    Wang, Zhijun; Yuan, Zhenghong; Hengge, Ulrich R

    2004-05-01

    With the increasing utilization of plasmid DNA as a biopharmaceutical drug, there is a rapidly growing need for high quality plasmid DNA for drug applications. Although there are several different kinds of replication origins, ColE1-like replication origin is the most extensively used origin in biotechnology. This review addresses problems in upstream and downstream processing of plasmid DNA with ColE1-like origin as drug applications. In upstream processing of plasmid DNA, regulation of replication of ColE1-like origin was discussed. In downstream processing of plasmid DNA, we analyzed simple, robust, and scalable methods, which can be used in the efficient production of pharmaceutical-grade plasmid DNA.

  19. 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

  20. CYP2E1 Potentiates Ethanol-induction of Hypoxia and HIF-1α in vivo

    PubMed Central

    Wang, Xiaodong; Wu, Defeng; Yang, Lili; Gan, Lixia; Cederbaum, Arthur I

    2013-01-01

    Ethanol induces hypoxia and elevates HIF-1α in the liver. CYP2E1 plays a role in the mechanisms by which ethanol generates oxidative stress, fatty liver and liver injury. The current study evaluated whether CYP2E1 contributes to ethanol-induced hypoxia and activation of HIF-1α in vivo and whether HIF-1α protects against or promotes CYP2E1-dependent toxicity in vitro. Wild type (WT), CYP2E1-knockin (KI) and CYP2E1 knockout (KO) mice were fed ethanol chronically; pair fed controls received isocaloric dextrose. Ethanol produced liver injury in the KI mice to a much greater extent than in the WT and KO mice. Protein levels of HIF-1α and downstream targets of HIF-1α activation were elevated in the ethanol-fed KI mice compared to the WT and KO mice. Levels of HIF prolylhydroxlase 2 which promotes HIF-1α degradation were decreased in the ethanol-fed KI mice in association with the increases in HIF-1α. Hypoxia occurred in the ethanol-fed CYP2E1 KI mice as shown by an increased area of staining using the hypoxia-specific marker pimonidazole. Hypoxia was lower in the ethanol-fed WT mice and lowest in the ethanol fed KO mice and all the dextrose-fed mice. In situ double staining showed that pimonidazole and CYP2E1 were co-localized to the same area of injury in the hepatic centrilobule. Increased protein levels of HIF-1α were also found after acute ethanol treatment of KI mice. Treatment of HepG2 E47 cells which express CYP2E1 with ethanol plus arachidonic (AA) acid or ethanol plus buthionine sulfoximine (BSO) which depletes GSH caused loss of cell viability to greater extent than in HepG2 C34 cells which do not express CYP2E1. These treatments elevated protein levels of HIF-1α to a greater extent in E47 cells than C34 cells. 2-Methoxyestradiol, an inhibitor of HIF-1α, blunted the toxic effects of ethanol plus AA and ethanol plus BSO in the E47 cells in association with inhibition of HIF-1α. The HIF-1α inhibitor also blocked the elevated oxidative stress produced

  1. Investigation of xenobiotics metabolism, genotoxicity, and carcinogenicity using Cyp2e1(-/-) mice.

    PubMed

    Ghanayem, Burhan I; Hoffler, Undi

    2007-10-01

    Cytochromes P450 (CYPs) comprise a number of enzyme subfamilies responsible for the oxidative metabolism of a wide range of therapeutic agents, environmental toxicants, mutagens, and carcinogens. In particular, cytochrome P450 2E1 (CYP2E1) is implicated in the oxidative bioactivation of a variety of small hydrophobic chemicals including a number of epoxide-forming drugs and environmentally important toxicants including urethane, acrylamide, acrylonitrile, benzene, vinyl chloride, styrene, 1-bromopropane, trichloroethylene, dichloroethylene, acetaminophen, and butadiene. Until recently, chemical modulators (inducers and inhibitors) were used in order to characterize the enzymatic basis of xenobiotic metabolism and the relationships between CYP-mediated bioactivation and chemical-induced toxicity/carcinogenicity. With the advent of genetically engineered knockout mice, the ability to evaluate the roles of specific CYPs in the metabolism of xenobiotics has become more attainable. The main focus of the current review is to present studies that characterized the enzymatic, metabolic, and molecular mechanisms of toxicity, genotoxicity, and carcinogenicity of various xenobiotics using Cyp2e1-/- mice. Data presented in this review demonstrated that the most comprehensive studies using Cyp2e1-/- mice, encompassing the entire paradigm of metabolism to toxicity, genotoxicity, and carcinogenicity were possible when a substrate was primarily metabolized via CYP2E1 (e.g. urethane and acrylamide). In contrast, when multiple CYP enzymes were prevalent in the oxidation of a particular substrate (e.g.: trichloroethylene, methacrylonitrile, crotononitrile), investigating the relationships between oxidative metabolism and biological activity became more complicated and required the use of chemical modulators. In conclusion, the current review showed that Cyp2e1-/- mice are a valuable animal model for the investigation of the metabolic and molecular basis of toxicity, genotoxicity, and

  2. Inhibitory potency of 4-carbon alkanes and alkenes toward CYP2E1 activity.

    PubMed

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

    2014-04-06

    CYP2E1 has been implicated in the bioactivation of many small molecules into reactive metabolites which form adducts with proteins and DNA, and thus a better understanding of the molecular determinants of its selectivity are critical for accurate toxicological predictions. In this study, we determined the potency of inhibition of human CYP2E1 for various 4-carbon alkanes, alkenes and alcohols. In addition, known CYP2E1 substrates and inhibitors including 4-methylpyrazole, aniline, and dimethylnitrosamine were included to determine their relative potencies. Of the 1,3-butadiene-derived metabolites studied, 3,4-epoxy-1-butene was the strongest inhibitor with an IC50 of 110 μM compared to 1700 μM and 6600 μM for 1,2-butenediol and 1,2:3,4-diepoxybutane, respectively. Compared to known inhibitors, inhibitory potency of 3,4-epoxy-1-butene is between 4-methylpyrazole (IC50 = 1.8 μM) and dimethylnitrosamine (IC50 = 230 μM). All three butadiene metabolites inhibit CYP2E1 activity through a simple competitive mechanism. Among the 4-carbon compounds studied, the presence and location of polar groups seems to influence inhibitory potency. To further examine this notion, the investigation was extended to include structurally and chemically similar analogues, including propylene oxide and various butane alcohols. Those results demonstrated preferential recognition of CYP2E1 toward the type and location of polar and hydrophobic structural elements. Taken together, CYP2E1 metabolism may be modified in vivo by exposure to 4-carbon compounds, such as drugs, and nutritional constituents, a finding that highlights the complexity of exposure to mixtures.

  3. p53/E1b58kDa complex regulates adenovirus replication.

    PubMed

    Ridgway, P J; Hall, A R; Myers, C J; Braithwaite, A W

    1997-10-27

    We have explored a role for the adenovirus (Ad5) E1b58kDa/p53 protein complex in adenovirus replication. This was done by using virus mutants containing different defects in the E1b58kDa gene and cell lines that express either a wild-type p53 protein or a mutant p53 protein. We find that infection of wild-type p53-containing cells with wild-type Ad5 causes a shutoff of p53 and alpha-actin protein synthesis by distinct mechanisms, but neither occurs in mutant p53 cells. Our data also indicate that the shutoff is dependent on formation of the p53/E1b complex and may also involve another virus protein, E4ORF6. Following from these observations we asked whether failure to form the complex resulted in impaired adenovirus replication. Our experiments showed that neither wild-type Ad5 nor the E1b mutant dl338 could replicate in cells expressing a mutant p53 protein, but that wild-type adenovirus replicated well in wild-type p53-expressing cells. Collectively, our data suggest that the interaction between p53 and the E1b58kDa protein is necessary for efficient adenovirus replication. This is the first time such a direct link between the complex and virus replication has been demonstrated. These data raise serious questions about the usefulness of E1b-defective viruses in tumor therapy.

  4. Propolis protects CYP 2E1 enzymatic activity and oxidative stress induced by carbon tetrachloride.

    PubMed

    Bhadauria, Monika; Nirala, Satendra Kumar; Shukla, Sangeeta

    2007-08-01

    Induction of CYP 2E1 by carbon tetrachloride (CCl(4)) is one of the central pathways by which CCl(4) generates oxidative stress in hepatocytes. Experimental liver injury was induced in rats by CCl(4) to determine toxicological actions on CYP 2E1 by microsomal drug metabolizing enzymes. In this report, ethanolic extract of propolis at a dose of 200 mg/kg (po) was used after 24 h of toxicant administration to validate its protective potential. Intraperitoneal injection of CCl(4) (1.5 ml/kg) induced hepatotoxicity after 24 h of its administration that was associated with elevated malonyldialdehyde (index of lipid peroxidation), lactate dehydrogenase and gamma-glutamyl transpeptidase release (index of a cytotoxic effect). Hepatic microsomal drug metabolizing enzymes of CYP 2E1 showed sharp depletion as assessed by estimating aniline hydroxylase and amidopyrine N-demethylase activity after CCl(4) exposure. Toxic effect of CCl(4) was evident on CYP 2E1 activity by increased hexobarbitone induced sleep time and bromosulphalein retention. Propolis extract showed significant improvement in the activity of both enzymes and suppressed toxicant induced increase in sleep time and bromosulphalein retention. Choleretic activity of liver did not show any sign of toxicity after propolis treatment at a dose of 200 mg/kg (id). Histopathological evaluation of the liver revealed that propolis reduced the incidence of liver lesions including hepatocyte swelling and lymphocytic infiltrations induced by CCl(4). Electron microscopic observations also showed improvement in ultrastructure of liver and substantiated recovery in biochemical parameters. Protective activity of propolis at 200 mg/kg dose was statistically compared with positive control silymarin (50 mg/kg, po), a known hepatoprotective drug seems to be better in preventing hepatic CYP 2E1 activity deviated by CCl(4). These results lead us to speculate that propolis may play hepatoprotective role via improved CYP 2E1 activity and

  5. Domain alternation and active site remodeling are conserved structural features of ubiquitin E1.

    PubMed

    Lv, Zongyang; Yuan, Lingmin; Atkison, James H; Aldana-Masangkay, Grace; Chen, Yuan; Olsen, Shaun K

    2017-07-21

    E1 enzymes for ubiquitin (Ub) and Ub-like modifiers (Ubls) harbor two catalytic activities that are required for Ub/Ubl activation: adenylation and thioester bond formation. Structural studies of the E1 for the Ubl small ubiquitin-like modifier (SUMO) revealed a single active site that is transformed by a conformational switch that toggles its competency for catalysis of these two distinct chemical reactions. Although the mechanisms of adenylation and thioester bond formation revealed by SUMO E1 structures are thought to be conserved in Ub E1, there is currently a lack of structural data supporting this hypothesis. Here, we present a structure of Schizosaccharomyces pombe Uba1 in which the second catalytic cysteine half-domain (SCCH domain) harboring the catalytic cysteine has undergone a 106° rotation that results in a completely different network of intramolecular interactions between the SCCH and adenylation domains and translocation of the catalytic cysteine 12 Å closer to the Ub C terminus compared with previous Uba1 structures. SCCH domain alternation is accompanied by conformational changes within the Uba1 adenylation domains that effectively disassemble the adenylation active site. Importantly, the structural and biochemical data suggest that domain alternation and remodeling of the adenylation active site are interconnected and are intrinsic structural features of Uba1 and that the overall structural basis for adenylation and thioester bond formation exhibited by SUMO E1 is indeed conserved in Ub E1. Finally, the mechanistic insights provided by the novel conformational snapshot of Uba1 presented in this study may guide efforts to develop small molecule inhibitors of this critically important enzyme that is an active target for anticancer therapeutics. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Infrared study of transitional disks in Ophiuchus with Herschel

    NASA Astrophysics Data System (ADS)

    Rebollido, Isabel; Merín, Bruno; Ribas, Álvaro; Bustamante, Ignacio; Bouy, Hervé; Riviere-Marichalar, Pablo; Prusti, Timo; Pilbratt, Göran L.; André, Philippe; Ábrahám, Péter

    2015-09-01

    Context. Observations of nearby star-forming regions with the Herschel Space Observatory complement our view of the protoplanetary disks in Ophiuchus with information about the outer disks. Aims: The main goal of this project is to provide new far-infrared fluxes for the known disks in the core region of Ophiuchus and to identify potential transitional disks using data from Herschel. Methods: We obtained PACS and SPIRE photometry of previously spectroscopically confirmed young stellar objects (YSO) in the region and analysed their spectral energy distributions. Results: From an initial sample of 261 objects with spectral types in Ophiuchus, we detect 49 disks in at least one Herschel band. We provide new far-infrared fluxes for these objects. One of them is clearly a new transitional disk candidate. Conclusions: The data from Herschel Space Observatory provides fluxes that complement previous infrared data and that we use to identify a new transitional disk candidate. Herschel is an ESA space observatory with science instruments provided by European-led Principal Investigator consortia and with important participation from NASA.Final reduced Herschel maps 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/581/A30Appendix A is available in electronic form at http://www.aanda.orgAll tables are also 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/581/A30

  7. Sound power measurements on the M1E1 engine and total power pack

    NASA Astrophysics Data System (ADS)

    Schomer, P. D.

    1983-05-01

    A new technique to measure power was used to gather one-third octave emissions data on the M1E1 engine (AGT 1500) at the Stratford Army Engine Plant, CT and on the M1E1 power pack at Aberdeen Proving Ground, MD. To calculate sound power, acoustic intensity (the product of the scaler pressure and the vector velocity) was measured and integrated over an arbitrary surface enclosing the source. The data gathered and test results show this new technique is very powerful and robust and is applicable to many machinery quieting, source emission, or sound transmission measurements.

  8. 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.

  9. [Intracavernous injections of prostaglandin E1 in the treatment of erection disorders].

    PubMed

    Beretta, G; Zanollo, A; Portalupi, W

    1991-12-01

    Vasoactive drugs have been widely used for the treatment of impotence in the last years. Recently Prostaglandin E1 has been employed with success as a therapy in erection problems. The Authors have treated with Prostaglandin E1 209 patients complaining erection failure. Positive results were obtained in 155 patients (74,16%). No complications or side effects occurred. 129 patients of the 155 in which the test resulted positive were proposed a self-injection program and 115 accepted. Until now no side effects or complications occurred.

  10. Influence of the adenovirus 5 E1A oncogene on chromatin remodelling.

    PubMed

    Mymryk, J S; Smith, M M

    1997-01-01

    In the eukaryotic nucleus, compaction of DNA into chromatin can limit the access of trans-acting factors, providing an additional level of regulation to processes such as transcription, replication, and repair. Recent studies have suggested that the protein products of the adenovirus 5 E1A oncogene can influence SWI-SNF and histone acetylase activities, two cellular processes that facilitate transcription in the context of chromatin. This review focuses on the unexpected effects of E1A on cellular processes that remodel chromatin in relation to its transcriptional and transforming activities.

  11. Thionin-D4E1 chimeric protein protects plants against bacterial infections

    DOEpatents

    Stover, Eddie W; Gupta, Goutam; Hao, Guixia

    2017-08-08

    The generation of a chimeric protein containing a first domain encoding either a pro-thionon or thionin, a second domain encoding D4E1 or pro-D4E1, and a third domain encoding a peptide linker located between the first domain and second domain is described. Either the first domain or the second domain is located at the amino terminal of the chimeric protein and the other domain (second domain or first domain, respectively) is located at the carboxyl terminal. The chimeric protein has antibacterial activity. Genetically altered plants and their progeny expressing a polynucleotide encoding the chimeric protein resist diseases caused by bacteria.

  12. 78 FR 44124 - Agency Information Collection Activities: Proposed Collection; Comment Request; Format and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-23

    ... March 1, 2010, estimate provided by the Consumer Healthcare Products Association (75 FR 49495 at 49496... consider exemptions or deferrals of the regulation allowed products under Sec. 201.66(e). Since publication... drug products 201.66(c) and (d) for new OTC 20 3 60 12 720 sunscreen products 201.66(e) 1 0.125...

  13. 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

    USDA-ARS?s Scientific Manuscript database

    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,...

  14. Transition operators

    NASA Astrophysics Data System (ADS)

    Alcock-Zeilinger, J.; Weigert, H.

    2017-05-01

    In this paper, we give a generic algorithm of the transition operators between Hermitian Young projection operators corresponding to equivalent irreducible representations of 𝖲𝖴 (N ) , using the compact expressions of Hermitian Young projection operators derived in the work of Alcock-Zeilinger and Weigert [eprint arXiv:1610.10088 [math-ph

  15. Presidential Transitions

    DTIC Science & Technology

    2006-06-09

    Podesta for the Heads of Executive Departments and Agencies, “Presidential Transition Guidance,” Nov. 13, 2000. 89 U.S. General Services Administration...2000, presidential election, White House Chief of Staff John Podesta issued a November 13, 2000, memorandum to executive branch agencies stating that

  16. Tessellations & Transitions.

    ERIC Educational Resources Information Center

    Cassidy, Joan

    1998-01-01

    Describes two sixth-grade lessons on the work of M. C. Escher: (1) the first lesson instructs students on tessellations, or tiles that interlock in a repeated pattern; (2) the second lesson explores Escher's drawings of transitions from two- to three-dimensional space. (DSK)

  17. Venus transit

    NASA Image and Video Library

    2012-06-05

    Leslie Lowes from the NASA Jet Propulsion Laboratory in Pasadena, Calif., views the June 5, 2012, Venus transit through a solar telescope. Lowes participated in an education workshop at the INFINITY at NASA Stennis Space Center visitor center and joined others to view the rare celestial event when Venus traverses the face of the sun.

  18. Venus transit

    NASA Image and Video Library

    2012-06-05

    Guests at the INFINITY at NASA Stennis Space Center visitor center use special solar sunglasses to catch a lifetime view of the Venus transit June 5, 2012. The rare celestial event in which the planet Venus traverses the face of the sun will not be visible from Earth again until 2117.

  19. Muted Transitions

    ERIC Educational Resources Information Center

    Kofoed, Jette

    2008-01-01

    This analysis concentrates on the case of a child, Jenny. The paper suggests that the concept of liminality may hold the key to an understanding of muted subject positions like the one assumed by Jenny in a school class. Liminality is proposed as a way of conceptualizing transitions where the subject in question transgresses established rules and…

  20. Tessellations & Transitions.

    ERIC Educational Resources Information Center

    Cassidy, Joan

    1998-01-01

    Describes two sixth-grade lessons on the work of M. C. Escher: (1) the first lesson instructs students on tessellations, or tiles that interlock in a repeated pattern; (2) the second lesson explores Escher's drawings of transitions from two- to three-dimensional space. (DSK)

  1. 29 CFR 2589.1 - Civil penalties under section 8477(e)(1)(B) of FERSA.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Civil penalties under section 8477(e)(1)(B) of FERSA. 2589.1 Section 2589.1 Labor Regulations Relating to Labor (Continued) EMPLOYEE BENEFITS SECURITY ADMINISTRATION, DEPARTMENT OF LABOR ADMINISTRATION AND ENFORCEMENT UNDER THE FEDERAL EMPLOYEES' RETIREMENT SYSTEM ACT OF 1986 RULES AND REGULATIONS...

  2. Scattering operators for E1-E2 x-ray resonant diffraction

    NASA Astrophysics Data System (ADS)

    Marri, Ivan; Carra, Paolo

    2004-03-01

    Resonant x-ray diffraction in noncentrosymmetric crystals is studied by considering E1-E2 processes in the fast-collision approximation. The scattering amplitude is expressed in terms of polar and magnetoelectric operators of the valence states, which are involved in the resonance. Near-edge Bragg peaks from ferroelectric, antiferroelectric, and magnetoelectric structures are predicted.

  3. US NDC Modernization Iteration E1 Prototyping Report: Common Object Interface

    SciTech Connect

    Lewis, Jennifer E.; Hess, Michael M.

    2014-12-01

    During the first iteration of the US NDC Modernization Elaboration phase (E1), the SNL US NDC modernization project team completed an initial survey of applicable COTS solutions, and established exploratory prototyping related to the Common Object Interface (COI) in support of system architecture definition. This report summarizes these activities and discusses planned follow-on work.

  4. 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 article...

  5. 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 article...

  6. 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 article...

  7. 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 article...

  8. 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 article...

  9. 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...

  10. 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...

  11. Perfluorooctanoic acid induces mitochondrial dysfunction in MC3T3-E1 osteoblast cells.

    PubMed

    Choi, Eun Mi; Suh, Kwang Sik; Rhee, Sang Youl; Oh, Seungjoon; Woo, Jeong-Taek; Kim, Sung Woon; Kim, Young Seol; Pak, Youngmi Kim; Chon, Suk

    2017-02-23

    Perfluorooctanoic acid (PFOA), a stable organic perfluorinated compound, is an emerging persistent organic pollutant, found widely in human and wildlife populations. Recent evidence suggests that exposure to environmental toxicants can be associated with higher risks of osteoporosis and fractures. We studied the cellular toxicology of PFOA in MC3T3-E1osteoblast cells. To examine the effect of PFOA, we measured cell viability, reactive oxygen species (ROS), mitochondrial superoxide, and mitochondrial parameters including adenosine triphosphate (ATP) level, mitochondrial membrane potential (MMP), cardiolipin content, and cytochrome c release in MC3T3-E1 cells. Incubating MC3T3-E1 cells in different concentrations of PFOA for 48 h resulted in a concentration-dependent decrease in cell viability and significant inductions of ROS and mitochondrial superoxide. Moreover, PFOA induced MMP collapse, cardiolipin peroxidation, cytochrome c release, and decreased ATP levels, which in turn induced apoptosis or necrosis. When osteoblast differentiation markers were assessed, PFOA treatment caused a significant reduction in alkaline phosphatase activity, collagen synthesis, and mineralization in the cells. In summary, we found an ROS- and mitochondria-mediated pathway for the induction of cell damage by PFOA in MC3T3-E1 cells. Together, our results indicate that mitochondrial toxicity could be a plausible mechanism for the toxic effects of PFOA on osteoblast function.

  12. 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.

  13. 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.

  14. 26 CFR 1.501(e)-1 - Cooperative hospital service organizations.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 7 2013-04-01 2013-04-01 false Cooperative hospital service organizations. 1... (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Exempt Organizations § 1.501(e)-1 Cooperative hospital service organizations. (a) General rule. Section 501(e) is the exclusive and controlling...

  15. 26 CFR 1.501(e)-1 - Cooperative hospital service organizations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 7 2011-04-01 2009-04-01 true Cooperative hospital service organizations. 1.501... (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Exempt Organizations § 1.501(e)-1 Cooperative hospital service organizations. (a) General rule. Section 501(e) is the exclusive and controlling...

  16. 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. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  17. 17 CFR 270.17e-1 - Brokerage transactions on a securities exchange.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... COMMISSION (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.17e-1 Brokerage... other remuneration shall be deemed as not exceeding the usual and customary broker's commission, if: (a) The commission, fee, or other remuneration received or to be received is reasonable and fair compared...

  18. The effect of prostaglandin E1 analog misoprostol on chronic cyclosporin nephrotoxicity.

    PubMed

    John, E G; Fornell, L C; Radhakrishnan, J; Anutrakulchai, S; Jonasson, O

    1993-11-01

    Cyclosporin A has markedly improved graft survival in transplant patients but its side effects, such as renal toxicity and hypertension, pose management problems in transplant recipients. This toxicity has been attributed to prostaglandin inhibition. Concurrent administration of misoprostol (a prostaglandin E1 analog) prevents chronic cyclosporin A-induced nephrotoxicity but not hypertension in rats.

  19. Induction of CYP2E1 in non-alcoholic fatty liver diseases

    PubMed Central

    Aljomah, Ghanim; Baker, Susan S.; Liu, Wensheng; Kozielski, Rafal; Oluwole, Janet; Lupu, Benita; Baker, Robert D.; Zhu, Lixin

    2015-01-01

    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 were 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

  20. Atomic Theory of Parity-Odd (E1-M1) Photon Absorption Event

    NASA Astrophysics Data System (ADS)

    Stephen William Lovesey,; Ewald Balcar,

    2010-07-01

    Light scattering proceeding through electric and magnetic dipole absorption events (E1-M1) exhibits natural circular dichroism, widely used in the characterization of chiral media, and the magneto-chiral effect, which is under consideration as a mechanism for the homo-chirality of life. Additional manifestations of E1-M1 scattering are resonance enhanced Bragg diffraction and non-reciprocal linear dichroism. In spite of its established importance for a raft of significant phenomena, there has not been a complete treatment of E1-M1 light scattering by electrons. Starting from the interaction that includes both electron spin and angular momentum variables, we construct scattering that proceeds via a spin-orbit split intermediate state for the photo-ejected electron. Employing new relations for re-coupling angular momentum we give a theoretical basis for the derivation of sum-rules for integrated dichroic signals. In order to assist in the interpretation of the algebraic terms present for E1-M1 we construct a family of equivalent operators that include monopoles for chirality and magnetic charge. Worked examples of corresponding expectation values are given for two sample wave functions to demonstrate the flavour and support the use of specific equivalent tensor operators.

  1. 29 CFR 2589.1 - Civil penalties under section 8477(e)(1)(B) of FERSA.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 9 2013-07-01 2013-07-01 false Civil penalties under section 8477(e)(1)(B) of FERSA. 2589.1 Section 2589.1 Labor Regulations Relating to Labor (Continued) EMPLOYEE BENEFITS SECURITY ADMINISTRATION, DEPARTMENT OF LABOR ADMINISTRATION AND ENFORCEMENT UNDER THE FEDERAL EMPLOYEES' RETIREMENT SYSTEM ACT OF 1986 RULES AND REGULATIONS FOR...

  2. 29 CFR 2589.1 - Civil penalties under section 8477(e)(1)(B) of FERSA.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 9 2012-07-01 2012-07-01 false Civil penalties under section 8477(e)(1)(B) of FERSA. 2589.1 Section 2589.1 Labor Regulations Relating to Labor (Continued) EMPLOYEE BENEFITS SECURITY ADMINISTRATION, DEPARTMENT OF LABOR ADMINISTRATION AND ENFORCEMENT UNDER THE FEDERAL EMPLOYEES' RETIREMENT SYSTEM ACT OF 1986 RULES AND REGULATIONS FOR...

  3. 26 CFR 1.401(e)-1 - Definitions relating to plans covering self-employed individuals.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ..., Stock Bonus Plans, Etc. § 1.401(e)-1 Definitions relating to plans covering self-employed individuals... self-employed individuals may be covered by a qualified pension, annuity, or profit-sharing plan. This section contains definitions contained in section 401(c) relating to plans covering...

  4. 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... self-employed individuals may be covered by a qualified pension, annuity, or profit-sharing plan. This section contains definitions contained in section 401(c) relating to plans covering...

  5. 26 CFR 1.401(e)-1 - Definitions relating to plans covering self-employed individuals.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ..., Stock Bonus Plans, Etc. § 1.401(e)-1 Definitions relating to plans covering self-employed individuals... self-employed individuals may be covered by a qualified pension, annuity, or profit-sharing plan. This section contains definitions contained in section 401(c) relating to plans covering...

  6. 26 CFR 1.401(e)-1 - Definitions relating to plans covering self-employed individuals.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Plans, Etc. § 1.401(e)-1 Definitions relating to plans covering self-employed individuals. (a) “Keogh... contains definitions contained in section 401(c) relating to plans covering self-employed individuals and...), (g), (h), and (i), are also generally applicable to any plan covering a self-employed...

  7. 26 CFR 1.401(e)-1 - Definitions relating to plans covering self-employed individuals.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ..., Stock Bonus Plans, Etc. § 1.401(e)-1 Definitions relating to plans covering self-employed individuals... self-employed individuals may be covered by a qualified pension, annuity, or profit-sharing plan. This section contains definitions contained in section 401(c) relating to plans covering...

  8. US NDC Modernization Iteration E1 Prototyping Report: User Interface Framework

    SciTech Connect

    Lober, Randall R.

    2014-12-01

    During the first iteration of the US NDC Modernization Elaboration phase (E1), the SNL US NDC modernization project team completed an initial survey of applicable COTS solutions, and established exploratory prototyping related to the User Interface Framework (UIF) in support of system architecture definition. This report summarizes these activities and discusses planned follow-on work.

  9. 17 CFR 240.14e-1 - Unlawful tender offer practices.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Unlawful tender offer... Securities Exchange Act of 1934 Regulation 14e § 240.14e-1 Unlawful tender offer practices. As a means... section 14(e) of the Act, no person who makes a tender offer shall: (a) Hold such tender offer open...

  10. US NDC Modernization Iteration E1 Prototyping Report: Processing Control Framework

    SciTech Connect

    Prescott, Ryan; Hamlet, Benjamin R.

    2014-12-01

    During the first iteration of the US NDC Modernization Elaboration phase (E1), the SNL US NDC modernization project team developed an initial survey of applicable COTS solutions, and established exploratory prototyping related to the processing control framework in support of system architecture definition. This report summarizes these activities and discusses planned follow-on work.

  11. 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.

  12. 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

  13. E1A, E1B double-restricted adenovirus enhances the cytotoxicity and antitumor activity of gemcitabine to renal cell carcinoma.

    PubMed

    Wang, Hua; Satoh, Makoto; Chen, Gui-Ping; Li, De-Chuan; Hamada, Hirofumi; Arai, Yoichi

    2011-04-01

    Our previous studies have demonstrated potent oncolysis efficacy of the E1A, E1B double-restricted replication-competent oncolytic adenovirus AxdAdB-3 for treatment of bladder cancer. Here, we reported the feasibility and efficacy of AxdAdB-3 alone, or in combination with gemcitabine for treating renal cell carcinoma. Cytopathic effects of AxdAdB-3 were evaluated in human renal cell carcinoma cell lines TOS-1, TOS-2, TOS-3, TOS-3LN, SMKT-R3, SMKT-R4 and ACHN, and in normal human renal proximal tubule epithelial cells (RPTEC). AxdAdB-3 induced down-regulation of the cell cycle was determined by flow cytometry. Combination therapies of AxdAdB-3 with gemcitabine were evaluated in vitro and in vivo on subcutaneous TOS-3LN tumors in a severe combined immunodeficiency disease (SCID) mouse model. AxdAdB-3 was potently cytopathic against the tested most renal cell carcinoma cell lines including TOS-2, TOS-3, TOS-3LN, SMKT-R3 and SMKT-R4, while normal human RPTEC were not destroyed. AxdAdB-3 effectively induced cell cycle S-phase entry. Combined therapy of AxdAdB-3 with gemcitabine demonstrated stronger antitumor effects in vitro and in vivo compared with either AxdAdB-3 or gemcitabine alone. AxdAdB-3 alone, or in combination with gemcitabine may be a promising strategy against renal cell carcinoma.

  14. The activation of OR51E1 causes growth suppression of human prostate cancer cells.

    PubMed

    Maßberg, Désirée; Jovancevic, Nikolina; Offermann, Anne; Simon, Annika; Baniahmad, Aria; Perner, Sven; Pungsrinont, Thanakorn; Luko, Katarina; Philippou, Stathis; Ubrig, Burkhard; Heiland, Markus; Weber, Lea; Altmüller, Janine; Becker, Christian; Gisselmann, Günter; Gelis, Lian; Hatt, Hanns

    2016-07-26

    The development of prostate cancer (PCa) is regulated by the androgen-dependent activity of the androgen receptor (AR). Androgen-deprivation therapy (ADT) is therefore the gold standard treatment to suppress malignant progression of PCa. Nevertheless, due to the development of castration resistance, recurrence of disease after initial response to ADT is a major obstacle to successful treatment. As G-protein coupled receptors play a fundamental role in PCa physiology, they might represent promising alternative or combinatorial targets for advanced diseases. Here, we verified gene expression of the olfactory receptors (ORs) OR51E1 [prostate-specific G-protein coupled receptor 2 (PSGR2)] and OR51E2 (PSGR) in human PCa tissue by RNA-Seq analysis and RT-PCR and elucidated the subcellular localization of both receptor proteins in human prostate tissue. The OR51E1 agonist nonanoic acid (NA) leads to the phosphorylation of various protein kinases and growth suppression of the PCa cell line LNCaP. Furthermore, treatment with NA causes reduction of androgen-mediated AR target gene expression. Interestingly, NA induces cellular senescence, which coincides with reduced E2F1 mRNA levels. In contrast, treatment with the structurally related compound 1-nonanol or the OR2AG1 agonist amyl butyrate, neither of which activates OR51E1, did not lead to reduced cell growth or an induction of cellular senescence. However, decanoic acid, another OR51E1 agonist, also induces cellular senescence. Thus, our results suggest the involvement of OR51E1 in growth processes of PCa cells and its impact on AR-mediated signaling. These findings provide novel evidences to support the functional importance of ORs in PCa pathogenesis.

  15. Cytochrome P450 2E1 inhibition prevents hepatic carcinogenesis induced by diethylnitrosamine in alcohol-fed rats

    USDA-ARS?s Scientific Manuscript database

    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...

  16. 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. Section...

  17. 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. Section...

  18. 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. Section...

  19. 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. Section...

  20. CYP1A1, CYP2E1 and EPHX1 polymorphisms in sporadic colorectal neoplasms

    PubMed Central

    Fernandes, Glaucia Maria M; Russo, Anelise; Proença, Marcela Alcântara; Gazola, Nathalia Fernanda; Rodrigues, Gabriela Helena; Biselli-Chicote, Patrícia Matos; Silva, Ana Elizabete; Netinho, João Gomes; Pavarino, Érika Cristina; Goloni-Bertollo, Eny Maria

    2016-01-01

    AIM To investigate the contribution of polymorphisms in the CYP1A1, CYP2E1 and EPHX1 genes on sporadic colorectal cancer (SCRC) risk. METHODS Six hundred forty-one individuals (227 patients with SCRC and 400 controls) were enrolled in the study. The variables analyzed were age, gender, tobacco and alcohol consumption, and clinical and histopathological tumor parameters. The CYP1A1*2A, CYP1A1*2C CYP2E1*5B and CYP2E1*6 polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The EPHX1 Tyr113His, EPHX1 His139Arg and CYP1A1*2C polymorphisms were detected by real-time PCR. Chi-squared test and binary logistic regression were used in the statistical analysis. Haplotype analysis was conducted using the Haploview program, version 2.05. RESULTS Age over 62 years was a risk factor for SCRC development (OR = 7.54, 95%CI: 4.94-11.50, P < 0.01). Male individuals were less susceptible to SCRC (OR = 0.55, 95%CI: 0.35-0.85, P < 0.01). The CYP2E1*5B polymorphism was associated with SCRC in the codominant (heterozygous genotype: OR = 2.66, 95%CI: 1.64-4.32, P < 0.01), dominant (OR = 2.82, 95%CI: 1.74-4.55, P < 0.01), overdominant (OR = 2.58, 95%CI: 1.59-4.19, P < 0.01), and log-additive models (OR = 2.84, 95%CI: 1.78-4.52, P < 0.01). The CYP2E1*6 polymorphism was associated with an increased SCRC risk in codominant (heterozygous genotype: OR = 2.81, 95%CI: 1.84-4.28, P < 0.01; homozygous polymorphic: OR = 7.32, 95%CI: 1.85-28.96, P < 0.01), dominant (OR = 2.97, 95%CI: 1.97-4.50, P < 0.01), recessive (OR = 5.26, 95%CI: 1.35-20.50, P = 0.016), overdominant (OR = 2.64, 95%CI: 1.74-4.01, P < 0.01), and log-additive models (OR = 2.78, 95%CI: 1.91-4.06, P < 0.01). The haplotype formed by the minor alleles of the CYP2E1*5B (C) and CYP2E1*6 (A) polymorphisms was associated with SCRC (P = 0.002). However, the CYP1A1*2A, CYP1A1*2C, EPHX1 Tyr113His and EPHX1 His139Arg polymorphisms were not associated with SCRC. CONCLUSION In conclusion, the

  1. 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…

  2. Transcription factor TFIID is a direct functional target of the adenovirus E1A transcription-repression domain.

    PubMed Central

    Song, C Z; Loewenstein, P M; Toth, K; Green, M

    1995-01-01

    The 243-amino acid adenovirus E1A oncoprotein both positively and negatively modulates the expression of cellular genes involved in the regulation of cell growth. The E1A transcription repression function appears to be linked with its ability to induce cellular DNA synthesis, cell proliferation, and cell transformation, as well as to inhibit cell differentiation. The mechanism by which E1A represses the transcription of various promoters has proven enigmatic. Here we provide several lines of evidence that the "TATA-box" binding protein (TBP) component of transcription factor TFIID is a cellular target of the E1A repression function encoded within the E1A N-terminal 80 amino acids. (i) The E1A N-terminal 80 amino acids [E1A-(1-80)protein] efficiently represses basal transcription from TATA-containing core promoters in vitro. (ii) TBP reverses completely E1A repression in vitro. (iii) TBP restores transcriptional activity to E1A-(1-80) protein affinity-depleted nuclear extracts. (iv) The N-terminal repression domain of E1A interacts directly and specifically with TBP in vitro. These results may help explain how E1A represses a set of genes that lack common upstream promoter elements. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:7479778

  3. 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.

  4. Dehydrocostus lactone prevents mitochondrial dysfunction in osteoblastic MC3T3-E1 cells.

    PubMed

    Choi, Eun Mi

    2011-08-16

    The dried root of Saussurea lappa Clarke (Compositae) has been used as a traditional medicine. Dehydrocostus lactone is one of the main bioactive constituents of this medicinal plant. In the present study, the protective effect of dehydrocostus lactone against antimycin A (an inhibitor of mitochondrial complex III)-induced cytotoxicity was investigated in osteoblastic MC3T3-E1 cells. Pre-treatment with dehydrocostus lactone prior to antimycin A exposure significantly prevented mitochondrial membrane potential dissipation, complex IV inactivation, ATP loss, cytochrome c release, intracellular calcium elevation and potassium loss, and reactive oxygen species production induced by antimycin A. These results suggest that dehydrocostus lactone protects osteoblastic MC3T3-E1 cells from antimycin A-induced cell damage through the improved mitochondrial function.

  5. Sonochemical synthesis of novel pyrano[3,4-e][1,3]oxazines: A green protocol.

    PubMed

    Saleh, Tamer S; Al-Bogami, Abdullah S; Mekky, Ahmed E M; Alkhathlan, Hamad Z

    2017-05-01

    The atom-efficient and green protocol for formation of pyrano[3,4-e][1,3]oxazines utilizing dimethyl carbonate under ultrasound irradiation in a presence of KF/basic alumina was reported. We provide a novel series of pyrano[3,4-e][1,3]oxazine derivatives interesting for biological screening tests. In general, it was found that ultrasound irradiations enable the reactions to occur which could not be carried out under silent conditions. These remarkable effects appeared in sonicated reactions can be reasonably interpreted in terms of acoustic cavitation phenomenon. Structures of the products were established on analytical and spectral data. This protocol offers several advantages attain many principles of green chemistry including, save energy, atom economy, clean reactions, inexpensive green reagent and use catalysts rather than stoichiometric reagents.

  6. Small Signal Modelling and Control of the Hydrogen Mixer for Facility E1

    NASA Technical Reports Server (NTRS)

    Barbieri, Enrique

    2003-01-01

    We have undertaken the theoretical modelling of an existing liquid hydrogen (LH2) and gas hydrogen (GH2) mixer subsystem of the E1 Ground Test Facility at NASA John C. Stennis Space Center. The E1 test facility carries out comprehensive ground-based testing and certification of various liquid rocket engines and their components. The mixer described in this work is responsible for combining high pressure LH2 and GH2 to produce a hydrogen flow that meets certain thermodynamic properties before it is fed into a test article. The desired properties are maintained by precise control of the mixture of LH2 and GH2 flows. The mixer is modelled as a general multi-flow lumped volume for single constituent fluids using density and internal energy as states. The set of nonlinear differential equations is linearized about an equilibrium point and the resulting two-state, 3-input linear model is analyzed as a possible candidate for control design.

  7. 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.

  8. 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

  9. Expression of cyclins E1 and E2 during mouse development and in neoplasia

    PubMed Central

    Geng, Yan; Yu, Qunyan; Whoriskey, Wendy; Dick, Fred; Tsai, Kenneth Y.; Ford, Heide L.; Biswas, Debajit K.; Pardee, Arthur B.; Amati, Bruno; Jacks, Tyler; Richardson, Andrea; Dyson, Nicholas; Sicinski, Piotr

    2001-01-01

    Cyclin E1 (formerly called cyclin E) and the recently described cyclin E2 belong to the family of E-type cyclins that operate during the G1/S phase progression in mammalian cells. The two E-cyclins share a catalytic partner, cyclin-dependent kinase 2 (CDK2), and activate their associated kinase activities at similar times during cell cycle progression. Despite these similarities, it is unknown whether the two proteins perform distinct functions, or, alternatively, they control S-phase entry of different cell types in a tissue-specific fashion. To start addressing in vivo functions of E-cyclins, we determined the expression pattern of cyclins E1 and E2 during normal mouse development. We found that the two E-cyclins showed very similar patterns of expression; both were expressed within the proliferating compartment during embryo development. Analyses of cells and tissues lacking members of the retinoblastoma (pRB) family of proteins revealed that the expression of both cyclins is controlled in a pRB-dependent, but p107- and p130-independent fashion, likely through the pRB-dependent E2F transcription factors. We also found that cyclins E1 and E2 are expressed at high levels in mouse breast tumors driven by the Myc oncogene. Last, we found that cyclin E2 is overexpressed in ≈24% of analyzed human mammary carcinomas. Collectively these findings suggest that the expression of cyclins E1 and E2 is governed by similar molecular circuitry. PMID:11687642

  10. Quadratic Hamilton-Poisson systems on $\\mathfrak{s}\\mathfrak{e}(1, 1)^{*}_{-}$: The homogeneous case

    NASA Astrophysics Data System (ADS)

    Barrett, Dennis I.; Biggs, Rory; Remsing, Claudiu C.

    2015-11-01

    In this paper we consider quadratic Hamilton-Poisson systems on the semi-Euclidean Lie-Poisson space {s}{e}(1, 1)*-. The homogeneous positive semidefinite systems are classified; there are exactly six equivalence classes. In each case, the stability nature of the equilibrium states is determined. Explicit expressions for the integral curves are found. A characterization of the equivalence classes, in terms of the equilibria, is identified. Finally, the relation of this work to optimal control is briefly discussed.

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

    PubMed Central

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

    2004-01-01

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

  12. Aminotriazole Alleviates Acetaminophen Poisoning via Downregulating P450 2E1 and Suppressing Inflammation

    PubMed Central

    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

  13. Mouse Spermatocytes Express CYP2E1 and Respond to Acrylamide Exposure

    PubMed Central

    Nixon, Belinda J.; Katen, Aimee L.; Stanger, Simone J.; Schjenken, John E.; Nixon, Brett; Roman, Shaun D.

    2014-01-01

    Metabolism of xenobiotics by cytochrome P450s (encoded by the CYP genes) often leads to bio-activation, producing reactive metabolites that interfere with cellular processes and cause DNA damage. In the testes, DNA damage induced by xenobiotics has been associated with impaired spermatogenesis and adverse effects on reproductive health. We previously reported that chronic exposure to the reproductive toxicant, acrylamide, produced high levels of DNA damage in spermatocytes of Swiss mice. CYP2E1 metabolises acrylamide to glycidamide, which, unlike acrylamide, readily forms adducts with DNA. Thus, to investigate the mechanisms of acrylamide toxicity in mouse male germ cells, we examined the expression of the CYP, CYP2E1, which metabolises acrylamide. Using Q-PCR and immunohistochemistry, we establish that CYP2E1 is expressed in germ cells, in particular in spermatocytes. Additionally, CYP2E1 gene expression was upregulated in these cells following in vitro acrylamide exposure (1 µM, 18 h). Spermatocytes were isolated and treated with 1 µM acrylamide or 0.5 µM glycidamide for 18 hours and the presence of DNA-adducts was investigated using the comet assay, modified to detect DNA-adducts. Both compounds produced significant levels of DNA damage in spermatocytes, with a greater response observed following glycidamide exposure. A modified comet assay indicated that direct adduction of DNA by glycidamide was a major source of DNA damage. Oxidative stress played a small role in eliciting this damage, as a relatively modest effect was found in a comet assay modified to detect oxidative adducts following glycidamide exposure, and glutathione levels remained unchanged following treatment with either compound. Our results indicate that the male germ line has the capacity to respond to xenobiotic exposure by inducing detoxifying enzymes, and the DNA damage elicited by acrylamide in male germ cells is likely due to the formation of glycidamide adducts. PMID:24788432

  14. 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.

  15. Expression of cyclins E1 and E2 during mouse development and in neoplasia.

    PubMed

    Geng, Y; Yu, Q; Whoriskey, W; Dick, F; Tsai, K Y; Ford, H L; Biswas, D K; Pardee, A B; Amati, B; Jacks, T; Richardson, A; Dyson, N; Sicinski, P

    2001-11-06

    Cyclin E1 (formerly called cyclin E) and the recently described cyclin E2 belong to the family of E-type cyclins that operate during the G(1)/S phase progression in mammalian cells. The two E-cyclins share a catalytic partner, cyclin-dependent kinase 2 (CDK2), and activate their associated kinase activities at similar times during cell cycle progression. Despite these similarities, it is unknown whether the two proteins perform distinct functions, or, alternatively, they control S-phase entry of different cell types in a tissue-specific fashion. To start addressing in vivo functions of E-cyclins, we determined the expression pattern of cyclins E1 and E2 during normal mouse development. We found that the two E-cyclins showed very similar patterns of expression; both were expressed within the proliferating compartment during embryo development. Analyses of cells and tissues lacking members of the retinoblastoma (pRB) family of proteins revealed that the expression of both cyclins is controlled in a pRB-dependent, but p107- and p130-independent fashion, likely through the pRB-dependent E2F transcription factors. We also found that cyclins E1 and E2 are expressed at high levels in mouse breast tumors driven by the Myc oncogene. Last, we found that cyclin E2 is overexpressed in approximately 24% of analyzed human mammary carcinomas. Collectively these findings suggest that the expression of cyclins E1 and E2 is governed by similar molecular circuitry.

  16. 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.

  17. Migraine: possible role of platelet insensitivity to prostaglandin E1 (PGE1).

    PubMed

    Cerneca, F; de Luyk, S; Radillo, O; Simeone, R; Mangiarotti, M

    1993-01-01

    Platelet aggregation inhibition, induced by prostaglandin E1 (PGE1), was evaluated in 38 patients affected by migraine. Our data indicate a complete insensitivity to PGE1 in these subjects. The insensitivity to PGE1 leads to decreased cyclic-AMP (cAMP) levels, determining an imbalance in the inhibitory mechanism. From this observation we can suppose that the decreased affinity of PGE1-receptors, causing decreased cAMP levels, may be involved in pathogenesis of migraine.

  18. Definition of a major p53 binding site on Ad2E1B58K protein and a possible nuclear localization signal on the Ad12E1B54K protein.

    PubMed

    Grand, R J; Parkhill, J; Szestak, T; Rookes, S M; Roberts, S; Gallimore, P H

    1999-01-28

    Previous studies have established that adenovirus 2/5 early region 1B (Ad E1B) 58K protein binds p53 strongly and co-localizes with it to cytoplasmic dense bodies whilst the homologous Ad12E1B54K protein binds only weakly and co-localizes primarily to the nucleus in Ad12E1 transformed cells. We have used these properties of the E1B proteins from different viral serotypes to map the p53 binding site on the Ad2/5 protein. A set of chimaeric genes was constructed containing different proportions of the Ad12 and Ad2E1B DNA. These, together with Ad12E1A and E1B19K DNA, were transfected into baby rat kidney cells and transformed lines isolated. From an examination of the properties of these Ad12/Ad2E1B fusion proteins in co-immunoprecipitation and subcellular localization experiments it has been concluded that the p53 binding site on Ad2E1B58K protein lies between amino acids 216 and 235 and that the homologous region on Ad12E1B54K protein also binds p53. In addition, a unique nuclear localization signal is located on Ad12E1B54K between residues 228 and 239. We suggest that primary structure differences in these regions of the Ad2 and Ad12E1B proteins are responsible for the different subcellular localizations in AdE1 transformants.

  19. 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.

  20. Effects of 6-Hydroxyflavone on Osteoblast Differentiation in MC3T3-E1 Cells

    PubMed Central

    Wu, Yu-Wei; Yeh, Shauh-Der; Lin, Yu-Hsaing; Tsai, Yu-Hui

    2014-01-01

    Osteoblast differentiation plays an essential role in bone integrity. Isoflavones and some flavonoids are reported to have osteogenic activity and potentially possess the ability to treat osteoporosis. However, limited information concerning the osteogenic characteristics of hydroxyflavones is available. This study investigates the effects of various hydroxyflavones on osteoblast differentiation in MC3T3-E1 cells. The results showed that 6-hydroxyflavone (6-OH-F) and 7-hydroxyflavone (7-OH-F) stimulated ALP activity. However, baicalein and luteolin inhibited ALP activity and flavone showed no effect. Up to 50 μM of each compound was used for cytotoxic effects study; flavone, 6-OH-F, and 7-OH-F had no cytotoxicity on MC3T3-E1 cells. Moreover, 6-OH-F activated AKT and serine/threonine kinases (also known as protein kinase B or PKB), extracellular signal-regulated kinases (ERK 1/2), and the c-Jun N-terminal kinase (JNK) signaling pathways. On the other hand, 7-OH-F promoted osteoblast differentiation mainly by activating ERK 1/ 2 signaling pathways. Finally, after 5 weeks of 6-OH-F induction, MC3T3-E1 cells showed a significant increase in the calcein staining intensity relative to merely visible mineralization observed in cells cultured in the osteogenic medium only. These results suggested that 6-OH-F could activate AKT, ERK 1/2, and JNK signaling pathways to effectively promote osteoblastic differentiation. PMID:24795772

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

    SciTech Connect

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

    2016-04-06

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

  2. Electric dipole strength distribution below the E1 giant resonance in N = 82 nuclei

    NASA Astrophysics Data System (ADS)

    Guliyev, Ekber; Kuliev, Ali; Guner, Mehmet

    2010-12-01

    In this study quasiparticle random-phase approximation with the translational invariant Hamiltonian using deformed mean field potential has been conducted to describe electric dipole excitations in 136Xe, 138Ba, 140Ce, 142Nd, 144Sm and 146Gd isotones. The distribution of the calculated E1 strength shows a resonance like structure at energies between 6-8 MeV exhausting up to 1% of the isovector electric dipole Energy Weighted Sum Rule and in some aspects nicely confirms the experimental data. It has been shown that the main part of E1 strength, observed below the threshold in these nuclei may be interpreted as main fragments of the Pygmy Dipole resonance. The agreement between calculated mean excitation energies as well as summed B(E1) value of the 1- excitations and the available experimental data is quite good. The calculations indicate the presence of a few prominent positive parity 1+ States in heavy N = 82 isotones in the energy interval 6-8 MeV which shows not all dipole excitations were of electric character in this energy range.

  3. Electric dipole strength distribution below the E1 giant resonance in N = 82 nuclei

    NASA Astrophysics Data System (ADS)

    Guliyev, Ekber; Kuliev, Ali; Guner, Mehmet

    2010-12-01

    In this study quasiparticle random-phase approximation with the translational invariant Hamiltonian using deformed mean field potential has been conducted to describe electric dipole excitations in 136Xe, 138Ba, 140Ce, 142Nd, 144Sm and 146Gd isotones. The distribution of the calculated E1 strength shows a resonance like structure at energies between 6-8 MeV exhausting up to 1% of the isovector electric dipole Energy Weighted Sum Rule and in some aspects nicely confirms the experimental data. It has been shown that the main part of E1 strength, observed below the threshold in these nuclei may be interpreted as main fragments of the Pygmy Dipole resonance. The agreement between calculated mean excitation energies as well as summed B( E1) value of the 1- excitations and the available experimental data is quite good. The calculations indicate the presence of a few prominent positive parity 1+ States in heavy N = 82 isotones in the energy interval 6-8 MeV which shows not all dipole excitations were of electric character in this energy range.

  4. Menaquinone-7 regulates gene expression in osteoblastic MC3T3E1 cells.

    PubMed

    Katsuyama, Hironobu; Saijoh, Kiyofumi; Otsuki, Takemi; Tomita, Masafumi; Fukunaga, Masao; Sunami, Shigeo

    2007-02-01

    Previous study has shown that the vitamin K2 analog menaquinone-7 (MK-7) induces expression of the osteoblast-specific genes osteocalcin, osteoprotegerin, receptor activator of NFkappaB, and its ligand. Since MK-7 may also regulate osteoblast cell function, we examined the expression of osteoblast genes regulated by MK-7 administration. Differences between gene expression in control and MK-7-administered MC3T3E1 cells were analyzed using the suppression subtractive hybridization method. After 24 h of MK-7 administration, genes upregulated by MK-7 included tenascin C and BMP2. Genes downregulated by MK-7 administration included biglycan and butyrophilin. Real-time PCR showed a marked increase in tenascin C. When the protein level was examined using Western blot analysis, tenascin C was higher in MK-7-administered cells than in control cells. These results indicated that MK-7 affected the cellular function of osteoblastic MC3T3E1 cells. Considering BMP2 mRNA expression was higher in MK-7-administered cells than in control cells, the effect of MK-7 administration on the signal transduction system was examined. Western blot analysis showed that cells administered MK-7 displayed a higher phosphorylated Smad1 level than control cells. Because MC3T3E1 cells have a nuclear binding receptor for MK-7, this result might indicate an indirect effect of MK-7 through BMP2 production.

  5. 75 FR 16120 - Proposed Agency Information Collection Activities; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-31

    ... 4010, FR 4011, FR 4012, FR 4017, FR 4019, FR 4023, FR 4013, or FR 4014 by any of the following methods... Delegated Authority the Extension for Three Years, With Revision, of the Following Reports 1. Report title: Report of Selected Balance Sheet Items for Discount Window Borrowers. Agency form numbers: FR 2046. OMB...

  6. 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.

  7. 78 FR 79435 - Records Governing Off-the-Record Communications

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-30

    ...-000 11-22-13 Department of the Army.\\1\\ CP13-492-000 2. CP13-73-000 12-03-13 Tony King. CP13-74-000 3.... Order No. 607 (64 FR 51222, September 22, 1999) requires Commission decisional employees, who make or... 18 CFR 385.2201(e)(1)(v). The following is a list of off-the-record communications recently...

  8. 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

  9. The adenovirus E1A N-terminal repression domain represses transcription from a chromatin template in vitro.

    PubMed

    Loewenstein, Paul M; Wu, Shwu-Yuan; Chiang, Cheng-Ming; Green, Maurice

    2012-06-20

    The adenovirus repression domain of E1A 243R at the E1A N-terminus (E1A 1-80) transcriptionally represses genes involved in differentiation and cell cycle progression. E1A 1-80 represses transcription in vitro from naked DNA templates through its interaction with p300 and TFIID. E1A 1-80 can also interact with several chromatin remodeling factors and associates with chromatin in vivo. We show here that E1A 243R and E1A 1-80 can repress transcription from a reconstituted chromatin template in vitro. Temporal analysis reveals strong repression by E1A 1-80 when added at pre-activation, activation and early transcription stages. Interestingly, E1A 1-80 can greatly enhance transcription from chromatin templates, but not from naked DNA, when added at pre-initiation complex (PIC) formation and transcription-initiation stages. These data reveal a new dimension for E1A 1-80's interface with chromatin and may reflect its interaction with key players in PIC formation, p300 and TFIID, and/or possibly a role in chromatin remodeling.

  10. 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

  11. The adenovirus E1A N-terminal repression domain represses transcription from a chromatin template in vitro

    PubMed Central

    Loewenstein, Paul M.; Wu, Shwu-Yuan; Chiang, Cheng-Ming

    2013-01-01

    The adenovirus repression domain of E1A 243R at the E1A N-terminus (E1A 1–80) transcriptionally represses genes involved in differentiation and cell cycle progression. E1A 1–80 represses transcription in vitro from naked DNA templates through its interaction with p300 and TFIID. E1A 1–80 can also interact with several chromatin remodeling factors and associates with chromatin in vivo. We show here that E1A 243R and E1A 1–80 can repress transcription from a reconstituted chromatin template in vitro. Temporal analysis reveals strong repression by E1A 1–80 when added at pre-activation, activation and early transcription stages. Interestingly, E1A 1–80 can greatly enhance transcription from chromatin templates, but not from naked DNA, when added at pre-initiation complex (PIC) formation and transcription-initiation stages. These data reveal a new dimension for E1A 1–80's interface with chromatin and may reflect its interaction with key players in PIC formation, p300 and TFIID, and/or possibly a role in chromatin remodeling. PMID:22521914

  12. Role of an adenovirus E2 promoter binding factor in E1A-mediated coordinate gene control.

    PubMed Central

    Kovesdi, I; Reichel, R; Nevins, J R

    1987-01-01

    A product of the adenovirus gene E1A is responsible for the stimulation of transcription from six viral promoters as well as at least two cellular promoters. We have detected a HeLa cell factor, termed E2 promoter binding factor (E2F), that appears to mediate the transcriptional stimulation of the viral E2 promoter. Competition experiments revealed that E2F did not recognize and bind to the E1B, E3, E4, or major late promoter sequences. Furthermore, three additional promoters stimulated by E1A, heat shock protein 70, beta-globin, and early simian virus 40, do not bind E2F. In contrast, the factor does recognize sequences in the E1A enhancer, and within the E1A enhancer are duplicated binding sites for E2F. Finally, a single E2F binding site from the E1A enhancer can confer increased transcription to a mouse beta-globin promoter, dependent on the action of the E1A gene product. This stimulation requires binding of E2F since methylation of the binding site, which blocks binding in vitro, reduces transcription stimulation in vivo. We, therefore, conclude that E2F is likely to be responsible for the E1A-mediated stimulation of the E1A gene as well as the E2 gene but is not involved in the activation of the other E1A-inducible promoters. Images PMID:2951737

  13. 75 FR 54213 - Privacy Act of 1974, as Amended; Computer Matching Program (SSA/Office of Personnel Management...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-03

    ...] [FR Doc No: 2010-22000] SOCIAL SECURITY ADMINISTRATION [Docket No. SSA 2010-0016] Privacy Act of 1974..., 1019, 1020, and 1021 AGENCY: Social Security Administration (SSA). ACTION: Notice of a renewal of an...) and (f) of the Social Security Act (Act) (42 U.S.C. 1383(e)(1)(B) and (f)) and for the SVB purposes...

  14. Identification of interactions in the E1E2 heterodimer of hepatitis C virus important for cell entry.

    PubMed

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

    2011-07-08

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

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

    PubMed Central

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

    2011-01-01

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

  16. Atomic data from the Iron Project. XVII. Radiative transition probabilities for dipole allowed and forbidden transitions in Fe III.

    NASA Astrophysics Data System (ADS)

    Nahar, S. N.; Pradhan, A. K.

    1996-11-01

    Transition probabilities are obtained for both the dipole allowed (E1) fine structure transitions and the forbidden electric quadrupole and magnetic dipole (E2, M1) transitions in Fe III. For the E1 transitions, ab initio calculations in the close coupling (CC) approximation using the R-matrix method are carried out in LS coupling with a 49-term eigenfunction expansion for Fe IV. The fine structure components are obtained through algebraic transformation of the LS line strengths, and the oscillator strengths and A-coefficients are computed using spectroscopic energies of the observed levels. Radiative transition probabilities for 9797 fine structure E1 transitions corresponding to 1408 LS multiplets among 200 bound states of Fe III are reported. Forbidden E2 and M1 transition probabilities are computed for 362 transitions among the 34 fine structure levels of all 16 LS terms dominated by the 3d^6^ configuration using optimised configuration-interaction wavefunctions from the SUPERSTRUCTURE program in the Breit-Pauli approximation. Comparison of the present results is made with previous calculations and significant differences are found. Theoretical line ratios computed using the present E2 and M1 A-coefficients show better agreement with observations for some prominent Fe III lines in the infra-red than those using the earlier data by Garstang (1957MNRAS.117..393G). This work is carried out as part of the Iron Project to obtain accurate radiative and collisional data for the Iron group elements.

  17. 78 FR 32387 - Proposed Agency Information Collection Activities; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-30

    ... 4010, FR 4011, FR 4012, FR 4017, FR 4019, or FR 4023 by any of the following methods: Agency Web Site... curing the deficiencies and to execute a formal cure agreement with the Federal Reserve.\\5\\ \\4\\ 12...

  18. Venus Transit

    NASA Image and Video Library

    2012-06-05

    A "transit of Venus" occurs when the planet Venus passes directly between the sun and the Earth. During the event, Venus will be seen from Earth as a small black sphere moving across the face of the sun. Such an event won’t occur again until the year 2117. The Goddard Visitor Center hosted a watch party that included near real-time images from NASA’s Solar Dynamics Observatory mission, coverage of the event from several locations via NASA TV, in-person presentations by NASA experts, hands-on activities for children of all ages. Heavy cloud cover did not allow viewing opportunities of the transit via solar telescopes. Credit: NASA/Goddard Space Flight Center/Bill Hrybyk NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

  19. Excitation rates for transitions in Ca XV

    NASA Astrophysics Data System (ADS)

    Aggarwal, K. M.; Keenan, F. P.

    2003-08-01

    Collision strengths for transitions among the energetically lowest 46 fine-structure levels belonging to the (1s2) 2s22p2, 2s2p3, 2p4, and 2s22p3l configurations of Ca XV are computed, over a wide electron energy range below 300 Ryd, using the Dirac Atomic R-matrix Code (DARC) of Norrington & Grant (\\cite{Norrington03}). Resonances in the threshold region have been resolved in a fine energy mesh, and excitation rates are determined over a wide electron temperature range below 107 K. The results are compared with those available in the literature, and the accuracy of the data is assessed. Table \\ref{tab3} is also (and Table 4 only) available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsweb.u-strasbg.fr/cgi-bin/qcat?J/A+A/407/769

  20. Effects of ethanol on CYP2E1 levels and related oxidative stress using a standard balanced diet.

    PubMed

    Azzalis, Ligia A; Fonseca, Fernando L A; Simon, Karin A; Schindler, Fernanda; Giavarotti, Leandro; Monteiro, Hugo P; Videla, Luis A; Junqueira, Virgínia B C

    2012-07-01

    Expression of cytochrome P4502E1 (CYP2E1) is very much influenced by nutritional factors, especially carbohydrate consumption, and various results concerning the expression of CYP2E1 were obtained with a low-carbohydrate diet. This study describes the effects of ethanol treatment on CYP2E1 levels and its relationship with oxidative stress using a balanced standard diet to avoid low or high carbohydrate consumption. Rats were fed for 1, 2, 3, or 4 weeks a commercial diet plus an ethanol-sucrose solution. The results have shown that ethanol administration was associated with CYP2E1 induction and stabilization without related oxidative stress. Our findings suggest that experimental models with a low-carbohydrate/high-fat diet produce some undesirable CYP2E1 changes that are not present when a balanced standard diet is given.

  1. Brucella abortus ΔrpoE1 confers protective immunity against wild type challenge in a mouse model of brucellosis.

    PubMed

    Willett, Jonathan W; Herrou, Julien; Czyż, Daniel M; Cheng, Jason X; Crosson, Sean

    2016-09-30

    The Brucella abortus general stress response (GSR) system regulates activity of the alternative sigma factor, σ(E1), which controls transcription of approximately 100 genes and is required for persistence in a BALB/c mouse chronic infection model. We evaluated the host response to infection by a B. abortus strain lacking σ(E1) (ΔrpoE1), and identified pathological and immunological features that distinguish ΔrpoE1-infected mice from wild-type (WT), and that correspond with clearance of ΔrpoE1 from the host. ΔrpoE1 infection was indistinguishable from WT in terms of splenic bacterial burden, inflammation and histopathology up to 6weeks post-infection. However, Brucella-specific serum IgG levels in ΔrpoE1-infected mice were 5 times higher than WT by 4weeks post-infection, and remained significantly higher throughout the course of a 12-week infection. Total IgG and Brucella-specific IgG levels peaked strongly in ΔrpoE1-infected mice at 6weeks, which correlated with reduced splenomegaly and bacterial burden relative to WT-infected mice. Given the difference in immune response to infection with wild-type and ΔrpoE1, we tested whether ΔrpoE1 confers protective immunity to wild-type challenge. Mice immunized with ΔrpoE1 completely resisted WT infection and had significantly higher serum titers of Brucella-specific IgG, IgG2a and IFN-γ after WT challenge relative to age-matched naïve mice. We conclude that immunization of BALB/c mice with the B. abortus GSR pathway mutant, ΔrpoE1, elicits an adaptive immune response that confers significant protective immunity against WT infection.

  2. 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.

  3. Subcellular Localization and Functional Analysis of the Arabidopsis GTPase RabE1[W][OA

    PubMed Central

    Speth, Elena Bray; Imboden, Lori; Hauck, Paula; He, Sheng Yang

    2009-01-01

    Membrane trafficking plays a fundamental role in eukaryotic cell biology. Of the numerous known or predicted protein components of the plant cell trafficking system, only a relatively small subset have been characterized with respect to their biological roles in plant growth, development, and response to stresses. In this study, we investigated the subcellular localization and function of an Arabidopsis (Arabidopsis thaliana) small GTPase belonging to the RabE family. RabE proteins are phylogenetically related to well-characterized regulators of polarized vesicle transport from the Golgi apparatus to the plasma membrane in animal and yeast cells. The RabE family of GTPases has also been proposed to be a putative host target of AvrPto, an effector protein produced by the plant pathogen Pseudomonas syringae, based on yeast two-hybrid analysis. We generated transgenic Arabidopsis plants that constitutively expressed one of the five RabE proteins (RabE1d) fused to green fluorescent protein (GFP). GFP-RabE1d and endogenous RabE proteins were found to be associated with the Golgi apparatus and the plasma membrane in Arabidopsis leaf cells. RabE down-regulation, due to cosuppression in transgenic plants, resulted in drastically altered leaf morphology and reduced plant size, providing experimental evidence for an important role of RabE GTPases in regulating plant growth. RabE down-regulation did not affect plant susceptibility to pathogenic P. syringae bacteria; conversely, expression of the constitutively active RabE1d-Q74L enhanced plant defenses, conferring resistance to P. syringae infection. PMID:19233904

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. Morbidly Obese Patients Exhibit Increased CYP2E1-Mediated Oxidation of Acetaminophen.

    PubMed

    van Rongen, Anne; Välitalo, Pyry A J; Peeters, Mariska Y M; Boerma, Djamila; Huisman, Fokko W; van Ramshorst, Bert; van Dongen, Eric P A; van den Anker, Johannes N; Knibbe, Catherijne A J

    2016-07-01

    Acetaminophen (paracetamol) is mainly metabolized via glucuronidation and sulphation, while the minor pathway through cytochrome P450 (CYP) 2E1 is held responsible for hepatotoxicity. In obese patients, CYP2E1 activity is reported to be induced, thereby potentially worsening the safety profile of acetaminophen. The aim of this study was to determine the pharmacokinetics of acetaminophen and its metabolites (glucuronide, sulphate, cysteine and mercapturate) in morbidly obese and non-obese patients. Twenty morbidly obese patients (with a median total body weight [TBW] of 140.1 kg [range 106-193.1 kg] and body mass index [BMI] of 45.1 kg/m(2) [40-55.2 kg/m(2)]) and eight non-obese patients (with a TBW of 69.4 kg [53.4-91.7] and BMI of 21.8 kg/m(2) [19.4-27.4]) received 2 g of intravenous acetaminophen. Fifteen blood samples were collected per patient. Population pharmacokinetic modelling was performed using NONMEM. In morbidly obese patients, the median area under the plasma concentration-time curve from 0 to 8 h (AUC0-8h) of acetaminophen was significantly smaller (P = 0.009), while the AUC0-8h ratios of the glucuronide, sulphate and cysteine metabolites to acetaminophen were significantly higher (P = 0.043, 0.004 and 0.010, respectively). In the model, acetaminophen CYP2E1-mediated clearance (cysteine and mercapturate) increased with lean body weight [LBW] (population mean [relative standard error] 0.0185 L/min [15 %], P < 0.01). Moreover, accelerated formation of the cysteine and mercapturate metabolites was found with increasing LBW (P < 0.001). Glucuronidation clearance (0.219 L/min [5 %]) and sulphation clearance (0.0646 L/min [6 %]) also increased with LBW (P < 0.001). Obesity leads to lower acetaminophen concentrations and earlier and higher peak concentrations of acetaminophen cysteine and mercapturate. While a higher dose may be anticipated to achieve adequate acetaminophen concentrations, the increased CYP2E1-mediated pathway may

  10. Occupational Survey Report. Ground Radio Communications, AFSC 2E1X3

    DTIC Science & Technology

    2003-10-01

    analyzed the data, and wrote the final report. Mr. Tyrone Hill provided computer-programming support, and Ms. Dolores Navarro and Ms. Sherry Evans...AFSC 2E1X3 members selected military-related education and training opportunities and medical/ dental care for AD members as their second and third...TRAINING OPPORTUNITIES 52 2.52 55 2.49 50 2.34 MEDICAL/ DENTAL CARE FOR AD MEMBER 60 2.57 55 2.56 53 2.48 MEDICAL/ DENTAL CARE FOR FAMILY MEMBERS 48

  11. Isotopic dependence of the predissociations of the E1Π state of CO

    NASA Astrophysics Data System (ADS)

    Lefebvre-Brion, H.; Majumder, M.

    2015-04-01

    The predissociations of the E1Π state of CO are again studied. They include both the background predissociation attributed to the continuum of the A1Π state and the accidental predissociation due to the k3Π state. They are calculated using a coupled equations method. The three components of the k state are introduced. These predissociations are studied for different isotopologues and are shown to decrease with increasing reduced mass, in agreement with the experimental results of Ubachs et al. [J. Chem. Phys. 113, 547 (2000)].

  12. 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.

  13. The E1 Protein of Human Papillomavirus Type 16 Is Dispensable for Maintenance Replication of the Viral Genome

    PubMed Central

    Egawa, Nagayasu; Nakahara, Tomomi; Ohno, Shin-ichi; Narisawa-Saito, Mako; Yugawa, Takashi; Fujita, Masatoshi; Yamato, Kenji; Natori, Yukikazu

    2012-01-01

    Papillomavirus genomes are thought to be amplified to about 100 copies per cell soon after infection, maintained constant at this level in basal cells, and amplified for viral production upon keratinocyte differentiation. To determine the requirement for E1 in viral DNA replication at different stages, an E1-defective mutant of the human papillomavirus 16 (HPV16) genome featuring a translation termination mutation in the E1 gene was used. The ability of the mutant HPV16 genome to replicate as nuclear episomes was monitored with or without exogenous expression of E1. Unlike the wild-type genome, the E1-defective HPV16 genome became established in human keratinocytes only as episomes in the presence of exogenous E1 expression. Once established, it could replicate with the same efficiency as the wild-type genome, even after the exogenous E1 was removed. However, upon calcium-induced keratinocyte differentiation, once again amplification was dependent on exogenous E1. These results demonstrate that the E1 protein is dispensable for maintenance replication but not for initial and productive replication of HPV16. PMID:22238312

  14. 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

  15. Ethanol induction of CYP2A5: role of CYP2E1-ROS-Nrf2 pathway.

    PubMed

    Lu, Yongke; Zhang, Xu Hannah; Cederbaum, Arthur I

    2012-08-01

    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.

  16. Smooth Transition

    NASA Technical Reports Server (NTRS)

    2006-01-01

    22 February 2006 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows a transition from one of the many layered troughs in the north polar region of Mars to the relatively homogeneous-looking upper surface of the polar cap. The difference in brightness across this scene is a function of several factors, one of which is the amount of dust versus that of ice in any given location. The bright material that dominates the scene is largely water ice.

    Location near: 83.2oN, 297.8oW Image width: 3 km (1.9 mi) Illumination from: lower right Season: Northern Summer

  17. 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

  18. Precise Calculations of Astrophysically Important Allowed and Forbidden Transitions of Xe VIII

    NASA Astrophysics Data System (ADS)

    Bhowmik, Anal; Nath Dutta, Narendra; Roy, Sourav

    2017-02-01

    The present work reports transition line parameters for Xe viii, which are potentially important for astrophysics in view of recent observations of multiply ionized xenon in hot white dwarfs. The relativistic coupled-cluster method is employed here to calculate the E1, E2, and M1 transition line parameters with high accuracy. The E1 oscillator strengths and probabilities of E2 and M1 transitions are determined using theoretical amplitudes and experimental energy values. The calculated branching ratios and the lifetimes are supplemented to the transition parameters. The accurate presentation of these calculated data is crucial for density estimation in several stellar and interstellar media.

  19. 75 FR 76921 - Tobacco Transition Payment Program; Tobacco Transition Assessments

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-10

    ... allocated among six statutorily-specified classes of tobacco products: Cigarettes, cigars, snuff, roll-your... cigarettes and cigars, pounds for the other classes) from the published TTB data and multiplied those numbers.... The initial percentage assigned to cigarette tobacco in FETRA was 96.331 percent, as specified in 7...

  20. Interaction of Adenovirus E1A with the HHV8 Promoter of Latent Genes: E1A Proteins are Able to Activate the HHV-8 LANAp in MV3 Reporter Cells

    PubMed Central

    Koehler-Hansner, Karin; Flore, Ornella; Opalka, Bertram; Hengge, Ulrich R

    2008-01-01

    Human herpesvirus 8 (HHV-8) is associated with Kaposi’s sarcoma, body cavity-based lymphoma, and Castleman’s disease. Adenoviral (Ad) E1A proteins regulate the activity of cellular and viral promoters/enhancers and transcription factors and can suppress tumorigenicity of human cancers. As (i) HHV-8 and Ad may co-exist in immunocompromised patients and (ii) E1A might be considered as therapeutic transgene for HHV-8-associated neoplasms we investigated whether the promoter of the latency-associated nuclear antigen (LANAp) controlling expression of vCyclin, vFLIP, and LANA proteins required for latent type infection is regulated by E1A. Transfection experiments in MV3 melanoma cells revealed activation of the LANAp by Ad5 E1A constructs containing an intact N terminus (aa 1-119). In particular, an Ad12 E1A mutant, Spm2, lacking six consecutive alanine residues in the “spacer” region activated the HHV-8 promoter about 15-fold compared to vector controls. In summary, we report the activation of the LANAp by E1A as a novel interaction of E1A with a viral promoter. These data may have relevance for the management of viral infections in immunocompromised patients. A role for E1A as a therapeutic in this context remains to be defined. PMID:19440465

  1. Interaction of Adenovirus E1A with the HHV8 Promoter of Latent Genes: E1A Proteins are Able to Activate the HHV-8 LANAp in MV3 Reporter Cells.

    PubMed

    Koehler-Hansner, Karin; Flore, Ornella; Opalka, Bertram; Hengge, Ulrich R

    2008-01-01

    Human herpesvirus 8 (HHV-8) is associated with Kaposi's sarcoma, body cavity-based lymphoma, and Castleman's disease. Adenoviral (Ad) E1A proteins regulate the activity of cellular and viral promoters/enhancers and transcription factors and can suppress tumorigenicity of human cancers. As (i) HHV-8 and Ad may co-exist in immunocompromised patients and (ii) E1A might be considered as therapeutic transgene for HHV-8-associated neoplasms we investigated whether the promoter of the latency-associated nuclear antigen (LANAp) controlling expression of vCyclin, vFLIP, and LANA proteins required for latent type infection is regulated by E1A. Transfection experiments in MV3 melanoma cells revealed activation of the LANAp by Ad5 E1A constructs containing an intact N terminus (aa 1-119). In particular, an Ad12 E1A mutant, Spm2, lacking six consecutive alanine residues in the "spacer" region activated the HHV-8 promoter about 15-fold compared to vector controls. In summary, we report the activation of the LANAp by E1A as a novel interaction of E1A with a viral promoter. These data may have relevance for the management of viral infections in immunocompromised patients. A role for E1A as a therapeutic in this context remains to be defined.

  2. [Genetic polymorphism of cytochrome P450 2E1 and the risk of nasopharyngeal carcinoma].

    PubMed

    Ben Chaaben, Arij; Abaza, Hajer; Douik, Hayet; Chaouch, Leila; Ayari, Fayza; Ouni, Nesrine; Mamoghli, Tasnim; Ben Guezella, Dorra; Mejri, Rachida; Harzallah, Latifa; Guemira, Fethi

    2015-12-01

    Cytochrome P450 2E1 (CYP2E1) is a detoxifying enzyme that belongs to the phase I metabolism of xenobiotics. This enzyme is encoded by a highly polymorphic gene whose common polymorphism corresponds to the substitution of cytosine (C) and thymine (T) at position -1019 (rs2031920). This polymorphism has been identified in several cancers including nasopharyngeal cancer (NPC). The study involved 124 patients with nasopharyngeal carcinoma, compared with 166 healthy controls. The presence or absence of the polymorphism is determined by PCR-RFLP. The frequency comparison between the two groups is determined by the χ(2) test. The analysis of our results showed a significant difference between the two groups regarding the mutant genotype (C2/C2) (5% vs. 0.5%, P=0.04) and has a risk factor for NPC in Tunisia (OR=8.39; CI 95% [0.99-388.1]). Also, the C2 allele was significantly associated with the group of patients than the control group (6% vs. 2%, P=0.016) and increased three times the risk of NPC in Tunisia (OR=2.99, CI 95% [1.12-8.79]). Our results confirm the results reported in other populations and emphasize the importance of the involvement of this gene in the development of detoxification of the NPC, which seems more and more strongly associated with environmental factors.

  3. Oral midodrine for prostaglandin e1 induced priapism in spinal cord injured patients.

    PubMed

    Soler, Jean-Marc; Previnaire, Jean-Gabriel; Mieusset, Roger; Plante, Pierre

    2009-09-01

    We evaluated midodrine as oral treatment for pharmacologically induced priapism in spinal cord injured patients. From 2004 to 2007 we treated 354 spinal cord injured patients with intracavernous injection of prostaglandin E1 to induce erection. Prolonged erection or priapism occurred in 14 cases (1.3% of intracavernous injections). High blood pressure and bradycardia (autonomic dysreflexia) were noted in 2 tetraplegic cases. Except in 2 patients oral midodrine was used as the only therapeutic approach to this event because of its alpha stimulant properties. All patients returned to the flaccid penile state within 30 to 45 minutes after midodrine administration. Oral midodrine was well tolerated with few side effects and without increasing the incidence of autonomic dysreflexia. At 6 months complete erection could be again induced by intracavernous injection in all treated patients. Midodrine administered orally is a simple and efficient treatment for the priapism induced by intracavernous injection of prostaglandin E1. It could be the first line therapeutic approach before more aggressive procedures.

  4. Phytocomponent p-hydroxycinnamic acid stimulates mineralization in osteoblastic MC3T3-E1 cells.

    PubMed

    Yamaguchi, Masayoshi; Lai, Ying Ling; Uchiyama, Satoshi; Nakagawa, Taeko

    2008-09-01

    Phytocomponent p-hydroxycinnamic acid (HCA) has been shown to have stimulatory effects on bone calcification and inhibitory effects on bone resorption in rat femoral tissues in vitro. Whether HCA has a stimulatory effect on mineralization in osteoblastic cells is unknown. This study was undertaken to determine the effect of HCA on mineralization in osteoblastic MC3T3-E1 cells in vitro. Cells were cultured for 72 h in a minimum essential medium (alpha-MEM) containing 10% fetal bovine serum (FBS), and the cells with subconfluency were changed to a medium containing either vehicle or HCA (10(-7)-10(-5) M) without FBS. Culture with HCA (10(-7)-10(-5) M) did not have a significant effect on cell proliferation and cell death. Deoxyribonucleic acid (DNA) content in osteoblastic cells was significantly increased after culture with HCA (10(-6) or 10(-5) M) for 48 or 72 h. Alkaline phosphatase activity in osteoblastic cells was significantly increased after culture with HCA (10(-7)-10(-5) M) for 24, 48, or 72 h. The results with Alizarin red staining for calcium showed that mineralization was significantly stimulated after culture with HCA (10(-8)-10(-5) M) for 7, 14, or 21 days. This study demonstrates that HCA has stimulatory effects on mineralization in osteoblastic MC3T3-E1 cells.

  5. Dechlorination of chloro-organics from E-1 effluents by sonolysis

    SciTech Connect

    Uraki, Y.; Chen, C.L.; Gratzl, J.S.

    1996-10-01

    Degradation of chloro-organics in bleach plant E-1 effluents by ultrasound sonication was investigated to evaluate the effects of ultrasonic treatment on the dechlorination. On sonolysis, ca. 65 mol% of 4-chlorophenol at concentration of 10{sup -4} M in aqueous solution was decomposed and ca. 35 mol% of chlorine in the substrate was released as chloride ions (Cl{sup -}) at the reaction time of 80 min at room temperature under the atmospheric pressure. By contrast, the decomposition rates were appreciably low at the concentrations of 10{sup -3} M and 10{sup -2} M. The kinetics for the disappearance of 1 follows the first-order law. However, it is dependent of the initial concentration. The addition of hydrogen peroxide, does not affect appreciably the kinetics for the disappearance of 1. On sonolysis, polychlorinated oxylignins (PCOLs) isolated from E-1 effluent were appreciably dechlorinated. The high relative mass PCOL released larger amounts of chloride ions than the low relative mass PCOL. The sonolysis resulted only in small decrease in the relative mass of PCOLs, indicating that no significant degradation of PCOLs occurred except for the release of chloride ions.

  6. 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.

  7. 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

  8. Watercress has no Importance for the elimination of ethanol by CYP2E1 inhibition.

    PubMed

    Desager, Jean-Pierre; Golnez, Jean-Luc; De Buck, Charlotte; Horsmans, Yves

    2002-09-01

    Watercress, a cruciferous vegetable, is known to inhibit the metabolism of several CYP2E1 substrates such as paracetamol and chlorzoxazone. Since ethanol and its metabolite, acetaldehyde, are CYP2E1 substrates, the influence of watercress on ethanol and acetaldehyde was investigated in healthy human volunteers. According to a randomized cross-over design, ethanol and acetaldehyde pharmacokinetic parameters were determined in 9 persons at 3 occasions: without watercress and after watercress ingestion preceding ethanol consumption from 1 or 10.5 hr, respectively. Ethanol tmax occurred significantly later when watercress was ingested 1 hr before ethanol ingestion. Likewise, acetaldehyde Cmax was significantly higher whereas acetaldehyde AUCs were increased by watercress but not significantly. All other ethanol and acetaldehyde pharmacokinetic parameters were similar between the 3 treatments. In healthy volunteers, no major watercress effect was observed on ethanol clearance but a weak inhibiting effect on acetaldehyde metabolism is possible. Ethanol absorption is also delayed by single ingestion of watercress immediately preceding ethanol consumption.

  9. 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

  10. Human Placental Lactogen Induces CYP2E1 Expression via PI 3-Kinase Pathway in Female Human Hepatocytes

    PubMed Central

    Lee, Jin Kyung; Chung, Hye Jin; Fischer, Liam; Fischer, James; Gonzalez, Frank J.

    2014-01-01

    The state of pregnancy is known to alter hepatic drug metabolism. Hormones that rise during pregnancy are potentially responsible for the changes. Here we report the effects of prolactin (PRL), placental lactogen (PL), and growth hormone variant (GH-v) on expression of major hepatic cytochromes P450 expression and a potential molecular mechanism underlying CYP2E1 induction by PL. In female human hepatocytes, PRL and GH-v showed either no effect or small and variable effects on mRNA expression of CYP1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, 3A4, and 3A5. On the other hand, PL increased expression level of CYP2E1 mRNA with corresponding increases in CYP2E1 protein and activity levels. Results from hepatocytes and HepaRG cells indicate that PL does not affect the expression or activity of HNF1α, the known transcriptional activator of basal CYP2E1 expression. Furthermore, transient transfection studies and Western blot results showed that STAT signaling, the previously known mediator of PL actions in certain tissues, does not play a role in CYP2E1 induction by PL. A chemical inhibitor of PI3-kinase signaling significantly repressed the CYP2E1 induction by PL in human hepatocytes, suggesting involvement of PI3-kinase pathway in CYP2E1 regulation by PL. CYP2E1-humanized mice did not exhibit enhanced CYP2E1 expression during pregnancy, potentially because of interspecies differences in PL physiology. Taken together, these results indicate that PL induces CYP2E1 expression via PI3-kinase pathway in human hepatocytes. PMID:24408518

  11. The degradation sequence of adenovirus E1A consists of the amino-terminal tetrapeptide Met-Arg-His-Ile.

    PubMed Central

    Simon, R; Richter, J D

    1990-01-01

    The adenovirus E1A gene product is a potent transcriptional activator and nuclear oncoprotein. Like other regulatory proteins, E1A has a short half-life, in the range of 30 to 120 min. This short half-life, which was measured in cells synthesizing E1A, is not observed in cells injected with E1A protein made in bacteria or in vitro. In these cases, E1A is essentially refractory to degradation. In an attempt to reconcile this apparent paradox, we suggested that E1A was marked for degradation during its synthesis. Furthermore, we showed that a domain in the amino terminus of E1A was required for rapid degradation in cells translating E1A mRNA (J. M. Slavicek, N. C. Jones, and J. D. Richter, EMBO J. 7:3171-3180, 1988). In this study, we have used Xenopus laevis oocytes injected with mRNAs encoding altered E1A proteins to show that the amino-terminal tetrapeptide Met-Arg-His-Ile is required for E1A degradation. Even conservative amino acid substitutions in this degradation sequence render it nonfunctional. This degradation sequence can function as a transferable signal, since it induces instability when fused to another normally stable protein. Furthermore, the degradation sequence requires a proximity of no more than six residues from the amino terminus for activity. These data suggest that a trans-acting factor recognizes the amino terminus of E1A during the translation of its message to mark the protein for subsequent destruction. Images PMID:2146491

  12. Ubiquitin-dependent proteolytic pathway in wheat germ: Isolation of multiple forms of ubiquitin-activating enzyme, E1

    SciTech Connect

    Hatfield, P.M.; Vierstra, R.D. )

    1989-01-24

    Ubiquitin is a highly conserved protein involved in several important regulatory processes through its ATP-dependent, covalent ligation to a variety of eukaryotic target proteins. The authors describe here the characterization of ubiquitin conjugation in wheat germ extracts and the subsequent isolation of enzymes involved in conjugation. With {sup 125}I-ubiquitin as a substrate, wheat germ extracts form conjugates with either endogenous or added proteins. Ubiquitin-activating enzyme (E1) was purified from wheat germ extracts by using a modification of the covalent affinity chromatography procedure of Ciechanover et al. E1 from wheat germ, like that from rabbit reticulocytes, formed thiol ester intermediates with ubiquitin in the presence of ATP. Purified E1 preparations contained three polypeptides of apparent molecular masses of 117, 123, and 126 kDa after NaDodSO{sub 4}-PAGE. Under nondenaturing conditions, these proteins have native molecular masses of {approx}115 kDa, indicating that they exist as monomers. They concluded that all three species were E1 on the basis of their coelution with E1 activity, by immunorecognition by anti-human E1 antibodies, and by the similarity of their peptide maps. Furthermore, antibodies prepared against wheat germ E1's recognized E1 from rabbit reticulocytes. All three wheat germ E1's were detected in crude extracts prepared under conditions that minimized proteolysis, suggesting that the heterogeneity of the purified E1 preparations was not the result of posthomogenization breakdown. The immunological similarity of animal and plant E1's indicates that this conjugation enzyme, like ubiquitin, has been conserved through evolution.

  13. The Apollo Number: Space Suits, Self-Support, and the Walk-Run Transition

    PubMed Central

    Carr, Christopher E.; McGee, Jeremy

    2009-01-01

    Background How space suits affect the preferred walk-run transition is an open question with relevance to human biomechanics and planetary extravehicular activity. Walking and running energetics differ; in reduced gravity (<0.5 g), running, unlike on Earth, uses less energy per distance than walking. Methodology/Principal Findings The walk-run transition (denoted *) correlates with the Froude Number (Fr = v2/gL, velocity v, gravitational acceleration g, leg length L). Human unsuited Fr* is relatively constant (∼0.5) with gravity but increases substantially with decreasing gravity below ∼0.4 g, rising to 0.9 in 1/6 g; space suits appear to lower Fr*. Because of pressure forces, space suits partially (1 g) or completely (lunar-g) support their own weight. We define the Apollo Number (Ap = Fr/M) as an expected invariant of locomotion under manipulations of M, the ratio of human-supported to total transported mass. We hypothesize that for lunar suited conditions Ap* but not Fr* will be near 0.9, because the Apollo Number captures the effect of space suit self-support. We used the Apollo Lunar Surface Journal and other sources to identify 38 gait events during lunar exploration for which we could determine gait type (walk/lope/run) and calculate Ap. We estimated the binary transition between walk/lope (0) and run (1), yielding Fr* (0.36±0.11, mean±95% CI) and Ap* (0.68±0.20). Conclusions/Significance The Apollo Number explains 60% of the difference between suited and unsuited Fr*, appears to capture in large part the effects of space suits on the walk-run transition, and provides several testable predictions for space suit locomotion and, of increasing relevance here on Earth, exoskeleton locomotion. The knowledge of how space suits affect gait transitions can be used to optimize space suits for use on the Moon and Mars. PMID:19672305

  14. 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

  15. Isotope shifts in francium isotopes Fr 206 - 213 and Fr 221

    DOE PAGES

    Collister, R.; Gwinner, G.; Tandecki, M.; ...

    2014-11-07

    We present the isotope shifts of the 7s1/2 to 7p1/2 transition for francium isotopes ²⁰⁶⁻²¹³Fr with reference to ²²¹Fr collected from two experimental periods. The shifts are measured on a sample of atoms prepared within a magneto-optical trap by a fast sweep of radio-frequency sidebands applied to a carrier laser. King plot analysis, which includes literature values for 7s1/2 to 7p3/2 isotope shifts, provides a field shift constant ratio of 1.0520(10) and a difference between the specific mass shift constants of 170(100) GHz amu between the D₁ and D₂ transitions, of sufficient precision to differentiate between ab initio calculations.

  16. Laser resonance photoionization spectroscopy of Rydberg levels in Fr

    SciTech Connect

    Andreev, S.V.; Letokhov, V.S.; Mishin, V.I.

    1987-09-21

    We investigated for the first time the high-lying Rydberg levels in the rare radioactive element francium (Fr). The investigations were conducted by the highly sensitive laser resonance atomic photoionization technique with Fr atoms produced at a rate of about 10/sup 3/ atoms/s in a hot cavity. We measured the wave numbers of the 7p/sup 2/P/sub 3/2/..-->..nd/sup 2/D (n = 22--33) and 7p/sup 2/P/sub 3/2/..-->..ns/sup 2/S (n = 23, 25--27,29--31) transitions and found the binding energy of the 7p/sup 2/P/sub 3/2/ state to be T = -18 924.8(3) cm/sup -1/, which made it possible to establish accurately the ionization potential of Fr.

  17. Role of CYP2E1 in mitochondrial dysfunction and hepatic tissue injury in alcoholic and non-alcoholic diseases

    PubMed Central

    Abdelmegeed, Mohamed A.; Ha, Seung-Kwon; Choi, Youngshim; Akbar, Mohammed; Song, Byoung-Joon

    2015-01-01

    Alcoholic fatty liver diseases (AFLD) and non-alcoholic fatty liver diseases (NAFLD) are two pathological conditions that are spreading worldwide. Both conditions are remarkably similar with regards to the pathophysiological mechanism and progression despite different causes. Oxidative stress-induced mitochondrial dysfunction through post-translational protein modifications and/or mitochondrial DNA damage has been a major risk factor in both AFLD and NAFLD development and progression. Cytochrome P450-2E1 (CYP2E1), a known important inducer of oxidative radicals in the cells, has been reported to remarkably increase in both AFLD and NAFLD. Interestingly, CYP2E1 isoforms expressed in both endoplasmic reticulum (ER) and mitochondria, likely lead to the deleterious consequences in response to alcohol or in conditions of NAFLD after exposure to high fat diet (HFD) and in obesity and diabetes. Whether CYP2E1 in both ER and mitochondria work simultaneously or sequentially in various conditions and whether mitochondrial CYP2E1 may exert more pronounced effects on mitochondrial dysfunction in AFLD and NAFLD are unclear. The aims of this review are to briefly describe the role of CYP2E1 and resultant oxidative stress in promoting mitochondrial dysfunction and the development or progression of AFLD and NAFLD, to shed a light on the function of the mitochondrial CYP2E1 as compared with the ER-associated CYP2E1. We finally discuss translational research opportunities related to this field. PMID:26278393

  18. Functional analysis of the C-terminal region of human adenovirus E1A reveals a misidentified nuclear localization signal

    SciTech Connect

    Cohen, Michael J.; King, Cason R.; Dikeakos, Jimmy D.; Mymryk, Joe S.

    2014-11-15

    The immortalizing function of the human adenovirus 5 E1A oncoprotein requires efficient localization to the nucleus. In 1987, a consensus monopartite nuclear localization sequence (NLS) was identified at the C-terminus of E1A. Since that time, various experiments have suggested that other regions of E1A influence nuclear import. In addition, a novel bipartite NLS was recently predicted at the C-terminal region of E1A in silico. In this study, we used immunofluorescence microscopy and co-immunoprecipitation analysis with importin-α to verify that full nuclear localization of E1A requires the well characterized NLS spanning residues 285–289, as well as a second basic patch situated between residues 258 and 263 ({sup 258}RVGGRRQAVECIEDLLNEPGQPLDLSCKRPRP{sup 289}). Thus, the originally described NLS located at the C-terminus of E1A is actually a bipartite signal, which had been misidentified in the existing literature as a monopartite signal, altering our understanding of one of the oldest documented NLSs. - Highlights: • Human adenovirus E1A is localized to the nucleus. • The C-terminus of E1A contains a bipartite nuclear localization signal (NLS). • This signal was previously misidentified to be a monopartite NLS. • Key basic amino acid residues within this sequence are highly conserved.

  19. 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

  20. 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. Section...