WorldWideScience

Sample records for unit e2 zim-sci

  1. 17 CFR 270.30e-2 - Reports to shareholders of unit investment trusts.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Reports to shareholders of... to shareholders of unit investment trusts. (a) At least semiannually every registered unit investment... transmit to each shareholder of record (including record holders of periodic payment plan certificates),...

  2. Attributes for MRB_E2RF1 Catchments by Major River Basins in the Conterminous United States: Surficial Geology

    Science.gov (United States)

    Wieczorek, Michael E.; LaMotte, Andrew E.

    2010-01-01

    This tabular data set represents the area of surficial geology types in square meters compiled for every MRB_E2RF1 catchment of selected Major River Basins (MRBs, Crawford and others, 2006). The source data set is the "Digital data set describing surficial geology in the conterminous US" (Clawges and Price, 1999).The MRB_E2RF1 catchments are based on a modified version of the U.S. Environmental Protection Agency's (USEPA) ERF1_2 and include enhancements to support national and regional-scale surface-water quality modeling (Nolan and others, 2002; Brakebill and others, 2008). Data were compiled for every MRB_E2RF1 catchment for the conterminous United States covering New England and Mid-Atlantic (MRB1), South Atlantic-Gulf and Tennessee (MRB2), the Great Lakes, Ohio, Upper Mississippi, and Souris-Red-Rainy (MRB3), the Missouri (MRB4), the Lower Mississippi, Arkansas-White-Red, and Texas-Gulf (MRB5), the Rio Grande, Colorado, and the Great basin (MRB6), the Pacific Northwest (MRB7) river basins, and California (MRB8).

  3. Attributes for MRB_E2RF1 Catchments by Major River Basins in the Conterminous United States: Physiographic Provinces

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This tabular data set represents the area of each physiographic province (Fenneman and Johnson, 1946) in square meters, compiled for every MRB_E2RF1 catchment of...

  4. Attributes for MRB_E2RF1 Catchments by Major River Basins in the Conterminous United States: Bedrock Geology

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This tabular data set represents the area of bedrock geology types in square meters compiled for every catchment of MRB_E2RF1 catchments for Major River Basins...

  5. Attributes for MRB_E2RF1 Catchments by Major River Basins in the Conterminous United States: Surficial Geology

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This tabular data set represents the area of surficial geology types in square meters compiled for every MRB_E2RF1 catchment of selected Major River Basins (MRBs,...

  6. Attributes for MRB_E2RF1 Catchments in Selected Major River Basins of the Conterminous United States: Contact Time, 2002

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This tabular data set represents the average contact time, in units of days, compiled for every MRB_E2RF1 catchment of Major River Basins (MRBs, Crawford and others,...

  7. Attributes for MRB_E2RF1 Catchments by Major River Basins in the Conterminous United States: NLCD 2001 Tree Canopy

    Science.gov (United States)

    Wieczorek, Michael; LaMotte, Andrew E.

    2010-01-01

    This tabular data set represents the mean percent tree canopy from the Canopy Layer of the National Land Cover Dataset 2001 (LaMotte and Wieczorek, 2010), compiled for every MRB_E2RF1 catchment of Major River Basins (MRBs, Crawford and others, 2006). The source data set represents tree canopy percentage for the conterminous United States for 2001. The Canopy Layer of the National Land Cover Data Set for 2001 was produced through a cooperative project conducted by the Multi-Resolution Land Characteristics (MRLC) Consortium. The MRLC Consortium is a partnership of Federal agencies (http://www.mrlc.gov), consisting of the U.S. Geological Survey (USGS), the National Oceanic and Atmospheric Administration (NOAA), the U.S. Environmental Protection Agency (USEPA), the U.S. Department of Agriculture (USDA), the U.S. Forest Service (USFS), the National Park Service (NPS), the U.S. Fish and Wildlife Service (USFWS), the Bureau of Land Management (BLM), and the USDA Natural Resources Conservation Service (NRCS). The MRB_E2RF1 catchments are based on a modified version of the U.S. Environmental Protection Agency's (USEPA) ERF1_2 and include enhancements to support national and regional-scale surface-water quality modeling (Nolan and others, 2002; Brakebill and others, 2011). Data were compiled for every MRB_E2RF1 catchment for the conterminous United States covering New England and Mid-Atlantic (MRB1), South Atlantic-Gulf and Tennessee (MRB2), the Great Lakes, Ohio, Upper Mississippi, and Souris-Red-Rainy (MRB3), the Missouri (MRB4), the Lower Mississippi, Arkansas-White-Red, and Texas-Gulf (MRB5), the Rio Grande, Colorado, and the Great basin (MRB6), the Pacific Northwest (MRB7) river basins, and California (MRB8).

  8. Attributes for MRB_E2RF1 Catchments by Major River Basins in the Conterminous United States: NLCD 2001 Imperviousness

    Science.gov (United States)

    Wieczorek, Michael; LaMotte, Andrew E.

    2010-01-01

    This tabular data set represents the mean percent impervious surface from the Imperviousness Layer of the National Land Cover Dataset 2001, (LaMotte and Wieczorek, 2010), compiled for every MRB_E2RF1 catchment of selected Major River Basins (MRBs, Crawford and others, 2006). The source data set represents imperviousness for the conterminous United States for 2001. The Imperviousness Layer of the National Land Cover Data Set for 2001 was produced through a cooperative project conducted by the Multi-Resolution Land Characteristics (MRLC) Consortium. The MRLC Consortium is a partnership of Federal agencies (http://www.mrlc.gov), consisting of the U.S. Geological Survey (USGS), the National Oceanic and Atmospheric Administration (NOAA), the U.S. Environmental Protection Agency (USEPA), the U.S. Department of Agriculture (USDA), the U.S. Forest Service (USFS), the National Park Service (NPS), the U.S. Fish and Wildlife Service (USFWS), the Bureau of Land Management (BLM), and the USDA Natural Resources Conservation Service (NRCS). The MRB_E2RF1 catchments are based on a modified version of the U.S. Environmental Protection Agency's (USEPA) ERF1_2 and include enhancements to support national and regional-scale surface-water quality modeling (Nolan and others, 2002;Brakebill and others, 2011). Data were compiled for every MRB_E2RF1 catchment for the conterminous United States covering New England and Mid-Atlantic (MRB1), South Atlantic-Gulf and Tennessee (MRB2), the Great Lakes, Ohio, Upper Mississippi, and Souris-Red-Rainy (MRB3), the Missouri (MRB4), the Lower Mississippi, Arkansas-White-Red, and Texas-Gulf (MRB5), the Rio Grande, Colorado, and the Great basin (MRB6), the Pacific Northwest (MRB7) river basins, and California (MRB8).

  9. Attributes for MRB_E2RF1 Catchments by Major River Basins in the Conterminous United States: NLCD 2001 Land Use and Land Cover

    Science.gov (United States)

    Wieczorek, Michael; LaMotte, Andrew E.

    2010-01-01

    This tabular data set represents the estimated area of land use and land cover from the National Land Cover Dataset 2001 (LaMotte, 2008), compiled for every MRB_E2RF1 catchment of the Major River Basins (MRBs, Crawford and others, 2006). The source data set represents land use and land cover for the conterminous United States for 2001. The National Land Cover Data Set for 2001 was produced through a cooperative project conducted by the Multi-Resolution Land Characteristics (MRLC) Consortium. The MRLC Consortium is a partnership of Federal agencies (http://www.mrlc.gov), consisting of the U.S. Geological Survey (USGS), the National Oceanic and Atmospheric Administration (NOAA), the U.S. Environmental Protection Agency (USEPA), the U.S. Department of Agriculture (USDA), the U.S. Forest Service (USFS), the National Park Service (NPS), the U.S. Fish and Wildlife Service (USFWS), the Bureau of Land Management (BLM), and the USDA Natural Resources Conservation Service (NRCS). The MRB_E2RF1 catchments are based on a modified version of the U.S. Environmental Protection Agency's (USEPA) ERF1_2 and include enhancements to support national and regional-scale surface-water quality modeling (Nolan and others, 2002; Brakebill and others, 2011). Data were compiled for every MRB_E2RF1 catchment for the conterminous United States covering the South Atlantic-Gulf and Tennessee (MRB2), the Great Lakes, Ohio, Upper Mississippi, and Souris-Red-Rainy (MRB3), the Missouri (MRB4), the Lower Mississippi, Arkansas-White-Red, and Texas-Gulf (MRB5) and the Pacific Northwest (MRB7) river basins.

  10. Attributes for MRB_E2RF1 Catchments by Major River Basins in the Conterminous United States: Artificial Drainage (1992) and Irrigation (1997)

    Science.gov (United States)

    Wieczorek, Michael; LaMotte, Andrew E.

    2010-01-01

    version of the U.S. Environmental Protection Agency's (USEPA) ERF1_2 and include enhancements to support national and regional-scale surface-water quality modeling (Nolan and others, 2002; Brakebill and others, 2011). Data were compiled for every MRB_E2RF1 catchment for the conterminous United States covering New England and Mid-Atlantic (MRB1), South Atlantic-Gulf and Tennessee (MRB2), the Great Lakes, Ohio, Upper Mississippi, and Souris-Red-Rainy (MRB3), the Missouri (MRB4), the Lower Mississippi, Arkansas-White-Red, and Texas-Gulf (MRB5), the Rio Grande, Colorado, and the Great basin (MRB6), the Pacific Northwest (MRB7) river basins, and California (MRB8).

  11. Attributes for MRB_E2RF1 Catchments by Major River Basins in the Conterminous United States: Mean Annual R-factor, 1971-2000

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This tabular data set represents the average annual R-factor, rainfall-runoff erosivity measure, compiled for every MRB_E2RF1 catchment of selected Major River...

  12. Attributes for MRB_E2RF1 Catchments by Major Rivers Basins in the Conterminous United States: Total Precipitation, 2002

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This tabular data set represents the catchment-average total precipitation in millimeters multiplied by 100 for 2002, compiled for every MRB_E2RF1 catchment of...

  13. Attributes for MRB_E2RF1 Catchments by Major River Basins in the Conterminous United States: Average Daily Minimum Temperature, 2002

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This tabular data set represents the average daily minimum temperature in Celsius multiplied by 100 for 2002, compiled for every MRB_E2RF1 catchment of selected...

  14. Attributes for MRB_E2RF1 Catchments by Major River Basins in the Conterminous United States: 30-Year Average Annual Precipitation, 1971-2000

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This tabular data set represents the 30-year (1971-2000) average annual precipitation in millimeters multiplied by 100 compiled for every MRB_E2RF1 catchment of...

  15. Attributes for MRB_E2RF1 Catchments by Major River Basins in the Conterminous United States: Mean Infiltration-Excess Overland Flow, 2002

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This tabular data set represents the mean value for infiltration-excess overland flow as estimated by the watershed model TOPMODEL, compiled for every MRB_E2RF1...

  16. Attributes for MRB_E2RF1 Catchments by Major River Basins in the Conterminous United States: STATSGO Soil Characteristics

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This tabular data set represents estimated soil variables compiled for every MRB_E2RF1 catchment of selected Major River Basins (MRBs, Crawford and others, 2006)....

  17. Attributes for MRB_E2RF1 Catchments by Major River Basins in the Conterminous United States: Basin Characteristics, 2002

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This tabular data set represents basin characteristics for the year 2002 compiled for every MRB_E2RF1 catchment of selected Major River Basins (MRBs, Crawford and...

  18. Attributes for MRB_E2RF1 Catchments by Major River Basins in the Conterminous United States: Hydrologic Landscape Regions

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This tabular data set represents the area of Hydrologic Landscape Regions (HLR) compiled for every MRB_E2RF1 catchment of the Major River Basins (MRBs, Crawford and...

  19. Attributes for MRB_E2RF1 Catchments by Major River Basins in the Conterminous United States: Average Saturation Excess-Overland Flow, 2002

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This tabular data set represents the average value of saturation overland flow, in percent of total streamflow, compiled for every MRB_E2RF1 catchment of selected...

  20. Attributes for MRB_E2RF1 Catchments by Major River Basins in the Conterminous United States: Level 3 Ecoregions

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This tabular data set represents the estimated area of level 3 ecological landscape regions (ecoregions), as defined by Omernik (1987), compiled for every MRB_E2RF1...

  1. Attributes for MRB_E2RF1 Catchments by Major River Basins in the Conterminous United States: Estimated Mean Annual Natural Groundwater Recharge, 2002

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This tabular data set represents the mean annual natural groundwater recharge, in millimeters, compiled for every MRB_E2RF1catchment of selected Major River Basins...

  2. Attributes for MRB_E2RF1 Catchments by Major River Basins in the Conterminous United States: Base-Flow Index, 2002

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This tabular data set represents the mean base-flow index expressed as a percent, compiled for every catchment of MRB_E2RF1 catchments of Major River Basins (MRBs,...

  3. Attributes for MRB_E2RF1 Catchments by Major River Basins in the Conterminous United States: Level 3 Nutrient Ecoregions, 2002

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This tabular data set represents the area of each level 3 nutrient ecoregion in square meters compiled for every MRB_E2RF1 catchment of the Major River Basins (MRBs,...

  4. Attributes for MRB_E2RF1 Catchments by Major River Basins in the Conterminous United States: Artificial Drainage (1992) and Irrigation (1997)

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This tabular data set represents the estimated area of artifical drainage for the year 1992 and irrigation types for the year 1997 compiled for every MRB_E2RF1...

  5. Attributes for MRB_E2RF1 Catchments by Major River Basins in the Conterminous United States: 30-Year Average Annual Precipitation, 1971-2000

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This tabular data set represents the 30-year (1971-2000) catchment-average total annual precipitation in millimeters multiplied by 100 compiled for every MRB_E2RF1...

  6. Attributes for MRB_E2RF1 Catchments by Major River Basins in the Conterminous United States: Basin Characteristics, 2002 Geospatial_Data_Presentation_Form: tabular digital data

    Science.gov (United States)

    Wieczorek, Michael; LaMotte, Andrew E.

    2010-01-01

    This tabular data set represents basin characteristics for the year 2002 compiled for every MRB_E2RF1 catchment of selected Major River Basins (MRBs, Crawford and others, 2006). These characteristics are reach catchment shape index, stream density, sinuosity, mean elevation, mean slope and number of road-stream crossings. The source data sets are based on a modified version of the U.S. Environmental Protection Agency's (USEPA) RF1_2 and include enhancements to support national and regional-scale surface-water quality modeling (Nolan and others, 2002; Brakebill and others, 2011) and the U.S. Census Bureau's TIGER/Line Files (U.S. Census Bureau,2006). The MRB_E2RF1 catchments are based on a modified version of the U.S. Environmental Protection Agency's (USEPA) ERF1_2 and include enhancements to support national and regional-scale surface-water quality modeling (Nolan and others, 2002; Brakebill and others, 2011). Data were compiled for every MRB_E2RF1 catchment for the conterminous United States covering New England and Mid-Atlantic (MRB1), South Atlantic-Gulf and Tennessee (MRB2), the Great Lakes, Ohio, Upper Mississippi, and Souris-Red-Rainy (MRB3), the Missouri (MRB4), the Lower Mississippi, Arkansas-White-Red, and Texas-Gulf (MRB5), the Rio Grande, Colorado, and the Great basin (MRB6), the Pacific Northwest (MRB7) river basins, and California (MRB8).

  7. Main: E2FAT [PLACE

    Lifescience Database Archive (English)

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

  8. The E(2) Particle

    CERN Document Server

    Ghosh, Subir

    2009-01-01

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

  9. Reference: E2FBNTRNR [PLACE

    Lifescience Database Archive (English)

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

  10. Attributes for MRB_E2RF1 Catchments by Major River Basins in the Conterminous United States: Nutrient Inputs from Fertilizer and Manure, Nitrogen and Phosphorus (N&P), 2002

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This tabular data set represents the total amount of nitrogen and phosphorus, in kilograms for the year 2002, compiled for every MRB_E2RF1 catchment of the Major...

  11. Reference: E2F1OSPCNA [PLACE

    Lifescience Database Archive (English)

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

  12. DNA-damage response control of E2F7 and E2F8

    OpenAIRE

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

    2008-01-01

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

  13. Loop 7 of E2 enzymes

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  14. Loop 7 of E2 enzymes

    DEFF Research Database (Denmark)

    Papaleo, Elena; Casiraghi, Nicola; Arrigoni, Alberto

    2012-01-01

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

  15. Main: E2F1OSPCNA [PLACE

    Lifescience Database Archive (English)

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

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

    DEFF Research Database (Denmark)

    Christensen, Jesper; Cloos, Paul; Toftegaard, Ulla

    2005-01-01

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

  17. Moist convection scheme in Model E2

    CERN Document Server

    Kim, Daehyun; Yao, Mao-Sung

    2013-01-01

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

  18. Bifunctional effect of E2 on macrophage

    Institute of Scientific and Technical Information of China (English)

    MinHONG; QuanZHU

    2004-01-01

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

  19. Theory of (e, 2e) reactions

    Science.gov (United States)

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

    1989-08-01

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

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

    OpenAIRE

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

    2003-01-01

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

  1. E2F1 is crucial for E2F-dependent apoptosis

    DEFF Research Database (Denmark)

    Lazzerini Denchi, Eros; Helin, Kristian

    2005-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    Rajesh Kharab; Pardeep Singh; Ravinder Kumar

    2007-01-01

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

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

    OpenAIRE

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

    2005-01-01

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

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

    OpenAIRE

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

    1995-01-01

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

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

    Science.gov (United States)

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

    2003-12-01

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

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

    NARCIS (Netherlands)

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

    1995-01-01

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

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

    NARCIS (Netherlands)

    Pandit, Shusil Kumar

    2014-01-01

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

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

    DEFF Research Database (Denmark)

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

    2003-01-01

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

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

    DEFF Research Database (Denmark)

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

    1998-01-01

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

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

    OpenAIRE

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

    1995-01-01

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

  11. Functionality of Chimeric E2 Glycoproteins of BVDV and CSFV in Virus Replication

    Directory of Open Access Journals (Sweden)

    H.G.P. van Gennip

    2008-01-01

    Full Text Available An intriguing difference between the E2 glycoprotein of CSFV and the other groups of pestiviruses (nonCSFV is a lack of two cysteine residues on positions cysteine 751 and 798. Other groups of pestivirus are not restricted to one species as swine, whereas CSFV is restricted to swine and wild boar. We constructed chimeric CSFV/BVDV E2 genes based on a 2D model of E2 proposed by van Rijn et al. (van Rijn et al. 1994, J Virol 68, 3934–42 and confirmed their expression by immunostaining of plasmid-transfected SK6 cells. No equivalents for the antigenic units B/C and A were found on E2 of BVDVII. This indicates major structural differences in E2. However, the immunodominant BVDVII domain A, containing epitopes with essential amino acids between position 760–764, showed to be dependent on the presence of the region defined by amino acids 684 to 796. As for the A domain of CSFV, the BVDVII A-like domain seemed to function as a separate unit. These combined domains in E2 proved to be the only combination which was functional in viral background of CSFV C-strain. The fitness of this virus (vfl c36BVDVII 684–796 seemed to be reduced compared to vfl c9 (with the complete antigenic region of BVDVII.

  12. The E2F family: specific functions and overlapping interests

    DEFF Research Database (Denmark)

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

    2004-01-01

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

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

    DEFF Research Database (Denmark)

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

    2000-01-01

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

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

    Lifescience Database Archive (English)

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

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

    DEFF Research Database (Denmark)

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

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

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

    Directory of Open Access Journals (Sweden)

    Osman Fikri SERTKAYA

    2011-01-01

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

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

    Lifescience Database Archive (English)

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

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

    Lifescience Database Archive (English)

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

  19. E2F-1 as an anticancer drug target

    Directory of Open Access Journals (Sweden)

    Joseph R. Bertino

    2011-12-01

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

  20. Expression of Structural Protein E2 of Hepatitis C Virus

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

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

    Science.gov (United States)

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

    2013-10-01

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

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

    Institute of Scientific and Technical Information of China (English)

    Pang Dan

    2010-01-01

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

  3. Energy Efficiency Management Platform (E2MP) Project

    Data.gov (United States)

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

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

    Science.gov (United States)

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

    2012-02-01

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

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

    Institute of Scientific and Technical Information of China (English)

    Zong He

    2010-01-01

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

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

    DEFF Research Database (Denmark)

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

    1993-01-01

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

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

    Science.gov (United States)

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

    2016-08-01

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

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

    OpenAIRE

    Jackson, M E; Campo, M S

    1995-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Mandy Muller

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

  10. Hepatitis C Virus E2 Envelope Glycoprotein Core Structure

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-08-26

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

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

    Science.gov (United States)

    Shepherd, J; Sims, C; Craft, I

    1976-10-02

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

  12. E2F target genes: unraveling the biology

    DEFF Research Database (Denmark)

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

    2004-01-01

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

  13. E2F target genes: unraveling the biology

    DEFF Research Database (Denmark)

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

    2004-01-01

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

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

    Science.gov (United States)

    Fortune, H. T.

    2017-01-01

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

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

    Science.gov (United States)

    Schuster, Lawrence S.

    2008-01-01

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

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

  17. Comparison of the structure of (E)-2-(2-benzylidenehydrazinylidene)quinoxaline with those of its chloro- and bromobenzylidene analogues.

    Science.gov (United States)

    Gomes, Ligia Rebelo; Low, John Nicolson; Rodrigues, Ana S M C; Wardell, James L; de Souza, Marcus V N; Noguiera, Thais C M; Pinheiro, Alessandra C

    2013-08-01

    (E)-2-(2-Benzylidenehydrazinylidene)quinoxaline, C₁₅H₁₂N₄, crystallized with two molecules in the asymmetric unit. The structures of six halogen derivatives of this compound were also investigated: (E)-2-[2-(2-chlorobenzylidene)hydrazinylidene]quinoxaline, C₁₅H₁₁ClN₄; (E)-2-[2-(3-chlorobenzylidene)hydrazinylidene]quinoxaline, C₁₅H₁₁ClN₄; (E)-2-[2-(4-chlorobenzylidene)hydrazinylidene]quinoxaline, C₁₅H₁₁ClN₄; (E)-2-[2-(2-bromobenzylidene)hydrazinylidene]quinoxaline, C₁₅H₁₁BrN₄; (E)-2-[2-(3-bromobenzylidene)hydrazinylidene]quinoxaline, C₁₅H₁₁BrN₄; (E)-2-[2-(4-bromobenzylidene)hydrazinylidene]quinoxaline, C₁₅H₁₁BrN₄. The 3-Cl and 3-Br compounds are isomorphous, as are the 4-Cl and 4-Br compounds. In all of these compounds, it was found that the supramolecular structures are governed by similar predominant patterns, viz. strong intermolecular N-H...N(pyrazine) hydrogen bonds supplemented by weak C-H∙∙∙N(pyrazine) hydrogen-bond interactions in the 2- and 3-halo compounds and by C-H∙∙∙Cl/Br interactions in the 4-halo compounds. In all compounds, there are π-π stacking interactions.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    CERN Document Server

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

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1997-10-01

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

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

    Science.gov (United States)

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

    2011-09-01

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

  2. Interesses e colaboração do Brasil e dos Estados Unidos com a ditadura de Stroessner (1954-63 - doi: 10.4025/dialogos.v11i1e2.62 Vested interests and collaboration between Brazil and the united states during the dictatorship of Stroessner (1954-63 - doi: 10.4025/dialogos.v11i1e2.62 Intereses y colaboración de Brasil y de EEUU con la dictadura de Stroessner (1954-1963

    Directory of Open Access Journals (Sweden)

    Ceres Moraes

    2010-05-01

    Full Text Available Neste artigo são abordados os interesses e a colaboração norte-americana e brasileira com a ditadura de Stroessner instalada no Paraguai a partir de meados de 1954. Esse regime, que durante cerca de 35 anos submeteu aquele país, foi um dos mais longos e violentos períodos de repressão do Mundo Ocidental contemporâneo. Sob a justificativa de combate ao avanço das idéias comunistas na América do Sul, os Estados Unidos colaboraram para a consolidação e permanência do regime através de ajuda econômica e da assistência técnica e militar, principalmente com a formação e treinamento de militares. O Brasil, que ainda disputava com a Argentina a supremacia regional, apesar de não mais manter a política de alinhamento incondicional com os Estados Unidos, buscava consolidar-se como parceiro preferencial e principal beneficiário de sua política na América do Sul. Na defesa de seus interesses, colaborou com o regime ditatorial de Stroessner tanto no campo econômico como no diplomático, cultural e militar. Ao contribuírem, especialmente, com assistência técnica e ajuda econômica, os Estados Unidos e o Brasil, este último de forma mais efetiva, colaboraram para a consolidação e longa permanência de Stroessner no poder.In this article are treated the interests and North American and Brazilian collaboration with the Stroessner’s dictatorship installed in Paraguay starting from1954. This regime which during about 35 years submitted that country was one of longest and violent periods of repression of the contemporary western world. Under the justification of combat to the progress of communist ideas in the South American, The United States collaborated for the consolidation and permanence of the regime through of economic help, technical assistance and military support, mainly with the formation and training of military, tend many of them studied in School of the Americas, in Panamá. The Brazil that still in this period fought

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

    Science.gov (United States)

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

    2016-06-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Yang Xianmei

    2010-09-01

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

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

    Science.gov (United States)

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

    2010-09-20

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    CERN Document Server

    Daily, K M; Greene, Chris H

    2014-01-01

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

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

    Science.gov (United States)

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

    2000-03-01

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

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

    DEFF Research Database (Denmark)

    Vigo, E; Müller, H; Prosperini, E

    1999-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1997-08-01

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

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

    Science.gov (United States)

    Sahin, Fikret; Sladek, Todd L

    2010-07-04

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

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

    Directory of Open Access Journals (Sweden)

    Suchada Chantrapromma

    2015-06-01

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

  15. Spectrin’s chimeric E2/E3 enzymatic activity

    Science.gov (United States)

    Goodman, Steven R; Petrofes Chapa, Rachel

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-09-28

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

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

    Institute of Scientific and Technical Information of China (English)

    吴朝栋; 陶其敏

    1998-01-01

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

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

    Science.gov (United States)

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

    2016-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Aileen Y. Alontaga

    2016-06-01

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

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

    Science.gov (United States)

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

    2016-08-01

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

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

    Directory of Open Access Journals (Sweden)

    Orla Gannon

    2011-12-01

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

  2. STS-70 Launch - Nikon E-2 Digital Image

    Science.gov (United States)

    1995-01-01

    This test images was taken with a Nikon E-2 Digital Imaging System camera and are provided courtesy of Nikon (GIF 450x450 JPEG 1280x1000): The second Shuttle launch in 16 days hurtles off the pad into a sweltering summer sky. The unstable weather typical to Florida in the summertime didn't have a chance to coalesce and impact this morning's launch window, and the Space Shuttle Discovery began its planned seven-day, 22-hour flight on Mission STS-70 from Launch Pad 39B at 9:41:55.078 a.m. EDT, just seconds off schedule. On board for Discovery's 21st spaceflight are a crew of five: Commander Terence 'Tom' Henricks; Pilot Kevin R. Kregel; and Mission Specialists Nancy Jane Currie, Donald A. Thomas and Mary Ellen Weber. The crew's primary objective during the 70th Shuttle flight is to deploy the Tracking and Data Relay Satellite (TDRS-G), which will join a constellation of other TDRS spacecraft already on orbit. TDRS-G is destined to become an on- orbit, fully operational 'ready reserve' satellite, available along with one other ready reserve TDRS spacecraft to back up the two primary TDRS satellites positions, TDRS East over the Atlantic Ocean and TDRS West over the Pacific. Assured capability of the TDRS communications network is essential for linking Earth-orbiting spacecraft such as the Shuttle and the Hubble Space Telescope with the ground.

  3. Prostaglandin E2-induced inflammation: Relevance of prostaglandin E receptors.

    Science.gov (United States)

    Kawahara, Kohichi; Hohjoh, Hirofumi; Inazumi, Tomoaki; Tsuchiya, Soken; Sugimoto, Yukihiko

    2015-04-01

    Prostaglandin E2 (PGE2) is one of the most typical lipid mediators produced from arachidonic acid (AA) by cyclooxygenase (COX) as the rate-limiting enzyme, and acts on four kinds of receptor subtypes (EP1-EP4) to elicit its diverse actions including pyrexia, pain sensation, and inflammation. Recently, the molecular mechanisms underlying the PGE2 actions mediated by each EP subtype have been elucidated by studies using mice deficient in each EP subtype as well as several compounds highly selective to each EP subtype, and their findings now enable us to discuss how PGE2 initiates and exacerbates inflammation at the molecular level. Here, we review the recent advances in PGE2 receptor research by focusing on the activation of mast cells via the EP3 receptor and the control of helper T cells via the EP2/4 receptor, which are the molecular mechanisms involved in PGE2-induced inflammation that had been unknown for many years. We also discuss the roles of PGE2 in acute inflammation and inflammatory disorders, and the usefulness of anti-inflammatory therapies that target EP receptors. This article is part of a Special Issue entitled "Oxygenated metabolism of PUFA: analysis and biological relevance". Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Prostaglandin E2 As a Modulator of Viral Infections

    Science.gov (United States)

    Sander, Willem J.; O'Neill, Hester G.; Pohl, Carolina H.

    2017-01-01

    Viral infections are a major cause of infectious diseases worldwide. Inflammation and the immune system are the major host defenses against these viral infection. Prostaglandin E2 (PGE2), an eicosanoid generated by cyclooxygenases, has been shown to modulate inflammation and the immune system by regulating the expression/concentration of cytokines. The effect of PGE2 on viral infection and replication is cell type- and virus-family-dependent. The host immune system can be modulated by PGE2, with regards to immunosuppression, inhibition of nitrogen oxide (NO) production, inhibition of interferon (IFN) and apoptotic pathways, and inhibition of viral receptor expression. Furthermore, PGE2 can play a role in viral infection directly by increasing the production and release of virions, inhibiting viral binding and replication, and/or stimulating viral gene expression. PGE2 may also have a regulatory role in the induction of autoimmunity and in signaling via Toll-like receptors. In this review the known effects of PGE2 on the pathogenesis of various infections caused by herpes simplex virus, rotavirus, influenza A virus and human immunodeficiency virus as well the therapeutic potential of PGE2 are discussed. PMID:28261111

  5. Confirmation/Observation of Hindered E2 Strengths in-16,18C

    Institute of Scientific and Technical Information of China (English)

    H.J.Ong; N.Imai; D.Suzuki; H.Iwasaki; H.Sakurai; T.Onishi; M.Suzuki; S.Otas; S.Takeuchi; T.Nakao; Y.Togano; Y.Kondo; N.Aoi; H.Baba; B.Shawn; Y.Ichikawa; M.Ishihara; T.Kubo; K.Kurita; T.Motobayashi; T.Nakamura; T.Okumura; Y.Yanagisawa

    2009-01-01

    The lifetime of the first excited 2~+ state in ~(18)C was measured using an upgraded recoil shadow method to determine the electric quadrupole transition.The measured mean lifetime is 18.9±0.9 (stat)±4.4 (syst) ps,which corresponds to a B(E2;2~+_1→0~+_(gs)) value of (4.3±0.2±1.0) e~2fm~4,or about 1.5 Weisskopf units.The mean lifetime of the first 2~+ state in ~(16)C was remeasured to be about 18 ps,about four times shorter than the value reported previously.This discrepancy was explained by incorporating the γ-ray angular distribution measured in this work into the previous measurement.The observed transition strengths in ~(16,18)C are hindered compared to the empirical transition strengths,indicating that the anomalous hindrance observed in ~(16)C persists in ~(18)C.

  6. Spectroscopic study and structure of ( E)-2-[(2-chlorobenzylimino)methyl]methoxyphenol

    Science.gov (United States)

    Ünver, Hüseyin; Yıldız, Mustafa; Özay, Hava; Durlu, Tahsin Nuri

    2009-12-01

    ( E)-2-[(2-Chlorobenzylimino)methyl]methoxyphenol has been synthesized from the reaction of 2-hydroxy-3-methoxy-1-benzaldehyde( o-vanillin) with 2-chlorobenzylamine. The title compound has been characterized by using elemental analysis, FT-IR, 1H NMR, 13C NMR and UV-vis spectroscopic techniques. The crystal structure of the title compound has also been examined cyrstallographically. It crystallizes in the orthorhombic space group Pbca with unit cell parameters: a = 7.208(1) Å, b = 13.726(2) Å, c = 27.858(4) Å, V = 2756.0(1) Å 3, Dc = 1.18 g cm -3 and Z = 8. The crystal structure was solved by direct methods and refined by full-matrix least squares to a find R = 0.046 for 2773 observed reflections.

  7. International Conference on Harmonisation; Guidance on E2F Development Safety Update Report; availability. Notice.

    Science.gov (United States)

    2011-08-23

    The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled "E2F Development Safety Update Report." The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The guidance describes the format, content, and timing of a development safety update report (DSUR) for an investigational drug. The DSUR will serve as a common standard for periodic reporting on drugs under development (including marketed drugs that are under further study) among the ICH regions. The DSUR can be submitted in the United States in place of an annual report for an investigational new drug application (IND). The harmonized DSUR is intended to promote a consistent approach to annual clinical safety reporting among the ICH regions and enhance efficiency by reducing the number of reports generated for submission to the regulatory authorities.

  8. International Conference on Harmonisation; draft guidance on E2F Development Safety Update Report; availability. Notice.

    Science.gov (United States)

    2008-08-05

    The Food and Drug Administration (FDA) is announcing the availability of a draft guidance entitled "E2F Development Safety Update Report." The draft guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The draft guidance describes the format, content, and timing of a development safety update report (DSUR) for an investigational drug. The DSUR would serve as a harmonized, annual clinical trial safety report that would be standard among the three ICH regions. The DSUR could be submitted in the United States in place of an annual report for an investigational new drug application (IND). The harmonized DSUR is intended to promote a consistent approach to annual clinical safety reporting among the ICH regions and enhance efficiency by reducing the number of reports generated for submission to the regulatory authorities.

  9. Tropical Cyclones in the GISS ModelE2

    Science.gov (United States)

    Camargo, Suzana J.; Sobel, Adam H.; Del Genio, Anthony; Jonas, Jeffrey A.; Kelley, Maxwell; Lu, Yun; Shaevitz, Daniel; Henderson, Naomi

    2016-01-01

    The authors describe the characteristics of tropical cyclone (TC) activity in the GISS general circulation ModelE2 with a horizontal resolution 1deg x 1deg. Four model simulations are analyzed. In the first, the model is forced with sea surface temperature (SST) from the recent historical climatology. The other three have different idealized climate change simulations, namely (1) a uniform increase of SST by 2 deg., (2) doubling of the CO2 concentration and (3) a combination of the two. These simulations were performed as part of the US Climate Variability and Predictability Program Hurricane Working Group. Diagnostics of standard measures of TC activity are computed from the recent historical climatological SST simulation and compared with the same measures computed from observations. The changes in TC activity in the three idealized climate change simulations, by comparison with that in the historical climatological SST simulation, are also described. Similar to previous results in the literature, the changes in TC frequency in the simulation with a doubling CO2 and an increase in SST are approximately the linear sum of the TC frequency in the other two simulations. However, in contrast with previous results, in these simulations the effects of CO2 and SST on TC frequency oppose each other. Large-scale environmental variables associated with TC activity are then analyzed for the present and future simulations. Model biases in the large-scale fields are identified through a comparison with ERA-Interim reanalysis. Changes in the environmental fields in the future climate simulations are shown and their association with changes in TC activity discussed.

  10. Prostaglandin E2 Reduces Cardiac Contractility via EP3 Receptor.

    Science.gov (United States)

    Gu, Xiaosong; Xu, Jiang; Zhu, Liping; Bryson, Timothy; Yang, Xiao-Ping; Peterson, Edward; Harding, Pamela

    2016-08-01

    Prostaglandin E2 (PGE2) EP receptors EP3 and EP4 signal via decreased and increased cAMP production, respectively. Previously, we reported that cardiomyocyte-specific EP4 knockout mice develop dilated cardiomyopathy with reduced ejection fraction. Thus, we hypothesized that PGE2 increases contractility via EP4 but decreases contractility via EP3. The effects of PGE2 and the EP1/EP3 agonist sulprostone on contractility were examined in the mouse Langendorff preparation and in adult mouse cardiomyocytes. Isolated hearts of adult male C57Bl/6 mice were perfused with PGE2 (10(-6) M) or sulprostone (10(-6) M) and compared with vehicle. Both PGE2 and sulprostone decreased +dp/dt (PEP3 antagonist. In contrast, the EP4 agonist had the opposite effect. Adult mouse cardiomyocytes contractility was also reduced after treatment with either PGE2 or sulprostone for 10 minutes. We then examined the acute effects of PGE2, sulprostone, and the EP4 agonist on expression of phosphorylated phospholamban and sarcoendoplasmic reticulum Ca(2+)-ATPase 2a in adult mouse cardiomyocytes using Western blot. Treatment with either PGE2 or sulprostone decreased expression of phosphorylated phospholamban corrected to total phospholamban, whereas treatment with the EP4 agonist had the opposite effect. Sarcoendoplasmic reticulum Ca(2+)-ATPase 2a expression was unaffected. Finally, we examined the effect of these compounds in vivo using pressure-volume loops. Both PGE2 and sulprostone decreased +dp/dt, whereas the EP4 agonist increased +dp/dt. Contractility is reduced via the EP3 receptor but increased via EP4. These effects may be mediated through changes in phospholamban phosphorylation and has relevance to detrimental effects of inflammation. © 2016 American Heart Association, Inc.

  11. Tropical Cyclones in the GISS ModelE2

    Science.gov (United States)

    Camargo, Suzana J.; Sobel, Adam H.; Del Genio, Anthony; Jonas, Jeffrey A.; Kelley, Maxwell; Lu, Yun; Shaevitz, Daniel; Henderson, Naomi

    2016-01-01

    The authors describe the characteristics of tropical cyclone (TC) activity in the GISS general circulation ModelE2 with a horizontal resolution 1deg x 1deg. Four model simulations are analyzed. In the first, the model is forced with sea surface temperature (SST) from the recent historical climatology. The other three have different idealized climate change simulations, namely (1) a uniform increase of SST by 2 deg., (2) doubling of the CO2 concentration and (3) a combination of the two. These simulations were performed as part of the US Climate Variability and Predictability Program Hurricane Working Group. Diagnostics of standard measures of TC activity are computed from the recent historical climatological SST simulation and compared with the same measures computed from observations. The changes in TC activity in the three idealized climate change simulations, by comparison with that in the historical climatological SST simulation, are also described. Similar to previous results in the literature, the changes in TC frequency in the simulation with a doubling CO2 and an increase in SST are approximately the linear sum of the TC frequency in the other two simulations. However, in contrast with previous results, in these simulations the effects of CO2 and SST on TC frequency oppose each other. Large-scale environmental variables associated with TC activity are then analyzed for the present and future simulations. Model biases in the large-scale fields are identified through a comparison with ERA-Interim reanalysis. Changes in the environmental fields in the future climate simulations are shown and their association with changes in TC activity discussed.

  12. Tropical cyclones in the GISS ModelE2

    Directory of Open Access Journals (Sweden)

    Suzana J. Camargo

    2016-07-01

    Full Text Available The authors describe the characteristics of tropical cyclone (TC activity in the GISS general circulation ModelE2 with a horizontal resolution 1°×1°. Four model simulations are analysed. In the first, the model is forced with sea surface temperature (SST from the recent historical climatology. The other three have different idealised climate change simulations, namely (1 a uniform increase of SST by 2 degrees, (2 doubling of the CO2 concentration and (3 a combination of the two. These simulations were performed as part of the US Climate Variability and Predictability Program Hurricane Working Group. Diagnostics of standard measures of TC activity are computed from the recent historical climatological SST simulation and compared with the same measures computed from observations. The changes in TC activity in the three idealised climate change simulations, by comparison with that in the historical climatological SST simulation, are also described. Similar to previous results in the literature, the changes in TC frequency in the simulation with a doubling CO2 and an increase in SST are approximately the linear sum of the TC frequency in the other two simulations. However, in contrast with previous results, in these simulations the effects of CO2 and SST on TC frequency oppose each other. Large-scale environmental variables associated with TC activity are then analysed for the present and future simulations. Model biases in the large-scale fields are identified through a comparison with ERA-Interim reanalysis. Changes in the environmental fields in the future climate simulations are shown and their association with changes in TC activity discussed.

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

    Directory of Open Access Journals (Sweden)

    Fikret Sahin, Todd L. Sladek

    2010-01-01

    Full Text Available E2F-1 is the major cellular target of pRB and is regulated by pRB during cell proliferation. Interaction between pRB and E2F-1 is dependent on the phosphorylation status of pRB. Despite the fact that E2F-1 and pRB have antagonistic activities when they are overexpressed, the role of the E2F-1-pRB interaction in cell growth largely remains unknown. Ideally, it would be better to study the properties of a pRB mutant that fails to bind to E2F, but retains all other activities. To date, no pRB mutation has been characterized in sufficient detail to show that it specifically eliminates E2F binding but leaves other interactions intact. An alternative approach to this issue is to ask whether mutations that change E2F proteins binding affinity to pRB are sufficient to change cell growth in aspect of cell cycle and tumor formation. Therefore, we used the E2F-1 mutants including E2F-1/S332-7A, E2F-1/S375A, E2F-1/S403A, E2F-1/Y411A and E2F-1/L132Q that have different binding affinities for pRB to better understand the roles of the E2F-1 phosphorylation and E2F-1-pRB interaction in the cell cycle, as well as in transformation and gene expression. Data presented in this study suggests that in vivo phosphorylation at amino acids 332-337, 375 and 403 is important for the E2F-1 and pRB interaction in vivo. However, although E2F-1 mutants 332-7, 375 and 403 showed similar binding affinity to pRB, they showed different characteristics in transformation efficiency, G0 accumulation, and target gene experiments.

  14. 3-Hydroxy-N′-[(E-2-thienylmethylidene]-2-naphthohydrazide

    Directory of Open Access Journals (Sweden)

    Qingkun Wu

    2011-02-01

    Full Text Available The asymmetric unit of the title compound, C16H12N2O2S, contains three independent molecules. Intramolecular N—H...O hydrogen bonds in the three molecules lead to very similar conformations: the thiopene ring and naphthalene ring system in the three molecules form dihedral angles of 10.3 (2, 9.1 (2 and 9.3 (3°. In the crystal structure, intermolecular O—H...O hydrogen bonds link the molecules into chains propagating in [031].

  15. (E-2-Hydroxy-6-[(4-propylphenyliminiomethyl]phenolate

    Directory of Open Access Journals (Sweden)

    Serap Yazıcı

    2010-01-01

    Full Text Available The title compound, C16H17NO2, crystallizes with three crystallographically independent zwitterionic molecules in the asymmetric unit which differ significantly in the orientations of the propyl side chains. The dihedral angles between the two benzene rings in the three molecules are 6.17 (7, 6.75 (7 and 23.67 (7°, respectively. In each independent molecule, an intramolecular N—H...O hydrogen bond generates an S(6 ring motif. In the crystal, each independent molecule exists as part of an O—H...O hydrogen-bonded centrosymmetric R22(10 dimer.

  16. E2F-4, a new member of the E2F gene family, has oncogenic activity and associates with p107 in vivo

    NARCIS (Netherlands)

    Beijersbergen, R.L.; Kerkhoven, R.M.; Zhu, L.; Carlée, L.; Voorhoeve, P.M.; Bernards, R.A.

    1994-01-01

    The E2F family of transcription factors controls the expression of genes that are involved in cell cycle regulation. E2F DNA-binding activity is found in complex with the retinoblastoma protein, pRb, and with the pRb-related p107 and p130. To date, cDNAs for three members of the E2F gene family have

  17. Feedback regulation between atypical E2Fs and APC/CCdh1 coordinates cell cycle progression.

    Science.gov (United States)

    Boekhout, Michiel; Yuan, Ruixue; Wondergem, Annelotte P; Segeren, Hendrika A; van Liere, Elsbeth A; Awol, Nesibu; Jansen, Imke; Wolthuis, Rob M F; de Bruin, Alain; Westendorp, Bart

    2016-03-01

    E2F transcription factors control the oscillating expression pattern of multiple target genes during the cell cycle. Activator E2Fs, E2F1-3, induce an upswing of E2F targets, which is essential for the G1-to-S phase transition, whereas atypical E2Fs, E2F7 and E2F8, mediate a downswing of the same targets during late S, G2, and M phases. Expression of atypical E2Fs is induced by E2F1-3, but it is unknown how atypical E2Fs are inactivated in a timely manner. Here, we demonstrate that E2F7 and E2F8 are substrates of the anaphase-promoting complex/cyclosome (APC/C). Removal of CDH1, or mutating the CDH1-interacting KEN boxes, stabilized E2F7/8 from anaphase onwards and during G1. Expressing KEN mutant E2F7 during G1 impairs S phase entry and eventually results in cell death. Furthermore, we show that E2F8, but not E2F7, interacts also with APC/C(C) (dc20). Importantly, atypical E2Fs can activate APC/C(C) (dh1) by repressing its inhibitors cyclin A, cyclin E, and Emi1. In conclusion, we discovered a feedback loop between atypical E2Fs and APC/C(C) (dh1), which ensures balanced expression of cell cycle genes and normal cell cycle progression.

  18. Characterization of competing distortions in YF e2O4

    Science.gov (United States)

    Blasco, J.; Lafuerza, S.; García, J.; Subías, G.; Cuartero, V.; García-Muñoz, J. L.; Popescu, C.; Peral, I.

    2016-05-01

    We report the structural changes of three YF e2O4 -δ (δ cell at room temperature (space group R 3 ¯m ). This cell becomes unstable for the three samples on cooling, and the oxygen-poor specimen (δ ˜0.1 ) shows a single transition at 240 K. The nearly stoichiometric (δ ≤0.03 ) compounds exhibit two structural transitions with decreasing temperature at about 240 and 200 K. Each transition is revealed by an anomaly in the heat capacity measurements and a jump in the electric resistivity. Below 240 K, a strong splitting of some diffraction peaks is accompanied by the occurrence of superstructure peaks that follow the propagation vector k =(1 /7 ,-2 /7 ,9 /7 ) . The cell symmetry is then triclinic, and the structural transition is characterized by an expansion of the c axis coupled to a contraction of the other two lattice parameters. There are 49 nonequivalent sites for Fe atoms with a maximum charge disproportionation of ˜0.5 e- . Upon cooling at 200 K, the previous superstructure peaks begin to vanish, and finally they are replaced by a new set of superstructure peaks following the propagation vector k =(1 /4 ,1 /2 ,1 /4 ) with respect to the rhombohedral cell. The transition is also reflected in sudden changes in the lattice parameters that seem to smooth the changes observed in the previous transition. The new cell is also triclinic, and there are 48 nonequivalent Fe sites with a maximum charge disproportionation of ˜0.7 e- . Both phases coexist in a wide temperature range because this second transition is not completed at 80 K. A symmetry mode analysis indicates a complicated pattern for the charge distribution in the Fe sublattice of both distorted structures but clearly discard any bimodal distribution of only two types of Fe cations. Therefore, the sharp jumps in the electric resistivity at the phase transitions are clearly correlated with two different structural changes. Finally, the oxygen stoichiometry seems to be a key factor in the stabilization

  19. Prostaglandin E2 and patent ductus arteriosus in premature infants

    Directory of Open Access Journals (Sweden)

    Mochammading,

    2016-01-01

    Full Text Available Background Patent ductus arteriosus (PDA is a congenital heart disease most commonly occurring in premature infants. Spontaneous ductus arteriosus (DA closure in premature infants has been suggested to be associated with duct lumen maturity and the DA sensitivity to prostaglandin E2 (PGE2. Objective To assess for a possible correlation between serum PGE2 levels and PDA size in premature infants. Methods This observational study using repeated measurements on premature infants with PDA detected at days 2-3 of life was undertaken in Cipto Mangunkusumo Hospital and Fatmawati Hospital, Jakarta, from April to May 2014. The PDA was diagnosed using 2-D echocardiography and PGE2 levels were measured by immunoassay. Pearson’s correlation test was used to evaluate a possible correlation between PGE2 level and DA diameter. Results Thirty-three premature infants of median gestational age 31 (range 28-32 weeks and median birth weight 1,360 (range 1,000-1,500 grams were enrolled. Almost two-thirds of the subjects were male. Almost all (30/33 subjects had spontaneous DA closure before the age of 10 days. Subjects’ mean DA diameter was 2.9 (SD 0.5 mm with maximum flow velocity of 0.2 (SD 0.06 cm/sec, and left atrial-to-aortic root ratio (LA/Ao of 1.5 (SD 0.2. Their mean PGE2 levels at the ages of 2-3, 5-7, and after 10 days were 5,238.6 (SD 1,225.2, 4,178.2 (SD 1,534.5, and 915.2 (SD 151.6 pg/mL, respectively. The PGE2 level at days 2-3 was significantly correlated with DA diameter (r = 0.667; P < 0.001, but not at days 5-7 (r = 0.292; P = 0.105 or at day 10 (r = 0.041; P = 0.941. Conclusion There is a strong, positive correlation between the PGE2 level and DA diameter in preterm infants at 2-3 days of age. However, there is no significant correlation between PGE2 level and persistence of PDA.

  20. E2 protein cage as a multifunctional nanoplatform

    Science.gov (United States)

    Dalmau Mallorqui, Merce

    Caged protein systems such as viral capsids, heat shock proteins, and ferritin are spherical structures that occur naturally in living organisms and are a growing class of biomimetic templates used to create new materials in nanotechnology. Such systems have been proposed as general drug carriers since they form highly symmetric nanoscale architectures that offer the potential to be tailored according to the desired application. Within this framework, this dissertation focuses on the design and development of a new drug delivery nanoplatform based on the E2 subunit of the pyruvate dehydrogenase protein from Bacillus stearothermophilus. This scaffold forms a 25-nm nanocapsule structure with a hollow cavity. We produced a variant of this protein consisting only of the structural core, and found the thermostability of this self-assembled scaffold to be unusually high, with an onset unfolding temperature of 81.1 +/- 0.9°C and an apparent midpoint unfolding temperature of 91.4 +/- 1.4°C. To evaluate the potential of this scaffold for encapsulation of guest molecules in the internal cavity, we made variants which altered the physicochemical properties of the hollow internal surface. These mutants, yielding up to 240 mutations within this cavity, assembled into correct architectures and exhibited high thermostability that was also comparable to the wild-type scaffold. To show the applicability of this scaffold we coupled two drug-like small molecules to the internal cavity. We also developed a new strategy for encapsulation of small hydrophobic drug molecules. This method is based on hydrophobic differences between the interior cavity and the external buffer to nucleate drug-like agents inside the protein cage. We demonstrate that internal mutations can introduce non-native functionality and enable molecular encapsulation within the cavity while still retaining the dodecahedral structure. Another surface amenable to modifications is the interface between subunits. Such

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-04-15

    The membrane anchors of viral envelope proteins play essential roles in cell entry. Recent crystal structures of the ectodomain of envelope protein E2 from a pestivirus suggest that E2 belongs to a novel structural class of membrane fusion machinery. Based on geometric constraints from the E2 structures, we generated atomic models of the E1 and E2 membrane anchors using computational approaches. The E1 anchor contains two amphipathic perimembrane helices and one transmembrane helix; the E2 anchor contains a short helical hairpin stabilized in the membrane by an arginine residue, similar to flaviviruses. A pair of histidine residues in the E2 ectodomain may participate in pH sensing. The proposed atomic models point to Cys987 in E2 as the site of disulfide bond linkage with E1 to form 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.

  2. A potential oncogenic role of the commonly observed E2F5 overexpression in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Yuzhu Jiang; Seon-Hee Yim; Hai-Dong Xu; Seung-Hyun Jung; So Young Yang; Hae-Jin Hu; Chan-Kwon Jung; Yeun-Jun Chung

    2011-01-01

    AIM: To explore the expression pattern of E2F5 in primary hepatocellular carcinomas (HCCs) and elucidate the roles of E2F5 in hepatocarcinogenesis. METHODS: E2F5 expression was analyzed in 120 primary HCCs and 29 normal liver tissues by immunohistochemistry analysis. E2F5-small interfering RNA was transfected into HepG2, an E2F5-overexpressed HCC cell line. After E2F5 knockdown, cell growth capacity and migrating potential were examined. RESULTS: E2F5 was significantly overexpressed in primary HCCs compared with normal liver tissues (P = 0.008). The E2F5-silenced cells showed significantly reduced proliferation (P = 0.004). On the colony formation and soft agar assays, the number of colonies was significantly reduced in E2F5-silenced cells (P = 0.004 and P = 0.009, respectively). E2F5 knockdown resulted in the accumulation of G0/G1 phase cells and a reduction of S phase cells. The number of migrating/invading cells was also reduced after E2F5 knockdown (P = 0.021). CONCLUSION: To our knowledge, this is the first evidence that E2F5 is commonly overexpressed in primary HCC and that E2F5 knockdown significantly repressed the growth of HCC cells.

  3. Inhibition of the entomopathogenic fungus Metarhizium anisopliae in vitro by the bed bug defensive secretions (E)-2-hexenal and (E)-2-octenal

    Science.gov (United States)

    The two major aldehydes (E)-2-hexenal and (E)-2-octenal emitted as defensive secretions by bed bugs Cimex lectularius L. (Hemiptera: Cimicidae), inhibit the in vitro growth of Metarhizium anisopliae (Metsch.) Sokorin (Hypocreales: Clavicipitaceae). These chemicals inhibit fungal growth by direct con...

  4. Ability of the bed bug (Hemiptera: Cimicidae) defensive secretions (E)-2-hexenal and (E)-2-octenal to attract adult bed bugs

    Science.gov (United States)

    Accurate and timely surveillance of bed bug infestations is critical for development of effective control strategies. While the bed bug produced volatiles (E)-2-hexenal and (E)-2-octenal are considered defensive secretions, through use of EthoVision® video-tracking software we demonstrate that low ...

  5. Regulation of cell proliferation by the E2F transcription factors

    DEFF Research Database (Denmark)

    Helin, K

    1998-01-01

    demonstrated that individual members of the E2F transcription factor family are likely to have distinct roles in mammalian development and homeostasis. Additional mechanisms regulating the activity of the E2F transcription factors have been reported, including subcellular localization and proteolysis of the E2......Experimental data generated in the past year have further emphasized the essential role for the E2F transcription factors in the regulation of cell proliferation. Genetic studies have shown that E2F activity is required for normal development in fruitflies, and the generation of E2F-1(-/-) mice has......Fs in the proteasomes. Novel target genes for the E2F transcription factors have been identified that link the E2Fs directly to the initiation of DNA replication....

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

    DEFF Research Database (Denmark)

    Helin, K; Harlow, E; Fattaey, A

    1993-01-01

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

  7. Differential expression of members of the E2F family of transcription factors in rodent testes

    Directory of Open Access Journals (Sweden)

    Toppari Jorma

    2006-12-01

    Full Text Available Abstract Background The E2F family of transcription factors is required for the activation or repression of differentially expressed gene programs during the cell cycle in normal and abnormal development of tissues. We previously determined that members of the retinoblastoma protein family that interacts with the E2F family are differentially expressed and localized in almost all the different cell types and tissues of the testis and in response to known endocrine disruptors. In this study, the cell-specific and stage-specific expression of members of the E2F proteins has been elucidated. Methods We used immunohistochemical (IHC analysis of tissue sections and Western blot analysis of proteins, from whole testis and microdissected stages of seminiferous tubules to study the differential expression of the E2F proteins. Results For most of the five E2F family members studied, the localizations appear conserved in the two most commonly studied rodent models, mice and rats, with some notable differences. Comparisons between wild type and E2F-1 knockout mice revealed that the level of E2F-1 protein is stage-specific and most abundant in leptotene to early pachytene spermatocytes of stages IX to XI of mouse while strong staining of E2F-1 in some cells close to the basal lamina of rat tubules suggest that it may also be expressed in undifferentiated spermatogonia. The age-dependent development of a Sertoli-cell-only phenotype in seminiferous tubules of E2F-1 knockout males corroborates this, and indicates that E2F-1 is required for spermatogonial stem cell renewal. Interestingly, E2F-3 appears in both terminally differentiated Sertoli cells, as well as spermatogonial cells in the differentiative pathway, while the remaining member of the activating E2Fs, E2F-2 is most concentrated in spermatocytes of mid to late prophase of meiosis. Comparisons between wildtype and E2F-4 knockout mice demonstrated that the level of E2F-4 protein displays a distinct

  8. Modulation of the E2F1-driven cancer cell fate by the DNA damage response machinery and potential novel E2F1 targets in osteosarcomas

    DEFF Research Database (Denmark)

    Liontos, Michalis; Niforou, Katerina; Velimezi, Georgia

    2009-01-01

    Osteosarcoma is the most common primary bone cancer. Mutations of the RB gene represent the most frequent molecular defect in this malignancy. A major consequence of this alteration is that the activity of the key cell cycle regulator E2F1 is unleashed from the inhibitory effects of pRb. Studies...... in animal models and in human cancers have shown that deregulated E2F1 overexpression possesses either "oncogenic" or "oncosuppressor" properties, depending on the cellular context. To address this issue in osteosarcomas, we examined the status of E2F1 relative to cell proliferation and apoptosis...... in a clinical setting of human primary osteosarcomas and in E2F1-inducible osteosarcoma cell line models that are wild-type and deficient for p53. Collectively, our data demonstrated that high E2F1 levels exerted a growth-suppressing effect that relied on the integrity of the DNA damage response network...

  9. E2 multimeric scaffold for vaccine formulation: immune response by intranasal delivery and transcriptome profile of E2-pulsed dendritic cells.

    Science.gov (United States)

    Trovato, Maria; Maurano, Francesco; D'Apice, Luciana; Costa, Valerio; Sartorius, Rossella; Cuccaro, Fausta; McBurney, Sean P; Krebs, Shelly J; Prisco, Antonella; Ciccodicola, Alfredo; Rossi, Mauro; Haigwood, Nancy L; De Berardinis, Piergiuseppe

    2016-07-16

    The E2 multimeric scaffold represents a powerful delivery system able to elicit robust humoral and cellular immune responses upon systemic administrations. Here recombinant E2 scaffold displaying the third variable loop of HIV-1 Envelope gp120 glycoprotein was administered via mucosa, and the mucosal and systemic immune responses were analysed. To gain further insights into the molecular mechanisms that orchestrate the immune response upon E2 vaccination, we analysed the transcriptome profile of dendritic cells (DCs) exposed to the E2 scaffold with the aim to define a specific gene expression signature for E2-primed immune responses. The in vivo immunogenicity and the potential of E2 scaffold as a mucosal vaccine candidate were investigated in BALB/c mice vaccinated via the intranasal route. Fecal and systemic antigen-specific IgA antibodies, cytokine-producing CD4(+) and CD8(+) cells were induced assessing the immunogenicity of E2 particles via intranasal administration. The cytokine analysis identified a mixed T-helper cell response, while the systemic antibody response showed a prevalence of IgG1 isotype indicative of a polarized Th2-type immune response. RNA-Sequencing analysis revealed that E2 scaffold up-regulates in DCs transcriptional regulators of the Th2-polarizing cell response, defining a type 2 DC transcriptomic signature. The current study provides experimental evidence to the possible application of E2 scaffold as antigen delivery system for mucosal immunization and taking advantages of genome-wide approach dissects the type of response induced by E2 particles.

  10. (E-2-{(2-Hydroxynaphthalen-1-ylmethylene}hydrazinecarboxamide

    Directory of Open Access Journals (Sweden)

    Jerry P. Jasinski

    2009-05-01

    Full Text Available In the title molecule, C12H11N3O2, the dihedral angle between the mean planes of the naphthalene and carboxamide groups is 28.9 (8°. The hydrazine N atoms are twisted slightly out of the plane of the carboxamide group [C—C—N—N torsion angle = −175.06 (13°]. The crystal packing is influenced by N—H...O hydrogen bonding which includes a bifurcated hydrogen bond between the amide N atom and nearby carboxyl and hydroxyl O atoms. A second bifurcated hydrogen bond occurs between the hydroxyl O atom and nearby amide (intermolecular and hydrazine (intramolecular N atoms. As a result, molecules are linked into a co-operative hydrogen-bonded network of infinite one-dimensional O—H...O—H...O—H chains along the (101 plane of the unit cell in a zigzag pattern, the dihedral angle between the mean planes of the naphthalene groups of adjacent molecules in the chain being 86.9 (2°. A MOPAC PM3 calculation provides support to these observations.

  11. E2fl1 is a meiosis-specific transcription factor in the protist Tetrahymena thermophila.

    Science.gov (United States)

    Zhang, Jing; Tian, Miao; Yan, Guan-Xiong; Shodhan, Anura; Miao, Wei

    2017-01-02

    Members of the E2F family of transcription factors have been reported to regulate the expression of genes involved in cell cycle control, DNA replication, and DNA repair in multicellular eukaryotes. Here, E2FL1, a meiosis-specific E2F transcription factor gene, was identified in the model ciliate Tetrahymena thermophila. Loss of this gene resulted in meiotic arrest prior to anaphase I. The cytological experiments revealed that the meiotic homologous pairing was not affected in the absence of E2FL1, but the paired homologous chromosomes did not separate and assumed a peculiar tandem arrangement. This is the first time that an E2F family member has been shown to regulate meiotic events. Moreover, BrdU incorporation showed that DSB processing during meiosis was abnormal upon the deletion of E2FL1. Transcriptome sequencing analysis revealed that E2FL1 knockout decreased the expression of genes involved in DNA replication and DNA repair in T. thermophila, suggesting that the function of E2F is highly conserved in eukaryotes. In addition, E2FL1 deletion inhibited the expression of related homologous chromosome segregation genes in T. thermophila. The result may explain the meiotic arrest phenotype at anaphase I. Finally, by searching for E2F DNA-binding motifs in the entire T. thermophila genome, we identified 714 genes containing at least one E2F DNA-binding motif; of these, 235 downregulated represent putative E2FL1 target genes.

  12. 26 CFR 1.669(e)-2A - Illustration of the provisions of section 669.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Illustration of the provisions of section 669. 1.669(e)-2A Section 1.669(e)-2A Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... Taxable Years Beginning Before January 1, 1969 § 1.669(e)-2A Illustration of the provisions of section...

  13. E2F Transcription Factors Control the Roller Coaster Ride of Cell Cycle Gene Expression

    NARCIS (Netherlands)

    Thurlings, Ingrid; de Bruin, Alain

    2016-01-01

    Initially, the E2F transcription factor was discovered as a factor able to bind the adenovirus E2 promoter and activate viral genes. Afterwards it was shown that E2F also binds to promoters of nonviral genes such as C-MYC and DHFR, which were already known at that time to be important for cell growt

  14. The Human p73 Promoter: Characterization and Identification of Functional E2F Binding Sites

    Directory of Open Access Journals (Sweden)

    Ratnam S. Seelan

    2002-01-01

    Full Text Available p73, a member of the p53 family, is overexpressed in many cancers. To understand the mechanism(s underlying this overexpression, we have undertaken a detailed characterization of the human p73 promoter. The promoter is strongly activated in cells expressing exogenous E2F1 and suppressed by exogenous Rb. At least three functional E2F binding sites, located immediately upstream of exon 1 (at-284,-155 and-132 mediate this induction. 5' serially deleted promoter constructs and constructs harboring mutated E2F sites were analyzed for their response to exogenously expressed E2F1 or Rb to establish functionality of these sites. Authenticity of E2F sites was further confirmed by electrophoretic mobility shift assay (EMSA using E2F1 /DP1 heterodimers synthesized in vitro, followed by competition assays with unlabeled wild-type or mutant oligonucleotides and supershift analysis using anti-E2F1 antibodies. In vivo binding of E2F1 to the p73 promoter was demonstrated using nuclear extracts prepared from E2F1-inducible Saos2 cells. The region conferring the highest promoter activity was found to reside between-113 to-217 of the p73 gene. Two of the three functional E2F sites (at-155 and-132 reside within this region. Our results suggest that regulation of p73 expression is primarily mediated through binding of E2 F1 to target sites at-155 and-132.

  15. Regulation of human genome expression and RNA splicing by human papillomavirus 16 E2 protein.

    Science.gov (United States)

    Gauson, Elaine J; Windle, Brad; Donaldson, Mary M; Caffarel, Maria M; Dornan, Edward S; Coleman, Nicholas; Herzyk, Pawel; Henderson, Scott C; Wang, Xu; Morgan, Iain M

    2014-11-01

    Human papillomavirus 16 (HPV16) is causative in human cancer. The E2 protein regulates transcription from and replication of the viral genome; the role of E2 in regulating the host genome has been less well studied. We have expressed HPV16 E2 (E2) stably in U2OS cells; these cells tolerate E2 expression well and gene expression analysis identified 74 genes showing differential expression specific to E2. Analysis of published gene expression data sets during cervical cancer progression identified 20 of the genes as being altered in a similar direction as the E2 specific genes. In addition, E2 altered the splicing of many genes implicated in cancer and cell motility. The E2 expressing cells showed no alteration in cell growth but were altered in cell motility, consistent with the E2 induced altered splicing predicted to affect this cellular function. The results present a model system for investigating E2 regulation of the host genome.

  16. E2F function in muscle growth is necessary and sufficient for viability in Drosophila.

    Science.gov (United States)

    Zappia, Maria Paula; Frolov, Maxim V

    2016-01-01

    The E2F transcription factor is a key cell cycle regulator. However, the inactivation of the entire E2F family in Drosophila is permissive throughout most of animal development until pupation when lethality occurs. Here we show that E2F function in the adult skeletal muscle is essential for animal viability since providing E2F function in muscles rescues the lethality of the whole-body E2F-deficient animals. Muscle-specific loss of E2F results in a significant reduction in muscle mass and thinner myofibrils. We demonstrate that E2F is dispensable for proliferation of muscle progenitor cells, but is required during late myogenesis to directly control the expression of a set of muscle-specific genes. Interestingly, E2f1 provides a major contribution to the regulation of myogenic function, while E2f2 appears to be less important. These findings identify a key function of E2F in skeletal muscle required for animal viability, and illustrate how the cell cycle regulator is repurposed in post-mitotic cells.

  17. E2F function in muscle growth is necessary and sufficient for viability in Drosophila

    Science.gov (United States)

    Zappia, Maria Paula; Frolov, Maxim V.

    2016-01-01

    The E2F transcription factor is a key cell cycle regulator. However, the inactivation of the entire E2F family in Drosophila is permissive throughout most of animal development until pupation when lethality occurs. Here we show that E2F function in the adult skeletal muscle is essential for animal viability since providing E2F function in muscles rescues the lethality of the whole-body E2F-deficient animals. Muscle-specific loss of E2F results in a significant reduction in muscle mass and thinner myofibrils. We demonstrate that E2F is dispensable for proliferation of muscle progenitor cells, but is required during late myogenesis to directly control the expression of a set of muscle-specific genes. Interestingly, E2f1 provides a major contribution to the regulation of myogenic function, while E2f2 appears to be less important. These findings identify a key function of E2F in skeletal muscle required for animal viability, and illustrate how the cell cycle regulator is repurposed in post-mitotic cells. PMID:26823289

  18. Structure of a RING E3 ligase and ubiquitin-loaded E2 primed for catalysis

    Science.gov (United States)

    Plechanovová, Anna; Jaffray, Ellis; Tatham, Michael H.; Naismith, James H.; Hay, Ronald T.

    2012-01-01

    SUMMARY Ubiquitin modification is mediated by a large family of specificity determining ubiquitin E3 ligases. To facilitate ubiquitin transfer, RING E3 ligases bind both substrate and a ubiquitin E2 conjugating enzyme linked to ubiquitin via a thioester bond, but the mechanism of transfer has remained elusive. Here we report the crystal structure of the dimeric RING of RNF4 in complex with E2 (UbcH5a) linked by an isopeptide bond to ubiquitin. While the E2 contacts a single protomer of the RING, ubiquitin is folded back onto the E2 by contacts from both RING protomers. The C-terminal tail of ubiquitin is locked into an active site groove on the E2 by an intricate network of interactions, resulting in changes at the E2 active site. This arrangement is primed for catalysis as it can deprotonate the incoming substrate lysine residue and stabilise the consequent tetrahedral transition state intermediate. PMID:22842904

  19. Inhibition of E2F-mediated transcription by p202.

    Science.gov (United States)

    Choubey, D; Li, S J; Datta, B; Gutterman, J U; Lengyel, P

    1996-01-01

    Many of the antimicrobial, immunomodulatory and cell growth inhibitory activities of the interferons are mediated by interferon-inducible proteins. Earlier we characterized an interferon-inducible murine protein, p202, whose expression in transfected cells inhibits cell proliferation and which can form a complex with retinoblastoma protein (pRb). Here we report that in transfected cells expression of p202 inhibits E2F-stimulated transcription of a reporter gene and of endogenous genes. Inhibition of the transcriptional activity of E2F by p202 does not depend on fully functional pRb and is correlated with inhibition of the sequence-specific DNA binding of E2F. p202 interacts with the transcription factor E2F (E2F-1/DP-1) in vitro and in vivo. Inhibition of E2F activity by p202 may contribute to growth inhibition by the interferons. Images PMID:8896460

  20. Cooperative activation of tissue-specific genes by pRB and E2F1.

    Science.gov (United States)

    Flowers, Stephen; Xu, Fuhua; Moran, Elizabeth

    2013-04-01

    The retinoblastoma tumor suppressor protein pRB is conventionally regarded as an inhibitor of the E2F family of transcription factors. Conversely, pRB is also recognized as an activator of tissue-specific gene expression along various lineages including osteoblastogenesis. During osteoblast differentiation, pRB directly targets Alpl and Bglap, which encode the major markers of osteogenesis alkaline phosphatase and osteocalcin. Surprisingly, p130 and repressor E2Fs were recently found to cooccupy and repress Alpl and Bglap in proliferating osteoblast precursors before differentiation. This raises the further question of whether these genes convert to E2F activation targets when differentiation begins, which would constitute a remarkable situation wherein pRB and E2F would be cotargeting genes for activation. Chromatin immunoprecipitation analysis in an osteoblast differentiation model shows that Alpl and Bglap are indeed targeted by an activator E2F, i.e., is E2F1. Promoter occupation of Alpl and Bglap by E2F1 occurs specifically during activation, and depletion of E2F1 severely impairs their induction. Mechanistically, promoter occupation by E2F1 and pRB is mutually dependent, and without this cooperative effect, activation steps previously shown to be dependent on pRB, including recruitment of RNA polymerase II, are impaired. Myocyte- and adipocyte-specific genes are also cotargeted by E2F1 and pRB during differentiation along their respective lineages. The finding that pRB and E2F1 cooperate to activate expression of tissue-specific genes is a paradigm distinct from the classical concept of pRB as an inhibitor of E2F1, but is consistent with the observed roles of these proteins in physiological models.

  1. The tumor suppressor gene hypermethylated in cancer 1 is transcriptionally regulated by E2F1

    DEFF Research Database (Denmark)

    Jenal, Mathias; Trinh, Emmanuelle; Britschgi, Christian;

    2009-01-01

    The Hypermethylated in Cancer 1 (HIC1) gene encodes a zinc finger transcriptional repressor that cooperates with p53 to suppress cancer development. We and others recently showed that HIC1 is a transcriptional target of p53. To identify additional transcriptional regulators of HIC1, we screened...... to the HIC1 promoter was shown by chromatin immunoprecipitation assays in human TIG3 fibroblasts expressing tamoxifen-activated E2F1. In agreement, activation of E2F1 in TIG3-E2F1 cells markedly increased HIC1 expression. Interestingly, expression of E2F1 in the p53(-/-) hepatocellular carcinoma cell line...

  2. E2-25K SUMOylation inhibits proteasome for cell death during cerebral ischemia/reperfusion

    Science.gov (United States)

    Jeong, Eun Il; Chung, Hae Won; Lee, Won Jea; Kim, Seo-Hyun; Kim, Hyunjoo; Choi, Seon-Guk; Jung, Yong-Keun

    2016-01-01

    Cerebral ischemia/reperfusion (I/R) causes brain damage accompanied by ubiquitin accumulation and impairment of proteasome activity. In this study, we report that E2-25K, an E2-conjugating enzyme, is SUMOylated during oxidative stress and regulates cerebral I/R-induced damage. Knockdown of E2-25K expression protects against oxygen/glucose deprivation and reoxygenation (OGD/R)-induced neuronal cell death, whereas ectopic expression of E2-25K stimulates it. Compared with the control mice, cerebral infarction lesions and behavioral/neurological disorders are ameliorated in E2-25K knockout mice during middle cerebral artery occlusion and reperfusion. In particular, E2-25K is SUMOylated at Lys14 under oxidative stress, OGD/R and I/R to prompt cell death. Further, E2-25K downregulates the proteasome subunit S5a to impair proteasome complex and thus restrain proteasome activity under oxidative stress. This proteasome inhibitory activity of E2-25K is dependent on its SUMOylation. These results suggest that E2-25K has a crucial role in oxidative stress and cerebral I/R-induced damage through inhibiting proteasome via its SUMOylation. PMID:28032866

  3. Comparison of gamma ray effects on EPROMs and E2PROMs

    Directory of Open Access Journals (Sweden)

    Vujisić Miloš

    2009-01-01

    Full Text Available This paper compares the reliability of standard commercial Erasable Programmable Read Only Memory (EPROM and Electrically Erasable Programmable Read Only Memory (E2PROM components exposed to gamma rays. The results obtained for CMOS-based EPROM (NM27C010 and E2PROM (NM93CS46 components provide the evidence that EPROMs have greater radiation hardness than E2PROMs. Moreover, the changes in EPROMs are reversible, and after erasure and reprogramming all EPROM components restore their functionality. On the other hand, changes in E2PROMs are irreversible. The obtained results are analyzed and interpreted on the basis of gamma ray interaction with the CMOS structure.

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

    Science.gov (United States)

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

    2014-12-05

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

  5. E2F-HDAC complexes negatively regulate the tumor suppressor gene ARHI in breast cancer

    DEFF Research Database (Denmark)

    Lu, Z; Luo, R Z; Peng, H;

    2006-01-01

    to the P2 region of the ARHI promoter and regulate its activity. Sequence analysis and oligonucleotide competition in electrophoretic mobility shift assays identified an A2 fragment containing an E2F-binding site. Using specific antibodies in supershift assays, we have shown that anti-E2F1 and 4 antibodies...... and increased E2F DNA-binding activity. Moreover, chromatin immunoprecipitation experiments revealed that both E2F1 and 4 bind to the ARHI promoter in breast cancer cells in vivo. This binding was reduced when the cells were treated with the histone deacetylase (HDAC) inhibitor--trichostatin A (TSA). When SKBr3...

  6. E2F1 transcription factor and its impact on growth factor and cytokine signaling.

    Science.gov (United States)

    Ertosun, Mustafa Gokhan; Hapil, Fatma Zehra; Osman Nidai, Ozes

    2016-10-01

    E2F1 is a transcription factor involved in cell cycle regulation and apoptosis. The transactivation capacity of E2F1 is regulated by pRb. In its hypophosphorylated form, pRb binds and inactivates DNA binding and transactivating functions of E2F1. The growth factor stimulation of cells leads to activation of CDKs (cyclin dependent kinases), which in turn phosphorylate Rb and hyperphosphorylated Rb is released from E2F1 or E2F1/DP complex, and free E2F1 can induce transcription of several genes involved in cell cycle entry, induction or inhibition of apoptosis. Thus, growth factors and cytokines generally utilize E2F1 to direct cells to either fate. Furthermore, E2F1 regulates expressions of various cytokines and growth factor receptors, establishing positive or negative feedback mechanisms. This review focuses on the relationship between E2F1 transcription factor and cytokines (IL-1, IL-2, IL-3, IL-6, TGF-beta, G-CSF, LIF), growth factors (EGF, KGF, VEGF, IGF, FGF, PDGF, HGF, NGF), and interferons (IFN-α, IFN-β and IFN-γ).

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

    Directory of Open Access Journals (Sweden)

    Ann R Hunt

    2010-07-01

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

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

    Directory of Open Access Journals (Sweden)

    Ann R Hunt

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

  9. Data of evolutionary structure change: 1CTMA-1E2ZC [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available M A 1CTMA IVDASNERQVI ...1CTMA-1E2ZC 1CTM 1E2Z A C YPIFAQQNYENPREATGRIVCANCHLASKPVDIEVPQAV...EEEEEE EEEEEEE - EEEEEEE EEE EEEEEEEEEE 0 1CT...M A 1CTMA KILRK--EKGGY ure>EEEEE-- EEure>

  10. Data of evolutionary structure change: 1CTMA-1E2WA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1CTMA-1E2WA 1CTM 1E2W A A YPIFAQQNYENPREATGRIVCANCHLASKPVDIEVPQAV...index> 1CTM A 1CTM...A ILRKE--KGGYE ure>EEEE -- EEEure> ITALSEKKGGFE ure>EE EEEure> IEKAN-GEVVV ure>EEE - EEEEure> <

  11. Data of evolutionary structure change: 1CTMA-1E2ZA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1CTMA-1E2ZA 1CTM 1E2Z A A YPIFAQQNYENPREATGRIVCANCHLASKPVDIEVPQAV...EEEEEEEE EEEEEEEE - EEEEEEE EEE EEEEEEEEEE 0 1CTM A 1CTMA ILRKE--KGGYE ure>EEEE -- EEEure> ITALSEKKGGFE EEEE EEEure>

  12. Data of evolutionary structure change: 1ACMA-3E2PL [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1ACMA-3E2PL 1ACM 3E2P A L ANPLYQKHIISINDLSRDDLNLVLATAAKLKA-----NP...HHHHGGHHHHHHHHHHHHHH - 0 1ACM... A 1ACMA KERLD-PSEYA ALA CA 215 LYS CA 143 1ACM... A 1ACMA SDSANTSLGKK

  13. Data of evolutionary structure change: 1ACMA-3E2PA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1ACMA-3E2PA 1ACM 3E2P A A ANPLYQKHIISINDLSRDDLNLVLATAAKLKA-----NP... -- EEE GGG HHHHHGGHHHHHHHHHHHHHHH 0 1ACM... A 1ACMA KERLD-PSEYA LYS CA 143 1ACM A 1ACM...433 ILE CA 513 ILE CA 559 ASN CA 517 1ACM

  14. Data of evolutionary structure change: 1ACMA-3E2PK [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1ACMA-3E2PK 1ACM 3E2P A K ANPLYQKHIISINDLSRDDLNLVLATAAKLKA-----NP...GG HHHHHGGHHHHHHHHHHHHHH - 0 1ACM... A 1ACMA KERLD-PSEYA SER CA 128 VAL CA 222 ALA CA 223 1ACM... A 1ACMA FSDSANTSLGK

  15. Functional Characterization of Intracellular and Secreted Forms of a Truncated Hepatitis C Virus E2 Glycoprotein†

    Science.gov (United States)

    Flint, Mike; Dubuisson, Jean; Maidens, Catherine; Harrop, Richard; Guile, Geoffrey R.; Borrow, Persephone; McKeating, Jane A.

    2000-01-01

    The E2 protein of hepatitis C virus (HCV) is believed to be a virion surface glycoprotein that is a candidate for inclusion in an antiviral vaccine. A truncated soluble version of E2 has recently been shown to interact with CD81, suggesting that this protein may be a component of the receptor for HCV. When expressed in eukaryotic cells, a significant proportion of E2 forms misfolded aggregates. To analyze the specificity of interaction between E2 and CD81, the aggregated and monomeric forms of a truncated E2 glycoprotein (E2661) were separated by high-pressure liquid chromatography and analyzed for CD81 binding. Nonaggregated forms of E2 preferentially bound CD81 and a number of conformation-dependent monoclonal antibodies (MAbs). Furthermore, intracellular forms of E2661 were found to bind CD81 with greater affinity than the extracellular forms. Intracellular and secreted forms of E2661 were also found to differ in reactivity with MAbs and human sera, consistent with differences in antigenicity. Together, these data indicate that proper folding of E2 is important for its interaction with CD81 and that modifications of glycans can modulate this interaction. Identification of the biologically active forms of E2 will assist in the future design of vaccines to protect against HCV infection. PMID:10623732

  16. Data of evolutionary structure change: 1E2TE-2PFRB [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1E2TE-2PFRB 1E2T 2PFR E B HMTSFLHAYFTRLHCQPLGVPTVEALRTLHLAHNCAIPF...ine>ARG CA 540 2PFR B 2PFR...U CA 192 GLN CA 212 VAL CA 235 2PFR... B 2PFRB RKFNYKDNTDLVEFK 2.9440479278564453 2 2PFR

  17. Data of evolutionary structure change: 1E2TG-2PFRB [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1E2TG-2PFRB 1E2T 2PFR G B HMTSFLHAYFTRLHCQPLGVPTVEALRTLHLAHNCAIPF...ine> ARG CA 539 2PFR B 2PFR...CA 191 GLN CA 212 VAL CA 236 2PFR B 2PFRB RKFNYKDNTDLVEFK 2.972101926803589 2 2PFR<

  18. p53 represses human papillomavirus type 16 DNA replication via the viral E2 protein

    Directory of Open Access Journals (Sweden)

    Morgan Iain M

    2008-01-01

    Full Text Available Abstract Background Human papillomavirus (HPV DNA replication can be inhibited by the cellular tumour suppressor protein p53. However, the mechanism through which p53 inhibits viral replication and the role that this might play in the HPV life cycle are not known. The papillomavirus E2 protein is required for efficient HPV DNA replication and also regulates viral gene expression. E2 represses transcription of the HPV E6 and E7 oncogenes and can thereby modulate indirectly host cell proliferation and survival. In addition, the E2 protein from HPV 16 has been shown to bind p53 and to be capable of inducing apoptosis independently of E6 and E7. Results Here we use a panel of E2 mutants to confirm that mutations which block the induction of apoptosis via this E6/E7-independent pathway, have little or no effect on the induction of apoptosis by the E6/E7-dependent pathway. Although these mutations in E2 do not affect the ability of the protein to mediate HPV DNA replication, they do abrogate the repressive effects of p53 on the transcriptional activity of E2 and prevent the inhibition of E2-dependent HPV DNA replication by p53. Conclusion These data suggest that p53 down-regulates HPV 16 DNA replication via the E2 protein.

  19. Data of evolutionary structure change: 3GD5D-3E2PJ [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 3GD5D-3E2PJ 3GD5 3E2P D J TRFRPDLLSLDDLDEAQLHALLTLAHQLKRGE---RVAN...-LHGKVLGLVFLKASTRTRVSFTVAMYQLGGQVIDL-----------EPVRDTARVLGRYVDGLAIRTFAQTELEEYAHYAGIPVINALTD-HEHPCQVVADLLTIRENFGRLAGLKLAYVGD...ISMKDIGKEEILEILDEARKMEELLNTKRPLKLLEGKILATVFYEPSTRTRLSFETAMKRLGGEVITMTDLKSSSVAKGESLIDTIRVISGYADIIVLRHPSEGAARLASEYSQVPIINAGD...GSNQHPTQTLLDLYTIMREIGRIDGIKIAFVGDLKYGRTVHSLVYALSLFENVEMYFVSPKELRLPKDIIEDLKAK----NIKFYEKESLDDLD...ex> 3GD5 D 3GD5D YVGD

  20. E2F-1-Induced p53-independent apoptosis in transgenic mice

    DEFF Research Database (Denmark)

    Holmberg, Christian Henrik; Helin, K.; Sehested, M.;

    1998-01-01

    involving increased apoptosis in the germinal epithelium. This effect was potentiated by simultaneous overexpression of DP-1. Testicular atrophy as a result of overexpression of E2F-1 and DP-1 is independent of functional p53, since p53-nullizygous transgenic mice overexpressing E2F-1 and DP-1 also suffered...

  1. Induction of DNA synthesis and apoptosis are separable functions of E2F-1

    DEFF Research Database (Denmark)

    Phillips, A C; Bates, S; Ryan, K M;

    1997-01-01

    The family of E2F transcription factors have an essential role in mediating cell cycle progression, and recently, one of the E2F protein family, E2F-1, has been shown to participate in the induction of apoptosis. Cooperation between E2F and the p53 tumor suppressor protein in this apoptotic...... response had led to the suggestion that cell cycle progression induced by E2F-1 expression provides an apoptotic signal when placed in conflict with an arrest to cell cycle progression, such as provided by p53. We show here that although apoptosis is clearly enhanced by p53, E2F-1 can induce significant...... apoptosis in the absence of p53. Furthermore, this apoptotic function of E2F-1 is separable from the ability to accelerate entry into DNA synthesis. Analysis of E2F-1 mutants indicates that although DNA-binding is required, transcriptional transactivation is not necessary for the induction of apoptosis by E...

  2. Data of evolutionary structure change: 1ACMC-3E2PA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1ACMC-3E2PA 1ACM 3E2P C A ANPLYQKHIISINDLSRDDLNLVLATAAKLKANPQ----...ntryChain> 1ACM C 1ACMC KANPQ----...14> 1ACM C 1ACMC...bID> C 1ACMC ATEFSGNV...yChain> 1ACM C 1ACMC DLHNAKANMKVL

  3. NRIP enhances HPV gene expression via interaction with either GR or E2

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Szu-Wei; Lu, Pei-Yu; Guo, Jih-Huong [Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 100, Taiwan (China); Tsai, Tzung-Chieh [Department of Microbiology and Immunology, National Chiayi University, Chiayi 600-04, Taiwan (China); Tsao, Yeou-Ping [Department of Ophthalmology, Mackay Memorial Hospital, Taipei 104, Taiwan (China); Chen, Show-Li, E-mail: showlic@ha.mc.ntu.edu.tw [Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 100, Taiwan (China)

    2012-02-05

    We previously identified a gene, nuclear receptor-interaction protein (NRIP), which functions as a transcription cofactor in glucocorticoid receptor (GR) and human papillomavirus E2 (HPV E2)-driven gene expression. Here, we comprehensively evaluated the role of NRIP in HPV-16 gene expression. NRIP acts as a transcription cofactor to enhance GR-regulated HPV-16 gene expression in the presence of hormone. NRIP also can form complex with E2 that caused NRIP-induced HPV gene expression via E2-binding sites in a hormone-independent manner. Furthermore, NRIP can associate with GR and E2 to form tri-protein complex to activate HPV gene expression via GRE, not the E2-binding site, in a hormone-dependent manner. These results indicate that NRIP and GR are viral E2-binding proteins and that NRIP regulates HPV gene expression via GRE and/or E2 binding site in the HPV promoter in a hormone-dependent or independent manner, respectively.

  4. E2f8 mediates tumor suppression in postnatal liver development

    NARCIS (Netherlands)

    Kent, Lindsey N.; Rakijas, Jessica B.; Pandit, Shusil K.; Westendorp, Bart; Chen, Hui Zi; Huntington, Justin T.; Tang, Xing; Bae, Sooin; Srivastava, Arunima; Senapati, Shantibhusan; Koivisto, Christopher; Martin, Chelsea K.; Cuitino, Maria C.; Perez, Miguel; Clouse, Julian M.; Chokshi, Veda; Shinde, Neelam; Kladney, Raleigh; Sun, Daokun; Perez-Castro, Antonio; Matondo, Ramadhan B.; Nantasanti, Sathidpak; Mokry, Michal; Huang, Kun; Machiraju, Raghu; Fernandez, Soledad; Rosol, Thomas J.; Coppola, Vincenzo; Pohar, Kamal S.; Pipas, James M.; Schmidt, Carl R.; De Bruin, Alain; Leone, Gustavo

    2016-01-01

    E2F-mediated transcriptional repression of cell cycle-dependent gene expression is critical for the control of cellular proliferation, survival, and development. E2F signaling also interacts with transcriptional programs that are downstream of genetic predictors for cancer development, including hep

  5. E2f8 mediates tumor suppression in postnatal liver development

    NARCIS (Netherlands)

    Kent, Lindsey N.; Rakijas, Jessica B.; Pandit, Shusil K.; Westendorp, Bart; Chen, Hui Zi; Huntington, Justin T.; Tang, Xing; Bae, Sooin; Srivastava, Arunima; Senapati, Shantibhusan; Koivisto, Christopher; Martin, Chelsea K.; Cuitino, Maria C.; Perez, Miguel; Clouse, Julian M.; Chokshi, Veda; Shinde, Neelam; Kladney, Raleigh; Sun, Daokun; Perez-Castro, Antonio; Matondo, Ramadhan B.; Nantasanti, Sathidpak; Mokry, Michal; Huang, Kun; Machiraju, Raghu; Fernandez, Soledad; Rosol, Thomas J.; Coppola, Vincenzo; Pohar, Kamal S.; Pipas, James M.; Schmidt, Carl R.; De Bruin, Alain; Leone, Gustavo

    2016-01-01

    E2F-mediated transcriptional repression of cell cycle–dependent gene expression is critical for the control of cellular proliferation, survival, and development. E2F signaling also interacts with transcriptional programs that are downstream of genetic predictors for cancer development, including hep

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

    Science.gov (United States)

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

    2017-01-01

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

  7. US NDC Modernization Iteration E2 Prototyping Report: OSD & PC Software Infrastructure

    Energy Technology Data Exchange (ETDEWEB)

    Prescott, Ryan [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Marger, Bernard L. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Chiu, Ailsa [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2014-12-01

    During the second iteration of the US NDC Modernization Elaboration phase (E2), the SNL US NDC Modernization project team completed follow-on COTS surveys & exploratory prototyping related to the Object Storage & Distribution (OSD) mechanism, and the processing control software infrastructure. This report summarizes the E2 prototyping work.

  8. Cloning of HPV16 E2 Gene from a Biopsied Cervical Cancer Sample

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective To clone HPV16 E2 gene from a biopsied cervical cancer sampleMaterials & Methods HPV 1 6 E2 gene was amplified from specimen derived from aHPV 16 positive patient, then cloned and sequenced. Results The full-length of HPV 16 E2 gene was successfully cloned. In comparisonwith the prototype accepted by GenBank, six point mutations in HPV 1 6 E2 nucleotideacid sequence were identified. Of them, three were missense, and one was in the over-lapping E4 gene and was synonymous to E4.Conclusion HPV 16 E2 gene was successfully cloned, and some nucleotide acids in itssequence were different from the prototype.

  9. Gender-dependent negative correlation of peripheral E2 estradiol levels with ventricular diastolic functions.

    Science.gov (United States)

    Tan, Bo; Zhao, Lili; FaweiHE, Fawei

    2016-08-01

    The aim of this study to investigate the correlation of the peripheral concentrations of one representative estrogen, E2 estradiol, with various indicators reflecting different aspects of cardiac structures and functions. A total of 84 typical patients with hypertrophic cardiomyopathy (HCM) and 77 healthy subjects were enrolled. Venous blood samples were taken to test E2 estradiol contents. Echocardiographic imaging was performed to record various indices of cardiac structures and functions. Concentrations of peripheral E2 estradiol were decreased in female HCM patients, compared to female normal controls; after medical treatment, peripheral E2 estradiol levels were elevated, nearly to normal levels. Peripheral E2 estradiol concentrations were negatively correlated with LAV (r2=0.5078, Pnegatively correlated with ventricular diastolic functions and this correlation was gender-dependent. Our study could provide clues to explore the molecular mechanisms of HCM, and clinic evidence for the diagnosis and prognostic management of HCM patients, as well as medical intervening for HCM.

  10. Point mutations in E2, NS3 and NS5A of hepatitis G virus

    Institute of Scientific and Technical Information of China (English)

    Wei Dong Liu; Toshikazu Hada; Ji Dong Cheng; Kazuya Higashino

    2000-01-01

    AIM To compare the point mutation deviations of HGV among E2, NS3 and NSSA.METHODS Seven patients with hepatic diseases from Japan and China were selected for this study. RNAwas extracted and amplified by semi-nested RT-PCR; and the PCR products were sequenced directly.RESULTS The point mutation deviations of HGV ia E2, NS3 and NS5A were 10% - 17%, 11% -23%,and 0% - 5%, in nuclcotide sequences and 4% - 12%, 0%, and 0% - 6% in amino acid sequencesrespectively.CONCLUSION The frequency of variation at the nucleotide level was in the order NS3>E2>NS5A, whileat the amino acid level the order was E2 >NS5A>NS3. The detected sequences from the N-terminus of E2may be the poorly conserved region of HGV.

  11. DEK Expression is controlled by E2F and deregulated in diverse tumor types.

    Science.gov (United States)

    Carro, Maria Stella; Spiga, Fabio Mario; Quarto, Micaela; Di Ninni, Valentina; Volorio, Sara; Alcalay, Myriam; Müller, Heiko

    2006-06-01

    Deregulation of the retinoblastoma (pRB) tumor suppressor pathway associated with aberrant activity of E2F transcription factors is frequently observed in human cancer. Microarray based analyses have revealed a large number of potential downstream mediators of the tumor suppressing activity of pRB, including DEK, a fusion partner of CAN found in a subset of acute myeloid leukaemia (AML) patients carrying a (6; 9) translocation. Here we report that the expression of DEK is under direct control of E2F transcription factors. Chromatin immunoprecipitation assays show that the DEK promoter is bound by endogenous E2F in vivo. The DEK promoter is transactivated by E2F and mutation of E2F binding sites eliminates this effect. Expression levels of DEK in human tumors have been investigated by tissue micro array analysis. We find that DEK is overexpressed in many solid tumors such as colon cancer, larynx cancer, bladder cancer, and melanoma.

  12. A role for E2-2 at the DN3 stage of early thymopoiesis

    DEFF Research Database (Denmark)

    Wikström, Ingela; Forssell, Johan; Penha-Goncalves, Mario N;

    2008-01-01

    proteins, Id2 displayed a prominent expression exclusively in DN1, whereas Id3 showed some expression in DN1, followed by a down regulation and then a prominent induction, peaking in the DP stage. E2-2 was expressed during the DN stages, as well as in the DP stage, suggesting that E2-2 operates in concert...... with the other E-proteins during early thymocyte development. We found that E2-2 null thymocytes displayed a partial block at the DN3 stage of development, as well as a reduced expression of pre-T alpha, known to be regulated also by E2A and HEB. The fact that E2-2 deficient thymocytes develop without gross...

  13. E2F family members are differentially regulated by reversible acetylation

    DEFF Research Database (Denmark)

    Marzio, G; Wagener, C; Gutierrez, M I;

    2000-01-01

    The six members of the E2F family of transcription factors play a key role in the control of cell cycle progression by regulating the expression of genes involved in DNA replication and cell proliferation. E2F-1, -2, and -3 belong to a structural and functional subfamily distinct from those...... of the other E2F family members. Here we report that E2F-1, -2, and -3, but not E2F-4, -5, and -6, associate with and are acetylated by p300 and cAMP-response element-binding protein acetyltransferases. Acetylation occurs at three conserved lysine residues located at the N-terminal boundary of their DNA...

  14. In vivo delivery of bovine viral diahorrea virus, E2 protein using hollow mesoporous silica nanoparticles

    Science.gov (United States)

    Mahony, D.; Cavallaro, A. S.; Mody, K. T.; Xiong, L.; Mahony, T. J.; Qiao, S. Z.; Mitter, N.

    2014-05-01

    Our work focuses on the application of mesoporous silica nanoparticles as a combined delivery vehicle and adjuvant for vaccine applications. Here we present results using the viral protein, E2, from bovine viral diarrhoea virus (BVDV). BVDV infection occurs in the target species of cattle and sheep herds worldwide and is therefore of economic importance. E2 is a major immunogenic determinant of BVDV and is an ideal candidate for the development of a subunit based nanovaccine using mesoporous silica nanoparticles. Hollow type mesoporous silica nanoparticles with surface amino functionalisation (termed HMSA) were characterised and assessed for adsorption and desorption of E2. A codon-optimised version of the E2 protein (termed Opti-E2) was produced in Escherichia coli. HMSA (120 nm) had an adsorption capacity of 80 μg Opti-E2 per mg HMSA and once bound E2 did not dissociate from the HMSA. Immunisation studies in mice with a 20 μg dose of E2 adsorbed to 250 μg HMSA was compared to immunisation with Opti-E2 (50 μg) together with the traditional adjuvant Quillaja saponaria Molina tree saponins (QuilA, 10 μg). The humoral responses with the Opti-E2/HMSA nanovaccine although slightly lower than those obtained for the Opti-E2 + QuilA group demonstrated that HMSA particles are an effective adjuvant that stimulated E2-specific antibody responses. Importantly the cell-mediated immune responses were consistently high in all mice immunised with Opti-E2/HMSA nanovaccine formulation. Therefore we have shown the Opti-E2/HMSA nanoformulation acts as an excellent adjuvant that gives both T-helper 1 and T-helper 2 mediated responses in a small animal model. This study has provided proof-of-concept towards the development of an E2 subunit nanoparticle based vaccine.Our work focuses on the application of mesoporous silica nanoparticles as a combined delivery vehicle and adjuvant for vaccine applications. Here we present results using the viral protein, E2, from bovine viral

  15. Absence of pRb facilitates E2F1-induced apoptosis in breast cancer cells.

    Science.gov (United States)

    Sun, Baohua; Wingate, Hannah; Swisher, Stephen G; Keyomarsi, Khandan; Hunt, Kelly K

    2010-03-15

    The transcription factor E2F1 is known for its interaction with pRb, controlling cell proliferation; however, E2F1 also has a pivotal role in regulating apoptosis.  The relationship between pRb and E2F1 balances cell proliferation and apoptosis giving pRb tumor suppressive properties. The intricacies of the pRb/E2F1 relationship and thus the regulation of cell fate is cell context dependent. To explore the role of pRb in the E2F1-induced apoptosis of human breast cancer cells, we examined cell growth and apoptosis induction in isogenic cell systems of immortalized breast epithelial cells lacking either pRb (76NE7) or p53 (76NE6). We found that E2F1 caused accumulation of cells in G2 and S phases of the cell cycle along with apoptosis in 76NE7 but not 76NE6 cells.  Variants of 76NE6 cells with functional p53 did not rescue the apoptotic response in these cells, whereas knocking down pRb resulted in significant E2F1-induced apoptosis. We also determined that the effect of E2F1 overexpression in two breast cancer cell lines, MDA-MB-436 and MDA-MB-468, which lack pRb and functional p53, was accumulation of cells in G2/S phase and apoptosis. However, E2F did not cause apotosis  in MCF-7 cells which harbor a functional pRb. Therefore, we conclude that in the absence of Rb, E2F1 overexpression results in apoptosis, not proliferation, and that this effect is independent of p53.

  16. CDK4, pRB and E2F1: connected to insulin

    Directory of Open Access Journals (Sweden)

    Blanchet Emilie

    2010-02-01

    Full Text Available Abstract Pancreatic β-cells are metabolic sensors involved in the control of glucose homeostasis. This particular cell type controls insulin secretion through a fine-tuned process, which dregulation have important pathological consequences, such as observed during type 2 diabetes. We recently implicated E2F1 in the control of glucose homeostasis. First we showed that E2f1-/- mice have decreased pancreatic size, as the result of impaired postnatal pancreatic growth. We observed in this study that E2F1 was highly expressed in non-proliferating pancreatic β-cells, suggesting that E2F1, besides the control of β-cell number could have a role in pancreatic β-cell function. We demonstrate in our recent study, both in vitro and in vivo that E2F1 directly regulates the expression of Kir6.2, a key component of the KATP channel involved in the regulation of glucose-induced insulin secretion in pancreatic β-cells. Expression of Kir6.2 is lost in pancreas of E2f1-/- mice, resulting in insulin secretion defects in these mice. Furthermore, we demonstrated by in tissue chromatin immunoprecipitation analysis that regulation of Kir6.2 expression by E2F1 follows the same regulatory pathway that the classical E2F1 target genes, implicating the participation of CDK4 and retinoblastoma protein. Moreover, in this context, E2F1 transcriptional activity is regulated by glucose and insulin through the CDK4-dependent inactivation of the pRB protein. In summary we provide evidence that the CDK4-pRB-E2F1 regulatory pathway is involved in glucose homeostasis. In our recent study we decipher a new function for these factors in the control of insulin secretion and open up new avenues for the treatment of metabolic diseases, in particular type 2 diabetes.

  17. E2F Transcription Factors Control the Roller Coaster Ride of Cell Cycle Gene Expression.

    Science.gov (United States)

    Thurlings, Ingrid; de Bruin, Alain

    2016-01-01

    Initially, the E2F transcription factor was discovered as a factor able to bind the adenovirus E2 promoter and activate viral genes. Afterwards it was shown that E2F also binds to promoters of nonviral genes such as C-MYC and DHFR, which were already known at that time to be important for cell growth and DNA metabolism, respectively. These findings provided the first clues that the E2F transcription factor might be an important regulator of the cell cycle. Since this initial discovery in 1987, several additional E2F family members have been identified, and more than 100 targets genes have been shown to be directly regulated by E2Fs, the majority of these are important for controlling the cell cycle. The progression of a cell through the cell cycle is accompanied with the increased expression of a specific set of genes during one phase of the cell cycle and the decrease of the same set of genes during a later phase of the cell cycle. This roller coaster ride, or oscillation, of gene expression is essential for the proper progression through the cell cycle to allow accurate DNA replication and cell division. The E2F transcription factors have been shown to be critical for the temporal expression of the oscillating cell cycle genes. This review will focus on how the oscillation of E2Fs and their targets is regulated by transcriptional, post-transcriptional and post-translational mechanism in mammals, yeast, flies, and worms. Furthermore, we will discuss the functional impact of E2Fs on the cell cycle progression and outline the consequences when E2F expression is disturbed.

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

    Science.gov (United States)

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

    2017-02-09

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

  19. Agrobacterium delivers VirE2 protein into host cells via clathrin-mediated endocytosis

    Science.gov (United States)

    Li, Xiaoyang; Pan, Shen Q.

    2017-01-01

    Agrobacterium tumefaciens can cause crown gall tumors on a wide range of host plants. As a natural genetic engineer, the bacterium can transfer both single-stranded DNA (ssDNA) [transferred DNA (T-DNA)] molecules and bacterial virulence proteins into various recipient cells. Among Agrobacterium-delivered proteins, VirE2 is an ssDNA binding protein that is involved in various steps of the transformation process. However, it is not clear how plant cells receive the T-DNA or protein molecules. Using a split–green fluorescent protein approach, we monitored the VirE2 delivery process inside plant cells in real time. We observed that A. tumefaciens delivered VirE2 from the bacterial lateral sides that were in close contact with plant membranes. VirE2 initially accumulated on plant cytoplasmic membranes at the entry points. VirE2-containing membranes were internalized through clathrin-mediated endocytosis to form endomembrane compartments. VirE2 colocalized with the early endosome marker SYP61 but not with the late endosome marker ARA6, suggesting that VirE2 escaped from early endosomes for subsequent trafficking inside the cells. Dual endocytic motifs at the carboxyl-terminal tail of VirE2 were involved in VirE2 internalization and could interact with the μ subunit of the plant clathrin-associated adaptor AP2 complex (AP2M). Both the VirE2 cargo motifs and AP2M were important for the transformation process. Because AP2-mediated endocytosis is well conserved, our data suggest that the A. tumefaciens pathogen hijacks conserved endocytic pathways to facilitate the delivery of virulence factors. This might be important for Agrobacterium to achieve both a wide host range and a high transformation efficiency.

  20. Materials characterization activities for %E2%80%9CTake Our Sons&Daughters to Work Day%E2%80%9D 2013.

    Energy Technology Data Exchange (ETDEWEB)

    Mowry, Curtis Dale; Pimentel, Adam S.; Sparks, Elizabeth Schares; Hanlon, Brittany Paula

    2013-09-01

    We created interactive demonstration activities for Take Our Daughters&Sons to Work Day (TODSTWD) 2013 in order to promote general interest in chemistry and also generate awareness of the type of work our laboratories can perform. %E2%80%9CCurious about Mars Rover Curiosity?%E2%80%9D performed an elemental analysis on rocks brought to our lab using the same technique utilized on the planet Mars by the NASA robotic explorer Curiosity. %E2%80%9CFood is Chemistry?%E2%80%9D utilized a mass spectrometer to measure, in seconds, each participant's breath in order to identify the food item consumed for the activity. A total of over 130 children participated in these activities over a 3 hour block, and feedback was positive. This document reports the materials (including handouts), experimental procedures, and lessons learned so that future demonstrations can benefit from the baseline work performed. We also present example results used to prepare the Food activity and example results collected during the Curiosity demo.

  1. How alkyl halide structure affects E2 and SN2 reaction barriers: E2 reactions are as sensitive as SN2 reactions.

    Science.gov (United States)

    Rablen, Paul R; McLarney, Brett D; Karlow, Brandon J; Schneider, Jean E

    2014-02-07

    High-level electronic structure calculations, including a continuum treatment of solvent, are employed to elucidate and quantify the effects of alkyl halide structure on the barriers of SN2 and E2 reactions. In cases where such comparisons are available, the results of these calculations show close agreement with solution experimental data. Structural factors investigated include α- and β-methylation, adjacency to unsaturated functionality (allyl, benzyl, propargyl, α to carbonyl), ring size, and α-halogenation and cyanation. While the influence of these factors on SN2 reactivity is mostly well-known, the present study attempts to provide a broad comparison of both SN2 and E2 reactivity across many cases using a single methodology, so as to quantify relative reactivity trends. Despite the fact that most organic chemistry textbooks say far more about how structure affects SN2 reactions than about how it affects E2 reactions, the latter are just as sensitive to structural variation as are the former. This sensitivity of E2 reactions to structure is often underappreciated.

  2. The Retinoblastoma Tumor Suppressor Protein (pRb)/E2 Promoter Binding Factor 1 (E2F1) Pathway as a Novel Mediator of TGFβ-induced Autophagy.

    Science.gov (United States)

    Korah, Juliana; Canaff, Lucie; Lebrun, Jean-Jacques

    2016-01-29

    TGFβ is a multifunctional cytokine that regulates cell proliferation, cell immortalization, and cell death, acting as a key homeostatic mediator in various cell types and tissues. Autophagy is a programmed mechanism that plays a pivotal role in controlling cell fate and, consequently, many physiological and pathological processes, including carcinogenesis. Although autophagy is often considered a pro-survival mechanism that renders cells viable in stressful conditions and thus might promote tumor growth, emerging evidence suggests that autophagy is also a tumor suppressor pathway. The relationship between TGFβ signaling and autophagy is context-dependent and remains unclear. TGFβ-mediated activation of autophagy has recently been suggested to contribute to the growth inhibitory effect of TGFβ in hepatocarcinoma cells. In the present study, we define a novel process of TGFβ-mediated autophagy in cancer cell lines of various origins. We found that autophagosome initiation and maturation by TGFβ is dependent on the retinoblastoma tumor suppressor protein/E2 promoter binding factor (pRb/E2F1) pathway, which we have previously established as a critical signaling axis leading to various TGFβ tumor suppressive effects. We further determined that TGFβ induces pRb/E2F1-dependent transcriptional activation of several autophagy-related genes. Together, our findings reveal that TGFβ induces autophagy through the pRb/E2F1 pathway and transcriptional activation of autophagy-related genes and further highlight the central relevance of the pRb/E2F1 pathway downstream of TGFβ signaling in tumor suppression.

  3. The vallue of AMH,FSH,E2 in POF%AMH、FSH、E2在卵巢早衰诊断中的价值

    Institute of Scientific and Technical Information of China (English)

    徐琳; 任莉; 韩雪松; 刘攀

    2011-01-01

    目的 研究顺铂所致化疗损伤性卵巢早衰大鼠血清AMH、FSH、E2水平变化,探讨血清AMH、FSH、E2能否作为评估成年雌性大鼠卵巢储备的早期预测指标.方法 通过给成熟雌性SD大鼠腹腔注射生理盐水、4.5mg/kg和6.0mg/kg顺铂,建立大鼠化疗损伤性卵巢早衰模型.检测血清AMH、FSH、E2水平.结果 腹腔注射后,大鼠血清AMH水平均明显降低;血清E2水平与对照组相比,低剂量组明显升高,高剂量组无统计学意义,高剂量组与低剂量组相比明显降低;血清FSH水平:低剂量组与时照组相比无统计学意义,高剂量组与对照组、低剂量组相比均升高.腹腔注射前后,各顺铂组血清AMH水平注射后均较注射前明显降低;血清E2水平于注射低剂量顺铂后升高,而注射高剂量顺铂后差异无统计学意义.各顺铂组血清FSH水平注射后均较注射前明显升高.结论 顺铂所致的卵巢损害早期血清E2代偿性升高,AMH明显降低,此两种激素的变化早于FSH的变化.血清E2的升高和AMH的降低可以作为暴露于化疗后的卵巢损害的早期预测指标,两者结合起来将有助于早期诊断卵巢早衰.%Obejective: To study the changes of serum AMH, FSH, E2 in rats of cisplatin - induced premature ovarian failure in order to investigate serum AMH, FSH, E2 which can be assessed to the early prediction indicators of ovarian reserve in adult female rats. Methods: Adult female SD rats were treated with saline, 4. 5mg/kg and 6. 0mg/kg cisplatin by intraperitoneal injection to establish successfully in rat model of chemotherapy induced premature ovarian failure. The serum AMH, FSH, E2 were measured. Results: The serum AMH levels were significantly lower in both cisplatin groups after intraperitoneal injection; The serum E2 levels were significantly higher in low - dose group but there were not significantly in high - dose group compared with the control group. The serum E2 levels were significantly

  4. Phosphorylation regulates binding of the human papillomavirus type 8 E2 protein to host chromosomes.

    Science.gov (United States)

    Sekhar, Vandana; McBride, Alison A

    2012-09-01

    The papillomavirus E2 proteins are indispensable for the viral life cycle, and their functions are subject to tight regulation. The E2 proteins undergo posttranslational modifications that regulate their properties and roles in viral transcription, replication, and genome maintenance. During persistent infection, the E2 proteins from many papillomaviruses act as molecular bridges that tether the viral genomes to host chromosomes to retain them within the host nucleus and to partition them to daughter cells. The betapapillomavirus E2 proteins bind to pericentromeric regions of host mitotic chromosomes, including the ribosomal DNA loci. We recently reported that two residues (arginine 250 and serine 253) within the chromosome binding region of the human papillomavirus type 8 (HPV8) E2 protein are required for this binding. In this study, we show that serine 253 is phosphorylated, most likely by protein kinase A, and this modulates the interaction of the E2 protein with cellular chromatin. Furthermore, we show that this phosphorylation occurs in S phase, increases the half-life of the E2 protein, and promotes chromatin binding from S phase through mitosis.

  5. Production of secondary metabolite E2.2 from Phaleria macrocarpa endophytic fungus

    Institute of Scientific and Technical Information of China (English)

    Beatrix Trikurnia Gasong; Raymond Rubianto Tjandrawinata

    2016-01-01

    Objective: To isolate new endophytic fungus from Phaleria macrocarpa (P. macrocarpa) that is able to produce E2.2 compound. Methods: Endophytic fungi were isolated from P. macrocarpa. Morphological and molecular identification was done to determine the species of the endophytic fungus. High performance liquid chromatography was used to determine the ability of this fungus to produce E2.2 compound and to quantify the total yield of E2.2 from fungal fermen-tation. Fermentation process was optimized by observing suitable medium, pH and length of fermentation process. Phloroglucinol and gallic acid addition were examined to determine the effect of each compound on E2.2 production. Results: One endophytic fungus was successfully isolated from P. macrocarpa plant. Morphological and molecular identification showed that it was a Colletotrichum gloeo-sporioides which belonged to Glomerellaceae family. This fungus showed highest pro-duction of E2.2 when incubated in potato dextrose broth with initial pH value of the medium at 5, and was incubated for 15 days. Phloroglucinol was found to better enhance E2.2 production. Conclusions: Colletotrichum gloeosporioides found in P. macrocarpa plant is prom-ising as a potential alternative source of E2.2.

  6. Repression of androgen receptor transcription through the E2F1/DNMT1 axis.

    Directory of Open Access Journals (Sweden)

    Conrad David Valdez

    Full Text Available Although androgen receptor (AR function has been extensively studied, regulation of the AR gene itself has been much less characterized. In this study, we observed a dramatic reduction in the expression of androgen receptor mRNA and protein in hyperproliferative prostate epithelium of keratin 5 promoter driven E2F1 transgenic mice. To confirm an inhibitory function for E2F1 on AR transcription, we showed that E2F1 inhibited the transcription of endogenous AR mRNA, subsequent AR protein, and AR promoter activity in both human and mouse epithelial cells. E2F1 also inhibited androgen-stimulated activation of two AR target gene promoters. To elucidate the molecular mechanism of E2F-mediated inhibition of AR, we evaluated the effects of two functional E2F1 mutants on AR promoter activity and found that the transactivation domain appears to mediate E2F1 repression of the AR promoter. Because DNMT1 is a functional intermediate of E2F1 we examined DNMT1 function in AR repression. Repression of endogenous AR in normal human prostate epithelial cells was relieved by DNMT1 shRNA knock down. DNMT1 was shown to be physically associated within the AR minimal promoter located 22 bps from the transcription start site; however, methylation remained unchanged at the promoter regardless of DNMT1 expression. Taken together, our results suggest that DNMT1 operates either as a functional intermediary or in cooperation with E2F1 inhibiting AR gene expression in a methylation independent manner.

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

    Science.gov (United States)

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

    2009-01-01

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

  8. The dynamic properties of the Hepatitis C Virus E2 envelope protein unraveled by molecular dynamics.

    Science.gov (United States)

    Barone, Daniela; Balasco, Nicole; Autiero, Ida; Vitagliano, Luigi

    2017-03-01

    Hepatitis C Virus (HCV) is one of the most persistent human viruses. Although effective therapeutic approaches have been recently discovered, their use is limited by the elevated costs. Therefore, the development of alternative/complementary strategies is an urgent need. The E2 glycoprotein, the most immunogenic HCV protein, and its variants represent natural candidates to achieve this goal. Here we report an extensive molecular dynamics (MD) analysis of the intrinsic properties of E2. Our data provide interesting clues on the global and local intrinsic dynamic features of the protein. Present MD data clearly indicate that E2 combines a flexible structure with a network of covalent bonds. Moreover, the analysis of the two most important antigenic regions of the protein provides some interesting insights into their intrinsic structural and dynamic properties. Our data indicate that a fluctuating β-hairpin represents a populated state by the region E2(412-423). Interestingly, the analysis of the epitope E2(427-446) conformation, that undergoes a remarkable rearrangement in the simulation, has significant similarities with the structure that the E2(430-442) fragment adopts in complex with a neutralizing antibody. Present data also suggest that the strict conservation of Gly436 in E2 protein of different HCV genotypes is likely dictated by structural restraints. Moreover, the analysis of the E2(412-423) flexibility provides insights into the mechanisms that some antibodies adopt to anchor Trp437 that is fully buried in E2. Finally, the present investigation suggests that MD simulations should systematically complement crystallographic studies on flexible proteins that are studied in combination with antibodies.

  9. Effect of a dimer of nanoparticles on the linewidth of forbidden E2 transitions

    Science.gov (United States)

    Guzatov, D. V.; Klimov, V. V.

    2016-07-01

    In the framework of classical electrodynamics we have obtained and investigated analytical expressions for the radiation linewidth of forbidden E2 transitions in an atom located near a dimer of spherical particles. It is shown that the material of particles, their location and size have a significant effect on the linewidth of the E2 transition in the atom. It is found that in the gap between metal spherical nanoparticles, the linewidth of E2 transitions in the atom can take on substantially larger values than in the case of an atom near a single metal nanoparticle.

  10. Silencing of E2F3 suppresses tumor growth of Her2+ breast cancer cells by restricting mitosis.

    Science.gov (United States)

    Lee, Miyoung; Oprea-Ilies, Gabriela; Saavedra, Harold I

    2015-11-10

    The E2F transcriptional activators E2F1, E2F2 and E2F3a regulate many important cellular processes, including DNA replication, apoptosis and centrosome duplication. Previously, we demonstrated that silencing E2F1 or E2F3 suppresses centrosome amplification (CA) and chromosome instability (CIN) in Her2+ breast cancer cells without markedly altering proliferation. However, it is unknown whether and how silencing a single E2F activator, E2F3, affects malignancy of human breast cancer cells. Thus, we injected HCC1954 Her2+ breast cancer cells silenced for E2F3 into mammary fat pads of immunodeficient mice and demonstrated that loss of E2F3 retards tumor growth. Surprisingly, silencing of E2F3 led to significant reductions in mitotic indices relative to vector controls, while the percentage of cells undergoing S phase were not affected. Nek2 is a mitotic kinase commonly upregulated in breast cancers and a critical regulator of Cdk4- or E2F-mediated CA. In this report, we found that Nek2 overexpression rescued back the CA caused by silencing of shE2F3. However, the effects of Nek2 overexpression in affecting tumor growth rates of shE2F3 and shE2F3; GFP cells were inconclusive. Taken together, our results indicate that E2F3 silencing decreases mammary tumor growth by reducing percentage of cells undergoing mitosis.

  11. A single mutation in the E2 glycoprotein important for neurovirulence influences binding of Sindbis virus to neuroblastoma cells

    NARCIS (Netherlands)

    Lee, PY; Knight, R; Smit, JM; Wilschut, J; Griffin, DE

    2002-01-01

    The amino acid at position 55 of the E2 glycoprotein (E2(55)) of Sindbis virus (SV) is a critical determinant of SV neurovirulence in mice. Recombinant virus strain TE (E2(55) = histidine) differs only at this position from virus strain 633 (E2(55) = glutamine), yet TE is considerably more neuroviru

  12. The Rimland E-2 Assessment of Autism: Its Relationship with Other Measures.

    Science.gov (United States)

    Deckner, C. William; And Others

    1982-01-01

    Scores of mental age, IQ, social competence, and language functioning of 17 autistic or autistic-like students (5 to 13 years old) were analyzed and compared with scores on B. Rimland's E-2 Scale. (CL)

  13. Expression and Characterization of HGV E2 cDNA in Pichia pastoris

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    A 559 base pair fragment of cDNA locating at the putative E2 region of GBV-C/HGV was in-serted into Pichia pastoris expression vector pPICgK in the reading frame of α-factor secreting signal pep-tide. The recombinant expression plasmid pPIC9K-E2 was introduced into P. pastoris GSll5 with electro-poration and recombined with the host genome by homological recombination. The His+Mut+ recombinantyeasts were selected and cultivated in the BMMY medium. After 3 days induction with 0. 5% methanol,the target protein(E2) accumulated up to 30% of total proteins in the supernatant. The expressed E2 pro-tein was proved possessing antigenicity and high specificity with Western blot and ELISA probed with serafrom the immunized rabbits and the patients infected by GBV-C/HGV.

  14. CMIP5 historical simulations (1850-2012) with GISS ModelE2

    National Research Council Canada - National Science Library

    Ron L Miller; Gavin A Schmidt; Larissa S Nazarenko; Nick Tausnev; Susanne E Bauer; Anthony D DelGenio; Max Kelley; Ken K Lo; Reto Ruedy; Drew T Shindell; Igor Aleinov; Mike Bauer; Rainer Bleck; Vittorio Canuto; Yonghua Chen; Ye Cheng; Thomas L Clune; Greg Faluvegi; James E Hansen; Richard J Healy; Nancy Y Kiang; Dorothy Koch; Andy A Lacis; Allegra N LeGrande; Jean Lerner; Surabi Menon; Valdar Oinas; Carlos Perez Garcia-Pando; Jan P Perlwitz; Michael J Puma; David Rind; Anastasia Romanou; Gary L Russell; Makiko Sato; Shan Sun; Kostas Tsigaridis; Nadine Unger; Apostolos Voulgarakis; Mao-Sung Yao; Jinlun Zhang

    2014-01-01

    Observations of climate change during the CMIP5 extended historical period (1850-2012) are compared to trends simulated by six versions of the NASA Goddard Institute for Space Studies ModelE2 Earth System Model...

  15. CMIP5 historical simulations (1850–2012) with GISS ModelE2

    National Research Council Canada - National Science Library

    Miller, Ron L; Schmidt, Gavin A; Nazarenko, Larissa S; Tausnev, Nick; Bauer, Susanne E; DelGenio, Anthony D; Kelley, Max; Lo, Ken K; Ruedy, Reto; Shindell, Drew T; Aleinov, Igor; Bauer, Mike; Bleck, Rainer; Canuto, Vittorio; Chen, Yonghua; Cheng, Ye; Clune, Thomas L; Faluvegi, Greg; Hansen, James E; Healy, Richard J; Kiang, Nancy Y; Koch, Dorothy; Lacis, Andy A; LeGrande, Allegra N; Lerner, Jean; Menon, Surabi; Oinas, Valdar; Pérez García‐Pando, Carlos; Perlwitz, Jan P; Puma, Michael J; Rind, David; Romanou, Anastasia; Russell, Gary L; Sato, Makiko; Sun, Shan; Tsigaridis, Kostas; Unger, Nadine; Voulgarakis, Apostolos; Yao, Mao‐Sung; Zhang, Jinlun

    2014-01-01

    Observations of climate change during the CMIP5 extended historical period (1850–2012) are compared to trends simulated by six versions of the NASA Goddard Institute for Space Studies ModelE2 Earth System Model...

  16. The RB/E2F pathway and regulation of RNA processing

    Energy Technology Data Exchange (ETDEWEB)

    Ahlander, Joseph [Department of Molecular and Cellular Biology, 1007 East Lowell Street, University of Arizona, Tucson, AZ 85721 (United States); Bosco, Giovanni, E-mail: gbosco@email.arizona.edu [Department of Molecular and Cellular Biology, 1007 East Lowell Street, University of Arizona, Tucson, AZ 85721 (United States)

    2009-07-03

    The retinoblastoma tumor suppressor protein (RB) is inactivated in a majority of cancers. RB restricts cell proliferation by inhibiting the E2F family of transcription factors. The current model for RB/E2F function describes its role in regulating transcription at gene promoters. Whether the RB or E2F proteins might play a role in gene expression beyond transcription initiation is not well known. This review describes evidence that points to a novel role for the RB/E2F network in the regulation of RNA processing, and we propose a model as a framework for future research. The elucidation of a novel role of RB in RNA processing will have a profound impact on our understanding of the role of this tumor suppressor family in cell and developmental biology.

  17. Amplification of the E2F1 transcription factor gene in the HEL erythroleukemia cell line

    DEFF Research Database (Denmark)

    Saito, M; Helin, K; Valentine, M B;

    1995-01-01

    and overexpressed in HEL erythroleukemia cells and translocated to other chromosomes in several established human leukemia cell lines. This study provides the first evidence of gene amplification involving a member of the E2F family of transcription factors. We propose that E2F1 overexpression in erythroid......The E2F transcription factor plays an important regulatory role in cell proliferation, mediating the expression of genes whose products are essential for inducing resting cells to enter the cell cycle and synthesize DNA. To investigate the possible involvement of E2F in hematopoietic malignancies...... progenitors may stimulate abnormal cell proliferation by overriding negative regulatory signals mediated by tumor suppressor proteins such as pRb....

  18. The E2A-HLF Oncoprotein Activates Groucho-Related Genes and Suppresses Runx1

    Science.gov (United States)

    Dang, Jinjun; Inukai, Takeshi; Kurosawa, Hidemitsu; Goi, Kumiko; Inaba, Toshiya; Lenny, Noel T.; Downing, James R.; Stifani, Stefano; Look, A. Thomas

    2001-01-01

    The E2A-HLF fusion gene, formed by the t(17;19)(q22;p13) chromosomal translocation in leukemic pro-B cells, encodes a chimeric transcription factor consisting of the transactivation domain of E2A linked to the bZIP DNA-binding and protein dimerization domain of hepatic leukemia factor (HLF). This oncoprotein blocks apoptosis induced by growth factor deprivation or irradiation, but the mechanism for this effect remains unclear. We therefore performed representational difference analysis (RDA) to identify downstream genetic targets of E2A-HLF, using a murine FL5.12 pro-B cell line that had been stably transfected with E2A-HLF cDNA under the control of a zinc-regulated metallothionein promoter. Two RDA clones, designated RDA1 and RDA3, were differentially upregulated in E2A-HLF-positive cells after zinc induction. The corresponding cDNAs encoded two WD40 repeat-containing proteins, Grg2 and Grg6. Both are related to the Drosophila protein Groucho, a transcriptional corepressor that lacks DNA-binding activity on its own but can act in concert with other proteins to regulate embryologic development of the fly. Expression of both Grg2 and Grg6 was upregulated 10- to 50-fold by E2A-HLF. Immunoblot analysis detected increased amounts of two additional Groucho-related proteins, Grg1 and Grg4, in cells expressing E2A-HLF. A mutant E2A-HLF protein with a disabled DNA-binding region also mediated pro-B cell survival and activated Groucho-related genes. Among the transcription factors known to interact with Groucho-related protein, only RUNX1 was appreciably downregulated by E2A-HLF. Our results identify a highly conserved family of transcriptional corepressors that are activated by E2A-HLF, and they suggest that downregulation of RUNX1 may contribute to E2A-HLF-mediated leukemogenesis. PMID:11486032

  19. Cloning and functional characterisation of avian transcription factor E2A

    Directory of Open Access Journals (Sweden)

    Meyer Kerstin B

    2004-06-01

    Full Text Available Abstract Background During B lymphocyte development the E2A gene is a critical regulator of cell proliferation and differentiation. With regards to the immunoglobulin genes the E2A proteins contribute to the regulation of gene rearrangement, expression and class switch recombination. We are now using the chicken cell line DT40 as a model system to further analyse the function of E2A. Results Here we report the cloning and functional analysis of the transcription factor E2A from chicken. Using RACE PCR on the chicken lymphoma cell line DT40 we have isolated full-length clones for the two E2A splice variants E12 and E47. Sequence conservation between the human and chicken proteins is extensive: the basic-helix-loop-helix DNA binding domain of human and chicken E47 and E12 are 93% and 92% identical, respectively. In addition high levels of conservation are seen in activation domain I, the potential NLS and the ubiquitin ligase interaction domain. E2A is expressed in a variety of tissues in chicken, with higher levels of expression in organs rich in immune cells. We demonstrate that chicken E12 and E47 proteins are strong transcriptional activators whose function depends on the presence of activation domain I. As in mammals, the dominant negative proteins Id1 and Id3 can inhibit the function of chicken E47. Conclusions The potential for homologous recombination in DT40 allows the genetic dissection of biochemical pathways in somatic cells. With the cloning of avian E2A and the recent description of an in vitro somatic hypermutation assay in this cell line, it should now be possible to dissect the potential role of E2A in the regulation of somatic hypermutation and gene conversion.

  20. Cloning and functional characterisation of avian transcription factor E2A.

    Science.gov (United States)

    Conlon, Thomas M; Meyer, Kerstin B

    2004-06-14

    During B lymphocyte development the E2A gene is a critical regulator of cell proliferation and differentiation. With regards to the immunoglobulin genes the E2A proteins contribute to the regulation of gene rearrangement, expression and class switch recombination. We are now using the chicken cell line DT40 as a model system to further analyse the function of E2A. Here we report the cloning and functional analysis of the transcription factor E2A from chicken. Using RACE PCR on the chicken lymphoma cell line DT40 we have isolated full-length clones for the two E2A splice variants E12 and E47. Sequence conservation between the human and chicken proteins is extensive: the basic-helix-loop-helix DNA binding domain of human and chicken E47 and E12 are 93% and 92% identical, respectively. In addition high levels of conservation are seen in activation domain I, the potential NLS and the ubiquitin ligase interaction domain. E2A is expressed in a variety of tissues in chicken, with higher levels of expression in organs rich in immune cells. We demonstrate that chicken E12 and E47 proteins are strong transcriptional activators whose function depends on the presence of activation domain I. As in mammals, the dominant negative proteins Id1 and Id3 can inhibit the function of chicken E47. The potential for homologous recombination in DT40 allows the genetic dissection of biochemical pathways in somatic cells. With the cloning of avian E2A and the recent description of an in vitro somatic hypermutation assay in this cell line, it should now be possible to dissect the potential role of E2A in the regulation of somatic hypermutation and gene conversion.

  1. Regression of human papillomavirus intraepithelial lesions is induced by MVA E2 therapeutic vaccine.

    Science.gov (United States)

    Rosales, Ricardo; López-Contreras, Mario; Rosales, Carlos; Magallanes-Molina, Jose-Roberto; Gonzalez-Vergara, Roberto; Arroyo-Cazarez, Jose Martin; Ricardez-Arenas, Antonio; Del Follo-Valencia, Armando; Padilla-Arriaga, Santiago; Guerrero, Miriam Veronica; Pirez, Miguel Angel; Arellano-Fiore, Claudia; Villarreal, Freddy

    2014-12-01

    Human papilloma viruses can induce warts, condylomas, and other intraepithelial cervical lesions that can progress to cancer. Cervical cancer is a serious problem in developing countries because early detection is difficult, and thus proper early treatment is many times missing. In this phase III clinical trial, we evaluated the potential use of MVA E2 recombinant vaccinia virus to treat intraepithelial lesions associated with papillomavirus infection. A total of 1176 female and 180 male patients with intraepithelial lesions were studied. They were injected with 10(7) MVA E2 virus particles directly into their uterus, urethra, vulva, or anus. Patients were monitored by colposcopy and cytology. Immune response was determined by measuring the antibody titer against MVA E2 virus and by analyzing the cytotoxic activity against cancer cells bearing papillomavirus DNA. Papillomavirus was determined by the Hybrid Capture method or by polymerase chain reaction analysis. By histology, 1051 (89.3%) female patients showed complete elimination of lesions after treatment with MVA E2. In 28 (2.4%) female patients, the lesion was reduced to CIN 1. Another 97 (8.3%) female patients presented isolated koilocytes after treatment. In men, all lesions were completely eliminated. All MVA E2-treated patients developed antibodies against the MVA E2 vaccine and generated a specific cytotoxic response against papilloma-transformed cells. Papillomavirus DNA was not detected after treatment in 83% of total patients treated. MVA E2 did not generate any apparent side effects. These data suggest that therapeutic vaccination with MVA E2 vaccine is an excellent candidate to stimulate the immune system and generate regression in intraepithelial lesions when applied locally.

  2. Mitogenic Sonic hedgehog signaling drives E2F1-dependent lipogenesis in progenitor cells and Medulloblastoma

    OpenAIRE

    Bhatia, Bobby; Hsieh, Michael; Kenney, Anna Marie; Nahlé, Zaher

    2010-01-01

    Deregulation of the Rb/E2F tumor suppressor complex and aberrantion of Sonic hedgehog (Shh) signaling are documented across the spectrum of human malignancies. Exaggerated de novo lipid synthesis is also found in certain highly proliferative, aggressive tumors. Here, we show that in Shh-driven medulloblastomas, Rb is inactivated and E2F1 is up-regulated, promoting lipogenesis. Extensive lipid accumulation and elevated levels of the lipogenic enzyme FASN mark those tumors. In primary cerebella...

  3. Regression of Human Papillomavirus Intraepithelial Lesions Is Induced by MVA E2 Therapeutic Vaccine

    Science.gov (United States)

    López-Contreras, Mario; Rosales, Carlos; Magallanes-Molina, Jose-Roberto; Gonzalez-Vergara, Roberto; Arroyo-Cazarez, Jose Martin; Ricardez-Arenas, Antonio; del Follo-Valencia, Armando; Padilla-Arriaga, Santiago; Guerrero, Miriam Veronica; Pirez, Miguel Angel; Arellano-Fiore, Claudia; Villarreal, Freddy

    2014-01-01

    Abstract Human papilloma viruses can induce warts, condylomas, and other intraepithelial cervical lesions that can progress to cancer. Cervical cancer is a serious problem in developing countries because early detection is difficult, and thus proper early treatment is many times missing. In this phase III clinical trial, we evaluated the potential use of MVA E2 recombinant vaccinia virus to treat intraepithelial lesions associated with papillomavirus infection. A total of 1176 female and 180 male patients with intraepithelial lesions were studied. They were injected with 107 MVA E2 virus particles directly into their uterus, urethra, vulva, or anus. Patients were monitored by colposcopy and cytology. Immune response was determined by measuring the antibody titer against MVA E2 virus and by analyzing the cytotoxic activity against cancer cells bearing papillomavirus DNA. Papillomavirus was determined by the Hybrid Capture method or by polymerase chain reaction analysis. By histology, 1051 (89.3%) female patients showed complete elimination of lesions after treatment with MVA E2. In 28 (2.4%) female patients, the lesion was reduced to CIN 1. Another 97 (8.3%) female patients presented isolated koilocytes after treatment. In men, all lesions were completely eliminated. All MVA E2–treated patients developed antibodies against the MVA E2 vaccine and generated a specific cytotoxic response against papilloma-transformed cells. Papillomavirus DNA was not detected after treatment in 83% of total patients treated. MVA E2 did not generate any apparent side effects. These data suggest that therapeutic vaccination with MVA E2 vaccine is an excellent candidate to stimulate the immune system and generate regression in intraepithelial lesions when applied locally. PMID:25275724

  4. 基于LPC2106的IIC总线E2PROM的应用%The Application of IIC E2PROM based on LPC2106

    Institute of Scientific and Technical Information of China (English)

    肖建辉; 袁易君

    2010-01-01

    本文利用Proteus软件仿真的特点.提出在此平台上仿真设计IIC总线E2PROM芯片AT24C02在Arm7内核LPC2106中的应用,用实例说明了LPC21XX系列单片机的标准IIC接口的使用.

  5. Comparison of prostaglandin E2 gel, prostaglandin E2 pessary and extra-amniotic saline infusion with oxytocin for induction of labour.

    Science.gov (United States)

    Qamar, Saima; Bashir, Adeela; Ibrar, Faiza

    2012-01-01

    Induction of labour is the intentional initiation of cervical ripening and uterine contraction for the purpose of accomplishing delivery, prior to onset of spontaneous parturition. This study was conducted to compare maternal and neonatal outcome in women induced with Prostaglandin E2 gel, Prostaglandin E2 pessary and extra-amniotic saline infusion with oxytocin at Bishops score prostaglandin gel, prostaglandinE2 pessary and extra-amniotic saline infusion with oxytocin) were collected. Systematic sampling was done. First woman admitted was induced with prostaglandin gel, the second one with prostaglandin pessary and the third was induced with extra amniotic saline infusion and oxytocin. The most common indication for induction was post dates followed by PIH. The induction labour interval was less in EASI with oxytocin group (5.18 +/- 3.4) hours, as compared to prostaglandin pessary (8.81 +/- 5.60) hours and prostaglandin gel (8.32 +/- 5.18) hours. Induction delivery interval in EASI with oxytocin was (10 +/- 5.6) hours as compared to prostaglandin pessary (14 +/- 6.3) hours and prostaglandin gel (13 +/- 7.1) hours. This difference was statistically significant. The primigravidas had longer duration of labour than multigravidas. Induction labour interval in primigravidas was (8.2 +/- 5.1) hours while in multigravidas it was (6.7 +/- 5.02) hours. Induction delivery interval was also more in primigravidas (13.6 +/- 6.80) hours as compared to multigravidas (11.4 +/- 6.20) hours. Vaginal delivery rate was 89.2% while the caesarean section rate was 10.4%. The most common indication for caesarean section was foetal distress. There was no significant difference in perinatal morbidity and mortality in the three groups. EASI with oxytocin is a better method of induction than prostaglandin E2 gel and pessary. Moreover it is more economical in our country.

  6. Broadband Data Converter Technical Presentation at CERN by e2v and ANATEC

    CERN Multimedia

    FI Department

    2008-01-01

    12 September 2008 10:00 – 11:45, Room B Main Building. Technical presentation e2v and ANATEC. e2v Grenoble (http://www.e2v.com) designs and manufactures standard and custom low latency and high speed ADCs that are true single core ADCs. Sampling speeds without interleaving range from 500MSPS to beyond 2.2GSPS with resolution ranging from 8 bits to 10bits and input bandwidths exceed 2.5GHz. With built-in interleaving feature some e2v multi-channel ADCs can reach 5GSPS sampling speed per device. e2v is known to offer 8, 10 and 12 bit ADCs with very low latency, exceptional linearity at high input frequency, that is in the 2nd Nyquist zone and beyond for some devices. This seminar will cover the following topics: Overview of existing standard 8bit, 10bit and 12bit ADCs up to 5GSPS. Key aspects of the e2v broadband ADC architecture. Benefits of true single core ADCs without internal interleaving. Choice of several possibilities to drive the ADC inputs, DC coupling at high spe...

  7. Transcriptional control of stem cell fate by E2Fs and Pocket Proteins

    Directory of Open Access Journals (Sweden)

    Lisa Marie Julian

    2015-04-01

    Full Text Available E2F transcription factors and their regulatory partners, the pocket proteins (PPs, have emerged as essential regulators of stem cell fate control in a number of lineages. In mammals, this role extends from both pluripotent stem cells to those encompassing all embryonic germ layers, as well as extra-embryonic lineages. E2F/PP-mediated regulation of stem cell decisions is highly evolutionarily conserved, and is likely a pivotal biological mechanism underlying stem cell homeostasis. This has immense implications for organismal development, tissue maintenance and regeneration. In this article, we discuss the roles of E2F factors and PPs in stem cell populations, focusing on mammalian systems. We discuss emerging findings that position the E2F and PP families as widespread and dynamic epigenetic regulators of cell fate decisions. Additionally, we focus on the ever expanding landscape of E2F/PP target genes, and explore the possibility that E2Fs are not simply regulators of general ‘multi-purpose’ cell fate genes but can execute tissue- and cell type-specific gene regulatory programs.

  8. E2F3 transcription factor: A promising biomarker in lung cancer.

    Science.gov (United States)

    Al Ahmed, Hala Abdel; Nada, Ola

    2017-01-01

    Many researches aiming to explore the pathogenesis of lung cancer have extensively studied the molecular alteration in such disease. In the present study we measured the blood E2F3 mRNA using real-time RT-PCR technique in order to evaluate its clinical significance in early diagnosis and monitoring of lung cancer. This case-control study included 50 lung cancer patients, 20 patients with benign lung diseases and 20 healthy controls. Relative quantification of blood E2F3 mRNA was done by real-time RT-PCR. Blood E2F3 mRNA levels were significantly higher in lung cancer patients when compared to either patients with benign lung diseases or healthy subjects. This elevation was significant in those with metastatic lung cancer as compared to those with localized lung cancer. At a cutoff^{(2-Δ Δ CT)} 1.5, blood E2F3 mRNA was able to distinguish malignant from benign lung conditions with a diagnostic sensitivity of 100%; while at a cutoff^{(2-Δ Δ CT)} 5.3, blood E2F3 mRNA discriminated localized from metastatic lung cancer with a sensitivity of 93.6%. Blood E2F3 mRNA is a sensitive diagnostic marker in lung cancer; moreover, it is a promising prognostic marker capable of efficiently discriminating early from late stages of the disease.

  9. Structural and Antigenic Definition of Hepatitis C Virus E2 Glycoprotein Epitopes Targeted by Monoclonal Antibodies

    Directory of Open Access Journals (Sweden)

    Giuseppe Sautto

    2013-01-01

    Full Text Available Hepatitis C virus (HCV is the major cause of chronic liver disease as well as the major indication for liver transplantation worldwide. Current standard of care is not completely effective, not administrable in grafted patients, and burdened by several side effects. This incomplete effectiveness is mainly due to the high propensity of the virus to continually mutate under the selective pressure exerted by the host immune response as well as currently administered antiviral drugs. The E2 envelope surface glycoprotein of HCV (HCV/E2 is the main target of the host humoral immune response and for this reason one of the major variable viral proteins. However, broadly cross-neutralizing monoclonal antibodies (mAbs directed against HCV/E2 represent a promising tool for the study of virus-host interplay as well as for the development of effective prophylactic and therapeutic approaches. In the last few years many anti-HCV/E2 mAbs have been evaluated in preclinical and clinical trials as possible candidate antivirals, particularly for administration in pre- and post-transplant settings. In this review we summarize the antigenic and structural characteristics of HCV/E2 determined through the use of anti-HCV/E2 mAbs, which, given the absence of a crystal structure of this glycoprotein, represent currently the best tool available.

  10. E2F1-mediated human POMC expression in ectopic Cushing's syndrome.

    Science.gov (United States)

    Araki, Takako; Liu, Ning-Ai; Tone, Yukiko; Cuevas-Ramos, Daniel; Heltsley, Roy; Tone, Masahide; Melmed, Shlomo

    2016-11-01

    Cushing's syndrome is caused by excessive adrenocorticotropic hormone (ACTH) secretion derived from pituitary corticotroph tumors (Cushing disease) or from non-pituitary tumors (ectopic Cushing's syndrome). Hypercortisolemic features of ectopic Cushing's syndrome are severe, and no definitive treatment for paraneoplastic ACTH excess is available. We aimed to identify subcellular therapeutic targets by elucidating transcriptional regulation of the human ACTH precursor POMC (proopiomelanocortin) and ACTH production in non-pituitary tumor cells and in cell lines derived from patients with ectopic Cushing's syndrome. We show that ectopic hPOMC transcription proceeds independently of pituitary-specific Tpit/Pitx1 and demonstrate a novel E2F1-mediated transcriptional mechanism regulating hPOMC We identify an E2F1 cluster binding to the proximal hPOMC promoter region (-42 to +68), with DNA-binding activity determined by the phosphorylation at Ser-337. hPOMC mRNA expression in cancer cells was upregulated (up to 40-fold) by the co-expression of E2F1 and its heterodimer partner DP1. Direct and indirect inhibitors of E2F1 activity suppressed hPOMC gene expression and ACTH by modifying E2F1 DNA-binding activity in ectopic Cushing's cell lines and primary tumor cells, and also suppressed paraneoplastic ACTH and cortisol levels in xenografted mice. E2F1-mediated hPOMC transcription is a potential target for suppressing ACTH production in ectopic Cushing's syndrome. © 2016 Society for Endocrinology.

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

    Directory of Open Access Journals (Sweden)

    Fan Chen

    2015-01-01

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

  12. Heterodimerization of the transcription factors E2F-1 and DP-1 leads to cooperative trans-activation

    DEFF Research Database (Denmark)

    Helin, K; Wu, C L; Fattaey, A R

    1993-01-01

    homolog of DP-1. Human DP-1 and E2F-1 associate both in vivo and in vitro, and this interaction leads to enhanced binding to E2F DNA-binding sites. The association of E2F-1 and DP-1 leads to cooperative activation of an E2F-responsive promoter. Finally, we demonstrate that E2F-1 and DP-1 association...

  13. Knockdown of E2F2 inhibits tumorigenicity, but preserves stemness of human embryonic stem cells.

    Science.gov (United States)

    Suzuki, Daniela Emi; Nakahata, Adriana Miti; Okamoto, Oswaldo Keith

    2014-06-01

    Tumorigenicity of human pluripotent stem cells is a major threat limiting their application in cell therapy protocols. It remains unclear, however, whether suppression of tumorigenic potential can be achieved without critically affecting pluripotency. A previous study has identified hyperexpressed genes in cancer stem cells, among which is E2F2, a gene involved in malignant transformation and stem cell self-renewal. Here we tested whether E2F2 knockdown would affect the proliferative capacity and tumorigenicity of human embryonic stem cells (hESC). Transient E2F2 silencing in hESC significantly inhibited expression of the proto-oncogenes BMI1 and HMGA1, in addition to proliferation of hESC, indicated by a higher proportion of cells in G1, fewer cells in G2/M phase, and a reduced capacity to generate hESC colonies in vitro. Nonetheless, E2F2-silenced cells kept expression of typical pluripotency markers and displayed differentiation capacity in vitro. More importantly, E2F2 knockdown in hESC significantly inhibited tumor growth in vivo, which was considerably smaller than tumors generated from control hESC, although displaying typical teratoma traits, a major indicator of pluripotency retention in E2F2-silenced cells. These results suggest that E2F2 knockdown can inhibit hESC proliferation and tumorigenicity without significantly harming stemness, providing a rationale to future protocols aiming at minimizing risks related to therapeutic application of cells and/or products derived from human pluripotent cells.

  14. ModelE2-TOMAS development and evaluation using aerosol optical depths, mass and number concentrations

    Directory of Open Access Journals (Sweden)

    Y. H. Lee

    2014-09-01

    Full Text Available The TwO-Moment Aerosol Sectional microphysics model (TOMAS has been integrated into the state-of-the-art general circulation model, GISS ModelE2. TOMAS has the flexibility to select a size resolution as well as the lower size cutoff. A computationally efficient version of TOMAS is used here, which has 15 size bins covering 3 nm to 10 μm aerosol dry diameter. For each bin, it simulates the total aerosol number concentration and mass concentrations of sulphate, pure elementary carbon (hydrophobic, mixed elemental carbon (hydrophilic, hydrophobic organic matter, hydrophilic organic matter, sea salt, mineral dust, ammonium, and aerosol-associated water. This paper provides a detailed description of the ModelE2-TOMAS model and evaluates the model against various observations including aerosol precursor gas concentrations, aerosol mass and number concentrations, and aerosol optical depths. Additionally, global budgets in ModelE2-TOMAS are compared with those of other global aerosol models, and the TOMAS model is compared to the default aerosol model in ModelE2, which is a bulk aerosol model. Overall, the ModelE2-TOMAS predictions are within the range of other global aerosol model predictions, and the model has a reasonable agreement with observations of sulphur species and other aerosol components as well as aerosol optical depth. However, ModelE2-TOMAS (as well as the bulk aerosol model cannot capture the observed vertical distribution of sulphur dioxide over the Pacific Ocean possibly due to overly strong convective transport. The TOMAS model successfully captures observed aerosol number concentrations and cloud condensation nuclei concentrations. Anthropogenic aerosol burdens in the bulk aerosol model running in the same host model as TOMAS (ModelE2 differ by a few percent to a factor of 2 regionally, mainly due to differences in aerosol processes including deposition, cloud processing, and emission parameterizations. Larger differences are found

  15. E2F6 Impairs Glycolysis and Activates BDH1 Expression Prior to Dilated Cardiomyopathy

    Science.gov (United States)

    Major, Jennifer L.; Dewan, Aaraf; Salih, Maysoon; Leddy, John J.; Tuana, Balwant S.

    2017-01-01

    Rationale The E2F pathway plays a critical role in cardiac growth and development, yet its role in cardiac metabolism remains to be defined. Metabolic changes play important roles in human heart failure and studies imply the ketogenic enzyme β-hydroxybutyrate dehydrogenase I (BDH1) is a potential biomarker. Objective To define the role of the E2F pathway in cardiac metabolism and dilated cardiomyopathy (DCM) with a focus on BDH1. Methods and Results We previously developed transgenic (Tg) mice expressing the transcriptional repressor, E2F6, to interfere with the E2F/Rb pathway in post-natal myocardium. These Tg mice present with an E2F6 dose dependent DCM and deregulated connexin-43 (CX-43) levels in myocardium. Using the Seahorse platform, a 22% decrease in glycolysis was noted in neonatal cardiomyocytes isolated from E2F6-Tg hearts. This was associated with a 39% reduction in the glucose transporter GLUT4 and 50% less activation of the regulator of glucose metabolism AKT2. The specific reduction of cyclin B1 (70%) in Tg myocardium implicates its importance in supporting glycolysis in the postnatal heart. No changes in cyclin D expression (known to regulate mitochondrial activity) were noted and lipid metabolism remained unchanged in neonatal cardiomyocytes from Tg hearts. However, E2F6 induced a 40-fold increase of the Bdh1 transcript and 890% increase in its protein levels in hearts from Tg pups implying a potential impact on ketolysis. By contrast, BDH1 expression is not activated until adulthood in normal myocardium. Neonatal cardiomyocytes from Wt hearts incubated with the ketone β-hydroxybutyrate (β-OHB) showed a 100% increase in CX-43 protein levels, implying a role for ketone signaling in gap junction biology. Neonatal cardiomyocyte cultures from Tg hearts exhibited enhanced levels of BDH1 and CX-43 and were not responsive to β-OHB. Conclusions The data reveal a novel role for the E2F pathway in regulating glycolysis in the developing myocardium

  16. Relationship between vitamin D, IFN-γ, and E2 levels in systemic lupus erythematosus.

    Science.gov (United States)

    Kokic, V; Martinovic Kaliterna, D; Radic, M; Perkovic, D; Cvek, M; Capkun, V

    2016-03-01

    In this study, we investigated the relationship between vitamin D, interferon-gamma (IFN-γ), and estradiol (E2) in females of childbearing age with inactive systemic lupus erythematosus (SLE). The study included 22 SLE patients, and 21 age- and gender-matched healthy individuals. Serum concentrations of 25-hydroxyvitamin D3 (25(OH)D3), E2, and IFN-γ were measured by radioimmunoassay using the gamma-counter and ELISA. Patients and control subjects were divided into two groups based on their vitamin D levels (25(OH)D3 ≤ 20 ng/mL; 25(OH)D3 > 20 ng/mL). The median values of IFN-γ and E2 were higher in SLE patients compared to the controls, irrespective of vitamin D level (p = 0.001, p = 0.009, p = 0.003, and p = 0.003, respectively). In SLE patients, there was a negative correlation between IFN-γ and 25(OH)D3 (rs = -0.330; p = 0.03) and a positive correlation between IFN-γ and E2 (rs = 0.404; p = 0.007). This study demonstrates an interesting interplay between vitamin D, INF-γ, and E2 in SLE patients with inactive disease.

  17. Conformational Flexibility in the Immunoglobulin-Like Domain of the Hepatitis C Virus Glycoprotein E2

    Directory of Open Access Journals (Sweden)

    Ieva Vasiliauskaite

    2017-05-01

    Full Text Available The hepatitis C virus (HCV glycoprotein E2 is the major target of neutralizing antibodies and is therefore highly relevant for vaccine design. Its structure features a central immunoglobulin (Ig-like β-sandwich that contributes to the binding site for the cellular receptor CD81. We show that a synthetic peptide corresponding to a β-strand of this Ig-like domain forms an α-helix in complex with the anti-E2 antibody DAO5, demonstrating an inside-out flip of hydrophobic residues and a secondary structure change in the composite CD81 binding site. A detailed interaction analysis of DAO5 and cross-competing neutralizing antibodies with soluble E2 revealed that the Ig-like domain is trapped by different antibodies in at least two distinct conformations. DAO5 specifically captures retrovirus particles bearing HCV glycoproteins (HCVpp and infectious cell culture-derived HCV particles (HCVcc. Infection of cells by DAO5-captured HCVpp can be blocked by a cross-competing neutralizing antibody, indicating that a single virus particle simultaneously displays E2 molecules in more than one conformation on its surface. Such conformational plasticity of the HCV E2 receptor binding site has important implications for immunogen design.

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

    Science.gov (United States)

    Schuck, Stephen; Ruse, Cristian; Stenlund, Arne

    2013-07-01

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

  19. PCOS women show significantly higher homocysteine level, independent to glucose and E2 level

    Science.gov (United States)

    Eskandari, Zahra; Sadrkhanlou, Rajab-Ali; Nejati, Vahid; Tizro, Gholamreza

    2016-01-01

    Background: It is reasonable to think that some biochemical characteristics of follicular fluid (FF) surrounding the oocyte may play a critical role in determining the quality of oocyte and the subsequent potential needed to achieve fertilization and embryo development. Objective: This study was carried out to evaluate the levels of FF homocysteine (Hcy) in IVF candidate polycystic ovary syndrome (PCOS) women and any relationships with FF glucose and estradiol (E2) levels. Materials and Methods: In this case control study which was performed in Dr. Tizro Day Care and IVF Center 70 infertile patients were enrolled in two groups: comprising 35 PCOS and 35 non PCOS women. Long protocol was performed for all patients. FF Hcy, glucose and E2 levels were analyzed at the time of oocyte retrieval. Results: It was observed that FF Hcy level was significantly higher in PCOS patients compared with non PCOSs (p<0.01). Observations demonstrated that in PCOS group, the Hcy level increased independent to E2, glucose levels, BMI and age, while the PCOS group showed significantly higher BMI compared with non-PCOS group (p=0.03). However, no significant differences were revealed between groups for FF glucose and E2 levels. Conclusion: Present data showed that although FF glucose and E2 levels were constant in PCOS and non PCOS patients, but the FF Hcy levels in PCOS were significantly increased (p=0.01). PMID:27679823

  20. E2F1 in renal cancer: Mr Hyde disguised as Dr Jekyll?

    Science.gov (United States)

    Tian, Weihua; Cui, Fenggong; Esteban, Miguel A

    2013-10-01

    The transcription factor E2F1 has both oncogenic and tumour suppressor properties, depending on the context. Clarifying the function of E2F1 in different types of cancer is relevant because in those situations in which it acts as an oncogene there may be a route for therapeutic interference. Renal cell carcinoma is the most frequent form of kidney cancer in adults and inactivation of the von Hippel-Lindau (VHL) gene underlies most cases. This malignancy represents a challenge for standard therapies due to drug- and radio-resistance, effects that fit well within the scope of functions of E2F1. A new report by Mans et al postulates that up-regulation of E2F1 in VHL-defective renal cell carcinoma induces cell senescence and can thus be considered a good prognostic factor. Here we discuss these findings in a wider context and propose that E2F1 may actually not play a uniform role in renal cell carcinoma but rather an ambiguous one whose deeper understanding could have practical implications. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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

    Directory of Open Access Journals (Sweden)

    Kamel El Omari

    2013-01-01

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

  2. Synergistic cooperation of MDM2 and E2F1 contributes to TAp73 transcriptional activity

    Energy Technology Data Exchange (ETDEWEB)

    Kasim, Vivi, E-mail: vivikasim78@gmail.com [The Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Huang, Can; Zhang, Jing; Jia, Huizhen; Wang, Yunxia [The Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Yang, Li [The Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); The 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Miyagishi, Makoto [Molecular Composite Medicine Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8566 (Japan); Wu, Shourong, E-mail: shourongwu@hotmail.com [The Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); The 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing 400044 (China)

    2014-07-04

    Highlights: • MDM2 is a novel positive regulator of TAp73 transcriptional activity. • MDM2 colocalizes together and physically interacts with E2F1. • Synergistic cooperation of MDM2 and E2F1 is crucial for TAp73 transcription. • MDM2 regulates TAp73 transcriptional activity in a p53-independent manner. - Abstract: TAp73, a structural homologue of p53, plays an important role in tumorigenesis. E2F1 had been reported as a transcriptional regulator of TAp73, however, the detailed mechanism remains to be elucidated. Here we reported that MDM2-silencing reduced the activities of the TAp73 promoters and the endogenous TAp73 expression level significantly; while MDM2 overexpression upregulated them. We further revealed that the regulation of TAp73 transcriptional activity occurs as a synergistic effect of MDM2 and E2F1, most probably through their physical interaction in the nuclei. Furthermore, we also suggested that MDM2 might be involved in DNA damage-induced TAp73 transcriptional activity. Finally, we elucidated that MDM2-silencing reduced the proliferation rate of colon carcinoma cells regardless of the p53 status. Our data show a synergistic effect of MDM2 and E2F1 on TAp73 transcriptional activity, suggesting a novel regulation pathway of TAp73.

  3. Purification, crystallization and initial crystallographic characterization of brazil-nut allergen Ber e 2

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Feng; Jin, Tengchuan; Howard, Andrew; Zhang, Yu-Zhu, E-mail: zhangy@iit.edu [Department of Biology, Illinois Institute of Technology, Chicago, IL 60616 (United States)

    2007-11-01

    The crystallization of the brazil nut allergen Ber e 2 is reported. Peanut and tree-nut allergies have attracted considerable attention because of their frequency and their lifelong persistence. Brazil-nut (Bertholletia excelsa) allergies have been well documented and the 11S legumin-like seed storage protein Ber e 2 (excelsin) is one of the two known brazil-nut allergens. In this study, Ber e 2 was extracted from brazil-nut kernels and purified to high purity by crystalline precipitation and gel-filtration chromatography. Well diffracting single crystals were obtained using the hanging-drop vapour-diffusion method. A molecular-replacement structural solution has been obtained. Refinement of the structure is currently under way.

  4. Distinct phosphorylation events regulate p130- and p107-mediated repression of E2F-4

    DEFF Research Database (Denmark)

    Farkas, Thomas; Hansen, Klaus; Holm, Karin;

    2002-01-01

    sites selectively targeted by cyclin D-Cdk4(6) kinases. Here we assessed the effects of alanine substitution at the individual or combined Cdk4(6)-specific sites in p130, compared with homologous sites in p107 (Thr(369)/Ser(650)/Ser(964)). In U-2-OS cells, the triple p107(DeltaCdk4)* mutant strongly...... inhibited E2F-4 activity and imposed a G(1) arrest resistant to cyclin D1 coexpression. In contrast, the p130(DeltaCdk4) mutant still responded to cyclin D1, suggesting the existence of additional phosphorylation sites critical for E2F-4 regulation. Extensive mutagenesis, sensitive E2F reporter assays...

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

    CERN Document Server

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

    2016-01-01

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

  6. DIVA vaccine properties of the live chimeric pestivirus strain CP7_E2gif

    DEFF Research Database (Denmark)

    von Rosen, Tanya; Rangelova, Desislava Yordanova; Nielsen, Jens

    2014-01-01

    Live modified vaccines to protect against classical swine fever virus (CSFV), based on chimeric pestiviruses, have been developed to enable serological Differentiation of Infected from Vaccinated Animals (DIVA). In this context, the chimeric virus CP7_E2gif vaccine candidate is unique as it does...... not include any CSFV components. In the present study, the DIVA vaccine properties of CP7_E2gif were evaluated in comparison to the conventional live attenuated Riemser C-strain vaccine. Sera and tonsil samples obtained from pigs immunised with these two vaccines were analysed. No viral RNA was found in serum...... after vaccination with CP7_E2gif, whereas some serum samples from C-strain vaccinated animals were positive. In both vaccinated groups, individual viral RNA-positive tonsil samples were detected in animals euthanised between 7 and 21 days post vaccination. Furthermore, serum samples from these animals...

  7. On the Equivalence of Experimental B(E2) Values Determined by Various Techniques

    CERN Document Server

    Birch, M; Singh, B

    2016-01-01

    We establish the equivalence of the various techniques for measuring B(E2) values using a statistical analysis. Data used in this work come from the re- cent compilation by B. Pritychenko et al., At. Data Nucl. Data Tables 107 (2016). We consider only those nuclei for which the B(E2) values were measured by at least two different methods, with each method being independently performed at least twice. Our results indicate that most prevalent methods of measuring B(E2) values are equivalent, with some weak evidence that Doppler-shift attenuation method (DSAM) measurements may differ from Coulomb excitation (CE) and nuclear resonance fuorescence (NRF) measurements. However, such an evidence appears to arise from discrepant DSAM measurements of the lifetimes for 60Ni and some Sn nuclei rather than a systematic deviation in the method itself.

  8. e2v CMOS and CCD sensors and systems for astronomy

    Science.gov (United States)

    Jorden, P. R.; Jerram, P. A.; Fryer, M.; Stefanov, K. D.

    2017-07-01

    e2v designs and manufactures a wide range of sensors for space and astronomy applications. This includes high performance CCDs for X-ray, visible and near-IR wavelengths. In this paper we illustrate the maturity of CMOS capability for these applications; examples are presented together with performance data. The majority of e2v sensors for these applications are back-thinned for highest spectral response and designed for very low read-out noise; the combination delivers high signal to noise ratio in association with a variety of formats and package designs. The growing e2v capability in delivery of sub-systems and cryogenic cameras is illustrated—including the 1.2 Giga-pixel J-PAS camera system.

  9. [Research progress in roles of high-risk human papillomavirus E2 protein].

    Science.gov (United States)

    Wu, En-Qi; Tang, Yuan-Yu

    2014-03-01

    High-risk human papillomavirus (HPV) is the principal cause of various cancers including cervical cancer, anal cancer, vulvar cancer, and some head and neck cancers. In the viral life cycle, by interacting with both viral and host DNA and proteins, the HPV E2 protein plays a pivotal role in viral transcriptional regulation and DNA replication, and it is also associated with modification of various cellular processes, including host gene transcription, RNA processing, apoptosis, ubiquitination, and intracellular trafficking, to create a convenient environment for a replicative cycle of the virus and contribute to the HPV pathogenesis. Elucidating the roles of E2 protein throughout the viral life cycle will improve our understanding of the viral life cycle and pathogenesis and help us identify novel antiviral agents with therapeutic potential. This article reviews the research progress in the structure, roles, and activity of high-risk HPV E2 protein, particularly that of HPV-16.

  10. Intermediate-energy Coulomb excitation of 104Sn: Moderate E2 strength decrease approaching 100Sn

    CERN Document Server

    Doornenbal, P; Aoi, N; Matsushita, M; Obertelli, A; Steppenbeck, D; Wang, H; Audirac, L; Baba, H; Bednarczyk, P; Boissinot, S; Ciemala, M; Corsi, A; Furumoto, T; Isobe, T; Jungclaus, A; Lapoux, V; Lee, J; Matsui, K; Motobayashi, T; Nishimura, D; Ota, S; Pollacco, E C; Sakurai, H; Santamaria, C; Shiga, Y; Sohler, D; Taniuchi, R

    2013-01-01

    The reduced transition probability B(E2) of the first excited 2+ state in the nucleus 104Sn was measured via Coulomb excitation in inverse kinematics at intermediate energies. A value of 0.163(26) e^2b^2 was extracted from the absolute cross-section on a Pb target, while the method itself was verified with the stable 112Sn isotope. Our result deviates significantly from the earlier reported value of 0.10(4) e^2b^2 and corresponds to a moderate decrease of excitation strength relative to the almost constant values observed in the proton-rich, even-A 106-114Sn isotopes. Present state-of-the-art shell-model predictions, which include proton and neutron excitations across the N=Z=50 shell closures as well as standard polarization charges, underestimate the experimental findings

  11. The challenges of classical swine fever control: modified live and E2 subunit vaccines.

    Science.gov (United States)

    Huang, Yu-Liang; Deng, Ming-Chung; Wang, Fun-In; Huang, Chin-Cheng; Chang, Chia-Yi

    2014-01-22

    Classical swine fever (CSF) is an economically important, highly contagious disease of swine worldwide. CSF is caused by classical swine fever virus (CSFV), and domestic pigs and wild boars are its only natural hosts. The two main strategies used to control CSF epidemic are systematic prophylactic vaccination and a non-vaccination stamping-out policy. This review compares the protective efficacy of the routinely used modified live vaccine (MLV) and E2 subunit vaccines and summarizes the factors that influence the efficacy of the vaccines and the challenges that both vaccines face to CSF control. Although MLV provide earlier and more complete protection than E2 subunit vaccines, it has the drawback of not allowing differentiation between infected and vaccinated animals (DIVA). The marker vaccine of E2 protein with companion discriminatory test to detect antibodies against E(rns) allows DIVA and is a promising strategy for future control and eradication of CSF. Maternal derived antibody (MDA) is the critical factor in impairing the efficacy of both MLV and E2 subunit vaccines, so the well-designed vaccination programs of sows and piglets should be considered together. Because of the antigen variation among various genotypes of CSFV, antibodies raised by either MLV or subunit vaccine neutralize genotypically homologous strains better than heterologous ones. However, although this is not a major concern for MLV as the induced immune responses can protect pigs against the challenge of various genotypes of CSFVs, it is critical for E2 subunit vaccines. It is thus necessary to evaluate whether the E2 subunit vaccine can completely protect against the current prevalent strains in the field. An ideal new generation of vaccine should be able to maintain the high protective efficiency of MLV and overcome the problem of antigenic variations while allowing for DIVA.

  12. Resveratrol enhances the radiosensitivity of nasopharyngeal carcinoma cells by downregulating E2F1.

    Science.gov (United States)

    Tan, Yuhui; Wei, Xianli; Zhang, Wenyin; Wang, Xiaolan; Wang, Kun; Du, Biaoyan; Xiao, Jianyong

    2017-03-01

    Identification of safe, effective radiosensitizing agents is urgently needed to improve the outcome of radiotherapy in nasopharyngeal cancer (NPC). In this study, we assessed the ability of the polyphenol resveratrol to act as a radiosensitizer in vitro and in vivo. CNE-1 cells were treated with 50 µM resveratrol for 24 h, then irradiated. E2F transcription factor 1 (E2F1) was stably knocked down and overexpressed using lentiviruses. A xenograft model of NPC was established in nude mice using CNE-1 cells. Compared to control DMSO‑treated CNE-1 cells, resveratrol inhibited colony-forming ability and induced G1 phase cell cycle arrest. Radiation survival curves confirmed resveratrol significantly sensitized CNE-1 cells, and resveratrol in combination with 2 Gy irradiation synergistically increased apoptosis. Immunoblotting showed resveratrol dose- and time-dependently downregulated E2F1 and phospho-AKT (p-AKT). Knockdown of E2F1 significantly increased radiosensitivity and downregulated p-AKT; overexpression of E2F1 reversed resveratrol-induced radiosensitivity and upregulated p-AKT. In vivo, 50 mg/kg/day resveratrol and 4 Gy irradiation led to significantly lower tumor volume and tumor weight compared to resveratrol or irradiation alone. Our findings show that resveratrol increases the radiosensitivity of NPC cells by downregulating E2F1 and inhibiting p-AKT, and therefore has potential as a radiosensitizer for NPC.

  13. Isolation, Characterization, and Degradation Performance of the 17β-Estradiol-Degrading Bacterium Novosphingobium sp. E2S

    Directory of Open Access Journals (Sweden)

    Shunyao Li

    2017-01-01

    Full Text Available A 17β-estradiol (E2-degrading bacterium E2S was isolated from the activated sludge in a sewage treatment plant (STP. The morphology, biological characteristics, and 16S ribosomal RNA (rRNA gene sequence of strain E2S indicated that it belonged to the genus Novosphingobium. The optimal degrading conditions were 30 °C and pH 7.0. The ideal inoculum volume was 5% (v/v, and a 20-mL degradation system was sufficient to support the removal ability of strain E2S. The addition of extra NaCl to the system did not benefit the E2 degradation in batch culture by this strain. Strain E2S exhibited high degradation efficiency with initial substrate concentrations of 10–50 mg·L−1. For example, in mineral salt medium containing 50 mg·L−1 of E2, the degradation efficiency was 63.29% after seven days. In cow manure samples supplemented with 50 mg·L−1 of E2, strain E2S exhibited 66.40% degradation efficiency after seven days. The finding of the E2-degrading strain E2S provided a promising method for removing E2 from livestock manure in order to reduce the potential environmental risks of E2.

  14. One-Dimensional Stacking of Bifunctional Dithia- and Diselenadiazolyl Radicals : Preparation and Structural and Electronic Properties of 1,3-[(E2N2C)C6H4(CN2E2)] (E = S, Se)

    NARCIS (Netherlands)

    Andrews, M.P.; Douglass, D.C.; Fleming, R.M.; Glarum, S.H.; Haddon, R.C.; Marsh, P.; Oakley, R.T.; Palstra, T.T.M.; Schneemeyer, L.F.; Trucks, G.W.; Tycko, R.; Waszczak, J.V.; Young, K.M.; Zimmerman, N.M.; Cordes, A.W.

    1991-01-01

    The preparation and solid-state characterization of the 1,3-phenylene-bridged bis(dithiadiazolyl) and bis(diselenadiazolyl) diradicals 1,3-[(E2N2C)C6H4(CN2E2)] (E = S, Se) are reported. The isomorphous crystals of 1,3-[(E2N2C)C6H4(CN2E2)] so obtained are tetragonal, space group I41/a. Stacks of dira

  15. Relatively Small Quantities of CO2, Ammonium Bicarbonate, and a Blend of (E)-2-Hexenal Plus (E)-2-Octenal Attract Bed Bugs (Hemiptera: Cimicidae).

    Science.gov (United States)

    Anderson, John F; Ferrandino, Francis J; Vasil, Michael P; Bedoukian, Robert H; Maher, Marie; Mckenzie, Karen

    2017-03-01

    Bed bugs, Cimex lectularius L., feed on humans, have increased exponentially in the past two decades in many major cities throughout the world, have caused intense infestations, and have become a significant health concern. Improved traps are needed to detect early infestations, to assess control programs, and for control of bed bugs. Carbon dioxide released alone or simultaneously with other attractants into three types of traps at the relatively low rate of 1 ml/min caught significantly more bed bugs than untreated controls in a 183- by 183-cm arena. This finding may enable CO2 to be used more economically in traps. Three percent ammonium bicarbonate released at a rate of ≤0.03 ml/h also caught significantly more bed bugs than untreated controls. A blend of (E)-2-hexenal and (E)-2-octenal at concentrations of 0.025% or 0.1% each and released at 0.02 ml/h attracted significantly more bed bugs than untreated controls. These findings ought to improve detection of bed bugs. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Positioning reduction in the real-time phase of Chang'E-2 satellite

    Science.gov (United States)

    Li, JinLing; Liu, Li; Zheng, WeiMin; Sun, ZhongMiao

    2012-02-01

    The precision of VLBI tracking delays and the positioning reduction results during the real-time tracking phase of the Chang'E-2 satellite are statistically analyzed. The application of the positioning reduction to the real-time monitoring of pivotal arcs of the Chang'E-2 satellite is discussed. The technical specifications of the tests of tracking and control systems in X-band are estimated and evaluated via the positioning reduction method. Useful methodology and software are prepared and practical experience in engineering and technology is accumulated for the follow-up lunar and deep space explorations of China.

  17. On the theory of (e, 2e) reactions in atomic hydrogen and helium

    Science.gov (United States)

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

    1984-12-01

    We compare the results of eikonal-Born series calculations which we have performed for the (e, 2e) reaction in atomic hydrogen with recent absolute measurements of triple differential cross sections for that process, carried out in the asymmetric coplanar geometry. We find that second-order effects play a crucial role in understanding both the angular positions and the magnitudes of the binary and recoil peaks. The implications of our analysis for the case of (e, 2e) reactions in helium are also discussed.

  18. E2F5 status significantly improves malignancy diagnosis of epithelial ovarian cancer

    KAUST Repository

    Kothandaraman, Narasimhan

    2010-02-24

    Background: Ovarian epithelial cancer (OEC) usually presents in the later stages of the disease. Factors, especially those associated with cell-cycle genes, affecting the genesis and tumour progression for ovarian cancer are largely unknown. We hypothesized that over-expressed transcription factors (TFs), as well as those that are driving the expression of the OEC over-expressed genes, could be the key for OEC genesis and potentially useful tissue and serum markers for malignancy associated with OEC.Methods: Using a combination of computational (selection of candidate TF markers and malignancy prediction) and experimental approaches (tissue microarray and western blotting on patient samples) we identified and evaluated E2F5 transcription factor involved in cell proliferation, as a promising candidate regulatory target in early stage disease. Our hypothesis was supported by our tissue array experiments that showed E2F5 expression only in OEC samples but not in normal and benign tissues, and by significantly positively biased expression in serum samples done using western blotting studies.Results: Analysis of clinical cases shows that of the E2F5 status is characteristic for a different population group than one covered by CA125, a conventional OEC biomarker. E2F5 used in different combinations with CA125 for distinguishing malignant cyst from benign cyst shows that the presence of CA125 or E2F5 increases sensitivity of OEC detection to 97.9% (an increase from 87.5% if only CA125 is used) and, more importantly, the presence of both CA125 and E2F5 increases specificity of OEC to 72.5% (an increase from 55% if only CA125 is used). This significantly improved accuracy suggests possibility of an improved diagnostics of OEC. Furthermore, detection of malignancy status in 86 cases (38 benign, 48 early and late OEC) shows that the use of E2F5 status in combination with other clinical characteristics allows for an improved detection of malignant cases with sensitivity

  19. US NDC Modernization Iteration E2 Prototyping Report: User Interface Framework

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, Jennifer E. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Palmer, Melanie A. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Vickers, James Wallace [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Voegtli, Ellen M. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2014-12-01

    During the second iteration of the US NDC Modernization Elaboration phase (E2), the SNL US NDC Modernization project team completed follow-on Rich Client Platform (RCP) exploratory prototyping related to the User Interface Framework (UIF). The team also developed a survey of browser-based User Interface solutions and completed exploratory prototyping for selected solutions. This report presents the results of the browser-based UI survey, summarizes the E2 browser-based UI and RCP prototyping work, and outlines a path forward for the third iteration of the Elaboration phase (E3).

  20. HMGA2 induces pituitary tumorigenesis by enhancing E2F1 activity

    DEFF Research Database (Denmark)

    Fedele, Monica; Visone, Rosa; De Martino, Ivana

    2006-01-01

    HMGA2 gene amplification and overexpression in human prolactinomas and the development of pituitary adenomas in HMGA2 transgenic mice showed that HMGA2 plays a crucial role in pituitary tumorigenesis. We have explored the pRB/E2F1 pathway to investigate the mechanism by which HMGA2 acts. Here we......2 mice. Thus, HMGA2-mediated E2F1 activation is a crucial event in the onset of these tumors in transgenic mice and probably also in human prolactinomas....

  1. Discovery and Classification of the z=1.86 SLSNe: DES15E2mlf

    Science.gov (United States)

    Pan, Y.-C.; Foley, R. J.; Galbany, L.; Gonzalez-Gaitan, S.; Forster, F.; Hamuy, M.; Prieto, J. L.; Yuan, F.; Tucker, B. E.; Lidman, C.; Martini, P.; Gshwend, Julia; Moller, A.; Zhang, B.; 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.; Brown, P. J.; Krisciunas, K.; Suntzeff, N.; Nichol, R.; Papadopoulos, A.; Childress, M.; D'Andrea, C.; Prajs, S.; Smith, M.; Sullivan, M.; 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.; Casas, R.; Castander, F. J.

    2015-12-01

    We report the spectroscopic classification of DES15E2mlf as a superluminous supernova (SLSN) discovered by the Dark Energy Survey (ATEL #4668). DES15E2mlf was discovered on 7 November 2015 at R.A. = 00:41:33.40, Decl = -43:27:17.2 with r = 24.1 mag. We obtained spectra using GMOS on Gemini-South (520-990nm) on 06 December 2015 which indicated a redshift of z = 1.86 from Mg II 2800 absorption.

  2. E2C(R2) Periodic Benefit-Risk Evaluation Report and E2C(R2) Periodic Benefit-Risk Evaluation Report--Questions and Answers; International Council for Harmonisation; Guidances for Industry; Availability. Notice.

    Science.gov (United States)

    2016-07-19

    The Food and Drug Administration (FDA or Agency) is announcing the availability of guidances for industry entitled ``E2C(R2) Periodic Benefit-Risk Evaluation'' (E2C(R2) guidance) and ``E2C(R2) Periodic Benefit-Risk Evaluation Report--Questions and Answers'' (E2C(R2) Q&A guidance). These guidances were prepared under the auspices of the International Council for Harmonisation (ICH), formerly the International Conference on Harmonisation. The E2C(R2) draft guidance, issued April 11, 2012, updated and combined two ICH guidances, ``E2C Clinical Safety Data Management: Periodic Safety Update Reports for Marketed Drugs'' (E2C guidance) and ``Addendum to E2C Clinical Safety Data Management: Periodic Safety Update Reports for Marketed Drugs'' (addendum to the E2C guidance). The E2C(R2) guidance is intended to describe the format, content, and timing of a Periodic Benefit-Risk Evaluation Report (PBRER) for an approved drug or biologic, and it finalizes the draft guidance. The E2C(R2) Q&A guidance is a supplementary guidance that is intended to clarify key issues in the E2C(R2) guidance.

  3. E2F1-Mediated Induction of NFYB Attenuates Apoptosis via Joint Regulation of a Pro-Survival Transcriptional Program.

    Directory of Open Access Journals (Sweden)

    Xiaolei Jiang

    Full Text Available The E2F1 transcription factor regulates cell proliferation and apoptosis through the control of a considerable variety of target genes. Previous work has detailed the role of other transcription factors in mediating the specificity of E2F function. Here we identify the NF-YB transcription factor as a novel direct E2F1 target. Genome-wide expression analysis of the effects of NFYB knockdown on E2F1-mediated transcription identified a large group of genes that are co-regulated by E2F1 and NFYB. We also provide evidence that knockdown of NFYB enhances E2F1-induced apoptosis, suggesting a pro-survival function of the NFYB/E2F1 joint transcriptional program. Bioinformatic analysis suggests that deregulation of these NFY-dependent E2F1 target genes might play a role in sarcomagenesis as well as drug resistance.

  4. Membrane-initiated actions of estradiol (E2 in the regulation of LH secretion in ovariectomized (OVX ewes

    Directory of Open Access Journals (Sweden)

    Oakley Amy E

    2010-05-01

    Full Text Available Abstract Background We demonstrated that E2 conjugated to BSA (E2BSA induces a rapid membrane-initiated inhibition of LH secretion followed hours later by a slight increase in LH secretion. Whether these actions of E2BSA are restricted to the pituitary gland and whether the membrane-initiated pathway of E2BSA contributes to the up-regulation of the number of GnRH receptors during the positive feedback effect of E2 were evaluated here. We have shown that the suppression of LH secretion induced by E2 and E2BSA is the result of a decreased responsiveness of the pituitary gland to GnRH. In this study we further tested the ability of E2BSA to decrease the responsiveness of the pituitary gland to GnRH under the paradigm of the preovulatory surge of LH induced by E2. Methods For the first experiment GnRH and LH secretions were determined in samples of pituitary portal and jugular blood, respectively, in ewes treated with 12 mg E2BSA. In the second experiment, the number of GnRH receptors was quantified in ewes 12 h after administration of 25 micrograms E2 (the expected time for the increase in the number of GnRH receptors and the positive feedback effect of E2 in LH secretion or 12 mg E2BSA. In the third experiment, the preovulatory-like surge of LH was characterized in ewes injected with 25 micrograms E2 alone or followed 8 h later (before the beginning of the LH surge with 60 mg E2BSA. Results a the decrease in LH secretion induced by E2BSA was not accompanied by changes in the pulsatile pattern of GnRH, b E2BSA increased the number of GnRH receptors, and c the presence of E2BSA in E2-treated ewes delayed the onset, reduced the length, and decreased the amount of LH released during the preovulatory surge of LH. Conclusions a the rapid suppression of LH secretion induced by E2BSA is mediated only via a direct action on the pituitary gland, b E2 acting via a membrane-initiated pathway contributes to increase the number of GnRH receptors and, c

  5. Virulence determinants within the E2 glycoprotein of Classical Swine Fever Virus

    DEFF Research Database (Denmark)

    Johnston, Camille Melissa; Fahnøe, Ulrik; Lohse, Louise

    Classical Swine Fever is a highly contagious disease of pigs caused by Classical Swine Fever Virus (CSFV), a member of the pestivirus genus within the family Flaviviridae. The E2 glycoprotein of CSFV has been shown to be an important factor for the virulence of the virus. In a recent study, we have...

  6. Virulence determinants within the E2 glycoprotein of Classical Swine Fever Virus

    DEFF Research Database (Denmark)

    Johnston, Camille Melissa; Fahnøe, Ulrik; Lohse, Louise

    Classical Swine Fever is a highly contagious disease of pigs caused by Classical Swine Fever Virus (CSFV), a member of the pestivirus genus within the family Flaviviridae. The E2 glycoprotein of CSFV has been shown to be an important factor for the virulence of the virus. In a recent study, we ha...

  7. Inhibition of HCV 3a genotype entry through Host CD81 and HCV E2 antibodies

    Directory of Open Access Journals (Sweden)

    Ashfaq Usman A

    2011-11-01

    Full Text Available Abstract Background HCV causes acute and chronic hepatitis which can eventually lead to permanent liver damage hepatocellular carcinoma and death. HCV glycoproteins play an important role in HCV entry by binding with CD81 receptors. Hence inhibition of virus at entry step is an important target to identify antiviral drugs against HCV. Methods and result The present study elaborated the role of CD81 and HCV glycoprotein E2 in HCV entry using retroviral pseudo-particles of 3a local genotype. Our results demonstrated that HCV specific antibody E2 and host antibody CD81 showed dose- dependent inhibition of HCV entry. HCV E2 antibody showed 50% reduction at a concentration of 1.5 ± 1 μg while CD81 exhibited 50% reduction at a concentration of 0.8 ± 1 μg. In addition, data obtained with HCVpp were also confirmed with the infection of whole virus of HCV genotype 3a in liver cells. Conclusion Our data suggest that HCV specific E2 and host CD81 antibodies reduce HCVpp entry and full length viral particle and combination of host and HCV specific antibodies showed synergistic effect in reducing the viral titer.

  8. 40 CFR Figure E-2 to Subpart E of... - Product Manufacturing Checklist

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 5 2010-07-01 2010-07-01 false Product Manufacturing Checklist E Figure E-2 to Subpart E of Part 53 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED...—Product Manufacturing Checklist PRODUCT MANUFACTURING CHECKLIST AuditeeAuditor signatureDate...

  9. DOE Challenge Home Case Study: e2 Homes – Winter Park, Florida

    Energy Technology Data Exchange (ETDEWEB)

    none,

    2013-01-01

    This Challenge Home case study describes the first certified DOE Challenge Home as constructed by e2 Homes. Completed in May 2012, the “Wilson Residence” in Winter Park, Florida, is a 4,305-ft2 custom home that scores a HERS 57 without solar and a better than zero net-energy HERS -7 with solar.

  10. The E2F transcription factors: key regulators of cell proliferation

    DEFF Research Database (Denmark)

    Müller, H; Helin, K

    2000-01-01

    . It is becoming more and more evident that the regulatory circuits governing the cell cycle are very complex and highly interlinked. Certain aspects of RB-1 function, for instance its role in differentiation, cannot be easily explained by the current models of pRB-E2F interaction. One reason is that pRB has...

  11. The E2 Domains of APP and APLP1 Share a Conserved Mode of Dimerization

    Energy Technology Data Exchange (ETDEWEB)

    S Lee; Y Xue; J Hulbert; Y Wang; X Liu; B Demeler; Y Ha

    2011-12-31

    Amyloid precursor protein (APP) is genetically linked to Alzheimer's disease. APP is a type I membrane protein, and its oligomeric structure is potentially important because this property may play a role in its function or affect the processing of the precursor by the secretases to generate amyloid {beta}-peptide. Several independent studies have shown that APP can form dimers in the cell, but how it dimerizes remains controversial. At least three regions of the precursor, including a centrally located and conserved domain called E2, have been proposed to contribute to dimerization. Here we report two new crystal structures of E2, one from APP and the other from APLP1, a mammalian APP homologue. Comparison with an earlier APP structure, which was determined in a different space group, shows that the E2 domains share a conserved and antiparallel mode of dimerization. Biophysical measurements in solution show that heparin binding induces E2 dimerization. The 2.1 {angstrom} resolution electron density map also reveals phosphate ions that are bound to the protein surface. Mutational analysis shows that protein residues interacting with the phosphate ions are also involved in heparin binding. The locations of two of these residues, Arg-369 and His-433, at the dimeric interface suggest a mechanism for heparin-induced protein dimerization.

  12. Data of evolutionary structure change: 1Q95E-2P2GD [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1Q95E-2P2GD 1Q95 2P2G E D ANPLYQKHIISINDLSRDDLNLVLATAAKLKANP-QPEL...LKH-KVIASCFFEASTRTRLSFETSMHRLGASVVGFSDSANTSLGKKGETLADTISVISTYVDAIVMRHPQEGAARLATEFSGNVPVLNAGDGSNQHPTQTLLDLFTIQETQGRLDNLHVAMVGD...RLDAMASVAT-VPVINALSD-EFHPCQVLADLQTIAERKGALRGLRLSYFGDGAN-NMAHSLLLGGVTAG-IHVTVAAPEGFLPDPSVRAAAERRAQDTGASVTVTAD...AHAAAAGADVLVTDTWV-----KPFRPF-----QLNSRLLALADSDAIVLHCLPAHRGDEITDAVMDGPASAVWDEAENRL.../pdbID> D 2P2GD RPLQG

  13. Data of evolutionary structure change: 1RE3E-2J3GD [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1RE3E-2J3GD 1RE3 2J3G E D SNIPTNLRVLRSILENLRSKIQKLESDVSAQMEYCRTPC...TVSCNIPVVSGKECEEIIRKGGETSEMYLIQPDSSVKPYRVYCDMNTENGGWTVIQNRQDGSVDFGRKWDPYKQGFGNVATNTDGKNYCGLPGEYWLGNDKISQLTRMGPTELLIEMEDWKGD...---GEFWLGNDNIHALTAQGTSELRTDLVDFEDNYQFAKYRSFKVADEAEKYNLVLGAFVEGSAGDSL------------TFH--NNQSFSTKDQDNDLNT-----GN... 2J3G D 2J3GD LGAFVEGSAGD...D 2J3GD YLPDC-RPLTV EE -EE

  14. Influence of HPV16 E2 and its localisation on the expression of matrix metalloproteinase-9.

    Science.gov (United States)

    Mühlen, Sabrina; Behren, Andreas; Iftner, Thomas; Simon, Christian

    2010-08-01

    Infection with the high-risk HPV types 16 and 18 is the major cause of cervical cancer and plays a role in the development of certain head and neck and skin cancers. We have previously demonstrated that the Early Protein 2 of the Cottontail Rabbit papillomavirus (CRPV), required for skin carcinogenesis in a rabbit model, is able to induce the expression of a matrix metalloproteinase (MMP-9); a protease known to play a key role in invasion and metastasis. However, as of now we do not understand the underlying mechanism of activation nor relevance for the human system. Here, we report that high-risk human papillomavirus HPV16 E2 similar to our previously reported results on CRPV E2 activates the human MMP-9 promoter predominantly via the MEK1-ERK1/2-AP-1-signaling pathway. In addition this activation is associated with a nuclear sub-localisation of HPV16-E2 suggesting a nuclear protein-protein or protein-DNA interaction of E2 as the underlying mechanism of activation.

  15. E2Fs regulate the expression of genes involved in differentiation, development, proliferation, and apoptosis

    DEFF Research Database (Denmark)

    Müller, H; Bracken, A P; Vernell, R;

    2001-01-01

    The retinoblastoma protein (pRB) and its two relatives, p107 and p130, regulate development and cell proliferation in part by inhibiting the activity of E2F-regulated promoters. We have used high-density oligonucleotide arrays to identify genes in which expression changed in response to activatio...

  16. Silvaco ATLAS model of ESA's Gaia satellite e2v CCD91-72 pixels

    CERN Document Server

    Seabroke, G M; Burt, D; Robbins, M S; 10.1117/12.856958

    2010-01-01

    The Gaia satellite is a high-precision astrometry, photometry and spectroscopic ESA cornerstone mission, currently scheduled for launch in 2012. Its primary science drivers are the composition, formation and evolution of the Galaxy. Gaia will achieve its unprecedented accuracy requirements with detailed calibration and correction for CCD radiation damage and CCD geometric distortion. In this paper, the third of the series, we present our 3D Silvaco ATLAS model of the Gaia e2v CCD91-72 pixel. We publish e2v's design model predictions for the capacities of one of Gaia's pixel features, the supplementary buried channel (SBC), for the first time. Kohley et al. (2009) measured the SBC capacities of a Gaia CCD to be an order of magnitude smaller than e2v's design. We have found the SBC doping widths that yield these measured SBC capacities. The widths are systematically 2 {\\mu}m offset to the nominal widths. These offsets appear to be uncalibrated systematic offsets in e2v photolithography, which could either be du...

  17. Prostaglandin E2 promotes MYCN non-amplified neuroblastoma cell survival via β-catenin stabilization

    NARCIS (Netherlands)

    Jansen, Sepp R.; Holman, Rian; Hedemann, Ilja; Frankes, Ewoud; Elzinga, Carolina R. S.; Timens, Wim; Gosens, Reinoud; de Bont, Eveline S.; Schmidt, Martina

    2015-01-01

    Amplification of MYCN is the most well-known prognostic marker of neuroblastoma risk classification, but still is only observed in 25% of cases. Recent evidence points to the cyclic adenosine monophosphate (cAMP) elevating ligand prostaglandin E2 (PGE2 ) and β-catenin as two novel players in neurobl

  18. Lesion of the tuberomammillary nucleus E2-region attenuates postictal seizure protection in rats.

    Science.gov (United States)

    Jin, Chun-Lei; Zhuge, Zheng-Bing; Wu, Deng-Chang; Zhu, Yuan-Yuan; Wang, Shuang; Luo, Jian-Hong; Chen, Zhong

    2007-03-01

    Postictal seizure protection (PSP) is an endogenous anticonvulsant phenomenon that follows an epileptic seizure and inhibits the induction of further seizures. The tuberomammillary nucleus (TM), located in the posterior hypothalamus, consists of five subregions and is the sole source of histaminergic neurons in the brain. To determine whether the TM is involved in PSP in rats, we tested the effects of bilateral electrolytic lesions of the TM E2-region on seizures induced by intermittent maximal electroshock (MES). The TM E2-region lesions significantly attenuated PSP during the intermittent MES procedure. Furthermore, intracerebroventricular injection of alpha-fluoromethylhistidine (100 microg), a selective and irreversible histidine decarboxylase inhibitor, mimicked the attenuation of PSP induced by the lesion of TM E2-region. In addition, neurochemical experiments revealed that the TM E2-region lesions markedly decreased basal histamine levels in the cortex, hippocampus, brainstem and hypothalamus, but had no significant effect on basal glutamate and GABA levels. Moreover, intermittent MES induced a persistent decrease of brain histamine levels in both sham-operated and lesioned rats. These results indicate that through its intrinsic histaminergic system, the TM may exert powerful inhibitory function during the intermittent MES procedure and actively participate in the mechanisms of PSP.

  19. CRYSTALLOGRAPHIC ANALYSIS OF SUBSTRATE BINDING AND CATALYSIS IN DIHYDROLIPOYL TRANSACETYLASE (E2P)

    NARCIS (Netherlands)

    MATTEVI, A; OBMOLOVA, G; KALK, KH; TEPLYAKOV, A; HOL, WGJ

    1993-01-01

    The catalytic domain of dihydrolipoyl transacetylase (E2pCD) forms the core of the pyruvate dehydrogenase multienzyme complex and catalyzes the acetyltransferase reaction using acetylCoA as acetyl donor and dihydrolipoamide (Lip(SH)2) as acceptor. The crystal structures of six complexes and

  20. Bim is a direct target of a neuronal E2F-dependent apoptotic pathway.

    Science.gov (United States)

    Biswas, Subhas C; Liu, David X; Greene, Lloyd A

    2005-09-14

    The inappropriate expression/activation of cell-cycle-related molecules is associated with neuron death in many experimental paradigms and human neuropathologic conditions. However, the means whereby this links to the core apoptotic machinery in neurons have been unclear. Here, we show that the pro-apoptotic Bcl-2 homology 3 domain-only molecule Bcl-2 interacting mediator of cell death (Bim) is a target of a cell-cycle-related apoptotic pathway in neuronal cells. Induction of Bim in NGF-deprived cells requires expression and activity of cyclin-dependent kinase 4 (cdk4) and consequent de-repression of E2 promoter binding factor (E2F)-regulated genes including members of the myb transcription factor family. The Bim promoter contains two myb binding sites, mutation of which abolishes induction of a Bim promoter-driven reporter by NGF deprivation or E2F-dependent gene de-repression. NGF deprivation significantly increases endogenous levels of C-myb and its occupancy of the endogenous Bim promoter. These findings support a model in which apoptotic stimuli lead to cdk4 activation, consequent de-repression of E2F-regulated mybs, and induction of pro-apoptotic Bim.

  1. Bone formation induced in an infant by systemic prostaglandin-E2 administration

    DEFF Research Database (Denmark)

    Jørgensen, H R; Svanholm, H; Høst, A

    1988-01-01

    We report a case of long-term systemic administration of prostaglandin E2 (PGE2) to a newborn infant with ductus-dependent congenital heart disease. After 46 days of treatment, radiography showed cortical hyperostosis of the long bones. The child died 62 days after discontinuation of prostaglandin...

  2. Antibegomoviral activity of the agrobacterial virulence protein VirE2.

    Science.gov (United States)

    Sunitha, Sukumaran; Marian, Dolly; Hohn, Barbara; Veluthambi, Karuppannan

    2011-12-01

    Mungbean yellow mosaic geminivirus (MYMV) causes severe yellow mosaic disease in blackgram, mungbean, Frenchbean, pigeonpea, soybean and mothbean. We attempted to induce resistance against this virus using the transcriptional activator protein gene deleted in the C-terminal activation domain (TrAP-∆AD) and Agrobacterium tumefaciens virE2. MYMV is known to replicate in agroinoculated tobacco leaf discs. Three transgenic tobacco plants which harboured a truncated MYMV transcriptional activator protein gene and two tobacco plants transformed with the octopine type A. tumefaciens virE2 gene were agroinoculated with an A. tumefaciens strain which harboured the partial dimers of both DNA A and DNA B of MYMV. The level of viral DNA accumulation in leaf discs of transgenic plants correlated inversely to the level of the MYMV TrAP-∆AD transcript. Two VirE2-transgenic plants, which complemented tumorigenesis of a virE2 mutant A. tumefaciens strain, effectively reduced MYMV DNA accumulation in the leaf disc agroinoculation assay.

  3. Data of evolutionary structure change: 1AW2E-2VENA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1AW2E-2VENA 1AW2 2VEN E A --RHPVVMGNWKLNGSKEMVVDLLNGLNAELEGVTGVDV...RQLDAVINTQGVEALEGAIIAYEPIWAIGTGKAATAEDAQRIHAQIRAHIAEK-SEAVAKNVVIQYGGSVKPENAAAYFAQPDIDGALVGGAALDAKSFAAIAKAAAE...entryChain> 2VEN A 2VENA 2VEN A 2VENA ERLSH--PK...indel> 2 2VEN A 2VENA

  4. Cell cycle-regulated expression of mammalian CDC6 is dependent on E2F

    DEFF Research Database (Denmark)

    Hateboer, G; Wobst, A; Petersen, B O

    1998-01-01

    The E2F transcription factors are essential regulators of cell growth in multicellular organisms, controlling the expression of a number of genes whose products are involved in DNA replication and cell proliferation. In Saccharomyces cerevisiae, the MBF and SBF transcription complexes have functi...

  5. Protective role of the apolipoprotein E2 allele in age-related disease traits and survival

    DEFF Research Database (Denmark)

    Kulminski, Alexander M; Raghavachari, Nalini; Arbeev, Konstantin G

    2016-01-01

    The apolipoprotein E (apoE) is a classic example of a gene exhibiting pleiotropism. We examine potential pleiotropic associations of the apoE2 allele in three biodemographic cohorts of long-living individuals, offspring, and spouses from the Long Life Family Study, and intermediate mechanisms, wh...

  6. "Expectations to Change" ((E2C): A Participatory Method for Facilitating Stakeholder Engagement with Evaluation Findings

    Science.gov (United States)

    Adams, Adrienne E.; Nnawulezi, Nkiru A.; Vandenberg, Lela

    2015-01-01

    From a utilization-focused evaluation perspective, the success of an evaluation is rooted in the extent to which the evaluation was used by stakeholders. This paper details the "Expectations to Change" (E2C) process, an interactive, workshop-based method designed to engage primary users with their evaluation findings as a means of…

  7. Prostaglandin (E2) induces immediate migraine-like attack in migraine patients without aura

    DEFF Research Database (Denmark)

    Antonova, Maria; Wienecke, Troels; Olesen, Jes

    2012-01-01

    without aura were randomly allocated to receive 0.4 µg/kg/min PGE(2) (Prostin®E2, dinoprostone) or placebo over 25 minutes in a two-way, crossover study. Headache intensity was recorded on a verbal rating scale, middle cerebral artery blood flow velocity (V(MCA)) was measured by transcranial Doppler (TCD...

  8. E2F1-mediated transcriptional inhibition of the plasminogen activator inhibitor type 1 gene

    DEFF Research Database (Denmark)

    Koziczak, M; Müller, H; Helin, K;

    2001-01-01

    -sensitive retinoblastoma protein (pRB), a shift to a permissive temperature induced PAI-1 mRNA expression. In U2OS cells stably expressing an E2F1-estrogen receptor chimeric protein that could be activated by tamoxifen, PAI-1 gene transcription was markedly reduced by tamoxifen even in the presence of cycloheximide...

  9. Aberrant E2F activation by polyglutamine expansion of androgen receptor in SBMA neurotoxicity.

    Science.gov (United States)

    Suzuki, Eriko; Zhao, Yue; Ito, Saya; Sawatsubashi, Shun; Murata, Takuya; Furutani, Takashi; Shirode, Yuko; Yamagata, Kaoru; Tanabe, Masahiko; Kimura, Shuhei; Ueda, Takashi; Fujiyama, Sally; Lim, Jinseon; Matsukawa, Hiroyuki; Kouzmenko, Alexander P; Aigaki, Toshiro; Tabata, Tetsuya; Takeyama, Ken-ichi; Kato, Shigeaki

    2009-03-10

    Spinal and bulbar muscular atrophy (SBMA) is a neurodegenerative disorder caused by a polyglutamine repeat (polyQ) expansion within the human androgen receptor (AR). Unlike other neurodegenerative diseases caused by abnormal polyQ expansion, the onset of SBMA depends on androgen binding to mutant human polyQ-AR proteins. This is also observed in Drosophila eyes ectopically expressing the polyQ-AR mutants. We have genetically screened mediators of androgen-induced neurodegeneration caused by polyQ-AR mutants in Drosophila eyes. We identified Rbf (Retinoblastoma-family protein), the Drosophila homologue of human Rb (Retinoblastoma protein), as a neuroprotective factor. Androgen-dependent association of Rbf or Rb with AR was remarkably potentiated by aberrant polyQ expansion. Such potentiated Rb association appeared to attenuate recruitment of histone deacetyltransferase 1 (HDAC1), a corepressor of E2F function. Either overexpression of Rbf or E2F deficiency in fly eyes reduced the neurotoxicity of the polyQ-AR mutants. Induction of E2F function by polyQ-AR-bound androgen was suppressed by Rb in human neuroblastoma cells. We conclude that abnormal expansion of polyQ may potentiate innate androgen-dependent association of AR with Rb. This appears to lead to androgen-dependent onset of SBMA through aberrant E2F transactivation caused by suppressed histone deacetylation.

  10. MPN patients harbor recurrent truncating mutations in transcription factor NF-E2

    NARCIS (Netherlands)

    Jutzi, J.S.; Bogeska, R.; Nikoloski, G.; Schmid, C.A.; Seeger, T.S.; Stegelmann, F.; Schwemmers, S.; Grunder, A.; Peeken, J.C.; Gothwal, M.; Wehrle, J.; Aumann, K.; Hamdi, K.; Dierks, C.; Wang, W.; Dohner, K.; Jansen, J.H.; Pahl, H.L.

    2013-01-01

    The molecular etiology of myeloproliferative neoplasms (MPNs) remains incompletely understood, despite recent advances incurred through the discovery of several different mutations in MPN patients. We have recently described overexpression of the transcription factor NF-E2 in MPN patients and shown

  11. E2A Antagonizes PU.1 Activity through Inhibition of DNA Binding.

    Science.gov (United States)

    Rogers, Jason H; Owens, Kristin S; Kurkewich, Jeffrey; Klopfenstein, Nathan; Iyer, Sangeeta R; Simon, M Celeste; Dahl, Richard

    2016-01-01

    Antagonistic interactions between transcription factors contribute to cell fate decisions made by multipotent hematopoietic progenitor cells. Concentration of the transcription factor PU.1 affects myeloid/lymphoid development with high levels of PU.1 directing myeloid cell fate acquisition at the expense of B cell differentiation. High levels of PU.1 may be required for myelopoiesis in order to overcome inhibition of its activity by transcription factors that promote B cell development. The B cell transcription factors, E2A and EBF, are necessary for commitment of multipotential progenitors and lymphoid primed multipotential progenitors to lymphocytes. In this report we hypothesized that factors required for early B cell commitment would bind to PU.1 and antagonize its ability to induce myeloid differentiation. We investigated whether E2A and/or EBF associate with PU.1. We observed that the E2A component, E47, but not EBF, directly binds to PU.1. Additionally E47 represses PU.1-dependent transactivation of the MCSFR promoter through antagonizing PU.1's ability to bind to DNA. Exogenous E47 expression in hematopoietic cells inhibits myeloid differentiation. Our data suggest that E2A antagonism of PU.1 activity contributes to its ability to commit multipotential hematopoietic progenitors to the lymphoid lineages.

  12. Selectivity of E2-E3 interactions in the human ubiquitin system

    NARCIS (Netherlands)

    van Wijk, S.J.L.

    2010-01-01

    Highly selective interactions between ubiquitin-conjugating enzymes and RING-type E3 ligases are crucial for the adequate and efficient action of ubiquitin and ubiquitin-like pathways. Within these cascades, E2 enzymes provide a connecting link between activation and the final covalent conjugation,

  13. E2A Antagonizes PU.1 Activity through Inhibition of DNA Binding

    Directory of Open Access Journals (Sweden)

    Jason H. Rogers

    2016-01-01

    Full Text Available Antagonistic interactions between transcription factors contribute to cell fate decisions made by multipotent hematopoietic progenitor cells. Concentration of the transcription factor PU.1 affects myeloid/lymphoid development with high levels of PU.1 directing myeloid cell fate acquisition at the expense of B cell differentiation. High levels of PU.1 may be required for myelopoiesis in order to overcome inhibition of its activity by transcription factors that promote B cell development. The B cell transcription factors, E2A and EBF, are necessary for commitment of multipotential progenitors and lymphoid primed multipotential progenitors to lymphocytes. In this report we hypothesized that factors required for early B cell commitment would bind to PU.1 and antagonize its ability to induce myeloid differentiation. We investigated whether E2A and/or EBF associate with PU.1. We observed that the E2A component, E47, but not EBF, directly binds to PU.1. Additionally E47 represses PU.1-dependent transactivation of the MCSFR promoter through antagonizing PU.1’s ability to bind to DNA. Exogenous E47 expression in hematopoietic cells inhibits myeloid differentiation. Our data suggest that E2A antagonism of PU.1 activity contributes to its ability to commit multipotential hematopoietic progenitors to the lymphoid lineages.

  14. Conditional E2F1 activation in transgenic mice causes testicular atrophy and dysplasia mimicking human CIS

    DEFF Research Database (Denmark)

    Agger, Karl; Santoni-Rugiu, Eric; Holmberg, Christian;

    2005-01-01

    E2F1 is a crucial downstream effector of the retinoblastoma protein (pRB) pathway. To address the consequences of short-term increase in E2F1 activity in adult tissues, we generated transgenic mice expressing the human E2F1 protein fused to the oestrogen receptor (ER) ligand-binding domain...

  15. 40 CFR Table E-2 to Subpart E of... - Spectral Energy Distribution and Permitted Tolerance for Conducting Radiative Tests

    Science.gov (United States)

    2010-07-01

    ... Permitted Tolerance for Conducting Radiative Tests E Table E-2 to Subpart E of Part 53 Protection of... Reference Methods and Class I and Class II Equivalent Methods for PM2.5 or PM10â2.5 Pt. 53, Subpt. E, Table E-2 Table E-2 to Subpart E of Part 53—Spectral Energy Distribution and Permitted Tolerance...

  16. TGFbeta-mediated formation of pRb-E2F complexes in human myeloid leukemia cells.

    Science.gov (United States)

    Hu, Xiao Tang

    2008-05-01

    TGFbeta is well known for its inhibitory effect on cell cycle G1 checkpoint kinases. However, its role in the control of pRb-E2F complexes is not well established. TGFbeta inhibits phosphorylation of pRb at several serine and threonine residues and regulates the association of E2F transcription factors with pRb family proteins. Recent studies found that predominantly E2F-4, p130, and histone deacetylase (HDAC) are found to bind to corresponding E2F-responsive promoters in G0/G1 phase. As cells progress through mid-G1, p130-E2F4 complex are replaced by p107-E2F4 followed by activators E2F1, 2, and 3. pRb was not detectable in the promoters containing the E2F-responsive site in cycling cells but was associated with E2F4-p130 complexes or E2F4-p107 complexes during G0/G1 phase. In human myeloid leukemia cell line, MV4-11, TGFbeta upregulated pRb-E2F-4 and p130-E2F-4, and downregulated p107-E2F-4 complexes. However, pRB-E2F1 and pRb-E2F3 complexes were found in proliferating cells but not in TGFbeta arrested G1 cells. In addition, electrophoretic gel mobility shift assay (EMSA) could not detect pRb-E2F DNA-binding activities either in S or G1 phase but exhibited the existence of p107-E2F4 in proliferating cells and p130-E2F4 complexes in TGFbeta-arrested G1 cells, respectively. Our data suggest that p107 and p130, but not pRb, and the repressor E2F, but not activator E2Fs, play a critical role in regulating E2F-responsive gene expression in TGFbeta-mediated cell cycle control in human myeloid leukemia cells.

  17. Prostaglandin I2 and Prostaglandin E2 Modulate Human Intrarenal Artery Contractility Through Prostaglandin E2-EP4, Prostacyclin-IP, and Thromboxane A2-TP Receptors

    DEFF Research Database (Denmark)

    Eskildsen, Morten P; Hansen, Pernille B L; Stubbe, Jane

    2014-01-01

    receptors. Intrarenal arteries were microdissected from human nephrectomy samples (n=53, median diameter ≈362 μm, 88% viable, 76% relaxed in response to acetylcholine). Rings were suspended in myographs to record force development. In vessels with K(+)-induced tension (EC70: -log [mol/L]=1.36±0.03), PGE2....../L elicited increased tension. This was abolished by thromboxane receptor (TP) antagonist (S18886, 10(-6) mol/L). A TP agonist (U46619, n=6) evoked tension (EC50=8.1±0.2) that was inhibited by S18886. Polymerase chain reaction and immunoblotting showed EP4, IP, and TP receptors in intrarenal arteries......Cyclooxygenase inhibitors decrease renal blood flow in settings with decreased effective circulating volume. The present study examined the hypothesis that prostaglandins, prostaglandin E2 (PGE2) and prostacyclin (PGI2), induce relaxation of human intrarenal arteries through PGE2-EP and PGI2-IP...

  18. PPARβ Regulates Liver Regeneration by Modulating Akt and E2f Signaling.

    Directory of Open Access Journals (Sweden)

    Hui-Xin Liu

    Full Text Available The current study tests the hypothesis that peroxisome proliferator-activated receptor β (PPARβ has a role in liver regeneration due to its effect in regulating energy homeostasis and cell proliferation. The role of PPARβ in liver regeneration was studied using two-third partial hepatectomy (PH in Wild-type (WT and PPARβ-null (KO mice. In KO mice, liver regeneration was delayed and the number of Ki-67 positive cells reached the peak at 60 hr rather than at 36-48 hr after PH shown in WT mice. RNA-sequencing uncovered 1344 transcriptomes that were differentially expressed in regenerating WT and KO livers. About 70% of those differentially expressed genes involved in glycolysis and fatty acid synthesis pathways failed to induce during liver regeneration due to PPARβ deficiency. The delayed liver regeneration in KO mice was accompanied by lack of activation of phosphoinositide-dependent kinase 1 (PDK1/Akt. In addition, cell proliferation-associated increase of genes encoding E2f transcription factor (E2f 1-2 and E2f7-8 as well as their downstream target genes were not noted in KO livers 36-48 hr after PH. E2fs have dual roles in regulating metabolism and proliferation. Moreover, transient steatosis was only found in WT, but not in KO mice 36 hr after PH. These data suggested that PPARβ-regulated PDK1/Akt and E2f signaling that controls metabolism and proliferation is involved in the normal progression of liver regeneration.

  19. Atmospheric reactions between E,E-2,4-hexadienal and OH, NO3 radicals and Cl atoms

    Science.gov (United States)

    Colmenar, I.; Martín, P.; Cabañas, B.; Salgado, S.; Martínez, E.

    2014-12-01

    E,E-2,4-Hexadienal is an α,β-unsaturated aldehyde whose presence in the atmosphere can arise from different sources. The rate coefficients for the reaction of this compound with Cl atoms, OH and NO3 radicals and for the photolysis process have been determined at atmospheric pressure and room temperature. A relative method has been developed with a Fourier Transform Infrared spectrometer (FTIR) or Solid Phase Micro Extraction fiber/chromatography-mass spectrometer (SPME/GC-MS) used as sampling/detection techniques. The absolute rate coefficients k (in units of cm3 molecule-1 s-1) obtained for Cl, OH and NO3 were (3.98 ± 0.44) × 10-10, (6.78 ± 0.47) × 10-11 and (1.34 ± 0.56) × 10-12, respectively. An estimation of the rate coefficient for the reaction of E,E-2,4-hexadienal with OH and NO3 radicals and Cl atoms has been carried out using correlations and SAR methods. The SAR substituent factor for the -C(O)H group, [G-(C(O)H)] = 3.58 × 10-3, has been obtained. This group reactivity factor allows the rate coefficients to be estimated for the reaction of unsaturated aldehydes with NO3 radicals. The results of this study confirm that the reaction of unsaturated aldehydes with Cl atoms is very fast and that the structure of the compound has little influence, with the influence of the structure being more marked in the case of the OH radical reaction and relatively large for the NO3 reaction. The results are consistent with a mechanism in which the first stage is addition of an atom or radical to the double bond of E,E-2,4-hexadienal as the main reaction channel and, to a minor extent, the abstraction of aldehydic hydrogen. These are the first data reported for the atmospheric reactions of this compound and this study therefore contributes to the database of rate coefficients for atmospheric reactions.

  20. An integrated bioinformatics approach identifies elevated cyclin E2 expression and E2F activity as distinct features of tamoxifen resistant breast tumors.

    Directory of Open Access Journals (Sweden)

    Lei Huang

    Full Text Available Approximately half of estrogen receptor (ER positive breast tumors will fail to respond to endocrine therapy. Here we used an integrative bioinformatics approach to analyze three gene expression profiling data sets from breast tumors in an attempt to uncover underlying mechanisms contributing to the development of resistance and potential therapeutic strategies to counteract these mechanisms. Genes that are differentially expressed in tamoxifen resistant vs. sensitive breast tumors were identified from three different publically available microarray datasets. These differentially expressed (DE genes were analyzed using gene function and gene set enrichment and examined in intrinsic subtypes of breast tumors. The Connectivity Map analysis was utilized to link gene expression profiles of tamoxifen resistant tumors to small molecules and validation studies were carried out in a tamoxifen resistant cell line. Despite little overlap in genes that are differentially expressed in tamoxifen resistant vs. sensitive tumors, a high degree of functional similarity was observed among the three datasets. Tamoxifen resistant tumors displayed enriched expression of genes related to cell cycle and proliferation, as well as elevated activity of E2F transcription factors, and were highly correlated with a Luminal intrinsic subtype. A number of small molecules, including phenothiazines, were found that induced a gene signature in breast cancer cell lines opposite to that found in tamoxifen resistant vs. sensitive tumors and the ability of phenothiazines to down-regulate cyclin E2 and inhibit proliferation of tamoxifen resistant breast cancer cells was validated. Our findings demonstrate that an integrated bioinformatics approach to analyze gene expression profiles from multiple breast tumor datasets can identify important biological pathways and potentially novel therapeutic options for tamoxifen-resistant breast cancers.

  1. An integrated bioinformatics approach identifies elevated cyclin E2 expression and E2F activity as distinct features of tamoxifen resistant breast tumors.

    Science.gov (United States)

    Huang, Lei; Zhao, Shuangping; Frasor, Jonna M; Dai, Yang

    2011-01-01

    Approximately half of estrogen receptor (ER) positive breast tumors will fail to respond to endocrine therapy. Here we used an integrative bioinformatics approach to analyze three gene expression profiling data sets from breast tumors in an attempt to uncover underlying mechanisms contributing to the development of resistance and potential therapeutic strategies to counteract these mechanisms. Genes that are differentially expressed in tamoxifen resistant vs. sensitive breast tumors were identified from three different publically available microarray datasets. These differentially expressed (DE) genes were analyzed using gene function and gene set enrichment and examined in intrinsic subtypes of breast tumors. The Connectivity Map analysis was utilized to link gene expression profiles of tamoxifen resistant tumors to small molecules and validation studies were carried out in a tamoxifen resistant cell line. Despite little overlap in genes that are differentially expressed in tamoxifen resistant vs. sensitive tumors, a high degree of functional similarity was observed among the three datasets. Tamoxifen resistant tumors displayed enriched expression of genes related to cell cycle and proliferation, as well as elevated activity of E2F transcription factors, and were highly correlated with a Luminal intrinsic subtype. A number of small molecules, including phenothiazines, were found that induced a gene signature in breast cancer cell lines opposite to that found in tamoxifen resistant vs. sensitive tumors and the ability of phenothiazines to down-regulate cyclin E2 and inhibit proliferation of tamoxifen resistant breast cancer cells was validated. Our findings demonstrate that an integrated bioinformatics approach to analyze gene expression profiles from multiple breast tumor datasets can identify important biological pathways and potentially novel therapeutic options for tamoxifen-resistant breast cancers.

  2. Enhanced $0_{g.s.}^+ \\to 2_1^+$ E2 Transition Strength in $^{112,114}$Sn

    CERN Document Server

    Kumar, R; Jhingan, A; Muralithar, S; Mukherjee, S; Reiter, P; Gorska, M; Bhowmik, R K; Cederkall, J; Siwal, D; Doornenbal, P; Garg, R; Appannababu, S; Kojouharov, I; Grawe, H; Singh, P P; Mandal, S; Sharma, A; Schaffner, H; Ekstrom, A; Caceres, L; Prokopowicz, W; Kaur, J; Gerl, J; Singh, R P; Bednarczyk, P

    2011-01-01

    The poorly known B(E2; 0(+) -> 2(+)) values of (112)Sn and (114)Sn have been measured to high precision. Two Coulomb excitation experiments were performed to determine the reduced transition probabilities relative to (116)Sn in order to minimize the systematic errors. The obtained B(E2 up arrow) values of 0.242(8) e(2)b(2) for (112)Sn and 0.232(8) e(2)b(2) for (114)Sn confirm the tendency of large B(E2 up arrow) values for the lighter tin isotopes below the midshell (116)Sn that has been observed recently in various radioactive ion beam experiments.

  3. pRB and E2F4 play distinct cell-intrinsic roles in fetal erythropoiesis.

    Science.gov (United States)

    Zhang, Jing; Lee, Eunice Y; Liu, Yangang; Berman, Seth D; Lodish, Harvey F; Lees, Jacqueline A

    2010-01-15

    The retinoblastoma tumor suppressor protein pRB functions, at least in part, by directly binding to and modulating the activity of the E2F transcription factors. Previous studies have shown that both E2F4 and pRB play important roles in fetal erythropoiesis. Given that these two proteins interact directly we investigated the overlap of E2F4 and pRB function in this process by analyzing E2f4(-/-), conditional Rb knockout (Rb(1lox/1lox)), and compound E2f4(-/-);Rb(1lox/1lox) embryos. At E15.5 E2f4(-/-) and Rb(1lox/1lox) fetal erythroid cells display distinct abnormalities in their differentiation profiles. When cultured in vitro, both E2f4(-/-) and Rb(1lox/1lox) erythroid cells show defects in cell cycle progression. Surprisingly, analysis of cell cycle profiling suggests that E2F4 and pRB control cell cycle exit through different mechanisms. Moreover, only pRB, but not E2F4, promotes cell survival in erythroid cells. We observed an additive rather than a synergistic impact upon the erythroid defects in the compound E2f4(-/-);Rb(1lox/1lox) embryos. We further found that fetal liver macrophage development is largely normal regardless of genotype. Taken together, our results show that E2F4 and pRB play independent cell-intrinsic roles in fetal erythropoiesis.

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

    Science.gov (United States)

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

    2008-05-01

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

  5. 抗HPV11 E2核酶的计算机设计%Computer design of anti-HPV11 E2 ribozyme

    Institute of Scientific and Technical Information of China (English)

    侯化; 王曙; 杨光彩

    2001-01-01

    HPV11 E2 mRNA was taken as the target RNA, ribozyme were designed accounting to the hammerhead structure described by Symons. Computer was used to analyze the possible secondary cleavage sites on HPV11 E2 mRNA and to predict the secondary structures of substrate and ribozymes. According to the theory of Symons headhammer ribozyme, there are 32 sites to targetting sequences. The secondary structures of HPV11 mRNA from nt2510 to nt3518 were relatively stable. The region was of important biological function and was the ideal attacking region for ribozyme. Two ribozymes targeting nt2777 and nt3281 on the HPV11 mRNA were designed and were named RZ2777 and RZ3281 respectively. No analogous sequence of substrate which combined with ribozyme was found in the mRNA of others genes in known Human Gene Bank through computer probe. Not all GUX or CUX could be taken as the cleavage site of ribozyme. The nt2777 and nt3281 onr HPV11 mRNA are the most ideal attacking sites for ribozymes. So computer analysis was used to select the optium ribozyme as soon as possible and to lay a solid foundation for using ribozyme in vivo.%借助计算机软件分析,设计出能特异性切割HPV11型644nt E2 mRNA的核酶。遵循Symons锤头状核酶结构和GUX剪切位点原则,靶序列存在32个剪切位点,通过计算机软件分析核酶的最佳剪切位点,并对底物及核酶的二级结构进行预测及进行相应基因生物学功能和基因同源性分析,筛选出2个锤头结构核酶。针对这两位点设计的核酶分别命名为RZ2777和RZ3281。计算机分析显示,两核酶与底物切点两翼碱基形成锤头状结构,切点所在基因序列具有相对松弛的二级结构,位于该基因重要生物功能区内,是核酶的理想攻击区域,通过基因库检索,在已知人类基因中排除了与上述两核酶切点两翼碱基有基因同源性序列的可能性。并非所有的GUX位点(X:C、U、A)或CUX均可作为核酶的最

  6. 猪瘟病毒E2蛋白研究进展%Application progress in E2 protein of Classical Swine Fever Virus

    Institute of Scientific and Technical Information of China (English)

    江馗语

    2013-01-01

    Classical swine fever(CSF)is a highly contagious, acute, hyperthermic, multi-systemic hemorrhagic viral disease of pigs, which caused by classical swine fe-ver virus(CSFV), a member of the genus Pestivirus of the Flaviviridae. CSF is preva-lent in all continents except North America and Oceania,it is distributed worldwide, and it has relapsed in some European countries(Netherlands, Belgium, Britain, Germa-ny, Italy, Spain, etc.)which had eliminated CSF. Although we have used HCLV vaccine for inoculation for a long time,but CSF still exists in our country and happens from frequency of pandemic into erratic regional dissemination. Latent and persistent in-fection has increased. Therefore, we need clear swine fever virus genome structure and the most research value immunological antigen protein structures to provide a theoretical basis for the development of new and effective vaccines and diagnostic reagents. In this paper,we have reviewed the research progress in genomic structure of CSFV,structure, function, epitopes,expression and applications of E2 protein.%猪瘟(Classical Swine Fever,CSF)是由猪瘟病毒(Classical Swine Fever Virus,CSFV)引起的一种急性、接触性传染病。目前该病流行于除北美洲和大洋洲以外的其他大洲和地区,呈世界性分布,在一些原已宣布消灭猪瘟的欧洲国家(荷兰、比利时、英国、德国、意大利、西班牙等)又相继复发。虽然我国长期坚持全面接种猪瘟兔化弱毒疫苗,但目前猪瘟在我国依然存在,流行特点从以往的频发大面积流行转变为无规律区域性的散发,隐性持续性感染病例增多,因此应明确猪瘟病毒的基因组结构和最具免疫防制研究价值的抗原蛋白结构,为研制新型有效的疫苗和诊断试剂提供理论依据。本文就猪瘟病毒的基因组结构、猪瘟病毒E2蛋白的结构、功能、所包含的抗原表位以及E2蛋白的表达应用等方面的研究进展作以综述。

  7. Modeling method and preliminary model of Asteroid Toutatis from Chang'E-2 optical images

    Science.gov (United States)

    Li, Xiang-Yu; Qiao, Dong

    2014-06-01

    Shape modeling is fundamental to the analysis of dynamic environment and motion around asteroid. Chang'E-2 successfully made a flyby of Asteroid 4179 Toutatis and obtained plenty of high-resolution images during the mission. In this paper, the modeling method and preliminary model of Asteroid Toutatis are discussed. First, the optical images obtained by Chang'E-2 are analyzed. Terrain and silhouette features in images are described. Then, the modeling method based on previous radar model and preliminary information from optical images is proposed. A preliminary polyhedron model of Asteroid Toutatis is established. Finally, the spherical harmonic coefficients of Asteroid Toutatis based on the polyhedron model are obtained. Some parameters of model are analyzed and compared. Although the model proposed in this paper is only a preliminary model, this work offers a valuable reference for future high-resolution models.

  8. Expression and Purification of E2 Glycoprotein from Insect Cells (Sf9) for Use in Serology.

    Science.gov (United States)

    Chua, Chong Long; Sam, I-Ching; Chan, Yoke Fun

    2016-01-01

    Chikungunya virus (CHIKV) is a mosquito-borne arbovirus which poses a major threat to global public health. Definitive CHIKV diagnosis is crucial, especially in distinguishing the disease from dengue virus, which co-circulates in endemic areas and shares the same mosquito vectors. Laboratory diagnosis is mainly based on serological or molecular approaches. The E2 glycoprotein is a good candidate for serological diagnosis since it is the immunodominant antigen during the course of infection, and reacts with seropositive CHIKV sera. In this chapter, we describe the generation of stable clone Sf9 (Spodoptera frugiperda) cells expressing secreted, soluble, and native recombinant CHIKV E2 glycoprotein. We use direct plasmid expression in insect cells, rather than the traditional technique of generating recombinant baculovirus. This recombinant protein is useful for serological diagnosis of CHIKV infection.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1969-10-15

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

  10. E2F1 and p53 Transcription Factors as Accessory Factors for Nucleotide Excision Repair

    Directory of Open Access Journals (Sweden)

    David G. Johnson

    2012-10-01

    Full Text Available Many of the biochemical details of nucleotide excision repair (NER have been established using purified proteins and DNA substrates. In cells however, DNA is tightly packaged around histones and other chromatin-associated proteins, which can be an obstacle to efficient repair. Several cooperating mechanisms enhance the efficiency of NER by altering chromatin structure. Interestingly, many of the players involved in modifying chromatin at sites of DNA damage were originally identified as regulators of transcription. These include ATP-dependent chromatin remodelers, histone modifying enzymes and several transcription factors. The p53 and E2F1 transcription factors are well known for their abilities to regulate gene expression in response to DNA damage. This review will highlight the underappreciated, transcription-independent functions of p53 and E2F1 in modifying chromatin structure in response to DNA damage to promote global NER.

  11. The Ionization of Accretion Flows in High Mass Star Formation: W51e2

    CERN Document Server

    Keto, Eric

    2008-01-01

    Previous observations show that the hypercompact HII region W51e2 is surrounded by a massive molecular accretion flow centered on the HII region. New observations of the H53alpha radio recombination line made with the VLA at 0.45 arc second angular resolution show a velocity gradient in the ionized gas within the HII region of > 500 kms-1 pc-1 comparable to the velocity gradient seen in the molecular accretion flow. New CO line observations made with the SMA at arc second angular resolution detect a molecular bipolar outflow immediately around the W51e2 HII region and extending along the axis of rotation of the molecular flow. These observations are consistent with an evolutionary phase for high mass star formation in which a newly formed massive star first begins to ionize its surroundings including its own accretion flow.

  12. Effect of combined siRNA of HCV E2 gene and HCV receptors against HCV

    Directory of Open Access Journals (Sweden)

    Ashfaq Usman Alli A

    2011-06-01

    Full Text Available Abstract Background/Aim Hepatitis C virus (HCV is a major threat as almost 3% of the world's population (350 million individual and 10% of the Pakistani population is chronically infected with this virus. RNA interference (RNAi, a sequence-specific degradation process of RNA, has potential to be used as a powerful alternative molecular therapeutic approach in spite of the current therapy of interferon-α and ribavirin against HCV which has limited efficiency. HCV structural gene E2 is mainly involved in viral cell entry via attachment with the host cell surface receptors i.e., CD81 tetraspanin, low density lipoprotein receptor (LDLR, scavenger receptor class B type 1 (SR-B1, and Claudin1 (CLDN1. Considering the importance of HCV E2 gene and cellular receptors in virus infection and silencing effects of RNAi, the current study was designed to target the cellular and viral factors as new therapeutic options in limiting HCV infection. Results In this study the potential of siRNAs to inhibit HCV-3a replication in serum-infected Huh-7 cells was investigated by combined treatment of siRNAs against the HCV E2 gene and HCV cellular receptors (CD81 and LDLR, which resulted in a significant decrease in HCV viral copy number. Conclusion From the current study it is concluded that the combined RNAi-mediated silencing of HCV E2 and HCV receptors is important for the development of effective siRNA-based therapeutic option against HCV-3a.

  13. Apaf-1 is a transcriptional target for E2F and p53

    DEFF Research Database (Denmark)

    Moroni, M C; Hickman, E S; Lazzerini Denchi, E

    2001-01-01

    between the deregulation of the pRB pathway and apoptosis. Furthermore, because the pRB pathway is functionally inactivated in most cancers, the identification of Apaf-1 as a transcriptional target for E2F might explain the increased sensitivity of tumour cells to chemotherapy. We also show that......, independently of the pRB pathway, Apaf-1 is a direct transcriptional target of p53, suggesting that p53 might sensitize cells to apoptosis by increasing Apaf-1 levels....

  14. Identification of Francisella novicida mutants that fail to induce prostaglandin E2 synthesis by infected macrophages

    OpenAIRE

    Woolard, Matthew D.; Barrigan, Lydia M.; Fuller, James R.; Buntzman, Adam S.; Bryan, Joshua; Manoil, Colin; Kawula, Thomas H.; Frelinger, Jeffrey A.

    2013-01-01

    Francisella tularensis is the causative agent of tularemia. We have previously shown that infection with F. tularensis Live Vaccine Strain (LVS) induces macrophages to synthesize prostaglandin E2 (PGE2). Synthesis of PGE2 by F. tularensis infected macrophages results in decreased T cell proliferation in vitro and increased bacterial survival in vivo. Although we understand some of the biological consequences of F. tularensis induced PGE2 synthesis by macrophages, we do not understand the cell...

  15. Identification of Francisella novicida mutants that fail to induce prostaglandin E2 synthesis by infected macrophages.

    OpenAIRE

    Matthew Dale Woolard; Barrigan, Lydia M.; Fuller, James R.; Buntzman, Adam S.; Joshua eBryan; Colin eManoil; Tom eKawula; Frelinger, Jeffrey A.

    2013-01-01

    Francisella tularensis is the causative agent of tularemia. We have previously shown that infection with F. tularensis Live Vaccine Strain (LVS) induces macrophages to synthesize prostaglandin E2 (PGE2). Synthesis of PGE2 by F. tularensis infected macrophages results in decreased T cell proliferation in vitro and increased bacterial survival in vivo. Although we understand some of the biological consequences of F. tularensis induced PGE2 synthesis by macrophages, we do not understand the ce...

  16. Energy to the Edge (E2E) U.S. Army Rapid Equipping Force

    Science.gov (United States)

    2014-03-21

    experienced: The E2E team found a typical base is a mix of buildings and tents at most sites visited, with very little commonality. Sites had poor to no...required to meet energy demands for hybrid technologies. The Sundial installed at Heredia was able to power the TOC and other buildings . The...solutions of OE. The REF sponsored several “ NetZero at the Tactical Edge” workshops as follows: • Arizona State University, February 13-14, 2012

  17. e2v CCD and CMOS sensors and systems designed for astronomical applications

    Science.gov (United States)

    Jorden, Paul; Jerram, Paul; Jordan, Douglas; Pratlong, Jérôme; Robbins, Mark

    2016-08-01

    e2v continues to evolve its product range of sensors and systems, with CCD and CMOS sensors. We describe recent developments of high performance image sensors and precision system components. Several low noise backthinned CMOS sensors have been developed for scientific applications. CCDs have become larger whilst retaining very low noise and high quantum efficiency. Examples of sensors and sub-systems are presented including the recently completed 1.2 GigaPixel J-PAS cryogenic camera.

  18. 基于LPC2106的IIC总线E2PROM的应用

    Institute of Scientific and Technical Information of China (English)

    袁易君

    2008-01-01

    本文利用Proteus软件仿真的特点,提出在此平台上仿真设计I-IC总线E2PROM芯片AT24C02在Arm7内核LPC2106中的应用,用实例说明了LPC21XX系列单片机的标准IIC接口的使用。

  19. 基于LPC2106的IIC总线E2PROM的应用

    Institute of Scientific and Technical Information of China (English)

    袁易君

    2008-01-01

    本文利用Proteus软件仿真的特点,提出在此平台上仿真设计IIC总线E2PROM芯片AT24C02在Arm7内核LPC2106中的应用,用实例说明了LPC21XX系列单片机的标准IIC接口的使用.

  20. Elucidating the Specificity Determinants of the AtxE2 Lasso Peptide Isopeptidase*

    OpenAIRE

    Maksimov, Mikhail O.; Koos, Joseph D.; Zong, Chuhan; Lisko, Bozhena; Link, A. James

    2015-01-01

    Lasso peptide isopeptidase is an enzyme that specifically hydrolyzes the isopeptide bond of lasso peptides, rendering these peptides linear. To carry out a detailed structure-activity analysis of the lasso peptide isopeptidase AtxE2 from Asticcacaulis excentricus, we solved NMR structures of its substrates astexin-2 and astexin-3. Using in vitro enzyme assays, we show that the C-terminal tail portion of these peptides is dispensable with regards to isopeptidase activity. A collection of astex...

  1. Draft Genome Sequence of Brazilian Escherichia coli Uropathogenic Strain E2

    Science.gov (United States)

    Pieta, Luiza; Prichula, Janira; Sambrano, Gustavo E.; Soares, Renata; Caierão, Juliana; Frazzon, Jeverson; d’Azevedo, Pedro A.

    2016-01-01

    Escherichia coli is a common pathogen recovered from cystitis infections. In this report, we announce the draft genome sequence of strain E2 isolated from the urine specimen from a female patient in South Brazil. The genome assembly has 5,081,209 bp, a G+C content of 50.57%, and virulence factors associated with both enteroaggregative and uropathogenic E. coli strains.

  2. Gene Knockdown of Venezuelan Equine Encephalitis Virus E2 Glycoprotein Using DNA-Directed RNA Interference

    Science.gov (United States)

    2006-12-01

    e _s~u~m mary - Introduction: Alphaviruses are a large family of RNA viruses that can cause acute infection resulting in arthritis and encephalitis...One of the important alphaviruses is the Venezuelan equine encephalitis virus. This virus has been linked to a number of outbreaks in both North and... replication of VEE virus in vitro. Bhogal, H.S., McLaws, L.J., and Jager, S.J. 2006. Gene Knockdown of Venezuelan Equine Encephalitis Virus E2

  3. Electrophile-modified lipoic derivatives of PDC-E2 elicits anti-mitochondrial antibody reactivity.

    Science.gov (United States)

    Naiyanetr, Phornnop; Butler, Jeffrey D; Meng, Liping; Pfeiff, Janice; Kenny, Thomas P; Guggenheim, Kathryn G; Reiger, Roman; Lam, Kit; Kurth, Mark J; Ansari, Aftab A; Coppel, Ross L; López-Hoyos, Marcos; Gershwin, M Eric; Leung, Patrick S C

    2011-11-01

    Our laboratory has hypothesized that xenobiotic modification of the native lipoyl moiety of the major mitochondrial autoantigen, the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2), may lead to loss of self-tolerance in primary biliary cirrhosis (PBC). This thesis is based on the finding of readily detectable levels of immunoreactivity of PBC sera against extensive panels of protein microarrays containing mimics of the inner lipoyl domain of PDC-E2 and subsequent quantitative structure-activity relationships (QSARs). Importantly, we have demonstrated that murine immunization with one such mimic, 2-octynoic acid coupled to bovine serum albumin (BSA), induces anti-mitochondrial antibodies (AMAs) and cholangitis. Based upon these data, we have focused on covalent modifications of the lipoic acid disulfide ring and subsequent analysis of such xenobiotics coupled to a 15mer of PDC-E2 for immunoreactivity against a broad panel of sera from patients with PBC and controls. Our results demonstrate that AMA-positive PBC sera demonstrate marked reactivity against 6,8-bis(acetylthio)octanoic acid, implying that chemical modification of the lipoyl ring, i.e. disruption of the S-S disulfide, renders lipoic acid to its reduced form that will promote xenobiotic modification. This observation is particularly significant in light of the function of the lipoyl moiety in electron transport of which the catalytic disulfide constantly opens and closes and, thus, raises the intriguing thesis that common electrophilic agents, i.e. acetaminophen or non-steroidal anti-inflammatory drugs (NSAIDs), may lead to xenobiotic modification in genetically susceptible individuals that results in the generation of AMAs and ultimately clinical PBC.

  4. Organon开始NOMAC/E2的Ⅲ期试验

    Institute of Scientific and Technical Information of China (English)

    杨绍杰(摘)

    2007-01-01

    荷兰Organon制药商称,它已开始评价其新型复合口服避孕药NOMAC/E2(Ⅰ)的Ⅲ期研究,该药是从德国Merck kGaA公司的法国Lab Theramex公司2005年签署的一项协议中得到的。

  5. Effect of layered nanostructures on the linewidth of forbidden E2 transitions

    Science.gov (United States)

    Guzatov, D. V.; Klimov, V. V.

    2017-08-01

    In the framework of classical electrodynamics, analytical expressions are derived and investigated for the linewidth of forbidden E2 transitions in an atom (molecule) located near layered metal – dielectric nanostructures. It is shown that the radiation intensity at the forbidden transition during detection in the halfspace behind a layered nanostructure can significantly exceed the intensity during detection in the half-space where an atom (molecule) is located.

  6. E2-2 Dependent Plasmacytoid Dendritic Cells Control Autoimmune Diabetes.

    Directory of Open Access Journals (Sweden)

    Lisbeth Hansen

    Full Text Available Autoimmune diabetes is a consequence of immune-cell infiltration and destruction of pancreatic β-cells in the islets of Langerhans. We analyzed the cellular composition of the insulitic lesions in the autoimmune-prone non-obese diabetic (NOD mouse and observed a peak in recruitment of plasmacytoid dendritic cells (pDCs to NOD islets around 8-9 weeks of age. This peak coincides with increased spontaneous expression of type-1-IFN response genes and CpG1585 induced production of IFN-α from NOD islets. The transcription factor E2-2 is specifically required for the maturation of pDCs, and we show that knocking out E2-2 conditionally in CD11c+ cells leads to a reduced recruitment of pDCs to pancreatic islets and reduced CpG1585 induced production of IFN-α during insulitis. As a consequence, insulitis has a less aggressive expression profile of the Th1 cytokine IFN-γ and a markedly reduced diabetes incidence. Collectively, these observations demonstrate a disease-promoting role of E2-2 dependent pDCs in the pancreas during autoimmune diabetes in the NOD mouse.

  7. E2-2 Dependent Plasmacytoid Dendritic Cells Control Autoimmune Diabetes

    Science.gov (United States)

    Hansen, Lisbeth; Schmidt-Christensen, Anja; Gupta, Shashank; Fransén-Pettersson, Nina; Hannibal, Tine D.; Reizis, Boris; Santamaria, Pere; Holmberg, Dan

    2015-01-01

    Autoimmune diabetes is a consequence of immune-cell infiltration and destruction of pancreatic β-cells in the islets of Langerhans. We analyzed the cellular composition of the insulitic lesions in the autoimmune-prone non-obese diabetic (NOD) mouse and observed a peak in recruitment of plasmacytoid dendritic cells (pDCs) to NOD islets around 8–9 weeks of age. This peak coincides with increased spontaneous expression of type-1-IFN response genes and CpG1585 induced production of IFN-α from NOD islets. The transcription factor E2-2 is specifically required for the maturation of pDCs, and we show that knocking out E2-2 conditionally in CD11c+ cells leads to a reduced recruitment of pDCs to pancreatic islets and reduced CpG1585 induced production of IFN-α during insulitis. As a consequence, insulitis has a less aggressive expression profile of the Th1 cytokine IFN-γ and a markedly reduced diabetes incidence. Collectively, these observations demonstrate a disease-promoting role of E2-2 dependent pDCs in the pancreas during autoimmune diabetes in the NOD mouse. PMID:26624013

  8. Broadly Neutralizing Alphavirus Antibodies Bind an Epitope on E2 and Inhibit Entry and Egress.

    Science.gov (United States)

    Fox, Julie M; Long, Feng; Edeling, Melissa A; Lin, Hueylie; van Duijl-Richter, Mareike K S; Fong, Rachel H; Kahle, Kristen M; Smit, Jolanda M; Jin, Jing; Simmons, Graham; Doranz, Benjamin J; Crowe, James E; Fremont, Daved H; Rossmann, Michael G; Diamond, Michael S

    2015-11-19

    We screened a panel of mouse and human monoclonal antibodies (MAbs) against chikungunya virus and identified several with inhibitory activity against multiple alphaviruses. Passive transfer of broadly neutralizing MAbs protected mice against infection by chikungunya, Mayaro, and O'nyong'nyong alphaviruses. Using alanine-scanning mutagenesis, loss-of-function recombinant proteins and viruses, and multiple functional assays, we determined that broadly neutralizing MAbs block multiple steps in the viral lifecycle, including entry and egress, and bind to a conserved epitope on the B domain of the E2 glycoprotein. A 16 Å resolution cryo-electron microscopy structure of a Fab fragment bound to CHIKV E2 B domain provided an explanation for its neutralizing activity. Binding to the B domain was associated with repositioning of the A domain of E2 that enabled cross-linking of neighboring spikes. Our results suggest that B domain antigenic determinants could be targeted for vaccine or antibody therapeutic development against multiple alphaviruses of global concern.

  9. Levels of the E2 interacting protein TopBP1 modulate papillomavirus maintenance stage replication

    Energy Technology Data Exchange (ETDEWEB)

    Kanginakudru, Sriramana, E-mail: skangina@iu.edu [Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN (United States); DeSmet, Marsha, E-mail: mdesmet@iupui.edu [Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN (United States); Thomas, Yanique, E-mail: ysthomas@umail.iu.edu [Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN (United States); Morgan, Iain M., E-mail: immorgan@vcu.edu [VCU Philips Institute for Oral Health Research, Virginia Commonwealth University, Richmond, Virginia (United States); Androphy, Elliot J., E-mail: eandro@iu.edu [Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN (United States); Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN (United States)

    2015-04-15

    The evolutionarily conserved DNA topoisomerase II beta-binding protein 1 (TopBP1) functions in DNA replication, DNA damage response, and cell survival. We analyzed the role of TopBP1 in human and bovine papillomavirus genome replication. Consistent with prior reports, TopBP1 co-localized in discrete nuclear foci and was in complex with papillomavirus E2 protein. Similar to E2, TopBP1 is recruited to the region of the viral origin of replication during G1/S and early S phase. TopBP1 knockdown increased, while over-expression decreased transient virus replication, without affecting cell cycle. Similarly, using cell lines harboring HPV-16 or HPV-31 genome, TopBP1 knockdown increased while over-expression reduced viral copy number relative to genomic DNA. We propose a model in which TopBP1 serves dual roles in viral replication: it is essential for initiation of replication yet it restricts viral copy number. - Highlights: • Protein interaction study confirmed In-situ interaction between TopBP1 and E2. • TopBP1 present at papillomavirus ori in G1/S and early S phase of cell cycle. • TopBP1 knockdown increased, over-expression reduced virus replication. • TopBP1 protein level change did not influence cell survival or cell cycle. • TopBP1 displaced from papillomavirus ori after initiation of replication.

  10. E2AODV Protocol for Load Balancing in Ad-Hoc Networks

    Directory of Open Access Journals (Sweden)

    R. S.D. Wahida Banu

    2012-01-01

    Full Text Available Problem statement: In mobile ad hoc networks there are a number of challenges in providing quality of service routing with energy efficiency and load balancing. Most routing protocols do not consider the problem of load balance. A routing protocol called energy Efficient Ad-hoc on Demand Vector (E2AODV is proposed. It addresses the quality of service issues such as throughput, end to end delay, load distribution and energy. Approach: This study presents a scheme to balance the load with energy efficiency considering both congestion and the nodes energy usage. A threshold value was used to judge if intermediate node was overloaded, variable and changing along with nodes interface queue length around the backward path. Results: The routing protocol called energy Efficient Ad hoc on Demand Vector (E2AODV that is intended to provide a reliable transmission with low energy consumption was compared with Ad-hoc on Demand Vector (AODV in terms of the packet delivery ratio, average end to end delay, load distribution and node energy consumption. Conclusion/Recommendation: E2AODV protocol chooses an optimum path with low energy usage. It provides a better scheme to balance the load with energy efficiency and packet delivery ratio. It can be further enhanced as a secure routing protocol for mobile ad-hoc networks.

  11. Identification of a novel molecular partner of the E2A gene in childhood leukemia.

    Science.gov (United States)

    Brambillasca, F; Mosna, G; Colombo, M; Rivolta, A; Caslini, C; Minuzzo, M; Giudici, G; Mizzi, L; Biondi, A; Privitera, E

    1999-03-01

    The 'promiscuous' E2A gene, at 19p13.3, is fused with two different molecular partners, PBX1 and HLF, following two chromosome translocations recurrent in childhood pre-B ALL. We have identified a novel gene, FB1, by virtue of its fusion with E2A and by a combination of molecular techniques. FB1 was localized on 19q13.4, suggesting that the novel chimera originated by a cryptic rearrangement of chromosome 19. Two FB1 transcripts, of 1.2 kb and 1.1 kb, are differentially expressed at low level in a variety of human tissues, including hemopoietic cell lines from different lineages. Accordingly, FB1 cDNA displays high homology with a number of cDNA clones from different human tissues. High homology was found also with cDNA clones from mouse and rat, suggesting that the sequence might be conserved at least among mammals. The function of the putative FB1 protein, however, is currently unknown as database sequence comparisons have failed to reveal strong homology with known proteins. The E2A/FB1 fusion appears to be a recurrent feature of pre-B ALLs, suggesting that it might have a role in the development and/or progression of leukemogenesis.

  12. Identification of ligands that target the HCV-E2 binding site on CD81

    Science.gov (United States)

    Olaby, Reem Al; Azzazy, Hassan M.; Harris, Rodney; Chromy, Brett; Vielmetter, Jost; Balhorn, Rod

    2013-04-01

    Hepatitis C is a global health problem. While many drug companies have active R&D efforts to develop new drugs for treating Hepatitis C virus (HCV), most target the viral enzymes. The HCV glycoprotein E2 has been shown to play an essential role in hepatocyte invasion by binding to CD81 and other cell surface receptors. This paper describes the use of AutoDock to identify ligand binding sites on the large extracellular loop of the open conformation of CD81 and to perform virtual screening runs to identify sets of small molecule ligands predicted to bind to two of these sites. The best sites selected by AutoLigand were located in regions identified by mutational studies to be the site of E2 binding. Thirty-six ligands predicted by AutoDock to bind to these sites were subsequently tested experimentally to determine if they bound to CD81-LEL. Binding assays conducted using surface Plasmon resonance revealed that 26 out of 36 (72 %) of the ligands bound in vitro to the recombinant CD81-LEL protein. Competition experiments performed using dual polarization interferometry showed that one of the ligands predicted to bind to the large cleft between the C and D helices was also effective in blocking E2 binding to CD81-LEL.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-04-06

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

  14. E2 regulates epigenetic signature on Neuroglobin enhancer-promoter in neuronal cells

    Directory of Open Access Journals (Sweden)

    Michela eGuglielmotto

    2016-06-01

    Full Text Available Estrogens are neuroprotective factors in several neurological diseases. Neuroglobin (NGB is one of the estrogen target gene involved in neuroprotection, but little is known about its transcriptional regulation. Estrogen genomic pathway in gene expression regulation is mediated by estrogen receptors (ERα and ERβ that bind to specific regulatory genomic regions. We focused our attention on E2-induced NGB expression in human differentiated neuronal cell lines (SK-N-BE and NT-2. Previously, using bioinformatics analysis we identified a putative enhancer in the first intron of NGB locus. Therefore, we observed that E2 increased the enrichment of the H3K4me3 epigenetic marks at the promoter and of the H3K4me1 and H3K27Ac at the intron enhancer. In these NGB regulatory regions, we found estrogen receptor alpha (ER binding suggesting that ER may mediate chromatin remodeling to induce NGB expression upon E2 treatment. Altogether our data show that NGB expression is regulated by ERa binding on genomic regulatory regions supporting hormone therapy applications for the neuroprotection against neurodegenerative disease.

  15. CMIP5 Historical Simulations (1850-2012) with GISS ModelE2

    Science.gov (United States)

    Miller, Ronald Lindsay; Schmidt, Gavin A.; Nazarenko, Larissa S.; Tausnev, Nick; Bauer, Susanne E.; DelGenio, Anthony D.; Kelley, Max; Lo, Ken K.; Ruedy, Reto; Shindell, Drew T.; hide

    2014-01-01

    Observations of climate change during the CMIP5 extended historical period (1850-2012) are compared to trends simulated by six versions of the NASA Goddard Institute for Space Studies ModelE2 Earth System Model. The six models are constructed from three versions of the ModelE2 atmospheric general circulation model, distinguished by their treatment of atmospheric composition and the aerosol indirect effect, combined with two ocean general circulation models, HYCOM and Russell. Forcings that perturb the model climate during the historical period are described. Five-member ensemble averages from each of the six versions of ModelE2 simulate trends of surface air temperature, atmospheric temperature, sea ice and ocean heat content that are in general agreement with observed trends, although simulated warming is slightly excessive within the past decade. Only simulations that include increasing concentrations of long-lived greenhouse gases match the warming observed during the twentieth century. Differences in twentieth-century warming among the six model versions can be attributed to differences in climate sensitivity, aerosol and ozone forcing, and heat uptake by the deep ocean. Coupled models with HYCOM export less heat to the deep ocean, associated with reduced surface warming in regions of deepwater formation, but greater warming elsewhere at high latitudes along with reduced sea ice. All ensembles show twentieth-century annular trends toward reduced surface pressure at southern high latitudes and a poleward shift of the midlatitude westerlies, consistent with observations.

  16. Identification of ligands that target the HCV-E2 binding site on CD81.

    Science.gov (United States)

    Olaby, Reem Al; Azzazy, Hassan M; Harris, Rodney; Chromy, Brett; Vielmetter, Jost; Balhorn, Rod

    2013-04-01

    Hepatitis C is a global health problem. While many drug companies have active R&D efforts to develop new drugs for treating Hepatitis C virus (HCV), most target the viral enzymes. The HCV glycoprotein E2 has been shown to play an essential role in hepatocyte invasion by binding to CD81 and other cell surface receptors. This paper describes the use of AutoDock to identify ligand binding sites on the large extracellular loop of the open conformation of CD81 and to perform virtual screening runs to identify sets of small molecule ligands predicted to bind to two of these sites. The best sites selected by AutoLigand were located in regions identified by mutational studies to be the site of E2 binding. Thirty-six ligands predicted by AutoDock to bind to these sites were subsequently tested experimentally to determine if they bound to CD81-LEL. Binding assays conducted using surface Plasmon resonance revealed that 26 out of 36 (72 %) of the ligands bound in vitro to the recombinant CD81-LEL protein. Competition experiments performed using dual polarization interferometry showed that one of the ligands predicted to bind to the large cleft between the C and D helices was also effective in blocking E2 binding to CD81-LEL.

  17. Acetic Acid, 2-Undecanone, and (E)-2-Decenal Ultrastructural Malformations on Meloidogyne incognita

    Science.gov (United States)

    Ntalli, Nikoletta; Ratajczak, Marlena; Oplos, Chrisostomos; Menkissoglu-Spiroudi, Urania; Adamski, Zbigniew

    2016-01-01

    The use of natural compounds to control phytonematodes is significantly increasing, as most of the old synthetic pesticides have been banned due to their eco-hostile character. Plant secondary metabolites are now evaluated as biologically active molecules against Meloidogyne spp. but their target site in the nematode body is rarely specified. Herein, we report on the ultrastructure modifications of the Meloidogyne incognita J2 after treatment with nematicidal plant secondary metabolites, that is acetic acid, (E)-2-decenal, and 2-undecanone. The commercial nematicide fosthiazate acting on acetylcholinesterase was used as control. For this reason, scanning electron microscopy and transmission electron microscopy have been employed. The acetic acid mainly harmed the cuticle, degenerated the nuclei of pseudocoel cells, and vacuolised the cytoplasm. The (E)-2-decenal and 2-undecanone did neither harm to the cuticle nor the somatic muscles but they degenerated the pseudocoel cells. (E)-2-decenal caused malformation of somatic muscles. According to the above, the nematicidal compounds seem to enter the nematode body principally via the digestive system rather than the cuticle, since the main part of the damage is internal. PMID:28154431

  18. Assessment of the role of in situ generated (E)-2,4-diene-valproic acid in the toxicity of valproic acid and (E)-2-ene-valproic acid in sandwich-cultured rat hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Surendradoss, Jayakumar; Chang, Thomas K.H.; Abbott, Frank S., E-mail: frank.abbott@ubc.ca

    2012-11-01

    Valproic acid (VPA) undergoes cytochrome P450-mediated desaturation to form 4-ene-VPA, which subsequently yields (E)-2,4-diene-VPA by β-oxidation. Another biotransformation pathway involves β-oxidation of VPA to form (E)-2-ene-VPA, which also generates (E)-2,4-diene-VPA by cytochrome P450-mediated desaturation. Although the synthetic form of (E)-2,4-diene-VPA is more hepatotoxic than VPA as shown in various experimental models, there is no conclusive evidence to implicate the in situ generated (E)-2,4-diene-VPA in VPA hepatotoxicity. The present study investigated the effects of modulating the in situ formation of (E)-2,4-diene-VPA on markers of oxidative stress (formation of 2′,7′-dichlorofluorescein; DCF), steatosis (accumulation of BODIPY 558/568 C{sub 12}), necrosis (release of lactate dehydrogenase; LDH), and on cellular total glutathione (GSH) levels in sandwich-cultured rat hepatocytes treated with VPA or (E)-2-ene-VPA. Treatment with either of these chemicals alone increased each of the toxicity endpoints. In VPA-treated hepatocytes, (E)-2,4-diene-VPA was detected only at trace levels, even after phenobarbital (PB) pretreatment and there was no effect on the toxicity of VPA. Furthermore, pretreatment with a cytochrome P450 enzyme inhibitor, 1-aminobenzotriazole (1-ABT), did not influence the extent of VPA toxicity in both PB-pretreated and vehicle-pretreated hepatocytes. However, in (E)-2-ene-VPA-treated hepatocytes, PB pretreatment greatly enhanced the levels of (E)-2,4-diene-VPA and this was accompanied by a further enhancement of the effects of (E)-2-ene-VPA on DCF formation, BODIPY accumulation, LDH release, and GSH depletion. Pretreatment with 1-ABT reduced the concentrations of (E)-2,4-diene-VPA and the extent of (E)-2-ene-VPA toxicity; however, this occurred in PB-pretreated hepatocytes, but not in control hepatocytes. In conclusion, in situ generated (E)-2,4-diene-VPA is not responsible for the hepatocyte toxicity of VPA, whereas it

  19. E2F1 promote the aggressiveness of human colorectal cancer by activating the ribonucleotide reductase small subunit M2

    Energy Technology Data Exchange (ETDEWEB)

    Fang, Zejun [Sanmen People' s Hospital of Zhejiang, Sanmen, Zhejiang, 317100 (China); Gong, Chaoju [Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058 (China); Liu, Hong [Zhejiang Normal University – Jinhua People' s Hospital Joint Center for Biomedical Research, Jinhua, Zhejiang, 321004 (China); Zhang, Xiaomin; Mei, Lingming [Sanmen People' s Hospital of Zhejiang, Sanmen, Zhejiang, 317100 (China); Song, Mintao [Department of Pathophysiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS), School of Basic Medicine, Peking Union Medical College (PUMC), Beijing, 100005 (China); Qiu, Lanlan; Luo, Shuchai; Zhu, Zhihua; Zhang, Ronghui; Gu, Hongqian [Sanmen People' s Hospital of Zhejiang, Sanmen, Zhejiang, 317100 (China); Chen, Xiang, E-mail: sychenxiang@126.com [Sanmen People' s Hospital of Zhejiang, Sanmen, Zhejiang, 317100 (China)

    2015-08-21

    As the ribonucleotide reductase small subunit, the high expression of ribonucleotide reductase small subunit M2 (RRM2) induces cancer and contributes to tumor growth and invasion. In several colorectal cancer (CRC) cell lines, we found that the expression levels of RRM2 were closely related to the transcription factor E2F1. Mechanistic studies were conducted to determine the molecular basis. Ectopic overexpression of E2F1 promoted RRM2 transactivation while knockdown of E2F1 reduced the levels of RRM2 mRNA and protein. To further investigate the roles of RRM2 which was activated by E2F1 in CRC, CCK-8 assay and EdU incorporation assay were performed. Overexpression of E2F1 promoted cell proliferation in CRC cells, which was blocked by RRM2 knockdown attenuation. In the migration and invasion tests, overexpression of E2F1 enhanced the migration and invasion of CRC cells which was abrogated by silencing RRM2. Besides, overexpression of RRM2 reversed the effects of E2F1 knockdown partially in CRC cells. Examination of clinical CRC specimens demonstrated that both RRM2 and E2F1 were elevated in most cancer tissues compared to the paired normal tissues. Further analysis showed that the protein expression levels of E2F1 and RRM2 were parallel with each other and positively correlated with lymph node metastasis (LNM), TNM stage and distant metastasis. Consistently, the patients with low E2F1 and RRM2 levels have a better prognosis than those with high levels. Therefore, we suggest that E2F1 can promote CRC proliferation, migration, invasion and metastasis by regulating RRM2 transactivation. Understanding the role of E2F1 in activating RRM2 transcription will help to explain the relationship between E2F1 and RRM2 in CRC and provide a novel predictive marker for diagnosis and prognosis of the disease. - Highlights: • E2F1 promotes RRM2 transactivation in CRC cells. • E2F1 promotes the proliferation of CRC cells by activating RRM2. • E2F1 promotes the migration and

  20. The prostaglandin E2 receptor EP4 is integral to a positive feedback loop for prostaglandin E2 production in human macrophages infected with Mycobacterium tuberculosis.

    Science.gov (United States)

    Nishimura, Tomoyasu; Zhao, Xiaomin; Gan, Huixian; Koyasu, Shigeo; Remold, Heinz G

    2013-09-01

    Prostaglandin E2 (PGE2) is an important biological mediator involved in the defense against Mycobacterium tuberculosis (Mtb) infection. Previously, we reported that in macrophages (Mϕs), infection with avirulent Mtb H37Ra resulted in inhibition of necrosis by an inhibitory effect on mitochondrial permeability transition via the PGE2 receptor EP2. However, human Mϕs also express EP4, a PGE2 receptor functionally closely related to EP2 that also couples to stimulatory guanine nucleotide binding protein, but the functional differences between EP2 and EP4 in Mtb-infected Mϕs have been unclear. EP4 antagonist addition to H37Ra-infected Mϕs inhibited the expression of cyclooxygenase 2 (COX2) and microsomal prostaglandin E synthase-1 (mPGES-1), which are involved in PGE2 production. Moreover, H37Ra infection induced PGE2 production through the Toll-like receptor (TLR) 2/p38 mitogen-activated protein kinase (MAPK) signaling pathway. Induction of COX2 and mPGES-1 expression by TLR2 stimulation or Mtb infection was increased after additional stimulation with EP4 agonist. Hence, in Mtb-infected Mϕs, PGE2 production induced by pathogen recognition receptors/p38 MAPK signaling is up-regulated by EP4-triggered signaling to maintain an effective PGE2 concentration.

  1. Double-balloon catheter and sequential vaginal prostaglandin E2 versus vaginal prostaglandin E2 alone for induction of labor after previous cesarean section.

    Science.gov (United States)

    Kehl, Sven; Weiss, Christel; Wamsler, Michael; Beyer, Jana; Dammer, Ulf; Heimrich, Jutta; Faschingbauer, Florian; Sütterlin, Marc; Beckmann, Matthias W; Schleussner, Ekkehard

    2016-04-01

    To evaluate the efficacy of inducing labor using a double-balloon catheter and vaginal prostaglandin E2 (PGE2) sequentially, in comparison with vaginal PGE2 alone after previous cesarean section. A total of 264 pregnant women with previous cesarean section undergoing labor induction at term were included in this prospective multicentre cohort study. Induction of labor was performed either by vaginal PGE2 gel or double-balloon catheter followed by vaginal PGE2. The primary outcome measure was the cesarean section rate. The cesarean section rate was 37 % without any statistically significant difference between the two groups (PGE2: n = 41, 37 % vs. balloon catheter/PGE2: n = 41, 42 %; P = 0.438). The median (range) number of applications of PGE2 [2 (1-10) versus 1 (0-8), P cesarean section were "no previous vaginal delivery" (OR 5.391; CI 2.671-10.882) and "no oxytocin augmentation during childbirth" (OR 2.119; CI 1.215-3.695). The sequential application of double-balloon catheter and vaginal PGE2 is as effective as the sole use of vaginal PGE2 with less applications and total amount of PGE2.

  2. (Z-2-(4-{[(E-2-Hydroxybenzylidene]amino}phenyl-3-[4-(1,4,7,10-tetraoxa-13-azacyclopentadecan-13-ylphenyl]acrylonitrile

    Directory of Open Access Journals (Sweden)

    Xin Zhang

    2016-10-01

    Full Text Available The title compound, C32H35N3O5, is an important fluorescence probe. It is composed of a 1,4,7,10-tetraoxa-13λ2-azacyclopentadecane unit linked to a twisted (Z-2-(4-{[(E-2-hydroxybenzylidene]amino}phenyl-3-phenylacrylonitrile chain. In the molecule, an O—H...N hydrogen bond forms an S(6 ring motif. There is also in intramolecular C—H...N hydrogen bond in the azacrown ether moiety, which also forms an S(6 ring motif. In the crystal, molecules are linked via pairs of C—H...O hydrogen bonds, forming inversion dimers.

  3. Oct3/4 directly regulates expression of E2F3a in mouse embryonic stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Kanai, Dai; Ueda, Atsushi; Akagi, Tadayuki; Yokota, Takashi; Koide, Hiroshi, E-mail: hkoide@med.kanazawa-u.ac.jp

    2015-04-10

    Embryonic stem (ES) cells, derived from the inner cell mass of blastocysts, have a characteristic cell cycle with truncated G1 and G2 phases. Recent findings that suppression of Oct3/4 expression results in a reduced proliferation rate of ES cells suggest the involvement of Oct3/4 in the regulation of ES cell growth, although the underlying molecular mechanism remains unclear. In the present study, we identified E2F3a as a direct target gene of Oct3/4 in ES cells. Oct3/4 directly bound to the promoter region of the E2F3a gene and positively regulated expression of E2F3a in mouse ES cells. Suppression of E2F3a activity by E2F6 overexpression led to the reduced proliferation in ES cells, which was relieved by co-expression of E2F3a. Furthermore, cell growth retardation caused by loss of Oct3/4 was rescued by E2F3a expression. These results suggest that Oct3/4 upregulates E2F3a expression to promote ES cell growth. - Highlights: • Oct3/4 positively regulates E2F3a expression in ES cells. • Oct3/4 binds to the promoter region of the E2F3a gene. • Overexpression of E2F6, an inhibitor of E2F3a, reduces ES cell growth. • E2F3a recovers growth retardation of ES cells caused by Oct3/4 reduction.

  4. Detection of vibrationally excited methyl formate in W51 e2

    Science.gov (United States)

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

    2008-10-01

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

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  6. Preparation and characterization of antisera against recombinant E2 protein of bovine viral diarrhea virus%牛病毒性腹泻病毒E2蛋白的多克隆抗体制备及鉴定

    Institute of Scientific and Technical Information of China (English)

    高欲燃; 朱远茂; 康健; 史鸿飞; 李娇; 任宪刚; 冯军科; 于作; 薛飞

    2011-01-01

    To prepare the polyclonal antibody against recombinant E2 protein of bovine viral diarrhea virus (BVDV) in rabbits, E. coli BL21 (DE3) was transformed with the recombinant plasmid pET30a-E2. The recombinant E2 protein was expressed in E. coli after cultivation and induction. The purified recombinant E2 protein could be recognized by specific BVDV antisera in western blot. Then the purified recombinant E2 protein was used as antigen for immunizing rabbit to prepare polyclonal antibody against the recombinant E2 protein. The result of virus nentralization test showed that the titer of the polyclonal antibody to neutralize BVDV was 1:2,048. The polyclonal antibody against the recombinant E2 protein of BVDV also had highly reactivity and specialty in immunofluorescence analysis and western blot. The polyclonal antibody against recombinant E2 protein of BVDV developed in rabbits could be used in detection of BVDV in China and provided a good basis for establishing an ELISA for detecting of E2 protein of BVDV.%为制备牛病毒性腹泻病毒(BVDV)重组E2蛋白的兔源多克隆抗体,本研究利用表达BVDV E2蛋白的重组质粒pET30a-E2转化E.coli BL21(DE3),经诱导表达获得重组E2蛋白.Western blot检测显示纯化蛋白能够与BVDV参考阳性血清反应.以纯化的重组E2蛋白免疫新西兰白兔制备多克隆抗体,病毒中和试验测定其中和效价为1:2 048,间接免疫荧光和western blot试验表明其具有良好的反应性和特异性.本研究制备的BVDV重组E2蛋白兔源多克隆抗体可应用于BVDV的检测,同时为进一步建立检测BVDV E2蛋白的ELISA方法奠定基础.

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

    DEFF Research Database (Denmark)

    Mannervik, M; Fan, S; Ström, A C

    1999-01-01

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

  8. Heterodimerization of the transcription factors E2F-1 and DP-1 leads to cooperative trans-activation

    DEFF Research Database (Denmark)

    Helin, K; Wu, C L; Fattaey, A R;

    1993-01-01

    the hypophosphorylated form of the retinoblastoma protein (pRB). The other protein, murine DP-1, was purified from an E2F DNA-affinity column, and it was subsequently shown to bind the consensus E2F DNA-binding site. To study a possible interaction between E2F-1 and DP-1, we have now isolated a cDNA for the human...... is required for stable interaction with pRB in vivo and that trans-activation by E2F-1/DP-1 heterodimers is inhibited by pRB. We suggest that "E2F" is the activity that is formed when an E2F-1-related protein and a DP-1-related protein dimerize....

  9. Epidermal growth factor receptor transactivation by intracellular prostaglandin E2-activated prostaglandin E2 receptors. Role in retinoic acid receptor-β up-regulation.

    Science.gov (United States)

    Fernández-Martínez, Ana B; Lucio Cazaña, Francisco J

    2013-09-01

    The pharmacological modulation of renoprotective factor vascular endothelial growth factor-A (VEGF-A) in the proximal tubule has therapeutic interest. In human proximal tubular HK-2 cells, treatment with all-trans retinoic acid or prostaglandin E2 (PGE2) triggers the production of VEGF-A. The pathway involves an initial increase in intracellular PGE2, followed by activation of EP receptors (PGE2 receptors, most likely an intracellular subset) and increase in retinoic acid receptor-β (RARβ) expression. RARβ then up-regulates transcription factor hypoxia-inducible factor-1α (HIF-1α), which increases the transcription and production of VEGF-A. Here we studied the role in this pathway of epidermal growth factor receptor (EGFR) transactivation by EP receptors. We found that EGFR inhibitor AG1478 prevented the increase in VEGF-A production induced by PGE2- and all-trans retinoic acid. This effect was due to the inhibition of the transcriptional up-regulation of RARβ, which resulted in loss of the RARβ-dependent transcriptional up-regulation of HIF-1α. PGE2 and all-trans retinoic acid also increased EGFR phosphorylation and this effect was sensitive to antagonists of EP receptors. The role of intracellular PGE2 was indicated by two facts; i) PGE2-induced EGFR phosphorylation was substantially prevented by inhibitor of prostaglandin uptake transporter bromocresol green and ii) all-trans retinoic acid treatment, which enhanced intracellular but not extracellular PGE2, had lower effect on EGFR phosphorylation upon pre-treatment with cyclooxygenase inhibitor diclofenac. Thus, EGFR transactivation by intracellular PGE2-activated EP receptors results in the sequential activation of RARβ and HIF-1α leading to increased production of VEGF-A and it may be a target for the therapeutic modulation of HIF-1α/VEGF-A. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Localization of Cyclo-Oxygenase and Prostaglandin E2 in the Secretory Granule of the Mast Cell

    Science.gov (United States)

    1989-01-01

    cascade during exocytosis. Keywords: Cyclo-oxygenase; Prostaglandin E2; Secretory granules; Mast cell ; Exocytosis; Lipid mediators; Inflammation; Arachidonic acid; Eicosanoids; Immunocytochemistry; Reprints. (KT)

  11. Sequence Variation in the E2-Binding Domain of HPV16 and Biological Function Evaluation in Tunisian Cervical Cancers

    Directory of Open Access Journals (Sweden)

    Saloua Kahla

    2014-01-01

    Full Text Available HPV16 E2 variants have different effects on the transcriptional activity of the LCR. In this study, we examined the nucleotide and amino acid sequence variation within the HPV16 E2 gene and to correlate with disease progression. E2 gene disruption was detected by PCR amplification of the entire E2 gene using a single set of primers. Nucleotide variations were analyzed by bidirectional sequencing. mRNA expression patterns of E6 and E7 gene transcripts were evaluated by a reverse transcriptase-PCR method (RT-PCR. The detection of intact E2 genes was significantly higher among controls than cases (81.8% versus 37.5%, resp., PA results in the amino acid substitution T310K and was more common among the E2 undisrupted cases (7/9; 77.7%, compared to controls (2/9; 22.2%. In addition, specific sequence variations identified in the E2 ORF at positions 3684 C>A were associated with increased viral oncogenes E6-E7 production. Besides HPV16 E2 disruption, the 3684 C>A variation within undisrupted E2 genes could be involved in an alternative mechanism for deregulating the expression of the HPV16 E6 and E7 oncogenes and appears to be a major factor contributing to the development of cervical cancer in Tunisian women.

  12. Maturation of the uterine cervix by repeated intracervical instillation of prostaglandin E2.

    Science.gov (United States)

    Milliez, J M; Jannet, D; Touboul, C; el Medjadji, M; Paniel, B J

    1991-09-01

    An attempt was made to ripen the uterine cervix in 100 high-risk pregnancy patients (pregnancy between 34 to 41 weeks' gestation), with the use of intracervical instillations of 0.25 mg of prostaglandin E2 mixed with a tylose gel. The maturation process was repeated every 48 hours. Forty-nine patients were delivered of infants after the first maturation and 51 patients required between two and nine instillations. In patients requiring multiple instillations, the mean delay between the first procedure and delivery was 9 +/- 4 days (range, 2.4 to 16 days). Among the 59 nulliparous women, only 23 were delivered of infants after a single maturation and 36 required multiple maturations (p less than 0.02). When the group of patients who were delivered of infants after a single maturation process was compared with the group requiring multiple maturations, no difference could be seen with regard to age, term of pregnancy, or Bishop cervical score at the time of inclusion in the study. The myometrial activity and the onset labor induced by prostaglandin E2, were similar in both groups. Fetal heart rate decelerations occurred in 16.3% (8/49) of the patients with single maturations and in 17.6% (9/51) of the patients who required multiple maturations. The outcome of the pregnancy and the rate of cesarean sections (24% and 27%) were similar in both groups. No patients required cesarean sections because of failed induction of labor. Cervical ripening after repeated applications of 0.25 mg of prostaglandin E2 seems to be safe for the fetus, providing that the patient is closely supervised.

  13. [Induced abortion using prostaglandin E2 and F2alpha gel].

    Science.gov (United States)

    Lippert, T H; Modly, T

    1974-01-01

    In this study of 20 patients in the 13th-17th week of pregnancy abortion was induced with intrauterine, extraamniotic application of prostaglandins (PG) E2 or F2 in gel form. The gel composition was as follows: 4% tylose MH 300, 2% glycerine, 1% chlorhexidine digluconate, 83% sterile distilled water and 10% PG stock solution. Both PGE2 and PGF2 gels were used. Final concentration was 2.5 mg E2 or 2.5 mg F2 per g of gel. Gel was applied via transcervical, extraamniotic polyethylene catheter every 2-3 hours. Results: PGE2-gel was used in 14 cases. After 3-4 applications both fetus and placenta were expelled. Average dose used was 4.6 mg E2/patient. First contractions started in 30 minutes; induction to expulsion time was 11 hours 35 minutes. F2-gel given to 6 patients resulted in expulsion of the fetus in all cases but placenta needed removal by curettage in 4 patients. Average dose per patient was 17.7 mg of F2; first contractions in 30 minutes, average expulsion time 17 hours 38 minutes. With both PGs there were painful contractions which were controlled with a combination of pentazocine and Valium. PGE2 caused vomiting in 5 patients. No increased bleeding or postabortion infection occurred. Follow-up curettage was done in all patients to ensure removal of all tissues. Overall evaluation of the PG-gels was considered good. PG stability in gel form is good; during 8 months of preservation in sterile aluminum tubes at -25 degrees Celsius no decline in clinical effectiveness was noted. The gel application is less expensive than the slow-injection pump method.

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

    Science.gov (United States)

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

    2016-05-01

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

  15. On-orbit calibration of soft X-ray detector on Chang'E-2 satellite

    Science.gov (United States)

    Xiao, Hong; Peng, Wen-Xi; Wang, Huan-Yu; Cui, Xing-Zhu; Guo, Dong-Ya

    2015-10-01

    The X-ray spectrometer is one of the satellite payloads on the Chang'E-2 satellite. The soft X-ray detector is one of the devices on the X-ray spectrometer, designed to detect the major rock-forming elements within the 0.5-10 keV range on the lunar surface. In this paper, energy linearity and energy resolution calibration is done using a weak 55Fe source. Temperature and time effects are found not to give a large error. The total uncertainty of calibration is estimated to be within 5% after correction. Supported by National Science Foundation of Ministry of Education

  16. Cervical priming and labor induction by multiple doses of intracervical prostaglandin E2 gel.

    Science.gov (United States)

    Norchi, S; Zanini, A; Regalia, A L; Pollini, A; Silva, A

    1992-05-01

    One hundred seventy-two term pregnant women with medical or obstetric conditions requiring induction of labor were treated with intracervical administration of 0.5 mg prostaglandin E2 in tylose gel. Multiple administrations were necessary in 42 cases (24.4%), two administrations in 31 cases (18.0%) and three administrations in 11 cases (6.4%). Intracervical administration of PGE2 tylose gel (0.5 mg dose) is useful to prime the cervix, induce labor, and significantly modify Bishop score.

  17. Routine induction of labour with extra-amniotic prostaglandin E2 in a viscous gel.

    Science.gov (United States)

    Sims, C D; Mellows, H J; Spencer, P J; Craft, I L

    1979-07-01

    Prostaglandin E2, 350 microgram dispersed in a viscous gel, tylose, was introduced into the extra-amniotic space as a single dose in 285 patients to induce labour. With a favourable cervix, 82 per cent of multiparae and 50 per cent of primiparae were successfully induced. With unfavourable induction features, the success rates were 48 per cent and 24 per cent respectively. In the remaining patients, all but four were successfully delivered when intravenous oxytocin was also used. The method was safe, simple and inexpensive and had many advantages for patients and nursing staff.

  18. Interband B (E2) ratios in the rigid triaxial model, a review

    Science.gov (United States)

    Gupta, J. B.; Sharma, S.

    1989-01-01

    Uptodate accurate extensive data on γ-g B(E2) ratios for even-even rare-earth nuclei is compared with the predictions of the rigid triaxial model of collective rotation to search for a correlation between the nuclear structure variation with Z, N and the γ0 parameter of the model. The internal consistency in the predictions of the model is investigated and the spectral features vis-a-vis the γ-soft and the γ-rigid potential are discussed.

  19. NPAT expression is regulated by E2F and is essential for cell cycle progression

    DEFF Research Database (Denmark)

    Gao, Guang; Bracken, Adrian P; Burkard, Karina

    2003-01-01

    NPAT is an in vivo substrate of cyclin E-Cdk2 kinase and is thought to play a critical role in coordinated transcriptional activation of histone genes during the G(1)/S-phase transition and in S-phase entry in mammalian cells. Here we show that NPAT transcription is up-regulated at the G(1)/S...... by small interfering RNA duplexes impedes cell cycle progression and histone gene expression in tissue culture cells. Thus, NPAT is an important E2F target that is required for cell cycle progression in mammalian cells. As NPAT is involved in the regulation of S-phase-specific histone gene transcription...

  20. The effect of prostaglandin E2 and arachidonic acid on dentinogenesis in pigs.

    Science.gov (United States)

    Burke, A; Weiler, H

    2001-01-01

    The rate of dentinogenesis for the pig is quantified and the effects of dietary arachidonic acid supplementation and/or exogenous prostaglandin on dentine formation are defined. Thirty-six pigs were randomised to four groups, receiving either standard or supplemented formula and either prostaglandin E2 or placebo injections for fifteen days. Double tetracycline banding is used to measure rate of growth in the teeth. The average rate of dentinogenesis for all the study animals is 17.96 microm/day. Results show that the rate of dentinogenesis is not significantly affected by the interaction of hormone and dietary supplementation.

  1. On-orbit calibration of soft X-ray detector on Chang'E-2 satellite

    CERN Document Server

    Xiao, Hong; Wang, Huanyu; Cui, Xingzhu; Guo, Dongya

    2015-01-01

    X-ray spectrometer is one of the satellite payloads on Chang'E-2 satellite. The soft X-ray detector is one of the device on X-ray spectrometer which is designed to detect the major rock-forming elements within 0.5-10keV range on lunar surface. In this paper, energy linearity and energy resolution calibration is done using a weak Fe55 source, while temperature and time effect is considered not take big error. The total uncertainty is estimated to be within 5% after correction.

  2. E2 transitions between excited single-phonon states: Role of ground-state correlations

    Energy Technology Data Exchange (ETDEWEB)

    Kamerdzhiev, S. P. [National Research Centre Kurchatov Institute (Russian Federation); Voitenkov, D. A., E-mail: dvoytenkov@ippe.ru [Institute for Physics and Power Engineering (Russian Federation)

    2016-11-15

    The probabilities for E2 transitions between low-lying excited 3{sup −} and 5{sup −} single-phonon states in the {sup 208}Pb and {sup 132}Sn magic nuclei are estimated on the basis of the theory of finite Fermi systems. The approach used involves a new type of ground-state correlations, that which originates from integration of three (rather than two, as in the random-phase approximation) single-particle Green’s functions. These correlations are shown to make a significant contribution to the probabilities for the aforementioned transitions.

  3. Role of putative neurotransmitters in the central gastric antisecretory effect of prostaglandin E2 in rats.

    OpenAIRE

    Puurunen, J.

    1985-01-01

    The role of putative neurotransmitters of the central nervous system in the central gastric antisecretory effect of prostaglandin E2 (PGE2) was investigated in pylorus-ligated rats. Pretreatment of the rats with an intracerebroventricular (i.c.v.) injection of 6-hydroxydopamine (6-OHDA) prevented the antisecretory effect of the i.c.v. administration of PGE2, whereas pretreatment with 5,6-dihydroxytryptamine (5,6-DHT) plus p-chlorophenylalanine (PCPA) had no effect. I.c.v.-administered phentol...

  4. Post-collision interactions and the polarization effect in (e, 2e) collisions of helium

    Institute of Scientific and Technical Information of China (English)

    Zang Shuang-Shuang; Ge Zi-Ming

    2012-01-01

    A modified distorted-wave Born approximation (DWBA) method is used to calculate the triple differential cross sections (TDCSs) in a coplanar asymmetric geometry for the electron impact single ionization of a He (1s2) atom at intermediate and lower energies.The post-collision interaction and the polarization effect in (e,2e) collisions of helium are considered in the calculations.The polarization potentials from the damping method and density functional theory (DFT) arc compared.Theoretical results are compared with the recent experimental data.

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

    Science.gov (United States)

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

    2004-12-01

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

  6. An Embedding for the E2-term of the Adams Spectral Sequence at Odd Primes

    Institute of Scientific and Technical Information of China (English)

    Maurizio BRUNETTI; Adriana CIAMPELLA; Luciano A. LOMONACO

    2006-01-01

    Let p be an odd prime. In this paper we introduce a quadratic linear Fp-algebra Q1 obtained by suitably changing the generators of Q, the homogeneous quadratic algebra of cohomology operations in the category of H∞-ring spectra, and study the map induced on cohomology by the quotient (π): Q1 → Ap.Like in the case p = 2, it turns out that (π)* is injective. Thus, its target contains the E2-term of the classical Adams spectral sequence as subalgebra. An explicit description of ExtQ1 (Fp, Fp) is given under the reasonable assumption on Q to be a Koszul algebra.

  7. Event display of a H -> 2e2mu candidate event

    CERN Multimedia

    ATLAS, Collaboration

    2012-01-01

    Event display of a H -> 2e2mu candidate event with m(4l) = 122.6 (123.9) GeV without (with) Z mass constraint. The masses of the lepton pairs are 87.9 GeV and 19.6 GeV. The event was recorded by ATLAS on 18-Jun-2012, 11:07:47 CEST in run number 205113 as event number 12611816. Zoom into the tracking detector. Muon tracks are colored red, electron tracks and clusters in the LAr calorimeter are colored green.

  8. International Conference on Harmonisation; guidance on E2E Pharmacovigilance Planning; availability. Notice.

    Science.gov (United States)

    2005-04-01

    The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled "E2E Pharmacovigilance Planning." The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The guidance describes a method for summarizing the important potential and identified risks of a drug. It proposes a structure for a pharmacovigilance plan and sets out principles of good practice for the design and conduct of observational studies. The guidance is intended to aid in planning pharmacovigilance activities, especially in preparation for the early postmarketing period of a new drug.

  9. Gene synthesis,cloning,prokaryotic expression and analysis of chikungunya virus E2 glycoprotein%基孔肯雅病毒包膜蛋白E2的全基因合成及原核表达

    Institute of Scientific and Technical Information of China (English)

    章萍萍; 邓松华; 潘卫; 曹洁; 陈秋莉; 王锦红; 张华群; 葛宜兵; 祁培培; 刘超

    2012-01-01

    目的 通过对全长基孔肯雅病毒包膜蛋白E2(CHIKV-E2,1~404 aa)及其跨膜疏水区(351~378 aa)缺失突变体E2(1~350 aa)进行原核表达,分析跨膜疏水区对E2蛋白在大肠杆菌中表达的影响.方法 利用ExPasy预测软件对E2蛋白跨膜疏水区进行预测分析,根据GenBank数据库中CHIKV-E2氨基酸序列获得其对应的基因序列.结合重叠延伸PCR(OE-PCR) 原理设计用于全基因合成的核酸引物对CHIKV-E2全长基因(404 aa)进行体外合成,构建全长E2蛋白及其缺失突变体原核表达质粒,将序列正确的两种重组质粒分别转至E.coli BL21(DE3),经IPTG诱导表达,SDS-PAGE检测重组质粒的表达情况.结果 OE-PCR法成功合成了大小为1 212 bp的编码CHIKV-E2(1~404 aa)蛋白的全长基因,构建了全长E2蛋白及其缺失突变体重组表达质粒 pET21b-E2(1~404)和pET21b-E2(1~350),经IPTG诱导表达后,SDS-PAGE结果显示缺失突变体pET21b-E2(1~350)融合蛋白表达量较pET21b-E2(1~404)有明显提高.结论 E2蛋白跨膜疏水区(351~378 aa)对该蛋白的原核表达具有重要影响,缺失该疏水区的突变体在大肠杆菌中表达量比全长E2蛋白表达量明显提高.%Objective To analyze the impact of hydrophobic transmembrane domain of chikimgunya vims E2 glyco-proteins on E2 expression in E. Coli by comparing E2 expression with the hydrophobic transmembrane domain-deleted mutant. Methods On-line software ExPasy was used to predict transmembrane domain of E2 protein and optimized gene sequence encoding E2 protein was obtained according to amino acids of the protein from GenBank; Primers were designed to synthesize E2 gene according to the principle of OE-PCR and prokaryotic expression plasmids of full-length E2 protein and its mutant were constructed. After being transfromed into E. Coli BL21( DE3 ), two plasmids in E. Coli were induced to express by IPTG and protein expression was identified by SDS-PAGE. Results In the study, the gene encoding CHIKV-E

  10. A comprehensive modular map of molecular interactions in RB/E2F pathway.

    Science.gov (United States)

    Calzone, Laurence; Gelay, Amélie; Zinovyev, Andrei; Radvanyi, François; Barillot, Emmanuel

    2008-01-01

    We present, here, a detailed and curated map of molecular interactions taking place in the regulation of the cell cycle by the retinoblastoma protein (RB/RB1). Deregulations and/or mutations in this pathway are observed in most human cancers. The map was created using Systems Biology Graphical Notation language with the help of CellDesigner 3.5 software and converted into BioPAX 2.0 pathway description format. In the current state the map contains 78 proteins, 176 genes, 99 protein complexes, 208 distinct chemical species and 165 chemical reactions. Overall, the map recapitulates biological facts from approximately 350 publications annotated in the diagram. The network contains more details about RB/E2F interaction network than existing large-scale pathway databases. Structural analysis of the interaction network revealed a modular organization of the network, which was used to elaborate a more summarized, higher-level representation of RB/E2F network. The simplification of complex networks opens the road for creating realistic computational models of this regulatory pathway.

  11. Characterization of the Ubiquitin E2 Enzyme Variant Gene Family in Arabidopsis

    Institute of Scientific and Technical Information of China (English)

    Yu Zhang; Pei Wen; On-Sun Lau; Xing-Wang Deng

    2007-01-01

    Ubiquitin E2 enzyme variant (UEV) proteins are similar to ubiquitin-conjugating enzyme (E2) in both sequence and structure, but the lack of a catalytic cysteine residue renders them incapable of forming a thiolester linkage with ubiquitin. While the functional roles of several UEVs have been defined in yeast and animal systems, Arabidopsis COP10, a photomorphogenesis repressor, is the only UEV characterized in plants. Phylogenetic analysis revealed that the eight Arabidopsis UEV genes belong to three subfamilies.The expression of those genes is supported by either the presence of ESTs or RT-PCR analysis. We also characterized the other members of the COP10 subfamily, UEV2. Semi-quantitative RT-PCR analysis indicated that the UEV2 transcripts can be detected in most organs of Arabidopsis. Analysis of UEV2::GUS transgenic lines also showed its ubiquitous expression in nearly all the developmental stages of Arabidopsis.Transient expression analysis indicated that the sGFP-UEV2 fusion protein can localize to both the cytoplasm and nucleus. A T-DNA insertion mutant, uev2-1, which abolished the transcription of UEV2, displays no visible phenotype. Further, the cop10-4 uev2-1 double mutant exhibits the same phenotype as the cop10-4mutant in darkness. UEV2 is therefore not functionally redundant with COP10.

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

    Science.gov (United States)

    Lykke, Julie M.; Favre, Cécile

    2014-07-01

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

  13. NOAO E2E Integrated Data Cache Initiative Using iRODS

    Science.gov (United States)

    Barg, I.; Scott, D.; Timmermann, E.

    2011-07-01

    The NOAO Mass Storage System (MSS) holds astronomical data collected from about two dozen different scientific instruments at eleven telescopes on three mountain tops in two different countries both north and south of the Equator. Data are transferred via the net, from each mountain to Data Centers in La Serena, Chile and Tucson, Arizona. Then replicated across both hemispheres. A third copy is saved on tape at NCSA. This system is collectively called the End-to-End system (E2E). The data flow and file repository management is accomplished using a collection of custom code built on top of the Storage Resource Broker (SRB) developed by Data Intensive Cyber Environments (DICE) research group at the University of North Carolina at Chapel Hill, and the Institute for Neural Computation at the University of California, San Diego. iRODS, the Integrated Rule-Oriented Data System, is a data grid software system developed by DICE and collaborators and the successor to SRB. Both SRB and iRODS provide the ability to manage large amounts of data which can be distributed across data centers. This paper will describe why NOAO Science Data Management (SDM) chose iRODS as the next generation file repository management system for the E2E data management system.

  14. The identification of prostaglandins E2, F2α and A2 from rabbit kidney medulla

    Science.gov (United States)

    Lee, J. B.; Crowshaw, K.; Takman, B. H.; Attrep, Katherine A.; Gougoutas, J. Z.

    1967-01-01

    Rabbit kidney medulla (10kg.) was homogenized in 5mm-disodium hydrogen phosphate and deproteinized with ethanol, and the concentrated supernatant solution was extracted at pH8 with light petroleum and at pH2 with chloroform. The acidic lipids present in the chloroform phase were separated on silicic acid columns into three biologically active fractions. The first fraction contained only vasodepressor activity; the second fraction contained both vasodepressor and non-vascular-smooth-muscle-stimulating activity; the third fraction contained both vasopressor and non-vascular-smooth-muscle-stimulating activity. Purification of each fraction by reversed-phase partition and thick-layer chromatography yielded three pure acids. Thin-layer chromatographic, spectroscopic and mass-spectral analysis of the acids and their methyl esters established their structures as prostaglandins E2, F2α and A2. Evidence is presented demonstrating that part or all of the prostaglandin A2 is formed during the isolation procedures from endogenous prostaglandin E2. PMID:16742553

  15. Prostaglandin E2 stimulates Fas ligand expression via the EP1 receptor in colon cancer cells.

    LENUS (Irish Health Repository)

    O'Callaghan, G

    2012-02-03

    Fas ligand (FasL\\/CD95L) is a member of the tumour necrosis factor superfamily that triggers apoptosis following crosslinking of the Fas receptor. Despite studies strongly implicating tumour-expressed FasL as a major inhibitor of the anti-tumour immune response, little is known about the mechanisms that regulate FasL expression in tumours. In this study, we show that the cyclooxygenase (COX) signalling pathway, and in particular prostaglandin E(2) (PGE(2)), plays a role in the upregulation of FasL expression in colon cancer. Suppression of either COX-2 or COX-1 by RNA interference in HCA-7 and HT29 colon tumour cells reduced FasL expression at both the mRNA and protein level. Conversely, stimulation with PGE(2) increased FasL expression and these cells showed increased cytotoxicity against Fas-sensitive Jurkat T cells. Prostaglandin E(2)-induced FasL expression was mediated by signalling via the EP1 receptor. Moreover, immunohistochemical analysis using serial sections of human colon adenocarcinomas revealed a strong positive correlation between COX-2 and FasL (r=0.722; P<0.0001) expression, and between EP1 receptor and FasL (r=0.740; P<0.0001) expression, in the tumour cells. Thus, these findings indicate that PGE(2) positively regulates FasL expression in colon tumour cells, adding another pro-neoplastic activity to PGE(2).

  16. Association of the Apolipoprotein E 2 Allele with Concurrent Occurrence of Endometrial Hyperplasia and Endometrial Carcinoma

    Directory of Open Access Journals (Sweden)

    Tatiana I. Ivanova

    2015-01-01

    Full Text Available Genes encoding proteins with antioxidant properties may influence susceptibility to endometrial hyperplasia (EH and endometrial carcinoma (ECa. Patients with EH (n = 89, EH concurrent with ECa (n = 76, ECa (n = 186, and healthy controls (n = 1110 were genotyped for five polymorphic variants in the genes involved in metabolism of lipoproteins (APOE Cys112Arg and Arg158Cys, iron (HFE Cys282Tyr and His63Asp, and catecholamines (COMT Val158Met. Patients and controls were matched by ethnicity (all Caucasians, age, body mass index (BMI, and incidence of hypertension and diabetes. The frequency of the APOE E 2 allele (158Cys was higher in patients with EH + ECa than in controls (P = 0.0012, PBonferroni = 0.018, OR = 2.58, 95% CI 1.49–4.45. The APOE E 4 allele (112Arg was more frequently found in patients with EH than in controls and HFE minor allele G (63Asp had a protective effect in the ECa group, though these results appeared to be nonsignificant after correction for multiple comparisons. The results of the study indicate that E 2 allele might be associated with concurrent occurrence of EH and ECa.

  17. Prostaglandin E2 regulates pancreatic stellate cell activity via the EP4 receptor.

    Science.gov (United States)

    Charo, Chantale; Holla, Vijaykumar; Arumugam, Thiruvengadam; Hwang, Rosa; Yang, Peiying; Dubois, Raymond N; Menter, David G; Logsdon, Craig D; Ramachandran, Vijaya

    2013-04-01

    Pancreatic stellate cells are source of dense fibrotic stroma, a constant pathological feature of chronic pancreatitis and pancreatic adenocarcinoma. We observed correlation between levels of cyclooxygenase 2 (COX-2) and its product prostaglandin E2 (PGE2) and the extent of pancreatic fibrosis. The aims of this study were to delineate the effects of PGE2 on immortalized human pancreatic stellate cells (HPSCs) and to identify the receptor involved. Immunohistochemistry, reverse transcription-polymerase chain reaction and quantitative reverse transcription-polymerase chain reaction were used to assess COX-2, extracellular matrix, and matrix metalloproteinase gene expression. Eicosanoid profile was determined by liquid chromatography-tandem mass spectrometry. Human pancreatic stellate cell proliferation was assessed by MTS assay, migration by Boyden chamber assay, and invasion using an invasion chamber. Transient silencing was obtained by small interfering RNA. Human pancreatic stellate cells express COX-2 and synthesize PGE2. Prostaglandin E2 stimulated HPSC proliferation, migration, and invasion and stimulated expression of both extracellular matrix and matrix metalloproteinase genes. Human pancreatic stellate cells expressed all 4 EP receptors. Only blocking the EP4 receptor resulted in abrogation of PGE2-mediated HPSC activation. Specificity of EP4 for the effects of PGE2 on stellate cells was confirmed using specific antagonists. Our data indicate that PGE2 regulates pancreatic stellate cell profibrotic activities via EP4 receptor, thus suggesting EP4 receptor as useful therapeutic target for pancreatic cancer to reduce desmoplasia.

  18. Towards a Collision-Free WLAN: Dynamic Parameter Adjustment in CSMA/E2CA

    Directory of Open Access Journals (Sweden)

    Bellalta Boris

    2011-01-01

    Full Text Available Carrier sense multiple access with enhanced collision avoidance (CSMA/ECA is a distributed MAC protocol that allows collision-free access to the medium in WLANs. The only difference between CSMA/ECA and the well-known CSMA/CA is that the former uses a deterministic backoff after successful transmissions. Collision-free operation is reached after a transient state during which some collisions may occur. This paper shows that the duration of the transient state can be shortened by appropriately setting the contention parameters. Standard absorbing Markov chain theory is used to describe the behaviour of the system in the transient state and to predict the expected number of slots to reach the collision-free operation. The paper also introduces CSMA/E2CA, in which a deterministic backoff is used two consecutive times after a successful transmission. CSMA/E2CA converges quicker to collision-free operation and delivers higher performance than CSMA/ECA, specially in harsh wireless scenarios with high frame-error rates. The last part of the paper addresses scenarios with a large number of contenders. We suggest dynamic parameter adjustment techniques to accommodate a varying (and potentially high number of contenders. The effectiveness of these adjustments in preventing collisions is validated by means of simulation.

  19. Antifibrotic effects of noscapine through activation of prostaglandin E2 receptors and protein kinase A.

    Science.gov (United States)

    Kach, Jacob; Sandbo, Nathan; La, Jennifer; Denner, Darcy; Reed, Eleanor B; Akimova, Olga; Koltsova, Svetlana; Orlov, Sergei N; Dulin, Nickolai O

    2014-03-14

    Myofibroblast differentiation is a key process in the pathogenesis of fibrotic disease. We have shown previously that differentiation of myofibroblasts is regulated by microtubule polymerization state. In this work, we examined the potential antifibrotic effects of the antitussive drug, noscapine, recently found to bind microtubules and affect microtubule dynamics. Noscapine inhibited TGF-β-induced differentiation of cultured human lung fibroblasts (HLFs). Therapeutic noscapine treatment resulted in a significant attenuation of pulmonary fibrosis in the bleomycin model of the disease. Noscapine did not affect gross microtubule content in HLFs, but inhibited TGF-β-induced stress fiber formation and activation of serum response factor without affecting Smad signaling. Furthermore, noscapine stimulated a rapid and profound activation of protein kinase A (PKA), which mediated the antifibrotic effect of noscapine in HLFs, as assessed with the PKA inhibitor, PKI. In contrast, noscapine did not activate PKA in human bronchial or alveolar epithelial cells. Finally, activation of PKA and the antifibrotic effect of noscapine in HLFs were blocked by the EP2 prostaglandin E2 receptor antagonist, PF-04418948, but not by the antagonists of EP4, prostaglandin D2, or prostacyclin receptors. Together, we demonstrate for the first time the antifibrotic effect of noscapine in vitro and in vivo, and we describe a novel mechanism of noscapine action through EP2 prostaglandin E2 receptor-mediated activation of PKA in pulmonary fibroblasts.

  20. Anti-inflammatory and bronchoprotective roles of endogenous prostaglandin E2

    Directory of Open Access Journals (Sweden)

    Hiroki Sakakibara

    1999-01-01

    Full Text Available Prostaglandin E2 (PGE2 is produced by resident cells in the airway, such as airway epithelial cells, airway smooth muscle cells and alveolar macrophages, and is always present in the airway. Various exogenous and endogenous stimuli cause immediate increases in PGE2 from several-fold to multiples of 10-fold. Prostaglandin E2 controls the function of cells that contribute to immune and inflammatory responses, such as lymphocytes, eosinophils, mast cells, macrophages and polymorphonuclear cells, and exhibits suppressor activity in the initial and advanced stages of allergic airway inflammation (establishment of sensitization, induction of early asthmatic response, chemotaxis of inflammatory cells and continuation of the late asthmatic response. Therefore, if the endogenous protective effects of PGE2 are weakened or absent, inflammation and hypersensitive responses readily occur in the airway. Although the effects of PGE2 remain to be clarified, the possibility of the involvement of decreased PGE2 activity in the pathogenesis of asthma exists. However, in aspirin-induced asthma the role of PGE2 as a protective factor, through an as yet undetermined mechanism, is marked. It is thought that, in this type of asthma, symptoms may be induced by the elimination of the protective action of PGE2 by non-steroidal anti-inflammatory drugs (NSAID. It is possible that PGE2 agonists that produce little airway irritation and drugs that raise the endogenous PGE2 level have potential as new types of anti-inflammatory or anti-asthma drugs.

  1. A dynamic Asp-Arg interaction is essential for catalysis in microsomal prostaglandin E2 synthase.

    Science.gov (United States)

    Brock, Joseph S; Hamberg, Mats; Balagunaseelan, Navisraj; Goodman, Michael; Morgenstern, Ralf; Strandback, Emilia; Samuelsson, Bengt; Rinaldo-Matthis, Agnes; Haeggström, Jesper Z

    2016-01-26

    Microsomal prostaglandin E2 synthase type 1 (mPGES-1) is responsible for the formation of the potent lipid mediator prostaglandin E2 under proinflammatory conditions, and this enzyme has received considerable attention as a drug target. Recently, a high-resolution crystal structure of human mPGES-1 was presented, with Ser-127 being proposed as the hydrogen-bond donor stabilizing thiolate anion formation within the cofactor, glutathione (GSH). We have combined site-directed mutagenesis and activity assays with a structural dynamics analysis to probe the functional roles of such putative catalytic residues. We found that Ser-127 is not required for activity, whereas an interaction between Arg-126 and Asp-49 is essential for catalysis. We postulate that both residues, in addition to a crystallographic water, serve critical roles within the enzymatic mechanism. After characterizing the size or charge conservative mutations Arg-126-Gln, Asp-49-Asn, and Arg-126-Lys, we inferred that a crystallographic water acts as a general base during GSH thiolate formation, stabilized by interaction with Arg-126, which is itself modulated by its respective interaction with Asp-49. We subsequently found hidden conformational ensembles within the crystal structure that correlate well with our biochemical data. The resulting contact signaling network connects Asp-49 to distal residues involved in GSH binding and is ligand dependent. Our work has broad implications for development of efficient mPGES-1 inhibitors, potential anti-inflammatory and anticancer agents.

  2. 基于概率模型的E-2D Mesh网络容错性分析%Fault Tolerance of E-2D Mesh Networks Based on Model of Probability

    Institute of Scientific and Technical Information of China (English)

    肖杰; 梁家荣; 黄亿海

    2009-01-01

    研究了太比特路由器核心交换网络拓扑的一种新结构-E-2D Mesh.提出一种计算E-2D Mesh网络连通率的新方法.证明了当网络结点失效率控制在0.66%以下时,具有四万多个结点的E-2D Mesh网络可保持不低于99%的连通率,且在同等规模条件下,E-2D Mesh网络结点容错率至少是Mesh网络的11.09倍.研究结果表明,该方法在计算E-2D Mesh网络连通率时显示出较强的生命力且能够用于研究其它层次的网络和其它网络通信问题.%A novel switching fabric is the core of the terabit router.--E-2D mesh networks are one of the most important network topologies In massively multiprocessor parallel systems. In this paper,a novel approach for calculating the probabilistic connectivity of E-2D mesh networks is proposed. The paper formally proves that when the networks'node failure probability is bounded by 0.66%, the E-2D mesh networks with over forty thousand nodes remain connected with probability larger than 99% , and in the same scale and conditions, the probability of E-2D mesh networks is 11.09 times greater than mesh networks. The results show that the method is a powerful technique for calculating the probabilistic connectivity in E-2D mesh networks,and the scheme is also applicable to the study of other hierarchical network structures and of other network communication problems.

  3. Generating Units

    Data.gov (United States)

    Department of Homeland Security — Generating Units are any combination of physically connected generators, reactors, boilers, combustion turbines, and other prime movers operated together to produce...

  4. 猪瘟病毒E2基因自杀性DNA疫苗的构建及动物免疫试验%Construction of suicidal DNA vaccine of CSFV E2 gene and immunity induction in animals

    Institute of Scientific and Technical Information of China (English)

    郭抗抗; 温肖会; 汤智慧; 侯勃; 张彦明; 谢林红; 王晶钰

    2011-01-01

    从含有猪瘟病毒(CSFV)Shimen株E2全长基因的重组质粒pMD18-T-E2上扩增得到带有BamHⅠ酶切位点的E2基因片段,构建重组克隆质粒pMD19-T-E2.用BamH Ⅰ酶切pMD19-T-E2和"自杀性"DNA疫苗表达载体pSCA1,构建"自杀性"DNA疫苗重组质粒pSCA1-E2.对目的基因E2的大小、插入位置、方向和读码框经PCR、酶切和序列测定进行鉴定.用纯化的阳性质粒pSCA1-E2转染PK-15细胞,转染后48 h荧光抗体法检测E2蛋白的表达;纯化的pSCA1-E2质粒分别免疫小鼠(10 μg/只)和试验猪(600μg/头),二免后分别检测小鼠脾淋巴细胞刺激指数和猪血清抗猪瘟特异性抗体水平.结果表明,构建的重组质粒中E2基因的大小、插入位置、方向和读码框均正确,获得了重组表达质粒pSCA1-E2;转染后48 h可检测到转染的PK-15细胞中E2蛋白的表达.免疫小鼠产生较高水平的淋巴细胞刺激指数,免疫猪可检测到抗CSFV特异性血清抗体;表明构建的pSCA1-E2重组质粒能激发实验动物的免疫反应.%The complete E2 gene of classical swine fever virus (CSFV) with the BamH I restriction site was cloned from the recombinant plasmid pMD18-T-E2 and inserted into pMD19-T plasmid to construct the recombinant plas-mid pMD19-T-E2. E2 gene was obtained from pMD19-T-E2 digested with BamH I ,and was inserted into the suicidal DNA vaccine vector pSCAl which was treated with the same enzyme. The recombinant plasmid pSCAl-E2 was obtained and identified the length. Insert sites, orientation and reading frame of E2 gene in pSCAl-E2 by polymerase chain reaction (PCR),enzyme digesting and sequencing. E2 protein was determined in PK15 cells transfected with purified recombinant plasmid pSCAl-E2 at 48 h post-transfection. The stimulation index (SI) of T lymphoid cell in experimental mice immunized with pSCAl-E2 (10 μg/each) were analyzed at 10 d,20 d,30 d after the second vaccination. Experimental pigs were immunized with pSCAl-E2 (600 μg/each) and

  5. A Digital Hydrologic Network Supporting NAWQA MRB SPARROW Modeling--MRB_E2RF1

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — A digital hydrologic network was developed to support SPAtially Referenced Regression on Watershed attributes (SPARROW) models within selected regions of the United...

  6. A Digital Hydrologic Network Supporting NAWQA MRB SPARROW Modeling--MRB_E2RF1WS

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — A digital hydrologic network was developed to support SPAtially Referenced Regression on Watershed attributes (SPARROW) models within selected regions of the United...

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

    Science.gov (United States)

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

    2016-01-01

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

  8. Prostaglandin-E-2 enhances EPO-mediated STAT5 transcriptional activity by serine phosphorylation of CREB

    NARCIS (Netherlands)

    Boer, AK; Drayer, AL; Rui, H; Vellenga, E

    2002-01-01

    Erythroid colony formation in response to erythropoietin (EPO) stimulation is enhanced by costimulating the cells with prostaglandin-E-2 (PGE(2)). The present study further analyzed the underlying mechanisms and demonstrated that EPO-mediated STAT5 transactivation in the erythroid AS-E-2 cell line w

  9. Deregulated E2F activity induces hyperplasia and senescence-like features in the mouse pituitary gland

    DEFF Research Database (Denmark)

    Lazzerini Denchi, Eros; Attwooll, Claire; Pasini, Diego

    2005-01-01

    The retinoblastoma gene, RB1, is one of the most frequently mutated genes in human cancer. Rb heterozygous mice develop pituitary tumors with 100% incidence, and the E2F transcription factors are required for this. To assess whether deregulated E2F activity is sufficient to induce pituitary tumor...

  10. E2/ER change and its relation with FasL expression in breast cancer patients before and after menopause

    Institute of Scientific and Technical Information of China (English)

    Yu Liu; Bing-Yu Gao; Li-Ping Xia; Yu-You Wu; Yu Wang; Chao-Qun Wang

    2016-01-01

    Objective:To explore the E2/ER changes both in the peripheral blood and tumors, as well as its effect on factor-related apoptosis ligand (FasL) gene expression of breast cancer patients before and after menopause.Methods:We chose premenopausal (n=21) and postmenopausal (n=19) breast cancer patients in this study to do a comparative analyze. Peripheral blood was extracted to detect the E2 and ER concentration by ELISA kit. At the same time, pathological slices of tumor and healthy tissue besides the tumor were both prepared to detect the E2, ER and FasL expression with immunofluorescence.Results: Postmenopausal patients had significantly lower peripheral levels of E2 and ER than premenopausal patients, while tumor levels of E2 and ER had no significant difference between groups. Further more, ER positive expression rate of patients before and after menopause was respectively 52.4% and 57.9% with out statistical differences between groups; and FasL gene expression had linear positive correlation with tumor E2 and ER expression both in patients with ER positive expression before and after menopause.Conclusion:Our research results show that E2 and ER level tumor tissues could keep high level independent of environment which contributes the progress of breast caner; and high dose E2 and ER level of the tumor tissues which up regulated the expression of FasL maybe an important factor for immune escape.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-07-20

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

  12. 17 CFR 240.14e-2 - Position of subject company with respect to a tender offer.

    Science.gov (United States)

    2010-04-01

    ... disclosing that the subject company: (1) Recommends acceptance or rejection of the bidder's tender offer; (2... accordance with such laws, regulations and policies. (d) Exemption for cross-border tender offers. The... with respect to a tender offer. 240.14e-2 Section 240.14e-2 Commodity and Securities...

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

    Science.gov (United States)

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

    2016-01-01

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

  14. Interaction of CSFV E2 protein with swine host factors as detected by yeast two-hybrid system

    Science.gov (United States)

    E2 is one of the envelope glycoproteins of pestiviruses, including classical swine fever virus (CSFV) and bovine viral diarrhea virus (BVDV). E2 is involved in several critical functions, including virus entry into target cells, induction of a protective immune response and virulence in swine. Howev...

  15. A cDNA encoding a pRB-binding protein with properties of the transcription factor E2F

    DEFF Research Database (Denmark)

    Helin, K; Lees, J A; Vidal, M

    1992-01-01

    The retinoblastoma protein (pRB) plays an important role in the control of cell proliferation, apparently by binding to and regulating cellular transcription factors such as E2F. Here we describe the characterization of a cDNA clone that encodes a protein with properties of E2F. This clone, RBP3...

  16. The Role of a Novel Nucleolar Protein in Regulation of E2F1 in Breast Cancer

    Science.gov (United States)

    2009-09-01

    copresence of RRP1B and E2F1 on specific E2F1 targets (see below), We would now like to discuss progress in the research program. Task 1...A similar assay was performed identically except that cells were grown in media containing 2% fetal bovine serum. Real time and semiquantitative

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

    Directory of Open Access Journals (Sweden)

    Elodie Beaumont

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

  18. Positive and negative regulation of cell proliferation by E2F-1: influence of protein level and human papillomavirus oncoproteins

    DEFF Research Database (Denmark)

    Melillo, R M; Helin, K; Lowy, D R;

    1994-01-01

    E2F-1 is a member of a family of transcription factors implicated in the activation of genes required for the progression through the S phase of the cell cycle. We have examined the biological activities of E2F-1 with short-term colony-forming assays and long-term immortalization assays. High lev...

  19. E2F and p53 induce apoptosis independently during Drosophila development but intersect in the context of DNA damage.

    Directory of Open Access Journals (Sweden)

    Nam-Sung Moon

    2008-08-01

    Full Text Available In mammalian cells, RB/E2F and p53 are intimately connected, and crosstalk between these pathways is critical for the induction of cell cycle arrest or cell death in response to cellular stresses. Here we have investigated the genetic interactions between RBF/E2F and p53 pathways during Drosophila development. Unexpectedly, we find that the pro-apoptotic activities of E2F and p53 are independent of one another when examined in the context of Drosophila development: apoptosis induced by the deregulation of dE2F1, or by the overexpression of dE2F1, is unaffected by the elimination of dp53; conversely, dp53-induced phenotypes are unaffected by the elimination of dE2F activity. However, dE2F and dp53 converge in the context of a DNA damage response. Both dE2F1/dDP and dp53 are required for DNA damage-induced cell death, and the analysis of rbf1 mutant eye discs indicates that dE2F1/dDP and dp53 cooperatively promote cell death in irradiated discs. In this context, the further deregulation in the expression of pro-apoptotic genes generates an additional sensitivity to apoptosis that requires both dE2F/dDP and dp53 activity. This sensitivity differs from DNA damage-induced apoptosis in wild-type discs (and from dE2F/dDP-induced apoptosis in un-irradiated rbf1 mutant eye discs by being dependent on both hid and reaper. These results show that pro-apoptotic activities of dE2F1 and dp53 are surprisingly separable: dp53 is required for dE2F-dependent apoptosis in the response to DNA damage, but it is not required for dE2F-dependent apoptosis caused simply by the inactivation of rbf1.

  20. Induction of S-phase entry by E2F transcription factors depends on their nuclear localization

    DEFF Research Database (Denmark)

    Müller, H; Moroni, M C; Vigo, E

    1997-01-01

    , and they are in a pathway that is frequently found altered in human cancers. There are five members of the E2F family, and they can be divided into two functional subgroups. Whereas, upon overexpression, E2F-1, -2, and -3 induce S phase in quiescent fibroblasts and override G1 arrests mediated by the p16INK4A tumor...... cytoplasmic after the pRB family members have become phosphorylated. We propose a novel mechanism for the regulation of E2F-dependent transcription in which E2F-4 regulates transcription only from G0 until mid- to late G1 phase whereas E2F-1 is active in late G1 and S phases, until it is inactivated by cyclin...

  1. E2F4 modulates differentiation and gene expression in hematopoietic progenitor cells during commitment to the lymphoid lineage.

    Science.gov (United States)

    Enos, Megan E; Bancos, Simona A; Bushnell, Timothy; Crispe, Ian N

    2008-03-15

    The E2F4 protein is involved in gene repression and cell cycle exit, and also has poorly understood effects in differentiation. We analyzed the impact of E2F4 deficiency on early steps in mouse hematopoietic development, and found defects in early hematopoietic progenitor cells that were propagated through common lymphoid precursors to the B and T lineages. In contrast, the defects in erythromyeloid precursor cells were self-correcting over time. This suggests that E2F4 is important in early stages of commitment to the lymphoid lineage. The E2F4-deficient progenitor cells showed reduced expression of several key lymphoid-lineage genes, and overexpression of two erythromyeloid lineage genes. However, we did not detect effects on cell proliferation. These findings emphasize the significance of E2F4 in controlling gene expression and cell fate.

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

    Science.gov (United States)

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

    2011-01-01

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

  3. A naturally occurring substitution in the E2 protein of Salmonid alphavirus subtype 3 changes viral fitness.

    Science.gov (United States)

    Karlsen, Marius; Andersen, Linda; Blindheim, Steffen H; Rimstad, Espen; Nylund, Are

    2015-01-22

    Phylogenetic analyses of the Salmonid alphavirus subtype 3 (SAV3) epizootic have suggested that a substitution from proline to serine in the receptor binding protein E2 position 206 has occurred after the introduction of virus from a wild reservoir to farmed salmonid fish in Norway. We modelled the 3D structure of P62, the uncleaved E3-E2 precursor, of SAVH20/03 based on its sequence homology to the Chikungunya virus (CHIKV), and studied in vitro and in vivo effects of the mutation using reverse genetics. E2(206) is located on the surface of the B-domain of E2, which is associated with receptor attachment in alphaviruses. Recombinant virus expressing the E2(206S) codon replicated slower and produced significantly less genomic copies than virus expressing the ancestral E2(206P) codon in vitro in Bluegill Fry (BF2) cells. The E2(206S) mutant was out-competed by the E2(206P) mutant after 5 passages in an in vitro competition assay, confirming that the substitution negatively affects the efficacy of virus multiplication in cell culture. Both mutants were highly infectious to Atlantic salmon (Salmo salar), produced similar viral RNA loads in gills, heart, kidney and brain, and induced similar histopathologic changes in these organs. The E2(206S) mutant produced a less persistent infection in salmon and was shed more rapidly to water than the E2(206P) mutant. Reduced generation time through more rapid shedding could therefore explain why a serine in this position became dominant in the viral population after SAV3 was introduced to farmed salmon from the wild reservoir.

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

    Directory of Open Access Journals (Sweden)

    Poulsen Steen S

    2010-01-01

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

  5. UNIT, TIBET.

    Science.gov (United States)

    Louisiana Arts and Science Center, Baton Rouge.

    THE UNIT OF STUDY DESCRIBED IN THIS BOOKLET DEALS WITH THE GEOGRAPHY AND HISTORY OF TIBET. THE UNIT COVERS SOME OF THE GENERAL FEATURES OF THE COUNTRY AND THEIR EFFECT UPON THE LIVES OF THE TIBETAN PEOPLE. DISCUSSION QUESTIONS ARE INSERTED TO STIMULATE THOUGHT. THE RELIGION OF TIBET IS DISCUSSED IN RELATION TO ITS INFLUENCE ON THE ART AND CULTURE…

  6. e-2 H Parity Violating Deep Inelastic Scattering (PVDIS) at CEBAF 6 GeV

    Science.gov (United States)

    Pan, Kai; Jefferson Lab Hall A Parity Collaboration

    2011-04-01

    The parity violating (PV) asymmetry Ad in e-2 H deep inelastic scattering (DIS) was measured in Hall A at Jefferson Lab at Q2 = 1.11 and 1.90(GeV / c) 2 at x ~ 0 . 3 to a statistical precision of 3 % and 4 % , respectively. The combination of the two measurements will provide the first significant constraint on higher-twist (HT) effects in PVDIS. With HT effects thus measured, this experiment will constrain the poorly known effective weak coupling constant combination (2C2 u -C2 d) . The measurement will also allow the extraction of couplings C3 q from high energy μ - C DIS data. Precision measurements of all these phenomenological couplings are essential to comprehensively search for possible physics beyond the Standard Model. The experiment DAQ system will be introduced. Current data analysis progress and preliminary results will be presented.

  7. Morphology of asteroid (4179) Toutatis as imaged by Chang'E-2 spacecraft

    Science.gov (United States)

    Zhu, Meng-Hua; Fa, Wenzhe; Ip, Wing-Huen; Huang, Jiangchuan; Liu, Tiantian; Meng, Linzhi; Yan, Jun; Xu, Aoao; Tang, Zesheng; Wang, Xiaolei; Qiao, Dong

    2014-01-01

    observations by the Chang'E-2 spacecraft reveal that the surface of asteroid (4179) Toutatis is characterized by abundant impact craters with most of them being degraded by surface resetting. The less degraded large crater with a diameter of ~800 m at the south pole is estimated to be produced by an impactor with a diameter of ~50 m from strength crater scaling relations. From the analysis of large-impact events on highly porous targets, we argue that Toutatis is likely a rubble-pile body and its two lobes are contact binaries. The fact that Toutatis suffered plenty of impacts with seismic shaking resetting the initial surface features but not resulting in catastrophic disruption is probably because of the material's high attenuation of shock wave.

  8. Comparative study of prostaglandin E2 production in chick spinal cord and meninges.

    Science.gov (United States)

    Billotte, C; Vesin, M F

    1997-03-01

    In chick spinal cord the presence of low affinity (KD = 2.2 microM) receptors for prostaglandin E2 (PGE2) raises the question whether spinal cord possesses a PGE2 biosynthetic capacity able to activate these receptors. The production of PGE2 in spinal cord and meninges was investigated by enzyme immunoassay. Spinal cord exhibited a 30- to 100-fold lower PGE2 biosynthetic capacity compared to meninges, but can generate PGE2 resulting in micromolar concentrations, sufficient to activate the low affinity PGE2 receptors. It is suggested that in physiological conditions, PGE2 synthesized within the spinal cord might locally activate the low affinity PGE2 receptors, whereas in pathological situations, after disruption of the blood-spinal cord barrier, PGE2 produced by the meninges might be accessible to spinal cord PGE2 receptors, and thus largely contribute to their saturation.

  9. Up-regulation of cyclooxygenase-2 by product-prostaglandin E2

    Science.gov (United States)

    Tjandrawinata, R. R.; Hughes-Fulford, M.

    1997-01-01

    The development of prostate cancer has been linked to high level of dietary fat intake. Our laboratory investigates the connection between cancer cell growth and fatty acid products. Studying human prostatic carcinoma PC-3 cells, we found that prostaglandin E2 (PGE2) increased cell growth and up-regulated the gene expression of its own synthesizing enzyme, cyclooxygenase-2 (COX-2). PGE2 increased COX-2 mRNA expression dose-dependently with the highest levels of stimulation seen at the 3-hour period following PGE2 addition. The NSAID flurbiprofen (5 microM), in the presence of exogenous PGE2, inhibited the up-regulation of COX-2 mRNA and cell growth. These data suggest that the levels of local intracellular PGE2 play a major role in the growth of prostate cancer cells through an activation of COX-2 gene expression.

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

    DEFF Research Database (Denmark)

    Kaltoft, Nicolai; Tilotta, Maria C; Witte, Anne-Barbara;

    2010-01-01

    BACKGROUND: The pathogenesis for colorectal cancer remains unresolved. A growing body of evidence suggests a direct correlation between cyclooxygenase enzyme expression, prostaglandin E2 metabolism and neoplastic development. Thus further understanding of the regulation of epithelial functions...... colorectal neoplasia. Patients without endoscopic findings of neoplasia served as controls. Biopsy specimens were obtained from normally appearing mucosa in the sigmoid part of colon. Biopsies were mounted in miniaturized modified Ussing air-suction chambers. Indomethacin (10 microM), various stimulators...... and inhibitors of prostanoid receptors and ion transport were subsequently added to the chamber solutions. Electrogenic ion transport parameters (short circuit current and slope conductance) were recorded. Tissue pathology and tissue damage before and after experiments was assessed by histology. RESULTS...

  11. The next-generation microcalorimeter array of XRS on Astro-E2

    Energy Technology Data Exchange (ETDEWEB)

    Stahle, C.K. E-mail: cak@lheapop.gsfc.nasa.gov; Allen, C.A.; Boyce, K.R.; Brekosky, R.P.; Brown, G.V.; Cottam, J.; Figueroa-Feliciano, E.; Galeazzi, M.; Gygax, J.D.; Jacobson, M.B.; Kelley, R.L.; Liu, D.; McCammon, D.; McClanahan, R.A.; Moseley, S.H.; Porter, F.S.; Rocks, L.E.; Szymkowiak, A.E.; Vaillancourt, J.E

    2004-03-11

    The square-format 32-pixel microcalorimeter array at the focal plane of the high-resolution X-ray spectrometer on the Astro-E2 X-ray Observatory is the first of a new generation of silicon-based microcalorimeters. This array has numerous advantages over its predecessor, the bilinear array that was launched on Astro-E. Foremost among its benefits are: (1) the energy resolution is improved by a factor of two at 6 keV (now 6 eV FWHM), (2) the thermal time constant is a factor of two faster, and (3) each pixel has a Gaussian line response. We will discuss the design changes that have led to these and other advantages.

  12. Revisit of rotational dynamics of Asteroid 4179 Toutatis from Chang'e-2's flyby

    Science.gov (United States)

    Zhao, Yuhui; Hu, Shoucun; Ji, Jianghui

    2016-01-01

    This paper presents analysis of the rotational parameters of Toutatis based on the observational results from Chang'e-2's close flyby. The 3-D shape model derived from ground-based radar observation is used to calculate the 3-1-3 Euler angles at the flyby epoch, which are evaluated to be -20.1° +/- 1°, 27.6° +/- 1° and 42.2° +/- 1°. The large amplitude of Toutatis' tumbling attitude is demonstrated to be the result of the large deviation of the angular momentum axis and the rotational axis. Two rotational periods are evaluated to be 5.38+/-0.03 days for rotation about the long axis and 7.40+/-0.03 days for precession of the long axis about the angular momentum vector based on Fourier analysis. These results provide a further understanding of rotational state of Toutatis.

  13. Localization of prostaglandin E(2) EP2 and EP4 receptors in the rat kidney

    DEFF Research Database (Denmark)

    Jensen, B L; Stubbe, J; Hansen, P B

    2001-01-01

    -selective agonist, dose dependently raised cAMP levels in microdissected DTL and outer medullary vasa recta specimens but had no effect in EP2-negative outer medullary collecting duct segments. Dietary salt intake did not alter EP2 expression in the kidney medulla. These results suggest that PGE(2) may act......We investigated the localization of cAMP-coupled prostaglandin E(2) EP2 and EP4 receptor expression in the rat kidney. EP2 mRNA was restricted to the outer and inner medulla in rat kidney, as determined by RNase protection assay. RT-PCR analysis of microdissected resistance vessels and nephron...... segments showed EP2 expression in descending thin limb of Henle's loop (DTL) and in vasa recta of the outer medulla. The EP4 receptor was expressed in distal convoluted tubule (DCT) and cortical collecting duct (CCD) in preglomerular vessels, and in outer medullary vasa recta. Butaprost, an EP2 receptor...

  14. Elucidating the Specificity Determinants of the AtxE2 Lasso Peptide Isopeptidase.

    Science.gov (United States)

    Maksimov, Mikhail O; Koos, Joseph D; Zong, Chuhan; Lisko, Bozhena; Link, A James

    2015-12-25

    Lasso peptide isopeptidase is an enzyme that specifically hydrolyzes the isopeptide bond of lasso peptides, rendering these peptides linear. To carry out a detailed structure-activity analysis of the lasso peptide isopeptidase AtxE2 from Asticcacaulis excentricus, we solved NMR structures of its substrates astexin-2 and astexin-3. Using in vitro enzyme assays, we show that the C-terminal tail portion of these peptides is dispensable with regards to isopeptidase activity. A collection of astexin-2 and astexin-3 variants with alanine substitutions at each position within the ring and the loop was constructed, and we showed that all of these peptides except for one were cleaved by the isopeptidase. Thus, much like the lasso peptide biosynthetic enzymes, lasso peptide isopeptidase has broad substrate specificity. Quantitative analysis of the cleavage reactions indicated that alanine substitutions in loop positions of these peptides led to reduced cleavage, suggesting that the loop is serving as a recognition element for the isopeptidase.

  15. Highest Occupied Molecular Orbital of Cyclopentanone by Binary (e, 2e) Spectroscopy

    Institute of Scientific and Technical Information of China (English)

    ZHANG Shu-Feng; NING Chuan-Gang; DENG Jing-Kang; REN Xue-Guang; SU Guo-Lin; YANG Tie-Cheng; HUANG Yan-Ru

    2006-01-01

    @@ We report the first measurements of the momentum profiles of highest occupied molecular orbital (HOMO) and the complete valence shell binding energy spectra of cyclopentanone with impact energies of 600 and 1200 eV by a binary (e, 2e) spectrometer. The experimental momentum profiles of the HOMO orbital are compared with the theoretical momentum distribution calculated using the Hartree-Fock and density functional theory methods with various basis sets. However, none of these calculations gives a completely satisfactory description of the momentum distributions of the HOMO 7b2. The inadequacy of the calculations could result in the intensity difference of the second maximum at p ~l.2a.u. between the experiment and the theory. The discrepancy between experimental and theoretical data in the low-momentum region is explained with the distorted wave effect.

  16. Boulders on asteroid Toutatis as observed by Chang'e-2

    CERN Document Server

    Jiang, Yun; Huang, Jiangchuan; Marchi, Simone; Li, Yuan; Ip, Wing-Huen

    2015-01-01

    Boulders are ubiquitously found on the surfaces of small rocky bodies in the inner solar system and their spatial and size distributions give insight into the geological evolution and collisional history of the parent bodies. Using images acquired by the Chang'e-2 spacecraft, more than 200 boulders have been identified over the imaged area of the near-Earth asteroid Toutatis. The cumulative boulder size frequency distribution (SFD) shows a steep slope of -4.4 $\\pm$ 0.1, which is indicative of a high degree of fragmentation. Similar to Itokawa, Toutatis probably has a rubble-pile structure, as most boulders on its surface cannot solely be explained by impact cratering. The significantly steeper slope for Toutatis' boulder SFD compared to Itokawa may imply a different preservation state or diverse formation scenarios. In addition, the cumulative crater SFD has been used to estimate a surface crater retention age of approximately 1.6 $\\pm$ 0.3 Gyr.

  17. Revisit of rotational dynamics of Asteroid 4179 Toutatis from Chang'e-2's flyby

    CERN Document Server

    Zhao, Yuhui; Ji, Jianghui

    2015-01-01

    This paper presents analysis of the rotational parameters of Toutatis based on the observational results from Chang'e-2's close flyby. The 3-D shape model derived from ground-based radar observation is used to calculate the 3-1-3 Euler angles at the flyby epoch, which are evaluated to be $-20.1^\\circ\\pm1^\\circ$, $27.6^\\circ\\pm1^\\circ$ and $42.2^\\circ\\pm1^\\circ$. The large amplitude of Toutatis' tumbling attitude is demonstrated to be the result of the large deviation of the angular momentum axis and the rotational axis. Two rotational periods are evaluated to be $5.38\\pm0.03$ days for rotation about the long axis and $7.40\\pm0.03$ days for precession of the long axis about the angular momentum vector based on Fourier analysis. These results provide a further understanding of rotational state of Toutatis.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2004-12-06

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

  19. Correlating charge radius with quadrupole deformation and $B(E2)$ in atomic nuclei

    CERN Document Server

    Sun, Bao-Hua; Wang, Hao-Xin

    2016-01-01

    A very good linear correlation is found between the four-point charge radius relation $\\delta R_{2p-2n}(Z,N)$ with that of quadrupole deformation data in even-even nuclei. This results in a further improved charge radius relation that holds in a precision of about 5$\\times 10^{-3}$ fm. Such correlations are also seen in global nuclear models, their precisions, however, are not enough to be consistent with the experimental data. The new relation between charge radii and deformation of even-even nuclei can be generalized to the reduced electric quadrupole transition probability $B(E2)$ between the first $2^+$ state and the $0^+$ ground state, and the mean lifetime $\\tau$ of the first 2$^+$ state.

  20. Nonsymmorphic Weyl superconductivity in UPt3 based on E2 u representation

    Science.gov (United States)

    Yanase, Youichi

    2016-11-01

    We show that a heavy fermion superconductor UPt3 is a topological Weyl superconductor with tunable Weyl nodes. Adopting a generic order parameter in the E2 u representation allowed by nonsymmorphic crystal symmetry, we clarify unusual gap structure and associated topological properties. The pair creation, pair annihilation, and coalescence of Weyl nodes are demonstrated in the time-reversal symmetry broken B-phase. At most 98 point nodes compatible with Blount's theorem give rise to line-node-like behaviors in low-energy excitations, consistent with experimental results. We also show an arc node protected by the nonsymmorphic crystal symmetry on the Brillouin zone face, which is a counterexample of Blount's theorem.

  1. Global phenomenology of B(E2) values in unique parity quasibands of odd- A nuclei

    Science.gov (United States)

    Bucurescu, D.; Marginean, N.; Cata-Danil, G.; Ivascu, M.; Stroe, L.; Ur, C. A.

    1996-03-01

    We have studied the evolution of the 0954-3899/22/3/010/img1 values in all the unique parity quasibands in odd-A nuclei, determined by the orbitals with j = 9/2, 11/2 and 13/2 (0954-3899/22/3/010/img2 and 0954-3899/22/3/010/img3). It is found that most of the known values, when normalized by the mass number and represented against 0954-3899/22/3/010/img4, follow a compact, universal envelope, well represented by a simple function. This universal correlation is similar in spirit to those existing for the 0954-3899/22/3/010/img5 values in the even - even nuclei. It also highlights deviating cases, which indicate interesting phenomena, other than simple quadrupole deformation. The B(E2) values in the odd-A nuclei are, on average, higher than those in even - even nuclei.

  2. Event display of a H -> 2e2mu candidate event

    CERN Multimedia

    ATLAS, Collaboration

    2012-01-01

    Event display of a H -> 2e2mu candidate event with m(4l) = 122.6 (123.9) GeV without (with) Z mass constraint. The masses of the lepton pairs are 87.9 GeV and 19.6 GeV. The event was recorded by ATLAS on 18-Jun-2012, 11:07:47 CEST in run number 205113 as event number 12611816. Muon tracks are colored red, electron tracks and clusters in the LAr calorimeter are colored green. The Lego plot inset indicates the amount of transverse energy Et measured in the calorimeters. The second inset shows a zoom into the vertex region, indicating that the 4 leptons originate from the same primary vertex.

  3. Event display of a H -> 2e2mu candidate event

    CERN Multimedia

    ATLAS, Collaboration

    2012-01-01

    Event display of a H -> 2e2mu candidate event with m(4l) = 122.6 (123.9) GeV without (with) Z mass constraint. The masses of the lepton pairs are 87.9 GeV and 19.6 GeV. The event was recorded by ATLAS on 18-Jun-2012, 11:07:47 CEST in run number 205113 as event number 12611816. Muon tracks are colored red, electron tracks and clusters in the LAr calorimeter are colored green. The larger inset shows a zoom into the tracking detector. The smaller inset shows a zoom into the vertex region, indicating that the 4 leptons originate from the same primary vertex.

  4. Endotoxin-free purification for the isolation of Bovine Viral Diarrhoea Virus E2 protein from insoluble inclusion body aggregates

    Directory of Open Access Journals (Sweden)

    Mahony Timothy J

    2011-07-01

    Full Text Available Abstract Background Protein expression in Escherichia coli may result in the recombinant protein being expressed as insoluble inclusion bodies. In addition, proteins purified from E. coli contain endotoxins which need to be removed for in vivo applications. The structural protein, E2, from Bovine Viral Diarrhoea Virus (BVDV is a major immunogenic determinant, and is an ideal candidate as a subunit vaccine. The E2 protein contains 17 cysteine residues creating difficulties in E. coli expression. In this report we outline a procedure for successfully producing soluble and endotoxin-free BVDV E2 protein from inclusion bodies (IB. Results The expression of a truncated form of BVDV-E2 protein (E2-T1 in E. coli resulted in predominantly aggregated insoluble IB. Solubilisation of E2-T1 with high purity and stability from IB aggregates was achieved using a strong reducing buffer containing 100 mM Dithiothreitol. Refolding by dialysis into 50 mM Tris (pH 7.0 containing 0.2% Igepal CA630 resulted in a soluble but aggregated protein solution. The novel application of a two-phase extraction of inclusion body preparations with Triton X-114 reduced endotoxin in solubilised E2-T1 to levels suitable for in vivo use without affecting protein yields. Dynamic light scattering analyses showed 37.5% of the protein was monomeric, the remaining comprised of soluble aggregates. Mice immunised with E2-T1 developed a high titre antibody response by ELISA. Western hybridisation analysis showed E2-T1 was recognised by sera from immunised mice and also by several BVDV-E2 polyclonal and monoclonal antibodies. Conclusion We have developed a procedure using E. coli to produce soluble E2-T1 protein from IB, and due to their insoluble nature we utilised a novel approach using Triton X-114 to efficiently remove endotoxin. The resultant protein is immunogenic and detectable by BVDV-E2 specific antibodies indicating its usefulness for diagnostic applications and as a subunit

  5. Use of E2 matrix elements to determine the centroids and fluctuation widths for triaxial quadrupole collective motion

    Science.gov (United States)

    Cline, Douglas; Wu, Ching-Yen

    2001-10-01

    Measured E2 properties are a sensitive and unambiguous probe of the collective shape parameters for quadrupole collective motion in nuclei. Collective motion produces strong correlations of the measured E2 matrix elements that can be related to the E2 properties in the principal axis frame of the rotating nucleus. By analogy with Bohr's quadrupole shape parameters (β,γ), the instantaneous principal axis frame E2 tensor can be expressed in terms of two parameters, Q,δ where E2(2,0)=Q\\cosδ, and E2(2,± 2)=fracQ√2sinδ. The E2 properties can be used to extract the E2 triaxiality parameter δ which can be related to γ by use of a geometrical collective model. The 1965 measurement [1] of the Q_2^+ state in ^114Cd provoked considerable interest in collective triaxial deformation in nuclei and stimulated measurement of Q_2^+ values in many other nuclei in order to probe the centroid of the E2 triaxial deformation. The heavy-ion Coulomb excitation experimental technique, plus the Coulomb excitation least-squares search code GOSIA, made it possible to measure rather complete sets of E2 matrix elements adding a new dimension to the study of triaxiality in nuclear collective motion [2]. This development also made it possible to exploit the rotational invariant technique [3-6] to extract directly from the measured E2 matrix elements, the expectation values of the centroids and fluctuation widths of principal axis E2 parameters for any state. The usefulness, range of validity, and results of this technique for determining the centroids and fluctuation widths for the triaxiality degree of freedom δ in a range of nuclei will be presented. The completeness required is a disadvantage of the rotational invariant technique. A comparison will be made of the use of the full rotational invariant technique with results obtained using restricted E2 data in conjunction with model-dependent analyses or truncation schemes. [1] J. de Boer et al, Phys. Rev. Lett. 14 (1965) 564; [2] D

  6. Api5 contributes to E2F1 control of the G1/S cell cycle phase transition.

    Directory of Open Access Journals (Sweden)

    Marina Garcia-Jove Navarro

    Full Text Available BACKGROUND: The E2f transcription factor family has a pivotal role in controlling the cell fate in general, and in particular cancer development, by regulating the expression of several genes required for S phase entry and progression through the cell cycle. It has become clear that the transcriptional activation of at least one member of the family, E2F1, can also induce apoptosis. An appropriate balance of positive and negative regulators appears to be necessary to modulate E2F1 transcriptional activity, and thus cell fate. METHODOLOGY/PRINCIPAL FINDINGS: In this report, we show that Api5, already known as a regulator of E2F1 induced-apoptosis, is required for the E2F1 transcriptional activation of G1/S transition genes, and consequently, for cell cycle progression and cell proliferation. Api5 appears to be a cell cycle regulated protein. Removal of Api5 reduces cyclin E, cyclin A, cyclin D1 and Cdk2 levels, causing G1 cell cycle arrest and cell cycle delay. Luciferase assays established that Api5 directly regulates the expression of several G1/S genes under E2F1 control. Using protein/protein and protein/DNA immunoprecipitation studies, we demonstrate that Api5, even if not physically interacting with E2F1, contributes positively to E2F1 transcriptional activity by increasing E2F1 binding to its target promoters, through an indirect mechanism. CONCLUSION/SIGNIFICANCE: The results described here support the pivotal role of cell cycle related proteins, that like E2F1, may act as tumor suppressors or as proto-oncogenes during cancer development, depending on the behavior of their positive and negative regulators. According to our findings, Api5 contributes to E2F1 transcriptional activation of cell cycle-associated genes by facilitating E2F1 recruitment onto its target promoters and thus E2F1 target gene transcription.

  7. Identification of prostaglandin E2 receptor subtype 2 as a receptor activated by OxPAPC.

    Science.gov (United States)

    Li, Rongsong; Mouillesseaux, Kevin P; Montoya, Dennis; Cruz, Daniel; Gharavi, Navid; Dun, Martin; Koroniak, Lukasz; Berliner, Judith A

    2006-03-17

    Oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OxPAPC), which has been shown to accumulate in atherosclerotic lesions and other sites of chronic inflammation, activates endothelial cells (EC) to bind monocytes by activation of endothelial beta1 integrin and subsequent deposition of fibronectin on the apical surface. Our previous studies suggest this function of OxPAPC is mediated via a Gs protein-coupled receptor (GPCR). PEIPC (1-palmitoyl-2-epoxyisoprostane E2-sn-glycero-3-phosphorylcholine) is the most active lipid in OxPAPC that activates this pathway. We screened a number of candidate GPCRs for their interaction with OxPAPC and PEIPC, using a reporter gene assay; we identified prostaglandin E2 receptor EP2 and prostaglandin D2 receptor DP as responsive to OxPAPC. We focused on EP2, which is expressed in ECs, monocytes, and macrophages. OxPAPC component PEIPC, but not POVPC, activated EP2 with an EC50 of 108.6 nmol/L. OxPAPC and PEIPC were also able to compete with PGE2 for binding to EP2 in a ligand-binding assay. The EP2 specific agonist butaprost was shown to mimic the effect of OxPAPC on the activation of beta1 integrin and the stimulation of monocyte binding to endothelial cells. Butaprost also mimicked the effect of OxPAPC on the regulation of tumor necrosis factor-alpha and interleukin-10 in monocyte-derived cells. EP2 antagonist AH6809 blocked the activation of EP2 by OxPAPC in HEK293 cells and blocked the interleukin-10 response to PEIPC in monocytic THP-1 cells. These results suggest that EP2 functions as a receptor for OxPAPC and PEIPC, either as the phospholipid ester or the released fatty acid, in both endothelial cells and macrophages.

  8. E-2-hexenal promotes susceptibility to Pseudomonas syringae by activating jasmonic acid pathways in Arabidopsis.

    Science.gov (United States)

    Scala, Alessandra; Mirabella, Rossana; Mugo, Cynthia; Matsui, Kenji; Haring, Michel A; Schuurink, Robert C

    2013-01-01

    Green leaf volatiles (GLVs) are C6-molecules - alcohols, aldehydes, and esters - produced by plants upon herbivory or during pathogen infection. Exposure to this blend of volatiles induces defense-related responses in neighboring undamaged plants, thus assigning a role to GLVs in regulating plant defenses. Here we compared Arabidopsis thaliana ecotype Landsberg erecta (Ler) with a hydroperoxide lyase line, hpl1, unable to synthesize GLVs, for susceptibility to Pseudomonas syringae pv. tomato (DC3000). We found that the growth of DC3000 was significantly reduced in the hpl1 mutant. This phenomenon correlated with lower jasmonic acid (JA) levels and higher salicylic acid levels in the hpl1 mutant. Furthermore, upon infection, the JA-responsive genes VSP2 and LEC were only slightly or not induced, respectively, in hpl1. This suggests that the reduced growth of DC3000 in hpl1 plants is due to the constraint of JA-dependent responses. Treatment of hpl1 plants with E-2-hexenal, one of the more reactive GLVs, prior to infection with DC3000, resulted in increased growth of DC3000 in hpl1, thus complementing this mutant. Interestingly, the growth of DC3000 also increased in Ler plants treated with E-2-hexenal. This stronger growth was not dependent on the JA-signaling component MYC2, but on ORA59, an integrator of JA and ethylene signaling pathways, and on the production of coronatine by DC3000. GLVs may have multiple effects on plant-pathogen interactions, in this case reducing resistance to Pseudomonas syringae via JA and ORA59.

  9. The relationship between heart rate variability and prostaglandin E2 in patients with renal insufficiencies

    Institute of Scientific and Technical Information of China (English)

    陈伊伦; 朱建华; 胡申江; 王磊; 赵力; 陈宝仙

    2003-01-01

    Objective To investigate the relationship between heart rate variability (HRV) and prostaglandin E2 (PGE2) in patients with renal insufficiencies. Methods HRV blood and 24-hour urine prostagladin E2 (PGE2) detection were detected in the following 4 groups of people: group A was a control group comprised of 20 normal individuals; group B had 20 patients with renal disease but exhibiting normal renal function; group C contained 20 patients with renal disease and compensatory renal function; group D had 20 patients demonstrating renal insufficiencies. The indices standard deviation of all NN intervals (SDNN), index of standard deviation of the averages of NN intervals (SDANN), mean of the standard deviation of all NN intervals performed on all 5-minute segments of the entire recording (SDNNindex), square root of the mean of the sum of the squares of differences between adjacent NN intervals (rMSSD) and NN50 count divided by the total number of all NN intervals (PNN50) were used to evaluate HRV, blood and 24-hour urine were determined by specific radioimmunoassay (RIA). Results PGE2 in blood and urine and HRV exactly within 24 hours in patients with renal insufficiencies, negatively correlated with worsening damage to renal function. There was a slight or moderate correlation between blood and urine PGE2 and the SDNNindex, SDANNindex, SDNN, rMSSD and PNN50 indices (P<0.05). Conclusions HRV and cardiac autonomic regulatory functions are decreased in the patients with renal insufficiencies, while lower levels of PGE2 may be a related factor.

  10. Prostaglandin E2 role in inhibition of joint cartilage collagen destruction in patients with osteoarthritis

    Directory of Open Access Journals (Sweden)

    E V Chetina

    2009-01-01

    Full Text Available Prostaglandin E2 role in inhibition of articular cartilage collagen degradation in patients with osteoarthritis. Objective. To assess prostaglandin E2 (PGE2 role in inhibition of type II collagen digestion in explants of articular cartilage of pts with osteoarthritis (OA. Material and methods. Explants of articular cartilage of pts with OA were cultured with PGE2 1pg to 10 ng/ml. Type II collagen digestion was assessed with immuno-enzyme assay. Gene expression was evaluated with PCR in real time. Results. PGE2 10 pg/ml as well as transforming growth factor β2 (TGFβ2 suppressed type II collagen digestion in explants of articular cartilage of pts with OA. This concentration of PGE2 did not suppress proteoglycan (aggrecan degradation. Gene expression analysis in 5 OA pts showed that PGE2 10 pg/ml suppressed metallomonooxigenase (MMP-13, MMP-1 and marker of chondrocyte hypertrophy type X collagen (COL10A1 as well as proinflammatory cytokines interleukine (IL-1β and tumor necrosis factor (TNFα. Naproxen, nonselective cyclooxygenase(COX-2 and 1 inhibitor concentration from 5 to 30 mcg/ml blocked TGFβ2 induced collagen digestion inhibition proving that PGE2 mediate influence of this growth factor. Naproxen concentration 5 mcg/ml increased collagen degradation. Conclusion. The study showed that PGE2 is a chondroprotector because it is able to suppress selectively OA pts cartilage collagen degradation. Beside that cartilage chondrocyte hypertrophy in OA connected functionally with increased collagen digestion is also regulated by low concentrations of PGE2

  11. Ketoprofen impairs immunosuppression induced by severe sepsis and reveals an important role for prostaglandin E2.

    Science.gov (United States)

    Brogliato, Ariane Rennó; Antunes, Carlos A; Carvalho, Renato S; Monteiro, Ana Paula T; Tinoco, Rodrigo F; Bozza, Marcelo T; Canetti, Claudio; Peters-Golden, Marc; Kunkel, Steven L; Vianna-Jorge, Rosane; Benjamim, Claudia Farias

    2012-12-01

    The mechanism of immunosuppression induced by severe sepsis is not fully understood. The production of prostaglandin E2 (PGE2) during sepsis is well known, but its role in long-term consequences of sepsis has not been explored. The current study evaluates the role of PGE2 in the development of immunosuppression secondary to sepsis and its potential as therapeutic target. Cecal ligation and puncture was used as an experimental model for sepsis induction in Balb/c and C57BL/6 mice. Immunosuppression was evaluated by the response to secondary infection with Aspergillus fumigatus in sepsis survivors. The role of prostanoids was evaluated in vivo and in vitro by treatment with the cyclooxygenase inhibitor ketoprofen. Balb/c mice were more susceptible than C57BL/6 to severe sepsis and to secondary infection, with a greater mortality rate. Prostaglandin E2 concentrations found in bronchoalveolar lavage in sham and cecal ligation and puncture group after fungal challenge were much higher in Balb/c than in C57BL/6 mice. Ketoprofen treatment improved survival of septic Balb/c mice subjected to secondary infection, while also enhancing macrophage phagocytosis and neutrophil recruitment to the lungs. We identified a pivotal role for PGE2 acting on EP4 receptors in modulating cytokine production differentially by sham and septic macrophages. Furthermore, sepsis also altered key enzymes in PGE2 synthesis and degradation. Our results indicate the involvement of PGE2 in severe sepsis-induced immunosuppression. Inhibition of PGE2 production represents an attractive target to improve innate immune response against secondary infection in the immunocompromised host.

  12. Lytic efficacy of apoli protein E2 (ApoE2) and recombinant tissue plasminogen activator (rt-PA) treatment with 120 kHz ultrasound in an in-vitro human clot model

    Science.gov (United States)

    Meunier, Jason M.; Cheng, Jason Y.; Clark, Joseph F.; Shaw, George J.

    2005-04-01

    Currently, the only FDA approved therapy for acute ischemic stroke is recombinant tissue plasminogen activator (rt-PA). However rt-PA has substantial side effects such as hemorrhage. This has led to interest in other potential therapies. For example, ultrasound (US) increases the lytic efficacy of rt-PA. Also, apolipoprotein E2 (ApoE2) increases rt-PA activity. This suggests combining US, ApoE2 and rt-PA to improve thrombolysis, but the efficacy is not known. Here, the lytic efficacy of apoE2, rt-PA and 120 kHz US is measured in a human clot model. Whole blood was obtained from volunteers, after local institutional approval. Clots were formed in 1.7 mm micropipettes, and placed in a water tank that allowed microscopic video imaging during US and thrombolytic exposure. Clots were treated with rt-PA ([rt-PA]=3.15 μg/ml), rt-PA and apoE2 ([apoE2]=9.8 μg/ml), or rt-PA, apoE2 and 120 kHz US (0.35 MPa, PRF=1667 Hz, 80% duty cycle) for 15 min at 37°C in human plasma. Clot lysis was visually recorded and the lysis depth (LD) determined from these data using an image analysis algorithm. LD was linear with time for all treatments (R2>=0.81), allowing the determination of a lytic rate (LR). LR was found to be 0.35+/-0.03, 1.55+/-0.11, and 0.75+/-0.04 μm/min for the rt-PA, rt-PA and apoE2, and US treated groups respectively. The thrombolytic efficacy of rt-PA is enhanced by ApoE2. The interaction of 120 kHz with apoE2 and rt-PA showed a reduced lytic efficacy compared with rt-PA and apoE2 treatment alone. It is possible that US interferes with the ApoE2-mediated activation of rt-PA.

  13. Interaction of hepatitis C virus envelope glycoprotein E2 with the large extracellular loop of tupaia CD81

    Institute of Scientific and Technical Information of China (English)

    Zhan-Fei Tian; Hong Shen; Xi-Hua Fu; Yi-Chun Chen; Hubert E Blum; Thomas F Baumert; Xi-Ping Zhao

    2009-01-01

    AIM: To further analyze the interaction of tupaia CD81 with hepatitis C virus (HCV) envelope protein E2. METHODS: A tupaia CD81 large extracellular loop (CD81 LEL), which binds to HCV E2 protein, was cloned and expressed as a GST-fusion protein, and interaction of HCV E2 protein with a tupaia CD81 LEL was evaluated by enzyme-linked immunosorbent assay (EIA). RESULTS: Although tupaia and human CD81 LEL differed in 6 amino acid changes, tupaia CD81 LEL was strongly recognized by anti-CD81 antibodies against human CD81 LEL conformation-dependent epitopes. Investigating LEL CD81-E2 interactions by EIA, we demonstrated that binding of tupaia CD81 LEL GST fusion protein to recombinant HCV E2 protein was markedly reduced compared to binding of human CD81 LEL GST fusion protein to recombinant HCV E2 protein. CONCLUSION: These data suggest that the structural differences in-between the tupaia and human CD81 may alter the interaction of the large extracellular loop with HCV envelope glycoprotein E2. These findings may be important for the understanding of the mechanisms of binding and entry of HCV to PTHs.

  14. WRKY40 and WRKY6 act downstream of the green leaf volatile E-2-hexenal in Arabidopsis.

    Science.gov (United States)

    Mirabella, Rossana; Rauwerda, Han; Allmann, Silke; Scala, Alessandra; Spyropoulou, Eleni A; de Vries, Michel; Boersma, Maaike R; Breit, Timo M; Haring, Michel A; Schuurink, Robert C

    2015-09-01

    Plants are known to be responsive to volatiles, but knowledge about the molecular players involved in transducing their perception remains scarce. We study the response of Arabidopsis thaliana to E-2-hexenal, one of the green leaf volatiles (GLV) that is produced upon wounding, herbivory or infection with pathogens. We have taken a transcriptomics approach to identify genes that are induced by E-2-hexenal, but not by defence hormones or other GLVs. Furthermore, by studying the promoters of early E-2-hexenal-induced genes we determined that the only statistically enriched cis-element was the W-box motif. Since members of the plant-specific family of WRKY transcription factors act in trans on this cis-element, we focused on WRKY6, 40 and 53 that were most strongly induced by E-2-hexenal. Root elongation of Arabidopsis seedlings of the wrky40 wrky6 double mutant was much less inhibited than in wt plants, similar to the E-2-hexenal-responsive mutant her1, which is perturbed in γ-amino butyric acid (GABA) metabolism. The induction of several of the E-2-hexenal-specific genes was much higher in the wrky40, wrky6 or wrky40 wrky6 mutants, including GAD4, a glutamate decarboxylase that catalyzes the formation of GABA from glutamate. In conclusion, WRKY6 and 40 seem to act as important players transducing E-2-hexenal perception.

  15. Preparation of human single chain Fv antibody against hepatitis C virus E2 protein and its identification in immunohistochemistry

    Institute of Scientific and Technical Information of China (English)

    Yan-Wei Zhong; Jun Cheng; Gang Wang; Shuang-Shuang Shi; Li Li; Ling-Xia Zhang; Ju-Mei Chen

    2002-01-01

    AIM: To screen human single chain Fv antibody (scFv)against hepatitis C virus E2 antigen and identify its applicationin immunohistochemistry.METHODS: The phage antibody library was panned by HCVE2 antigen, which was coated in microtiter plate. After fiverounds of biopanning,56 phage clones were identified specificto HCV E2 antigen. The selected scFv clones were digestedby SfiI/NotI and DNA was sequenced. Then it was subclonedinto the vector pCANTABSE for expression as E-taggedsoluble scFv. The liver tissue sections from normal personand patients with chronic hepatitis B and chronic hepatitis Cwere immunostained with HCV E2 scFv antibody.RESULTS: The data of scFv-E2 DNA digestion and DNAsequencing showed that the scFv gene is composed of 750bp. ELISA and immunohistochemistry demonstrated that thehuman single chain Fy antibody against hepatitis C E2 antigenhas a specific binding character with hepatitis virus E2 antigenand paraffin-embedded tissue, but did not react with liver tissuesfrom healthy persons or patients with chronic hepatitis B.CONCLUSION: We have successfully screened andidentified HCV E2 scFv and the scFv could be used in theimmunostaining of liver tissue sections from patients withchronic hepatitis C.

  16. Interaction of CSFV E2 protein with swine host factors as detected by yeast two-hybrid system.

    Directory of Open Access Journals (Sweden)

    Douglas P Gladue

    Full Text Available E2 is one of the envelope glycoproteins of pestiviruses, including classical swine fever virus (CSFV and bovine viral diarrhea virus (BVDV. E2 is involved in several critical functions, including virus entry into target cells, induction of a protective immune response and virulence in swine. However, there is no information regarding any host binding partners for the E2 proteins. Here, we utilized the yeast two-hybrid system and identified fifty-seven host proteins as positive binding partners which bound E2 from both CSFV and BVDV with the exception of two proteins that were found to be positive for binding only to CSFV E2. Alanine scanning of CSFV E2 demonstrated that the binding sites for these cellular proteins on E2 are likely non-linear binding sites. The possible roles of the identified host proteins are discussed as the results presented here will be important for future studies to elucidate mechanisms of host protein-virus interactions during pestivirus infection. However, due to the limitations of the yeast two hybrid system, the proteins identified is not exhaustive and each interaction identified needs to be confirmed by independent experimental approaches in the context of virus-infected cells before any definitive conclusion can be drawn on relevance for the virus life cycle.

  17. Functional interaction of CCAAT/enhancer-binding-protein-α basic region mutants with E2F transcription factors and DNA.

    Science.gov (United States)

    Kowenz-Leutz, Elisabeth; Schuetz, Anja; Liu, Qingbin; Knoblich, Maria; Heinemann, Udo; Leutz, Achim

    2016-07-01

    The transcription factor CCAAT/enhancer-binding protein α (C/EBPα) regulates cell cycle arrest and terminal differentiation of neutrophils and adipocytes. Mutations in the basic leucine zipper domain (bZip) of C/EBPα are associated with acute myeloid leukemia. A widely used murine transforming C/EBPα basic region mutant (BRM2) entails two bZip point mutations (I294A/R297A). BRM2 has been discordantly described as defective for DNA binding or defective for interaction with E2F. We have separated the two BRM2 mutations to shed light on the intertwined reciprocity between C/EBPα-E2F-DNA interactions. Both, C/EBPα I294A and R297A retain transactivation capacity and interaction with E2F-DP. The C/EBPα R297A mutation destabilized DNA binding, whereas the C/EBPα I294A mutation enhanced binding to DNA. The C/EBPα R297A mutant, like BRM2, displayed enhanced interaction with E2F-DP but failed to repress E2F-dependent transactivation although both mutants were readily suppressed by E2F1 for transcription through C/EBP cis-regulatory sites. In contrast, the DNA binding enhanced C/EBPα I294A mutant displayed increased repression of E2F-DP mediated transactivation and resisted E2F-DP mediated repression. Thus, the efficient repression of E2F dependent S-phase genes and the activation of differentiation genes reside in the balanced DNA binding capacity of C/EBPα.

  18. Different effects of growth hormone-releasing hormone (GRH) and somatostatin on growth hormone and stable metabolite of prostaglandin E2, 13, 14-dihydro-15-keto-prostaglandin E2 (PGE2-M) in normal subjects.

    Science.gov (United States)

    Zacharieva, S; Muchá, I; Popova, J; Andonova, K

    1992-01-01

    Twenty four healthy subjects were placed in two treatment groups: 1. The first group consisted of twelve subjects in whom growth releasing hormone (GRH) (1 microgram/kg.BW) resulted in a marked and sustained elevation of serum growth hormone (GH) and a slight and delayed increase in plasma prostaglandin E2-M. In the second group, consisting also of twelve subjects, somatostatin infusion (500 micrograms/250 ml) was initiated and maintained for 60 min. Serum GH significantly decreased at 30 and 60 min during infusion and 15 min thereafter. We did not observe any changes in plasma prostaglandin E2-M during or after somatostatin infusion. The results obtained confirm previous in vitro studies and suggest a possible link between growth releasing hormone and prostaglandin E2 in their action on growth hormone secretion. It seems that somatostatin does not play a role in the control of prostaglandin E2 release.

  19. Silica Vesicle Nanovaccine Formulations Stimulate Long-Term Immune Responses to the Bovine Viral Diarrhoea Virus E2 Protein.

    Directory of Open Access Journals (Sweden)

    Karishma T Mody

    Full Text Available Bovine Viral Diarrhoea Virus (BVDV is one of the most serious pathogen, which causes tremendous economic loss to the cattle industry worldwide, meriting the development of improved subunit vaccines. Structural glycoprotein E2 is reported to be a major immunogenic determinant of BVDV virion. We have developed a novel hollow silica vesicles (SV based platform to administer BVDV-1 Escherichia coli-expressed optimised E2 (oE2 antigen as a nanovaccine formulation. The SV-140 vesicles (diameter 50 nm, wall thickness 6 nm, perforated by pores of entrance size 16 nm and total pore volume of 0.934 cm3 g(-1 have proven to be ideal candidates to load oE2 antigen and generate immune response. The current study for the first time demonstrates the ability of freeze-dried (FD as well as non-FD oE2/SV140 nanovaccine formulation to induce long-term balanced antibody and cell mediated memory responses for at least 6 months with a shortened dosing regimen of two doses in small animal model. The in vivo ability of oE2 (100 μg/SV-140 (500 μg and FD oE2 (100 μg/SV-140 (500 μg to induce long-term immunity was compared to immunisation with oE2 (100 μg together with the conventional adjuvant Quil-A from the Quillaja saponira (10 μg in mice. The oE2/SV-140 as well as the FD oE2/SV-140 nanovaccine generated oE2-specific antibody and cell mediated responses for up to six months post the final second immunisation. Significantly, the cell-mediated responses were consistently high in mice immunised with oE2/SV-140 (1,500 SFU/million cells at the six-month time point. Histopathology studies showed no morphological changes at the site of injection or in the different organs harvested from the mice immunised with 500 μg SV-140 nanovaccine compared to the unimmunised control. The platform has the potential for developing single dose vaccines without the requirement of cold chain storage for veterinary and human applications.

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

    Science.gov (United States)

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

    2016-04-01

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

  1. E2F-dependent induction of p14ARF during cell cycle re-entry in human T cells

    DEFF Research Database (Denmark)

    del Arroyo, Ana Gutierrez; El Messaoudi, Selma; Clark, Paula A

    2007-01-01

    The ARF protein, encoded by alternate exon usage within the CDKN2A locus, provides a link between the retinoblastoma (pRb) and p53 tumor suppressor pathways. Agents that disable pRb or otherwise impinge on the E2F family of transcription factors induce expression of ARF, resulting in stabilization...... of p53 and activation of p53-regulated genes. However, in some cell types ARF is not induced upon cell cycle re-entry, as expected of a conventional E2F target gene, leading to the suggestion that the ARF promoter only responds to supra-physiological or aberrant levels of E2F. These properties have...

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

    Science.gov (United States)

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

    2017-05-15

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

  3. ROS production is essential for the apoptotic function of E2F1 in pheochromocytoma and neuroblastoma cell lines.

    Directory of Open Access Journals (Sweden)

    Lilia Espada

    Full Text Available In this study we demonstrate that accumulation of reactive oxygen species (ROS is essential for E2F1 mediated apoptosis in ER-E2F1 PC12 pheochromocytoma, and SH-SY5Y and SK-N-JD neuroblastoma stable cell lines. In these cells, the ER-E2F1 fusion protein is expressed in the cytosol; the addition of 4-hydroxytamoxifen (OHT induces its translocation to the nucleus and activation of E2F1target genes. Previously we demonstrated that, in ER-E2F1 PC12 cells, OHT treatment induced apoptosis through activation of caspase-3. Here we show that caspase-8 activity did not change upon treatment with OHT. Moreover, over-expression of Bcl-xL arrested OHT-induced apoptosis; by contrast, over-expression of c-FLIP, did not have any effect on OHT-induced apoptosis. OHT addition induces BimL expression, its translocation to mitochondria and activation of Bax, which is paralleled by diminished mitochondrial enrichment of Bcl-xL. Treatment with a Bax-inhibitory peptide reduced OHT-induced apoptosis. These results point out the essential role of mitochondria on the apoptotic process driven by E2F1. ROS accumulation followed E2F1 induction and treatment with the antioxidant N-acetylcysteine, inhibited E2F1-induced Bax translocation to mitochondria and subsequent apoptosis. The role of ROS in mediating OHT-induced apoptosis was also studied in two neuroblastoma cell lines, SH-SY5Y and SK-N-JD. In SH-SY5Y cells, activation of E2F1 by the addition of OHT induced ROS production and apoptosis, whereas over-expression of E2F1 in SK-N-JD cells failed to induce either response. Transcriptional profiling revealed that many of the genes responsible for scavenging ROS were down-regulated following E2F1-induction in SH-SY5Y, but not in SK-N-JD cells. Finally, inhibition of GSK3β blocked ROS production, Bax activation and the down regulation of ROS scavenging genes. These findings provide an explanation for the apparent contradictory role of E2F1 as an apoptotic agent versus a cell

  4. 老年冠心病患者血清GH、T和E2的变化探讨%Study on the Changes of Serum GH, T and E2 Levels in Elderly Patients with Coronary Heart Disease

    Institute of Scientific and Technical Information of China (English)

    吴少琴; 季乃军; 梅益斌; 樊必夫; 陈东海; 童丽军; 王成尧; 李付远; 考验

    2005-01-01

    目的:探讨老年冠心病患者血清生长激素(GH)、睾酮(T)和雌二醇(E2)水平的变化及其临床意义.方法:采用放射免疫分析测定了112例老年冠心病患者和40例健康对照组的血清GH、T和E2水平.结果:老年冠心病组血清GH和E2水平显著低于对照组(P<0.01,P<0.05),T与对照组无显著差异(P>0.05).GH与E2水平呈显著的正相关(P<0.05),但两者与T均无相关性(P均>0.05).Ⅰ、Ⅱ、Ⅲ和Ⅳ级心功能组患者血清GH、T、E2均依次显著递减(P<0.05,P<0.01,P<0.01).伴急性心肌梗死组血清GH和E2水平显著低于无心肌梗死组(P均<0.01),但T却元显著差异(P>0.05).住院死亡组血清GH、T、E2均显著低于好转出院组(P<0.05,P<0.01,P<0.01).结论:EH组血清GH和E2水平显著降低,GH、T和E2均随心功能降低而依次显著递减,伴急性心肌梗死组GH和E2水平显著降低,死亡组血清GH、T、E2均显著降低.

  5. 前列腺癌E2F3蛋白的表达及临床意义%Expression and Clinical Significance of E2F3 in Human Prostate Cancer

    Institute of Scientific and Technical Information of China (English)

    李云祥; 苟欣; 王安果; 张宗平; 伍季

    2011-01-01

    To study the expression and clinical significance of E2F3 in pnmary prostate cancer (PCa). Methods E2F3 protein expression was detected by EliVisioTM plus immunohistochemical staining in 49 PCa, 20 benign prostatic hyperplasia ( BPH) , 10 normal prostate tissues ( NP) . The relationship between E2F3 expression and clinico - pathological parameters was analyzed.Results The expression level of E2F3 in PCa was significantly higher than that in BPH (P <0. 05) and NP ( P <0. 05) , and was positively correlated with pathological grades, clinical stages and serum PSA of PCa, respectively ( P <0. 05) . The expression level of E2F3 was closely association with prognosis (P <0. 05). Conclusion E2F3 may play an important role in the development and prognosis of primary prostate cancer.%目的 探讨前列腺癌组织中E2F3蛋白的表达及临床意义.方法 应用免疫组化EliVisionTM plus二步法,检测49例前列腺癌(prostate cancer,PCa),20例良性前列腺增生(benign prostatic hyperplasia,BPH)及10例肾移植正常前列腺组织(normal prostate,NP)中E2F3蛋白的表达,分析其表达与肿瘤分级、分期及血清PSA和预后间的关系.结果 前列腺癌中E2F3的水平明显高于BPH(P<0.05)及NP(P<0.05),且与PCa病理分级和临床分期与血清PSA及预后有密切的联系.结论 E2F3可作为PCa新的标志物,检测E2F3有助于判定PCa恶性程度及预后.

  6. Turnley Unit

    Data.gov (United States)

    Federal Laboratory Consortium — Facilities at this unit include cattle working pens, hydraulic squeeze chute and electronic scale, a maintenance building, and four hay storage sheds. There is one...

  7. Operable Units

    Data.gov (United States)

    U.S. Environmental Protection Agency — This dataset consists of operable unit data from multiple Superfund sites in U.S. EPA Region 8. These data were acquired from multiple sources at different times and...

  8. Detector Unit

    CERN Multimedia

    1960-01-01

    Original detector unit of the Instituut voor Kernfysisch Onderzoek (IKO) BOL project. This detector unit shows that silicon detectors for nuclear physics particle detection were already developed and in use in the 1960's in Amsterdam. Also the idea of putting 'strips' onto the silicon for high spatial resolution of a particle's impact on the detector were implemented in the BOL project which used 64 of these detector units. The IKO BOL project with its silicon particle detectors was designed, built and operated from 1965 to roughly 1977. Detector Unit of the BOL project: These detectors, notably the ‘checkerboard detector’, were developed during the years 1964-1968 in Amsterdam, The Netherlands, by the Natuurkundig Laboratorium of the N.V. Philips Gloeilampen Fabrieken. This was done in close collaboration with the Instituut voor Kernfysisch Onderzoek (IKO) where the read-out electronics for their use in the BOL Project was developed and produced.

  9. Assessing the usefulness of prostaglandin E2 (Cervidil) for transcervical artificial insemination in ewes.

    Science.gov (United States)

    Bartlewski, Pawel M; Candappa, Ivanka B R

    2015-12-01

    The underlying theme of this study involved the evaluation of the dilatory effects of prostaglandin E2 on the ovine cervix and thus the assessment of its potential applicability to transcervical artificial insemination (TCAI) in ewes. A novel method of prostaglandin E2 administration (controlled slow-release vaginal inserts) was examined, and the practical implications of this approach including cervical penetrability and posttreatment pregnancy rates were evaluated. The Guelph method of TCAI was performed during the seasonal anestrus (n = 40) and the breeding season (n = 40) on multiparous Rideau Arcott × Polled Dorset ewes, with or without the pretreatment with Cervidil (for a duration of 12 hours or 24 hours before TCAI). Cervical penetration rates averaged 82.5% (66 of 80), and they varied neither (P > 0.05) between the two seasons nor between Cervidil-treated ewes and their respective controls. Cervidil priming significantly reduced the total time required for TCAI during the breeding season in comparison with controls (54 vs. 98 seconds), especially after the 24-hour exposure (38 vs. 108 seconds). The time taken to traverse the uterine cervix was negatively correlated (P < 0.05) with the breed (percentage of Rideau Arcott genotype) and lifetime lamb production in seasonally anestrous ewes. Four out of 36 (11%) successfully penetrated ewes in the breeding season (three ewes allocated to the 12-hour control group and one ewe that had received Cervidil for 12 hours) became pregnant and carried the lambs to term. Vaginal mucus impedance at TCAI was significantly and positively correlated with the total time required to complete the procedure in cyclic ewes, and the negative correlation between vaginal mucus impedance and total time values at the time of controlled intravaginal drug release device removal approached to significance in anestrous ewes. The present results indicate a moderate benefit of using Cervidil for inducing cervical dilation before

  10. Arsenic treatment increase Aurora-A overexpression through E2F1 activation in bladder cells.

    Science.gov (United States)

    Kao, Yu-Ting; Wu, Chin-Han; Wu, Shan-Ying; Lan, Sheng-Hui; Liu, Hsiao-Sheng; Tseng, Ya-Shih

    2017-04-18

    Arsenic is a widely distributed metalloid compound that has biphasic effects on cultured cells. In large doses, arsenic can be toxic enough to trigger cell death. In smaller amounts, non-toxic doses may promote cell proliferation and induces carcinogenesis. Aberration of chromosome is frequently detected in epithelial cells and lymphocytes of individuals from arsenic contaminated areas. Overexpression of Aurora-A, a mitotic kinase, results in chromosomal instability and cell transformation. We have reported that low concentration (≦1 μM) of arsenic treatment increases Aurora-A expression in immortalized bladder urothelial E7 cells. However, how arsenic induces carcinogenesis through Aurora-A activation remaining unclear. Bromodeoxyuridine (BrdU) staining, MTT assay, and flow cytometry assay were conducted to determine cell proliferation. Messenger RNA and protein expression levels of Aurora-A were detected by reverse transcriptional-PCR and Western blotting, respectively. Centrosome of cells was observed by immunofluorescent staining. The transcription factor of Aurora-A was investigated by promoter activity, chromosome immunoprecipitation (ChIP), and small interfering RNA (shRNA) assays. Mouse model was utilized to confirm the relationship between arsenic and Aurora-A. We reveal that low dosage of arsenic treatment increased cell proliferation is associated with accumulated cell population at S phase. We also detected increased Aurora-A expression at mRNA and protein levels in immortalized bladder urothelial E7 cells exposed to low doses of arsenic. Arsenic-treated cells displayed increased multiple centrosome which is resulted from overexpressed Aurora-A. Furthermore, the transcription factor, E2F1, is responsible for Aurora-A overexpression after arsenic treatment. We further disclosed that Aurora-A expression and cell proliferation were increased in bladder and uterus tissues of the BALB/c mice after long-term arsenic (1 mg/L) exposure for 2 months. We

  11. E2F1蛋白的表达及与Sedlin蛋白共定位研究%The expression of human E2F1 and the co-localization with Sedlin

    Institute of Scientific and Technical Information of China (English)

    汪燕燕; 潘林鑫; 王梦媛; 刘晓颖; 范礼斌

    2015-01-01

    目的 研究人E2F1 蛋白在真核细胞内的表达及其与 Sedlin 蛋白的共定位. 方法 构建 pcDNA3. 1-E2F1-FLAG真核表达质粒,然后瞬时转染至 HEK 293T 细胞内, Western blot法检测E2F1蛋白的表达;瞬时单转E2F1-FLAG和共转E2F1-FLAG+Sedlin-绿色荧光蛋白( GFP)至非洲绿猴肾细胞( COS7 )内,免疫荧光制片,荧光显微镜下观察E2F1-FLAG在细胞内的定位及其和Sedlin的共定位. 结果真核表达质粒 pcDNA3. 1-E2F1-FLAG 构建成功,且在HEK 293T细胞中能够成功表达,在COS7 细胞中主要定位在细胞核,且与Sedlin共定位于细胞核. 结论 人E2F1 在HEK 293T、COS7细胞中都能够正常表达,且与 Sedlin蛋白存在共定位现象,为进一步了解人E2F1的功能及其蛋白质相互作用提供了一定的细胞学基础.%Objective To investigate the expression and localization of E2F1 in eukaryotic cells and the co-locali-zation with Sedlin. Methods To construct eukaryotic expression plasmid pcDNA3. 1-E2F1-FLAG. The plsamid was transfected into HEK 293T cells and the expression was checked by Western blot. Its expression in COS7 cells was detected by fluorescence microscopy. Results The eukaryotic expression plasmid of pcDNA3. 1-E2F1-FLAG was constructed successfully, which could be effectively expressed in HEK 293T and COS7 cells. E2F1 was pre-dominantly distributed in the nucleus, and it co-localized in the nucleus with Sedlin. Conclusion E2F1 can over-express efficiently in HEK 293T and COS7 cells, and it can colocalize with Seldin, which provides important bases for further study on E2F1 including its functions and associated proteins.

  12. The geranyl-modified tryptophan residue is crucial for ComXRO-E-2 pheromone biological activity.

    Science.gov (United States)

    Tsuji, Fumitada; Kobayashi, Ko; Okada, Masahiro; Yamaguchi, Hisao; Ojika, Makoto; Sakagami, Youji

    2011-07-01

    The ComX pheromone is an isoprenoidal oligopeptide containing a modified tryptophan residue, which stimulates natural genetic competence in gram-positive bacteria, Bacillus. We have reported the structure of the ComX(RO-E-2) pheromone, which is produced by the RO-E-2 strain of Bacillus subtilis. ComX(RO-E-2) analogs with substituted amino acids and isoprenoid modified tryptophan residues (e.g., prenyl, geranyl, and farnesyl), were synthesized and examined for biological activity. These results indicate that Phe-Trp(∗)(Ger)-NH(2) is the minimum pharmacophore of the ComX(RO-E-2) pheromone. Furthermore, the length of the isoprenoid moiety (i.e., modification style), and the presence of double bonds, are crucial for biological activity. The modification style of the ComX pheromone is more important than the peptide sequence with respect to biological activity.

  13. Classical swine fever virus marker vaccine strain CP7_E2alf: genetic stability in vitro and in vivo.

    Science.gov (United States)

    Goller, Katja V; Dräger, Carolin; Höper, Dirk; Beer, Martin; Blome, Sandra

    2015-12-01

    Recently, CP7_E2alf (SuvaxynCSF Marker), a live marker vaccine against classical swine fever virus, was licensed through the European Medicines Agency. For application of such a genetically engineered virus under field conditions, knowledge about its genetic stability is essential. Here, we report on stability studies that were conducted to assess and compare the mutation rate of CP7_E2alf in vitro and in vivo. Sequence analyses upon passaging confirmed the high stability of CP7_E2alf, and no recombination events were observed in the experimental setup. The data obtained in this study confirm the genetic stability of CP7_E2alf as an important safety component.

  14. A role of NF-E2 in chronic inflammation and clonal evolution in essential thrombocythemia, polycythemia vera and myelofibrosis?

    Science.gov (United States)

    Hasselbalch, Hans C

    2014-02-01

    A novel murine model for myeloproliferative neoplasms (MPNs) generated by overexpression of the transcription factor NF-E2 has recently been described. Sustained overexpression of NF-E2 in this model induced myeloid expansion with anemia, leukocytosis and thrombocytosis. Herein, it is debated if NF-E2 overexpression also might have induced a sustained state of in vivo leukocyte and platelet activation with chronic and self-perpetuating production of inflammatory products from activated leukocytes and platelets. If so, this novel murine model also may excellently describe the deleterious impact of sustained chronic NF-E2 overexpression during uncontrolled chronic inflammation upon the hematopoietic system--the development of clonal myeloproliferation. Accordingly, this novel murine model may also have delivered the proof of concept of chronic inflammation as a trigger and driver of clonal evolution in MPNs.

  15. Disruption of Rb/E2F pathway results in increased cyclooxygenase-2 expression and activity in prostate epithelial cells.

    Science.gov (United States)

    Davis, Joanne N; McCabe, Michael T; Hayward, Simon W; Park, John M; Day, Mark L

    2005-05-01

    The loss of the retinoblastoma tumor suppressor gene (RB) is common in many human cancers, including prostate. We previously reported that engineered deletion of RB in prostate epithelial cells results in sustained cell growth in serum-free media, a predisposition to develop hyperplasia and dysplasia in prostate tissue recombinant grafts, and sensitization to hormonal carcinogenesis. Examining the molecular consequence of RB loss in this system, we show that cyclooxygenase-2 (COX-2) is significantly up-regulated following RB deletion in prostate tissue recombinants. To study the effect of RB deletion on COX-2 regulation, we generated wild-type (PrE) and Rb-/- (Rb-/-PrE) prostate epithelial cell lines rescued by tissue recombination. We show elevated COX-2 mRNA and protein expression in Rb-/-PrE cell lines with increased prostaglandin synthesis. We also find that loss of Rb leads to deregulated E2F activity, with increased expression of E2F target genes, and that exogenous expression of E2F1 results in elevated COX-2 mRNA and protein levels. COX-2 promoter studies reveal that E2F1 transcriptionally activates COX-2, which is dependent on the transactivation and DNA-binding domains of E2F1. Further analysis revealed that the E2F1 target gene, c-myb, is elevated in Rb-/-PrE cells and E2F1-overexpressing cells, whereas ectopic overexpression of c-myb activates the COX-2 promoter in prostate epithelial cells. Additionally, cotransfection with E2F1 and a dominant-negative c-myb inhibited E2F1 activation of the COX-2 promoter. Taken together, these results suggest activation of a transcriptional cascade by which E2F1 regulates COX-2 expression through the c-myb oncogene. This study reports a novel finding describing that deregulation of the Rb/E2F complex results in increased COX-2 expression and activity.

  16. Expression of E2F -1 and cyclinD1 in colorectal adenocarcinoma and its significance%大肠癌E2F -1、CyclinD1的表达及其意义

    Institute of Scientific and Technical Information of China (English)

    王蕾; 何妍; 李希芳; 刘岩; 时志民; 刘惠民

    2011-01-01

    Objective To study the expression of E2K - 1 and ryclinDl in human colorectal adenocarcinoma and its significance. Methods Terminal deoxynucleotidyl transferase - mediated nick end labeling TUNEL method and immunohistochemical SP method were used to detect 78 cases of colorectal adenocarcinoma, 20 cases of normal eoloreclal mucosa, 30 cases of colorectal polyps, and 30 cases of coloreotal adenoma cells in situ withered death ( Al) , and E2F - 1 and cyclinDl expression. Results The positive expression rate of E2F - 1 and cyclinDl in esophageal carcinoma was much higher than that in colorectal mucosa, colorectal polyps, and colorectal adenoma (P < 0. 05 ). The expression of E2F - 1 was closely correlated with the differentiation, TNM and lymph node metastasis (P <0. 05). Conclusions E2F - 1 and cyclinDl are closely related to the occurrence of colorectal adenocarcinoma. Both of them are important biological markers in colorectal adenocarcinoma occurrence and development.%目的 探讨E2F -1和cyclinD1在大肠腺癌组织中的表达及其意义 方法 采用脱氧核糖核酸末端转移酶介导的TUNEL法缺口末端标记和免疫组化SP法检测大肠腺癌78例、正常大肠黏膜20例、大肠息肉30例,以及大肠腺瘤细胞30例的原位凋亡(Al)及E2F-1和cyclin D1的表达情况.结果 E2F-1和cyclin D1在大肠腺癌中的阳性率显著高于正常大肠黏膜、大肠息肉以及大肠腺瘤(P<0.05).E2F-1表达与大肠腺癌的病理分化程度、淋巴结转移和临床分期具有相关性(P<0 05).从正常大肠黏膜、大肠息肉、大肠腺瘤到大肠腺癌细胞凋亡呈梯度降低.结论 E2F -1和cyclinD1的表达与大肠腺癌发生关系密切,是大肠腺癌发生、发展的重要生物学标记物

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

    Institute of Scientific and Technical Information of China (English)

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

    2002-01-01

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

  18. DAPK2 is a novel E2F1/KLF6 target gene involved in their proapoptotic function

    DEFF Research Database (Denmark)

    Britschgi, A; Trinh, E; Rizzi, M

    2008-01-01

    that is markedly decreased upon DAPK2 knockdown. Moreover, E2F1 and KLF6 show cooperation in activating the DAPK2 promoter. In summary, our findings establish DAPK2 as a novel Sp1-dependent target gene for E2F1 and KLF6 in cell death response.Oncogene advance online publication, 2 June 2008; doi:10.1038/onc.2008.179....

  19. E2/ER β inhibit ISO-induced cardiac cellular hypertrophy by suppressing Ca2+-calcineurin signaling.

    Science.gov (United States)

    Tsai, Cheng-Yen; Kuo, Wei-Wen; Shibu, Marthandam Asokan; Lin, Yueh-Min; Liu, Chien-Nam; Chen, Yi-Hui; Day, Cecilia-Hsuan; Shen, Chia-Yao; Viswanadha, Vijaya Padma; Huang, Chih-Yang

    2017-01-01

    Cardiovascular incidences are markedly higher in men than in pre-menstrual women. However, this advantage in women declines with aging and therefore can be correlated with the sex hormone 17β-Estradiol (E2) which is reported to protect heart cells by acting though estrogen receptors (ERs). In this study we have determined the effect of E2/ERβ against ISO induced cellular hypertrophy in H9c2 cardiomyoblast cells. The results confirm that ISO induced cardiac-hypertrophy by elevating the levels of hypertrophy associated proteins, ANP and BNP and further by upregulating p-CaMKII, calcineurin, p-GATA4 and NFATc3 which was correlated with a significant enlargement of the H9c2 cardiomyoblast. However, overexpression of ERβ and/or administration of E2 inhibited ISO-induced hypertrophy in H9c2 cells. In addition, E2/ERβ also inhibited ISO-induced NFATc3 translocation, and reduced the protein level of downstream marker, BNP. Furthermore, by testing with the calcineurin inhibitor (CsA), it was confirmed that calcineurin acted as a key mediator for the anti-hypertrophic effect of E2/ERβ. In cells treated with calcium blocker (BATPA), the inhibitory effect of E2/ERβ on ISO-induced Ca2+ influx and hypertrophic effects were totally blocked suggesting that E2/ERβ inhibited calcineurin activity to activate I-1 protein and suppress PP1, then induce PLB protein phosphorylation and activation, resulting in Ca2+ reuptake into sarcoplasmic reticulum through SR Ca2+ cycling modification. In conclusion, E2/ERβ suppresses the Ca2+ influx and calcineurin activity induced by ISO to enhance the PLB protein activity and SR Ca2+ cycling.

  20. Differential methylation of E2 binding sites in episomal and integrated HPV 16 genomes in preinvasive and invasive cervical lesions.

    Science.gov (United States)

    Chaiwongkot, Arkom; Vinokurova, Svetlana; Pientong, Chamsai; Ekalaksananan, Tipaya; Kongyingyoes, Bunkerd; Kleebkaow, Pilaiwan; Chumworathayi, Bandit; Patarapadungkit, Natcha; Reuschenbach, Miriam; von Knebel Doeberitz, Magnus

    2013-05-01

    Enhanced expression of the HPV 16 E6-E7 oncogenes may trigger neoplastic transformation of the squamous epithelial cells at the uterine cervix. The HPV E2 protein is a key transcriptional regulator of the E6-E7 genes. It binds to four E2 binding sites (E2BSs 1-4) in the viral upstream regulatory region (URR). Modification of E2 functions, for example, by methylation of E2BSs is hypothesized to trigger enhanced expression of the viral E6-E7 oncogenes. In the majority of HPV-transformed premalignant lesions and about half of cervical carcinomas HPV genomes persist in an extra-chromosomal, episomal state, whereas they are integrated into host cells chromosomes in the remaining lesions. Here we compared the methylation profile of E2BSs 1-4 of the HPV 16 URR in a series of 18 HPV16-positive premalignant lesions and 33 invasive cervical cancers. CpGs within the E2BSs 1, 3, and 4 were higher methylated in all lesions with only episomal HPV16 genomes compared with lesions displaying single integrated copies. Samples with multiple HPV16 integrated copies displayed high methylation levels for all CpGs suggesting that the majority of multiple copies were silenced by extensive methylation. These data support the hypothesis that differential methylation of the E2BSs 1, 3 and 4 is related to the activation of viral oncogene expression in cervical lesions as long as the viral genome remains in the episomal state. Once the virus becomes integrated into host cell chromosomes these methylation patterns may be substantially altered due to complex epigenetic changes of integrated HPV genomes.

  1. NUV performance of e2v large BICMOS array for CASTOR

    Science.gov (United States)

    Scott, Alan; Beaton, Alexander; Roy, Niladri; Côté, Patrick; Hutchings, John

    2016-07-01

    We have characterized the e2v CIS113 16 μm pitch 4608 x 1920 back-illuminated CMOS (BICMOS) array with near Ultraviolet (NUV) sensitization surface processing and measured its quantum efficiency over the wavelength range from 150 to 350 nm. The Cosmological Advanced Survey Telescope for Optical and UV Research (CASTOR), one of the top priorities in the Canadian astronomical community's decadal plan, is a space-based survey mission that would provide panoramic, high-resolution imaging of 1/8th of the sky in the UV/optical (150-550 nm) spectral region. This small-satellite class mission would provide high angular resolution ultra-deep imaging in three broad filters to supplement data from planned international dark energy missions (Euclid, WFIRST) as well as from the Large Synoptic Survey Telescope (LSST). One of the leading technical risks on this mission is the UV sensitivity required to approach 26th magnitude in the near UV band. In this paper we briefly describe the architecture of this new high speed, high sensitivity CMOS detector and report on the results of our characterization and the implications for the proposed CASTOR survey mission.

  2. Prostaglandin E2 regulates macrophage colony stimulating factor secretion by human bone marrow stromal cells.

    Science.gov (United States)

    Besse, A; Trimoreau, F; Faucher, J L; Praloran, V; Denizot, Y

    1999-07-08

    Bone marrow stromal cells regulate marrow haematopoiesis by secreting growth factors such as macrophage colony stimulating factor (M-CSF) that regulates the proliferation, differentiation and several functions of cells of the mononuclear-phagocytic lineage. By using a specific ELISA we found that their constitutive secretion of M-CSF is enhanced by tumour necrosis factor-alpha (TNF-alpha). The lipid mediator prostaglandin E2 (PGE2) markedly reduces in a time- and dose-dependent manner the constitutive and TNF-alpha-induced M-CSF synthesis by bone marrow stromal cells. In contrast, other lipid mediators such as 12-HETE, 15-HETE, leukotriene B4, leukotriene C4 and lipoxin A4 have no effect. EP2/EP4 selective agonists (11-deoxy PGE1 and 1-OH PGE1) and EP2 agonist (19-OH PGE2) inhibit M-CSF synthesis by bone marrow stromal cells while an EP1/EP3 agonist (sulprostone) has no effect. Stimulation with PGE2 induces an increase of intracellular cAMP levels in bone marrow stromal cells. cAMP elevating agents (forskolin and cholera toxin) mimic the PGE2-induced inhibition of M-CSF production. In conclusion, PGE2 is a potent regulator of M-CSF production by human bone marrow stromal cells, its effects being mediated via cAMP and PGE receptor EP2/EP4 subtypes.

  3. Prostaglandin E2 signals through PTGER2 to regulate sclerostin expression.

    Science.gov (United States)

    Genetos, Damian C; Yellowley, Clare E; Loots, Gabriela G

    2011-03-16

    The Wnt signaling pathway is a robust regulator of skeletal homeostasis. Gain-of-function mutations promote high bone mass, whereas loss of Lrp5 or Lrp6 co-receptors decrease bone mass. Similarly, mutations in antagonists of Wnt signaling influence skeletal integrity, in an inverse relation to Lrp receptor mutations. Loss of the Wnt antagonist Sclerostin (Sost) produces the generalized skeletal hyperostotic condition of sclerosteosis, which is characterized by increased bone mass and density due to hyperactive osteoblast function. Here we demonstrate that prostaglandin E(2) (PGE(2)), a paracrine factor with pleiotropic effects on osteoblasts and osteoclasts, decreases Sclerostin expression in osteoblastic UMR106.01 cells. Decreased Sost expression correlates with increased expression of Wnt/TCF target genes Axin2 and Tcf3. We also show that the suppressive effect of PGE(2) is mediated through a cyclic AMP/PKA pathway. Furthermore, selective agonists for the PGE(2) receptor EP2 mimic the effect of PGE(2) upon Sost, and siRNA reduction in Ptger2 prevents PGE(2)-induced Sost repression. These results indicate a functional relationship between prostaglandins and the Wnt/β-catenin signaling pathway in bone.

  4. Prostaglandin E2 signals through PTGER2 to regulate sclerostin expression.

    Directory of Open Access Journals (Sweden)

    Damian C Genetos

    Full Text Available The Wnt signaling pathway is a robust regulator of skeletal homeostasis. Gain-of-function mutations promote high bone mass, whereas loss of Lrp5 or Lrp6 co-receptors decrease bone mass. Similarly, mutations in antagonists of Wnt signaling influence skeletal integrity, in an inverse relation to Lrp receptor mutations. Loss of the Wnt antagonist Sclerostin (Sost produces the generalized skeletal hyperostotic condition of sclerosteosis, which is characterized by increased bone mass and density due to hyperactive osteoblast function. Here we demonstrate that prostaglandin E(2 (PGE(2, a paracrine factor with pleiotropic effects on osteoblasts and osteoclasts, decreases Sclerostin expression in osteoblastic UMR106.01 cells. Decreased Sost expression correlates with increased expression of Wnt/TCF target genes Axin2 and Tcf3. We also show that the suppressive effect of PGE(2 is mediated through a cyclic AMP/PKA pathway. Furthermore, selective agonists for the PGE(2 receptor EP2 mimic the effect of PGE(2 upon Sost, and siRNA reduction in Ptger2 prevents PGE(2-induced Sost repression. These results indicate a functional relationship between prostaglandins and the Wnt/β-catenin signaling pathway in bone.

  5. Prostaglandin E2 negatively regulates AMP-activated protein kinase via protein kinase A signaling pathway.

    Science.gov (United States)

    Funahashi, Koji; Cao, Xia; Yamauchi, Masako; Kozaki, Yasuko; Ishiguro, Naoki; Kambe, Fukushi

    2009-01-01

    We investigated possible involvement of prostaglandin (PG) E2 in regulation of AMP-activated protein kinase (AMPK). When osteoblastic MG63 cells were cultured in serum-deprived media, Thr-172 phosphorylation of AMPK alpha-subunit was markedly increased. Treatment of the cells with PGE2 significantly reduced the phosphorylation. Ser-79 phosphorylation of acetyl-CoA carboxylase, a direct target for AMPK, was also reduced by PGE2. On the other hand, PGE2 reciprocally increased Ser-485 phosphorylation of the alpha-subunit that could be associated with inhibition of AMPK activity. These effects of PGE2 were mimicked by PGE2 receptor EP2 and EP4 agonists and forskolin, but not by EP1 and EP3 agonists, and the effects were suppressed by an adenylate cyclase inhibitor SQ22536 and a protein kinase A inhibitor H89. Additionally, the PGE2 effects were duplicated in primary calvarial osteoblasts. Together, the present study demonstrates that PGE2 negatively regulates AMPK activity via activation of protein kinase A signaling pathway.

  6. Circadian variations of prostaglandin E2 and F2 alpha release in the golden hamster retina.

    Science.gov (United States)

    de Zavalía, Nuria; Fernandez, Diego C; Sande, Pablo H; Keller Sarmiento, María I; Golombek, Diego A; Rosenstein, Ruth E; Silberman, Dafne M

    2010-02-01

    Circadian variations of prostaglandin E2 and F2alpha release were examined in the golden hamster retina. Both parameters showed significant diurnal variations with maximal values at midnight. When hamsters were placed under constant darkness for 48 h, the differences in prostaglandin release between subjective mid-day and subjective midnight persisted. Western blot analysis showed that cyclooxygenase (COX)-1 levels were significantly higher at midnight than at mid-day, and at subjective midnight than at subjective mid-day, whereas no changes in COX-2 levels were observed among these time points. Immunohistochemical studies indicated the presence of COX-1 and COX-2 in the inner (but not outer) retina. Circadian variations of retinal prostaglandin release were also assessed in suprachiasmatic nuclei (SCN)-lesioned animals. Significant differences in retinal prostaglandin release between subjective mid-day and subjective midnight were observed in SCN-lesioned animals. These results indicate that hamster retinal prostaglandin release is regulated by a retinal circadian clock independent from the SCN. Thus, the present results suggest that the prostaglandin/COX-1 system could be a retinal clock output or part of the retinal clock mechanism.

  7. Boulders on asteroid Toutatis as observed by Chang’e-2

    Science.gov (United States)

    Jiang, Yun; Ji, Jianghui; Huang, Jiangchuan; Marchi, Simone; Li, Yuan; Ip, Wing-Huen

    2015-11-01

    Boulders are ubiquitously found on the surfaces of small rocky bodies in the inner solar system and their spatial and size distributions give insight into the geological evolution and collisional history of the parent bodies. Using images acquired by the Chang’e-2 spacecraft, more than 200 boulders have been identified over the imaged area of the near-Earth asteroid Toutatis. The cumulative boulder size frequency distribution (SFD) shows a steep slope of -4.4 ± 0.1, which is indicative of a high degree of fragmentation. Similar to Itokawa, Toutatis probably has a rubble-pile structure, as most boulders on its surface cannot solely be explained by impact cratering. The significantly steeper slope for Toutatis’ boulder SFD compared to Itokawa may imply a different preservation state or diverse formation scenarios. In addition, the cumulative crater SFD has been used to estimate a surface crater retention age of approximately 1.6 ± 0.3 Gyr.

  8. A preliminary result of self-calibration bundle adjustment of Chang'E-2 stereo imagery

    Science.gov (United States)

    Liu, Yiliang; Liu, Bin; Peng, Man; Di, Kaichang

    2014-05-01

    The high resolution lunar global images acquired by Chang'E-2 (CE-2) CCD camera orbiter are of great importance for lunar science research as well as preparation of the landing and surface operation of Chang'E-3 (CE-3) lunar rover. In this paper, a rigorous geometric model of CE-2 CCD camera is developed based on the push-broom imaging principle. A self-calibration bundle adjustment (SCBA) method is proposed to eliminate the inconsistencies between forward- and backward-looking images, which are caused by the inaccuracy of exterior orientation (EO) parameters and the uncertain relationship between the two CCD line arrays of the camera. The interior orientation (IO) model is refined by adding several additional parameters and the EO parameters are fitted by a third-order polynomial model. Strategies for ensuring the robustness and reliability of the solution are also adopted, including EO pseudo observations selection, reasonable weight determination, and truncated singular value decomposition method. After adjustment, the inconsistencies between the forward- and backward-looking images are eliminated effectively by reducing the image-space residuals from around 20 pixels to sub-pixel. Based on the adjustment, high precision DEM (Digital Elevation Model) and DOM (Digital Ortho Map) of a local area at Sinus Iridum (pre-selected CE-3 landing site) are generated automatically.

  9. Gliotransmission by Prostaglandin E2: a prerequisite for GnRH neuronal function?

    Directory of Open Access Journals (Sweden)

    Jerome eClasadonte

    2011-12-01

    Full Text Available Over the past four decades it has become clear that prostaglandin E2 (PGE2, a phospholipid-derived signaling molecule, plays a fundamental role in modulating the GnRH neuroendocrine system and in shaping the hypothalamus. In this review, after a brief historical overview, we highlight studies revealing that PGE2 released by glial cells such as astrocytes and tanycytes is intimately involved in the active control of GnRH neuronal activity and neurosecretion. Recent evidence suggests that hypothalamic astrocytes surrounding GnRH neuronal cell bodies may respond to neuronal activity with an activation of the erbB receptor tyrosine-kinase signaling, triggering the release of PGE2 as a chemical transmitter from the glia themselves, and, in turn, leading to the feedback regulation of GnRH neuronal activity. At the GnRH neurohemal junction, in the median eminence of the hypothalamus, PGE2 is released by tanycytes in response to cell-cell signaling initiated by glial cells and vascular endothelial cells. Upon its release, PGE2 causes the retraction of the tanycyte end feet enwrapping the GnRH nerve terminals, enabling them to approach the adjacent pericapillary space and thus likely facilitating neurohormone diffusion from these nerve terminals into the pituitary portal blood. In view of these new insights, we suggest that synaptically-associated astrocytes and perijunctional tanycytes are integral modulatory elements of GnRH neuronal function at the cell soma/dendrite and nerve terminal levels, respectively.

  10. Prostaglandin E2 in tylose gel for cervical ripening before induction of labor.

    Science.gov (United States)

    Turner, J E; Burke, M S; Porreco, R P; Weiss, M A

    1987-11-01

    Two hundred seventeen women who received 3 mg of prostaglandin E2 (PGE2) gel applied to the cervix followed by adjunctive oxytocin were compared to 94 patients whose labor was induced with oxytocin alone (OA). Postdatism, pregnancy-induced hypertension and rupture of the membranes were the major indications for induction of labor, accounting for 70% of the PGE2 group and 88% of the OA group. Mean initial cervical scores were found to be significantly less favorable among PGE2 patients as compared with OA patients. Though PGE2 was associated with a significant improvement in mean cervical scores, responsiveness of the cervix to PGE2, as determined by clinical examination, was not necessary for a successful induction. Failed inductions were infrequent in both groups. Nulliparous PGE2 patients with unfavorable cervical scores had fewer cesarean sections (CSs) and shorter labors than did their OA counterparts. Complications were uncommon but largely due to the subsequent use of oxytocin. Patients with prior CSs were safely induced following PGE2 cervical ripening.

  11. Prostaglandin E2 promotes intestinal repair through an adaptive cellular response of the epithelium.

    Science.gov (United States)

    Miyoshi, Hiroyuki; VanDussen, Kelli L; Malvin, Nicole P; Ryu, Stacy H; Wang, Yi; Sonnek, Naomi M; Lai, Chin-Wen; Stappenbeck, Thaddeus S

    2017-01-04

    Adaptive cellular responses are often required during wound repair. Following disruption of the intestinal epithelium, wound-associated epithelial (WAE) cells form the initial barrier over the wound. Our goal was to determine the critical factor that promotes WAE cell differentiation. Using an adaptation of our in vitro primary epithelial cell culture system, we found that prostaglandin E2 (PGE2) signaling through one of its receptors, Ptger4, was sufficient to drive a differentiation state morphologically and transcriptionally similar to in vivo WAE cells. WAE cell differentiation was a permanent state and dominant over enterocyte differentiation in plasticity experiments. WAE cell differentiation was triggered by nuclear β-catenin signaling independent of canonical Wnt signaling. Creation of WAE cells via the PGE2-Ptger4 pathway was required in vivo, as mice with loss of Ptger4 in the intestinal epithelium did not produce WAE cells and exhibited impaired wound repair. Our results demonstrate a mechanism by which WAE cells are formed by PGE2 and suggest a process of adaptive cellular reprogramming of the intestinal epithelium that occurs to ensure proper repair to injury. © 2016 The Authors.

  12. A high efficiency spectrometer for reflection (e,2e) experiments at surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Liscio, A. [CNR - IMIP, Area della Ricerca di Roma, Via Salaria km 29.300, 00016 Monterotondo (Italy); Dip.to di Fisica Universita di Roma Tre, Via Vasca Navale 84, 00146 Roma (Italy); Ruocco, A.; Stefani, G. [Dip.to di Fisica Universita di Roma Tre, Via Vasca Navale 84, 00146 Roma (Italy); Iacobucci, S. [CNR - ISC, Area della Ricerca di Roma, Via Salaria km 29.300, 00016 Monterotondo (Italy)], E-mail: stefano.iacobucci@isc.cnr.it

    2007-10-15

    To study electron momentum densities in solids by grazing angle reflection kinematics has been shown to be feasible [S. Iacobucci, S. Rioual, A. Ruocco, M. Mastropietro, G. Stefani, Surf. Sci. 454 (2000) 1026], but development of this spectroscopy has been hampered by long acquisition time; to fully exploit potentialities of this method is mandatory to reduce duration of the experiment within times comparable with clean surface lifetimes in ultra-high vacuum. This paper reports on recent developments of the reflection (e,2e) spectrometer that make a sizeable step forward in attaining this goal. It operates in asymmetric kinematics and at small grazing angle, thus allowing to enhance the surface sensitivity. A drastic reduction in acquisition time has been achieved by implementing parallel acquisition, both in energy and angle, of the detected electron pairs. To achieve parallel acquisition in energy and momentum, each of the two electron analysers is equipped with a two-dimensional position sensitive detector. A custom-made electronic hardware and software have been developed for the automatic control of the experiment and for acquisition and storage of the coincidence events. After discussing in some details the relevant features of the new spectrometer, few examples of valence band mapping and electron momentum densities measured in highly oriented pyrolitic graphite with energy and momentum resolutions of 1.3 eV and 0.15 A{sup -1} are given.

  13. Prostaglandin E2 Regulates Liver versus Pancreas Cell Fate Decisions and Endodermal Outgrowth

    Science.gov (United States)

    Nissim, Sahar; Sherwood, Richard I.; Wucherpfennig, Julia; Saunders, Diane; Harris, James M.; Esain, Virginie; Carroll, Kelli J.; Frechette, Gregory M.; Kim, Andrew J.; Hwang, Katie L.; Cutting, Claire C.; Elledge, Susanna; North, Trista E.; Goessling, Wolfram

    2014-01-01

    SUMMARY The liver and pancreas arise from common endodermal progenitors. How these distinct cell fates are specified is poorly understood. Here, we describe prostaglandin E2 (PGE2) as a regulator of endodermal fate specification during development. Modulating PGE2 activity has opposing effects on liver-versus-pancreas specification in zebrafish embryos as well as mouse endodermal progenitors. The PGE2 synthetic enzyme cox2a and receptor ep2a are patterned such that cells closest to PGE2 synthesis acquire a liver fate whereas more distant cells acquire a pancreas fate. PGE2 interacts with the bmp2b pathway to regulate fate specification. At later stages of development, PGE2 acting via the ep4a receptor promotes outgrowth of both the liver and pancreas. PGE2 remains important for adult organ growth, as it modulates liver regeneration. This work provides in vivo evidence that PGE2 may act as a morphogen to regulate cell fate decisions and outgrowth of the embryonic endodermal anlagen. PMID:24530296

  14. Crystal structure of (E)-2-hy-droxy-4'-meth-oxy-aza-stilbene.

    Science.gov (United States)

    Chantrapromma, Suchada; Kaewmanee, Narissara; Boonnak, Nawong; Chantrapromma, Kan; Ghabbour, Hazem A; Fun, Hoong-Kun

    2015-06-01

    The title aza-stilbene derivative, C14H13NO2 {systematic name: (E)-2-[(4-meth-oxy-benzyl-idene)amino]-phenol}, is a product of the condensation reaction between 4-meth-oxy-benzaldehyde and 2-amino-phenol. The mol-ecule adopts an E conformation with respect to the azomethine C=N bond and is almost planar, the dihedral angle between the two substituted benzene rings being 3.29 (4)°. The meth-oxy group is coplanar with the benzene ring to which it is attached, the Cmeth-yl-O-C-C torsion angle being -1.14 (12)°. There is an intra-molecular O-H⋯N hydrogen bond generating an S(5) ring motif. In the crystal, mol-ecules are linked via C-H⋯O hydrogen bonds, forming zigzag chains along [10-1]. The chains are linked via C-H⋯π inter-actions, forming a three-dimensional structure.

  15. E2F1 activation is responsible for pituitary adenomas induced by HMGA2 gene overexpression

    Directory of Open Access Journals (Sweden)

    Fusco Alfredo

    2006-08-01

    Full Text Available Abstract The High Mobility Group protein HMGA2 is a nuclear architectural factor that plays a critical role in a wide range of biological processes including regulation of gene expression, embryogenesis and neoplastic transformation. Several studies are trying to identify the mechanisms by which HMGA2 protein is involved in each of these activities, and only recently some new significant insights are emerging from the study of transgenic and knock-out mice. Overexpression of HMGA2 gene leads to the onset of prolactin and GH-hormone induced pituitary adenomas in mice, suggesting a critical role of this protein in pituitary tumorigenesis. This was also confirmed in the human pathology by the finding that HMGA2 amplification and/or overexpression is present in human prolactinomas. This review focuses on recent data that explain the mechanism by which HMGA2 induces the development of pituitary adenomas in mice. This mechanism entails the activation of the E2F1 protein by the HMGA2-mediated displacement of HDAC1 from pRB protein.

  16. Cyclooxygenase-1-selective inhibitors based on the (E)-2'-des-methyl-sulindac sulfide scaffold.

    Science.gov (United States)

    Liedtke, Andy J; Crews, Brenda C; Daniel, Cristina M; Blobaum, Anna L; Kingsley, Philip J; Ghebreselasie, Kebreab; Marnett, Lawrence J

    2012-03-08

    Prostaglandins (PGs) are powerful lipid mediators in many physiological and pathophysiological responses. They are produced by oxidation of arachidonic acid (AA) by cyclooxygenases (COX-1 and COX-2) followed by metabolism of endoperoxide intermediates by terminal PG synthases. PG biosynthesis is inhibited by nonsteroidal anti-inflammatory drugs (NSAIDs). Specific inhibition of COX-2 has been extensively investigated, but relatively few COX-1-selective inhibitors have been described. Recent reports of a possible contribution of COX-1 in analgesia, neuroinflammation, or carcinogenesis suggest that COX-1 is a potential therapeutic target. We designed, synthesized, and evaluated a series of (E)-2'-des-methyl-sulindac sulfide (E-DMSS) analogues for inhibition of COX-1. Several potent and selective inhibitors were discovered, and the most promising compounds were active against COX-1 in intact ovarian carcinoma cells (OVCAR-3). The compounds inhibited tumor cell proliferation but only at concentrations >100-fold higher than the concentrations that inhibit COX-1 activity. E-DMSS analogues may be useful probes of COX-1 biology in vivo and promising leads for COX-1-targeted therapeutic agents.

  17. Neonatal DHT but not E2 speeds induction of sexual receptivity in the musk shrew.

    Science.gov (United States)

    Ewton, Tiffany A; Siboni, Ruth B; Jackson, Andrea; Freeman, Louise M

    2010-06-01

    Neural aromatization of testosterone (T) to estrogen during development is thought to be important for sexual differentiation of many altricial mammals. We evaluated the effects of neonatal injections of the non-aromatizable androgen dihydrotestosterone propionate (DHTP) and estradiol (E2) on the copulatory behavior of the female musk shrew, an altricial insectivore. Following adult ovariectomy and replacement T, animals were paired with a stimulus female for two 60-minute copulatory behavior tests. The latency to induce sexual receptivity (in the form of tail-wagging by the female), mount latency and total number of mounts were recorded in experimental females and in a group of untreated control males. While neither hormone treatment significantly affected mounting behavior, DHTP-treated animals induced receptivity faster and with latencies not significantly different from intact males, suggesting that early non-aromatizable androgens can have masculinizing actions by either increasing sexual motivation or making the treated animal more attractive to the stimulus female. Reliance on androgenic rather than estrogenic metabolites for the differentiation of courtship behaviors conforms to the pattern seen more typically in primates than rodents. Copyright 2009 Elsevier Inc. All rights reserved.

  18. A Novel Selective Prostaglandin E2 Synthesis Inhibitor Relieves Pyrexia and Chronic Inflammation in Rats.

    Science.gov (United States)

    Sugita, Ryusuke; Kuwabara, Harumi; Sugimoto, Kotaro; Kubota, Kazufumi; Imamura, Yuichiro; Kiho, Toshihiro; Tengeiji, Atsushi; Kawakami, Katsuhiro; Shimada, Kohei

    2016-04-01

    Prostaglandin E2 (PGE2) is a terminal prostaglandin in the cyclooxygenase (COX) pathway. Inhibition of PGE2 production may relieve inflammatory symptoms such as fever, arthritis, and inflammatory pain. We report here the profile of a novel selective PGE2 synthesis inhibitor, compound A [N-[(1S,3S)-3-carbamoylcyclohexyl]-1-(6-methyl-3-phenylquinolin-2-yl)piperidine-4-carboxamide], in animal models of pyrexia and inflammation. The compound selectively suppressed the synthesis of PGE2 in human alveolar adenocarcinoma cell line A549 cells and rat macrophages. In the lipopolysaccharide-induced pyrexia model, this compound selectively reduced PGE2 production in cerebrospinal fluid and showed an anti-pyretic effect. In the adjuvant-induced arthritis model, compound A therapeutically decreased foot swelling in the established arthritis. Our data demonstrates that selective suppression of PGE2 synthesis shows anti-pyretic and anti-inflammatory effects, suggesting that selective PGE2 synthesis inhibitors can be applied as an alternative treatment to nonsteroidal, anti-inflammatory drugs (NSAIDs) or COX-2-selective inhibitors.

  19. Production of New Trabecular Bone in Osteopenic Ovariectomized Rats by Prostaglandin E2

    Science.gov (United States)

    Mori, S.; Jee, W. S. S.; Li, X. J.

    1992-01-01

    Serum chemistry and bone morphometry of the proximal tibial metaphysis were performed in 3 month-old double fluorescent-labeled, female Sprague-Dawley rats subjected to bilateral ovariectomy or sham surgery for 4 months prior to treatment with 0, 0.3, 1,3, or 6 mg of prostaglandin E2 (PGE2)/kg/day subcutaneously for 30 days. The 4 month postovariectomized rats possessed an osteopenic proximal tibial metaphysis with 7% trabecular area compared with controls (19%). PGE2 treatment elevated osteocalcin levels and augmented proximal tibial metaphyseal bone area in ovariectomized and sham-operated rats. Osteopenic, ovariectomized rats treated with 6 mg (PGE2)/kg/day for 30 days restored bone area to levels of agematched sham-operated rats. Morphometric analyses showed increased woven and lamellar bone area, fluorescent-labeled perimeter (osteoblastic recruitment), mineral apposition rate (osteoblastic activity), bone formation rate (BFR/BV), and longitudinal bone growth. These dramatic bone changes were all significantly increased at the doseresponse manner. This study showed that in vivo PGE2 is a powerful activator of bone remodeling, it increases both bone resorption and bone formation, and produces an anabolic effect by shifting bone balance to the positive direction. Furthermore, PGE2-induced augmentation of metaphyseal bone area in ovariectomized rats was at least two times greater than in sham-operated rats.

  20. Persistent magnetism in silver-doped BaF e2A s2 crystals

    Science.gov (United States)

    Li, Li; Cao, Huibo; Parker, David S.; Kuhn, Stephen J.; Sefat, Athena S.

    2016-10-01

    We investigate the thermodynamic and transport properties of silver-substituted BaF e2A s2 (122) crystals up to ˜4.5 % . Similar to other transition-metal substitutions in 122, Ag diminishes the antiferromagnetic (TN) and structural (TS) transition temperatures, but unlike other electron-doped 122s, TN and TS coincide without splitting. Although magnetism drops precipitously to TN= 84 K at doping x =0.029 , it only weakly changes above this x , settling at TN= 80 K at x =0.045 . Compared to this persistent magnetism in Ag-122, doping other group 11 elements of either Cu or Au in 122 diminished TN and induced superconductivity near Tc= 2 K at x =0.044 or 0.031, respectively. Ag-122 crystals show reflective surfaces with surprising thicker cross sections for x ≥0.019 , the appearance that is in contrast to the typical thin stacked layered feature seen in all other flux-grown x122 and lower Ag-122. This physical trait may be a manifest of intrinsic weak changes in c lattice and TN. Our theoretical calculations suggest that Ag doping produces strong electronic scattering and yet a relatively small disruption of the magnetic state, both of which preclude superconductivity in this system.

  1. Gamma-type gliadins cause secretion of prostaglandin E2 in patients with coeliac disease.

    Science.gov (United States)

    Friis, S; Anthonsen, D; Norén, O; Sjöström, H

    1994-12-16

    Coeliac disease is induced by polypeptides in the prolamin fraction of wheat, termed gliadin. It has previously been demonstrated that the alpha-, the beta- and the gamma-gliadin fractions contain toxic components and it has furthermore been strongly indicated that alpha-type gliadins are toxic. Due to insufficient protein separation methods there has been no information as to whether also the gamma-type gliadins are injurious in coeliac disease. We have therefore purified one alpha-type (alpha-39) and two gamma-type gliadins (gamma-36 and gamma-47) in a preparative scale by a combination of different ion exchange chromatographies. The purity was analyzed by high performance liquid chromatography and by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate, while the typing was based on determination of N-terminal amino acid sequence. Six patients with coeliac disease in remission were included in the study. Each of the purified gliadins was given by an intestinal perfusion technique to two patients. The perfusion fluid was collected and analyzed for the concentration of prostaglandin E2 (PGE2) as a marker for a toxic effect. All patients reacted with increased PGE2 secretion. For the first time it is clearly demonstrated that gamma-type gliadins are active in coeliac disease.

  2. Fever Is Mediated by Conversion of Endocannabinoid 2-Arachidonoylglycerol to Prostaglandin E2.

    Directory of Open Access Journals (Sweden)

    Yoshihiro Kita

    Full Text Available Fever is a common response to inflammation and infection. The mechanism involves prostaglandin E2 (PGE2-EP3 receptor signaling in the hypothalamus, which raises the set point of hypothalamic thermostat for body temperature, but the lipid metabolic pathway for pyretic PGE2 production remains unknown. To reveal the molecular basis of fever initiation, we examined lipopolysaccharides (LPS-induced fever model in monoacylglycerol lipase (MGL-deficient (Mgll-/- mice, CB1 receptor-MGL compound-deficient (Cnr1-/-Mgll-/- mice, cytosolic phospholipase A2α (cPLA2α-deficient (Pla2g4a-/- mice, and diacylglycerol lipase α (DGLα-deficient (Dagla-/- mice. Febrile reactions were abolished in Mgll-/- and Cnr1-/-Mgll-/- mice, whereas Cnr1-/-Mgll+/+, Pla2g4a-/- and Dagla-/- mice responded normally, demonstrating that MGL is a critical enzyme for fever, which functions independently of endocannabinoid signals. Intracerebroventricular administration of PGE2 caused fever similarly in Mgll-/- and wild-type control mice, suggesting a lack of pyretic PGE2 production in Mgll-/- hypothalamus, which was confirmed by lipidomics analysis. Normal blood cytokine responses after LPS administration suggested that MGL-deficiency does not affect pyretic cytokine productions. Diurnal body temperature profiles were normal in Mgll-/- mice, demonstrating that MGL is unrelated to physiological thermoregulation. In conclusion, MGL-dependent hydrolysis of endocannabinoid 2-arachidonoylglycerol is necessary for pyretic PGE2 production in the hypothalamus.

  3. Comparative Study of Intracervical Prostaglandin E2 and Intravenous Oxytocin for Induction of Term Labor

    Directory of Open Access Journals (Sweden)

    S Khavari

    2001-06-01

    Full Text Available A randomized clinical trial study was undertaken to evaluate the effect of intravenous oxytoxin (50 cases and intracervical prostaglandin E2 (0.5 mg Tab, 50 cases on the ripening of the cervix and frequency of successful inductions in patients with low Bishop score (<5. Means of maternal age, gestational age, parity, BS at admission did not show any significant differences between the two groups. Until 6 hrs after beginning treatment, 72% of oxytoxin group and 74% of PGE2 group were achieved active labor and until 12 hrs, 70% and 76% delivered respectively. It was no statistically significant difference. The mean drug administration to delivery time was 7.3±3.1 hrs in oxytoxin group and 7.6±3.1 hrs in PGE2 group (without significant difference. No difference in route of delivery was found between the two groups. Maternal complications were seen in 60% of oxytocin group and 46% of PGE2 group, without significant difference. Between maternal complications, frequency of diarrhea was higher at PGE2 group (P=0.02. Fetal complications were seen 4% in the PGE2 group and 16% in oxytocin group, that was less in the first (RR=0.25 CI 95%: 0.06-0.97.

  4. Prostaglandin E2 gel In ripening of cervix in induction of labour.

    Directory of Open Access Journals (Sweden)

    Warke H

    1999-10-01

    Full Text Available A study was done in 75 patients who underwent induction of labour with Prostaglandin E2 gel. All these patients had an unripe cervix. The commonest indications were post-datism, intrauterine growth retardation and pregnancy-induced hypertension. All patients were primigravidas with singleton pregnancy and beyond 35 weeks of pregnancy. The mean Bishop score at the time of instillation was less than three. The improvement of another 2-3 points within six hours and by 7-8 points within 12 hours was found after instillation of the gel. 92% of the patients went into spontaneous labour and 8% required reinstillation. The incidence of failed induction was 1.33%. The mean duration of latent phase was 10.34 hours. Induction delivery time was 16.43 hours. 68.1% patients required augmentation of labour and 31.9% did not require augmentation of labour with oxytocin drip. The incidence of vaginal delivery was 81.33% and that of caesarean section was 17.33%. The commonest indication of caesarean section was foetal distress.

  5. Prostaglandin E2 induces expression of MAPK phosphatase 1 (MKP-1) in airway smooth muscle cells.

    Science.gov (United States)

    Rumzhum, Nowshin N; Ammit, Alaina J

    2016-07-05

    Prostaglandin E2 (PGE2) is a prostanoid with diverse actions in health and disease. In chronic respiratory diseases driven by inflammation, PGE2 has both positive and negative effects. An enhanced understanding of the receptor-mediated cellular signalling pathways induced by PGE2 may help us separate the beneficial properties from unwanted actions of this important prostaglandin. PGE2 is known to exert anti-inflammatory and bronchoprotective actions in human airways. To date however, whether PGE2 increases production of the anti-inflammatory protein MAPK phosphatase 1 (MKP-1) was unknown. We address this herein and use primary cultures of human airway smooth muscle (ASM) cells to show that PGE2 increases MKP-1 mRNA and protein upregulation in a concentration-dependent manner. We explore the signalling pathways responsible and show that PGE2-induces CREB phosphorylation, not p38 MAPK activation, in ASM cells. Moreover, we utilize selective antagonists of EP2 (PF-04418948) and EP4 receptors (GW 627368X) to begin to identify EP-mediated functional outcomes in ASM cells in vitro. Taken together with earlier studies, our data suggest that PGE2 increases production of the anti-inflammatory protein MKP-1 via cAMP/CREB-mediated cellular signalling in ASM cells and demonstrates that EP2 may, in part, be involved. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Cloning and expression of prostaglandin E2 receptor subtype 1 (ep 1 ) in Bostrichthys sinensis.

    Science.gov (United States)

    Lai, Xiao Jian; Hong, Wan Shu; Liu, Fang; Zhang, Yu Ting; Chen, Shi Xi

    2014-08-01

    Our previous studies suggested that prostaglandin E2 (PGE2) is a putative sex pheromone in Chinese black sleeper Bostrichthys sinensis, a fish species that inhabits intertidal zones and mates and spawns inside a muddy burrow. We found immunoreactivities of PGE2 receptor subtypes (Ep1-3) expressed in the olfactory sac, but only Ep1 presented higher density of immunoreactivity in mature fish than that in immature fish in both sexes. To gain a better understanding of the underlying molecular mechanism for the detection of PGE2 in the olfactory system, we cloned an ep 1 cDNA from the adult olfactory sac. The open-reading frame of the ep 1 consisted of 1,134-bp nucleotides that encoded a 378-amino acid-long protein with a seven-transmembrane domain, typical for the G protein-coupled receptors superfamily. Expression of ep 1 mRNA was observed in all tissues examined, with higher levels obtained in the olfactory sacs and testes. The expression of ep 1 mRNA in the olfactory sacs and gonads was significantly higher in both sexes of mature fish than in those of immature ones. Taken together, our results suggested that Ep1, which is highly expressed in the olfactory sacs and gonads of mature fish, is important for the control of reproduction and may be involved in PGE2-initiated spawning behavior in B. sinensis.

  7. Localization and steroid regulation of prostaglandin E2 receptor protein expression in ovine cervix.

    Science.gov (United States)

    Schmitz, Thomas; Levine, Brian A; Nathanielsz, Peter W

    2006-04-01

    Although prostaglandin E2 (PGE2) has been identified as a central mediator of the cervical ripening process, the mechanisms responsible for PGE2 ripening are still poorly understood, partly because of the lack of information concerning the precise cellular localization and regulation of PGE2 (EP) receptors in the cervix. To provide new insights into the mechanisms of cervical ripening, we used indirect immunofluorescence to localize cervical EP receptor protein expression in ovariectomized ewes and examined the effect of administration of progesterone or estradiol. EP receptors were widely distributed in cervical blood vessels, epithelium of the cervical canal, circular and longitudinal muscles, and stroma. Estradiol replacement decreased EP1 and EP3 receptor protein in blood vessel media (by 23 and 31% respectively, P EP1 receptor protein expression in the longitudinal muscle layer (by 27%, P EP1 and EP3 receptor protein expression was also reduced by estradiol (by 29 and 20% respectively, P EP receptor protein expression. The arterial changes would favor PGE2-induced vasodilatation, subsequent edema and leukocyte infiltration during the cervical ripening process whereas the muscular alterations would facilitate smooth muscle relaxation and cervical dilatation. Furthermore, estradiol provoked perinuclear localization of EP3 receptor protein in the longitudinal muscle layer. This latter result suggests that cellular EP receptor localization is regulated by estradiol and that PGE2 may also control smooth muscle contraction and regulate ovine cervical dilatation in an intracrine manner via EP3 receptors.

  8. Elucidating the Specificity Determinants of the AtxE2 Lasso Peptide Isopeptidase*

    Science.gov (United States)

    Maksimov, Mikhail O.; Koos, Joseph D.; Zong, Chuhan; Lisko, Bozhena; Link, A. James

    2015-01-01

    Lasso peptide isopeptidase is an enzyme that specifically hydrolyzes the isopeptide bond of lasso peptides, rendering these peptides linear. To carry out a detailed structure-activity analysis of the lasso peptide isopeptidase AtxE2 from Asticcacaulis excentricus, we solved NMR structures of its substrates astexin-2 and astexin-3. Using in vitro enzyme assays, we show that the C-terminal tail portion of these peptides is dispensable with regards to isopeptidase activity. A collection of astexin-2 and astexin-3 variants with alanine substitutions at each position within the ring and the loop was constructed, and we showed that all of these peptides except for one were cleaved by the isopeptidase. Thus, much like the lasso peptide biosynthetic enzymes, lasso peptide isopeptidase has broad substrate specificity. Quantitative analysis of the cleavage reactions indicated that alanine substitutions in loop positions of these peptides led to reduced cleavage, suggesting that the loop is serving as a recognition element for the isopeptidase. PMID:26534965

  9. Major role of adipocyte prostaglandin E2 in lipolysis-induced macrophage recruitment[S

    Science.gov (United States)

    Hu, Xiaoqian; Cifarelli, Vincenza; Sun, Shishuo; Kuda, Ondrej; Abumrad, Nada A.; Su, Xiong

    2016-01-01

    Obesity induces accumulation of adipose tissue macrophages (ATMs), which contribute to both local and systemic inflammation and modulate insulin sensitivity. Adipocyte lipolysis during fasting and weight loss also leads to ATM accumulation, but without proinflammatory activation suggesting distinct mechanisms of ATM recruitment. We examined the possibility that specific lipid mediators with anti-inflammatory properties are released from adipocytes undergoing lipolysis to induce macrophage migration. In the present study, we showed that conditioned medium (CM) from adipocytes treated with forskolin to stimulate lipolysis can induce migration of RAW 264.7 macrophages. In addition to FFAs, lipolytic stimulation increased release of prostaglandin E2 (PGE2) and prostaglandin D2 (PGD2), reflecting cytosolic phospholipase A2 α activation and enhanced cyclooxygenase (COX) 2 expression. Reconstituted medium with the anti-inflammatory PGE2 potently induced macrophage migration while different FFAs and PGD2 had modest effects. The ability of CM to induce macrophage migration was abolished by treating adipocytes with the COX2 inhibitor sc236 or by treating macrophages with the prostaglandin E receptor 4 antagonist AH23848. In fasted mice, macrophage accumulation in adipose tissue coincided with increases of PGE2 levels and COX1 expression. Collectively, our data show that adipocyte-originated PGE2 with inflammation suppressive properties plays a significant role in mediating ATM accumulation during lipolysis. PMID:26912395

  10. Effects of esculentoside A on production of interleukin-1,2,and prostaglandin E2

    Institute of Scientific and Technical Information of China (English)

    Zhen-yu XIAO; Qin-yue ZHENG; Yuan-ying JIANG; Bin ZHOU; Ming YIN; Hong-bin WANG; Jun-ping ZHANG

    2004-01-01

    AIM: To investigate the influence of esculentoside A (EsA) on immunological function and its mechanism of antiinflammation. METHODS: Interleukin-1 production was measured by thymocyte co-stimulating assay; the radioactivity of [3H]arachidonic acid (AA) was used to evaluate the release of AA; prostaglandin E2 production was measured with radioimmunoassay (RIA); IL-2 and IFN-γ were detected by ELISA method. RESULTS: EsA (3-12μmol/L)could potently inhibit the production of IL- 1 and PGE2 from both silent and LPS induced macrophages.EsA had no significant effect on the release of AA from murine macrophages. EsA could inhibit the production of IL-2 from murine lymphocytes induced by ConA, but not affect the production from silent lymphocytes. EsA showed no effect on the production of IFN-γ from both silent and ConA induced lymphocytes. CONCLUSION: EsA could affect the immunological function through inhibiting the production of IL-2 from activated splenocytes and the inhibition of production of IL- 1 and PGE2 might be one of the anti-inflammation mechanisms of EsA.

  11. Boulders on asteroid Toutatis as observed by Chang’e-2

    Science.gov (United States)

    Jiang, Yun; Ji, Jianghui; Huang, Jiangchuan; Marchi, Simone; Li, Yuan; Ip, Wing-Huen

    2015-01-01

    Boulders are ubiquitously found on the surfaces of small rocky bodies in the inner solar system and their spatial and size distributions give insight into the geological evolution and collisional history of the parent bodies. Using images acquired by the Chang’e-2 spacecraft, more than 200 boulders have been identified over the imaged area of the near-Earth asteroid Toutatis. The cumulative boulder size frequency distribution (SFD) shows a steep slope of −4.4 ± 0.1, which is indicative of a high degree of fragmentation. Similar to Itokawa, Toutatis probably has a rubble-pile structure, as most boulders on its surface cannot solely be explained by impact cratering. The significantly steeper slope for Toutatis’ boulder SFD compared to Itokawa may imply a different preservation state or diverse formation scenarios. In addition, the cumulative crater SFD has been used to estimate a surface crater retention age of approximately 1.6 ± 0.3 Gyr. PMID:26522880

  12. Induction of prostaglandin E(2) and interleukin-6 in gingival fibroblasts by oral biofilms.

    Science.gov (United States)

    Belibasakis, Georgios N; Guggenheim, Bernhard

    2011-12-01

    Polymicrobial oral biofilms attaching on tooth surfaces can trigger inflammatory responses by the neighbouring tooth-supporting periodontal tissues. An excessive inflammatory response can cause destruction of the periodontal tissues, including the alveolar bone, thus resulting in periodontitis. Mediators of inflammation, such as prostaglandin E(2) (PGE(2) ) and interleukin-6, are primary regulators of alveolar bone destruction in periodontitis. The present study aimed to comparatively investigate the effects of in vitro supragingival and subgingival biofilms, on the regulation of PGE(2) and interleukin-6 in human gingival fibroblasts. The cells were challenged with culture supernatants of the two biofilms for 6 h. Cyclo-oxygenase (COX)-2, an enzyme responsible for the conversion of PGE(2) , and interleukin-6 gene expression were analysed by quantitative real-time PCR. The production of PGE(2) and interleukin-6 by the cells was analysed by ELISA. While the supragingival biofilm did not induce significant changes, the subgingival biofilm caused an 8.6- and 2.9-fold enhancement of COX-2 and interleukin-6 gene expression, respectively, and a 72.5- and 1.5-fold enhancement of PGE(2) and interleukin-6 production, respectively. In conclusion, subgingival biofilms are potent inducers of PGE(2) in gingival fibroblasts, providing further mechanistic insights into the association of subgingival biofilms with bone resorption periodontitis.

  13. Sulforaphane inhibits prostaglandin E2 synthesis by suppressing microsomal prostaglandin E synthase 1.

    Directory of Open Access Journals (Sweden)

    Jiping Zhou

    Full Text Available Sulforaphane (SFN is a dietary cancer preventive with incompletely characterized mechanism(s of cancer prevention. Since prostaglandin E2 (PGE2 promotes cancer progression, we hypothesized that SFN may block PGE2 synthesis in cancer cells. We found that SFN indeed blocked PGE2 production in human A549 cancer cells not by inhibiting COX-2, but rather by suppressing the expression of microsomal prostaglandin E synthase (mPGES-1, the enzyme that directly synthesizes PGE2. We identified the Hypoxia Inducible Factor 1 alpha (HIF-1α as the target of SFN-mediated mPGES-1 suppression. SFN suppressed HIF-1α protein expression and the presence of HIF-1α at the mPGES-1 promoter, resulting in reduced transcription of mPGES-1. Finally, SFN also reduced expression of mPGES-1 and PGE2 production in A549 xenograft tumors in mice. Together, these results point to the HIF-1α, mPGES-1 and PGE2 axis as a potential mediator of the anti-cancer effects of SFN, and illustrate the potential of SFN for therapeutic control of cancer and inflammation. Harmful side effects in patients taking agents that target the more upstream COX-2 enzyme render the downstream target mPGES-1 a significant target for anti-inflammatory therapy. Thus, SFN could prove to be an important therapeutic approach to both cancer and inflammation.

  14. Thorium distribution on the lunar surface observed by Chang'E-2 gamma-ray spectrometer

    Science.gov (United States)

    Wang, Xianmin; Zhang, Xubing; Wu, Ke

    2016-07-01

    The thorium distribution on the lunar surface is critical for understanding the lunar evolution. This work reports a global map of the thorium distribution on the lunar surface observed by Chang'E-2 gamma-ray spectrometer (GRS). Our work exhibits an interesting symmetrical structure of thorium distribution along the two sides of the belt of Th hot spots. Some potential positions of KREEP volcanism are suggested, which are the Fra Mauro region, Montes Carpatus, Aristarchus Plateau and the adjacent regions of Copernicus Crater. Based on the lunar map of thorium distribution, we draw some conclusions on two critical links of lunar evolution: (1) the thorium abundance within the lunar crust and mantle, in the last stage of Lunar Magma Ocean (LMO) crystallization, may have a positive correlation with the depth in the crust, reaches a peak when coming through the transitional zone between the crust and mantle, and decreases sharply toward the inside of the mantle; thus, the Th-enhanced materials originated from the lower crust and the layer between the crust and mantle, (2) in PKT, KREEP volcanism might be the primary mechanism of Th-elevated components to the lunar surface, whereas the Imbrium impact acted as a relatively minor role.

  15. 16,16-Dimethyl prostaglandin E2 increases survival in mice following irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Walden, T.L.; Patchen, M.; Snyder, S.L.

    1987-01-01

    16,16-Dimethyl prostaglandin E2(DiPGE2), a stable analog of PGE2, increases the LD 50/30 survival in CD2F1 male mice when given prior to ionizing radiation. Subcutaneous administration of 40 microgram of DiPGE2 30 min prior to /sup 60/Co gamma irradiation extends the LD 50/30 from 9.39 Gy in the control animals to 16.14 Gy in DiPGE2 treated, with a dose-reduction factor of 1.72p95% confidence limits: 1.62, 1.82. The degree of protection is dependent on both the time of administration and the dose of the prostaglandin. Ten micrograms administered 5 min prior to receiving a lethal dose of 10 Gy provides 90% survival but only 10% survival if administered 30 min prior to irradiation. Experiments to determine the in vivo concentration of DiPGE2 in organs post injection show increased levels over time, but these are not correlated with protection. At 30 min after injection, as much as 80% of the DiPGE2 present in the spleen and plasma is unmetabolized. These results suggest that the protection results from the physiologic action of DiPGE2 rather than direct in vivo detoxification of radicals.

  16. 16,16-Dimethyl prostaglandin E2 increases survival in mice following irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Walden, T.L. Jr.; Patchen, M.; Snyder, S.L.

    1987-03-01

    16,16-Dimethyl prostaglandin E2 (DiPGE2), a stable analog of PGE2, increases the LD50/30 survival in CD2F1 male mice when given prior to ionizing radiation. Subcutaneous administration of 40 micrograms of DiPGE2 30 min prior to /sup 60/Co gamma irradiation extends the LD50/30 from 9.39 Gy in the control animals to 16.14 Gy in DiPGE2 treated, with a dose reduction factor of 1.72 (95% confidence limits: 1.62, 1.82). The degree of protection is dependent on both the time of administration and the dose of the prostaglandin. Ten micrograms administered 5 min prior to receiving a lethal dose of 10 Gy provides 90% survival but only 10% survival if administered 30 min prior to irradiation. Experiments to determine the in vivo concentration of DiPGE2 in organs postinjection show increased levels over time, but these are not correlated with protection. At 30 min after injection, as much as 80% of the DiPGE2 present in the spleen and plasma is unmetabolized. These results suggest that the protection results from the physiologic action of DiPGE2 rather than direct in vivo detoxification of radicals.

  17. The structure and immunomodulatory activity on intestinal epithelial cells of the EPSs isolated from Lactobacillus helveticus sp. Rosyjski and Lactobacillus acidophilus sp. 5e2.

    Science.gov (United States)

    Patten, Daniel A; Leivers, Shaun; Chadha, Marcus J; Maqsood, Mohammed; Humphreys, Paul N; Laws, Andrew P; Collett, Andrew

    2014-01-30

    The Lactic acid bacteria (LAB) Lactobacillus acidophilus sp. 5e2 and Lactobacillus helveticus sp. Rosyjski both secrete exopolysaccharides (EPSs) into their surrounding environments during growth. A number of EPSs have previously been shown to exhibit immunomodulatory activity with professional immune cells, such as macrophages, but only limited studies have been reported of their interaction with intestinal epithelial cells. An investigation of the immunomodulatory potential of pure EPSs, isolated from cultures of Lactobacillus acidophilus sp. 5e2 and Lactobacillus helveticus sp. Rosyjski, with the HT29-19A intestinal epithelial cell line are reported here. For the first time the structure of the EPS from Lactobacillus helveticus sp. Rosyjski which is a hetropolysaccharide with a branched pentasaccharide repeat unit containing d-glucose, d-galactose and N-acetyl-d-mannosamine is described. In response to exposure to lactobacilli EPSs HT29-19A cells produce significantly increased levels of the proinflammatory cytokine IL-8. Additionally, the EPSs differentially modulate the mRNA expression of Toll-like receptors. Finally, the pre-treatment of HT29-19A cells with the EPSs sensitises the cells to subsequent challenge with bacterial antigens. The results reported here suggest that EPSs could potentially play a role in intestinal homeostasis via a specific interaction with intestinal epithelial cells.

  18. Regulation of Trib2 by an E2F1-C/EBPα feedback loop in AML cell proliferation.

    LENUS (Irish Health Repository)

    Rishi, Loveena

    2014-04-10

    The loss of regulation of cell proliferation is a key event in leukemic transformation, and the oncogene tribbles (Trib)2 is emerging as a pivotal target of transcription factors in acute leukemias. Deregulation of the transcription factor E2F1, normally repressed by CCAAT enhancer-binding protein α (C\\/EBPα)-p42, occurs in acute myeloid leukemia (AML), resulting in the perturbation of cell cycle and apoptosis, emphasizing its importance in the molecular pathogenesis of AML. Here we show that E2F family members directly regulate Trib2 in leukemic cells and identify a feedback regulatory loop for E2F1, C\\/EBPα, and Trib2 in AML cell proliferation and survival. Further analyses revealed that E2F1-mediated Trib2 expression was repressed by C\\/EBPα-p42, and in normal granulocyte\\/macrophage progenitor cells, we detect C\\/EBPα bound to the Trib2 promoter. Pharmacological inhibition of the cell cycle or Trib2 knockdown resulted in a block in AML cell proliferation. Our work proposes a novel paradigm whereby E2F1 plays a key role in the regulation of Trib2 expression important for AML cell proliferation control. Importantly, we identify the contribution of dysregulated C\\/EBPα and E2F1 to elevated Trib2 expression and leukemic cell survival, which likely contributes to the initiation and maintenance of AML and may have significant implications for normal and malignant hematopoiesis.

  19. Analysis of E2 gene integrity in HPV16 and HPV58 viruses isolated from women with cervical pathology

    Science.gov (United States)

    González-Losa, María del R; Puerto-Solis, Marylin; Tenorio Ruiz, Juan; Rosado-López, Ariel I; Hau-Aviles, Oscar; Ayora-Talavera, Guadalupe; Cisneros-Cutz, Isidro; Conde-Ferráez, Laura

    2016-01-01

    Integration of human papillomavirus (HPV) DNA into human cells accompanied by the disruption of the viral genome has been described as a prerequisite for cancer development. This study aimed to investigate E2 gene integrity of HPV16 and HPV58 viruses isolated from infected women with cervical lesions. Forty-two HPV16- and 31 HPV58-positive samples were analysed. E2 integrity was assumed when all fragments covering the E2 gene were amplified with specific polymerase chain reaction primers. Overall, in 59% of the samples, at least one fragment was not amplified in HPV16- (57%) and HPV58-positive samples (61%). Samples from high-grade squamous intraepithelial lesions had the highest frequency of E2 gene disruptions (73%), followed by samples from low-grade squamous intraepithelial lesions (63%) and, finally, samples from invasive cervical cancer (35%). Association between the integrity status of the E2 gene, and lesion grade was assessed by the chi-squared test applied to the combined set of viruses (p = 0.6555) or to populations of the same virus type (HPV58, p = 0.3101; HPV16, p = 0.3024). In conclusion, in this study, no association was found between the presence of E2 gene disruptions and the grade of cervical lesions caused by HPV16 and HPV58. PMID:27812600

  20. G1/S-regulated E2F-containing protein complexes bind to the mouse thymidine kinase gene promoter

    DEFF Research Database (Denmark)

    Dou, Q P; Zhao, S; Levin, A H;

    1994-01-01

    By performing DNase I footprint analysis, we had identified three distinct protein binding sequences (MT1, MT2, and MT3) located on the mouse thymidine kinase (TK) upstream promoter (Dou, Q.-P., Fridovich-Keil, J. L., and Pardee, A.B. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 1157-1161). Here we...... report that MT2 includes an E2F-like binding site (GTTCGCGGGCAAA), as shown by the following evidence. (i) MT2 bound specifically to an affinity-purified fusion human E2F protein. (ii) Both MT2 and an authentic E2F site (TTTCGCGCGCTTT) bound specifically to similar or identical nuclear protein complexes....... (iii) Formation of both these DNA-protein complexes were cell cycle-dependent: a G0/G1 phase-specific complex (E2F.G0/G1) was replaced by an S phase-specific complex(es) (E2F.S), whereas "free" E2F increased after the G1/S transition. (iv) Pulse inhibition of protein synthesis with cycloheximide...

  1. Dysfunctional memory CD8+ T cells after priming in the absence of the cell cycle regulator E2F4.

    Science.gov (United States)

    Bancos, Simona; Cao, Qingyu; Bowers, William J; Crispe, Ian Nicholas

    2009-01-01

    The transcriptional repressor E2F4 is important for cell cycle exit and terminal differentiation in epithelial cells, neuronal cells and adipocytes but its role in T lymphocytes proliferation and memory formation is not known. Herein, we investigated the function of E2F4 protein for the formation of functional murine memory T cells. Murine transgenic CD8+ T cells were infected in vitro with lentivirus vector expressing a shRNA targeted against E2F4 followed by in vitro stimulation with SIINFEKL antigenic peptide. For in vivo assays, transduced cells were injected into congenic mice which were then infected with HSV-OVA. The primary response, memory formation and secondary stimulation were determined for CD8+ lentivirus transduced cells. In the absence of E2F4 cell cycle repressor, activated CD8+ T cells underwent intensive proliferation in vitro and in vivo. These cells had the ability to differentiate into memory cells in vivo, but they were defective in recall proliferation. We show that transient suppression of E2F4 during CD8+ T cell priming enhances primary proliferation and has a negative effect on secondary stimulation. These findings demonstrate that the cell cycle repressor E2F4 is essential for the formation of functional memory T cells. A decrease in CD8+ T-lymphocyte compartment would diminish our capacity to control viral infections.

  2. E2F-1蛋白在大鼠泌乳素瘤中的表达

    Institute of Scientific and Technical Information of China (English)

    程海梅; 徐春

    2011-01-01

    目的 通过检测腺病毒F2启动子结合因子1(E2F-1)在大鼠泌乳素(PRL)瘤中的表达来探讨E2F-1在PRL瘤发生发展过程中的作用.方法 用皮下植入17β-雌二醇的方法诱发大鼠PRL瘤;免疫组化SP方法检测两组大鼠E2F-1蛋白的表达.结果 雌二醇作用10周后,据垂体重量、垂体组织学变化和血清PRL水平证实PRL瘤诱导成功.PRL瘤组中,E2F-1蛋白明显高于对照组,差异具有统计学意义(P<0.01).结论 E2F-1在大鼠PRL瘤中呈现高表达,提示E2F-1的高表达促进了大鼠PRL瘤的发生发展.

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

    Science.gov (United States)

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

    2014-10-29

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

  4. EFFECTS OF EXOGENOUS PROSTAGLANDIN E2 ON COLLAGEN CONTENT OF Achilles TENDON OF RABBITS IN VlVO%外源性前列腺素E2对兔跟腱胶原含量的影响

    Institute of Scientific and Technical Information of China (English)

    李辉; 唐康来; 邓银栓; 谢美明; 常德海; 陶旭; 许建中

    2012-01-01

    目的 肌腱损伤后周围前列腺素E2(prostaglandin E2,PGE2)及体外牵伸载荷条件下肌腱细胞产生的PGE2均升高,通过观察外源性PGE2对兔跟腱胶原含量的影响,探讨其与肌腱病发生的关系. 方法 取健康3~4月龄日本短耳兔24只,体重2.0~2.5 kg,雌雄不限;根据PGE2注射剂量不同随机分为两组(n=12):低剂量组(50 ng)和高剂量组(500 ng).随机选择一侧后肢跟腱中部经皮注射0.2 mL对应剂量PGE2,对侧对应部位注射0.2 mL生理盐水作为对照,每周注射1次至处死.注射4、8周后两组各处死6只实验动物,大体观察跟腱情况后,取双侧跟腱HE染色观察细胞结构、基质形态,苦味酸-天狼星红染色偏振光显微镜下观察肌腱组织的胶原变化并定量分析Ⅰ、Ⅲ型胶原含量,透射电镜观测胶原纤维密度及直径. 结果 HE染色示两组实验侧均出现胶原纤维结构破坏.苦味酸-天狼星红染色示4、8周时两组实验侧Ⅲ型胶原纤维均较对照侧增加,Ⅰ型胶原减少(P<0.05);与低剂量组比较,高剂量组实验侧Ⅲ型胶原纤维增加,Ⅰ型胶原减少,Ⅲ/Ⅰ型胶原比值增高(P<0.05).透射电镜示两组4、8周时实验侧单位面积内总胶原纤维横截面积所占百分比均较对照侧降低,直径> 100nm的纤维比例均较对照侧降低,直径<100nm的纤维比例均增加(P<0.05);与低剂量组比较,高剂量组实验侧单位面积内总胶原纤维横截面积所占百分比更低,直径> 100nm的纤维比例均明显降低,直径< 100nm的比例明显增加(P<0.05). 结论 重复注射PGE2能导致兔跟腱Ⅰ型胶原减少,Ⅲ型胶原增多,Ⅰ/Ⅲ型胶原比例倒置,单位面积总胶原纤维密度降低,直径变细,可能与肌腱病发生相关.%Objective Prostaglandin E2 (PGE2) production increases in human tendon fibroblasts after the tendon injuries and repetitive mechanical loading in vitro. To analyze the relations between PGE2 and

  5. professora do 1º e 2º ciclos do Ensino Básico

    Directory of Open Access Journals (Sweden)

    José António Fernandes

    2005-01-01

    Full Text Available This study researched the impact of the teaching of Statistics unit to 6th graders on the difficulties of a student-teacher (Joana in stochastic. Before any experience of teaching, Joana answered a questionnaire about the theme, in order to allow the identification of their conceptual difficulties; afterwards, she taught the Statistics unit; finally, she was interviewed about the issues in which she had shown difficulties when answering the questionnaire. The results of the study indicated that the teaching of the Statistics unit had a moderate success in overcoming the student-teacher’s difficulties, as many changes on her answers and/or reasoning were not a result of her own initiative, but were a consequence of the questioning of the researcher. In addition, the difficulties to relate the localization measures and their meanings, as well as the comparison of probabilities were not at all overcome. It was verified yet that, besides being very limited, Joana’s knowledge in stochastic was greatly algorithmic and routinised and seems to have a reduced level of integration.

  6. Crystal structure of bis{μ-(E-2-[(2-oxidophenyliminomethyl]quinolin-8-olato-κ4O,N,N′,O′}bis[dibutyltin(IV

    Directory of Open Access Journals (Sweden)

    Camacho-Camacho Carlos

    2017-01-01

    Full Text Available Condensation of 8-hydroxyquinoline-2-carbaldehyde with 2-aminophenol gave the (E-2-[(2-hydroxyphenyliminomethyl]quinolin-8-ol derivative that reacted with di-n-butyltin oxide with release of H2O to yield the chelate title complex, [Sn2(C4H94(C16H10N2O22]. The compound crystallizes in the triclinic space group P-1, with two independent centrosymmetric dimers in the unit cell. Each features a typical pincer-type structure where the dianionic ligand is tetradentate, coordinating to the central tin atom through both phenolate oxygen atoms, as well as through the quinoline and imine N atoms. Each metal atom adopts a distorted pentagonal–bipyramidal SnC2N2O3 coordination arising from the N,N′,O,O′-tetradentate deprotonated Schiff base, one bridging phenolate O atom of the neighbouring ligand and two butyl groups in the axial sites.

  7. X-ray structures of precursors of styrylpyridine-derivatives used to obtain 4-((E)-2-(pyridin-2-yl)vinyl)benzamido-TEMPO: synthesis and characterization.

    Science.gov (United States)

    Soriano-Moro, Guillermo; Percino, María Judith; Sánchez, Ana Laura; Chapela, Víctor Manuel; Cerón, Margarita; Castro, María Eugenia

    2015-04-02

    The synthesis and characterization of the precursor isomers trans-4-(2-(pyridin-2-yl)vinylbenzaldehyde (I), trans-4-(2-(pyridin-4-yl)vinylbenzaldehyde (II), trans-4-(2-(pyridin-2-yl)vinylbenzoic acid (III) and (E)-4-(2-(pydridin-4-yl)vinylbenzoic acid (IV) are reported. These compounds were prepared in order to obtain trans-4-((E)-2-(pyridin-2-yl)vinyl)benzamide-TEMPO (V). Compounds I and II were obtained by using a Knoevenagel reaction in the absence of a condensing agent and solvent. Oxidation of the aldehyde group using the Jones reagent afforded the corresponding acid forms III and IV. A condensation reaction with 4-amino-TEMPO using oxalyl chloride/DMF/CH2Cl2 provided the 4-((E)-2-(pyridin-2-yl)vinyl)benzamide-TEMPO. Single crystals of compounds I, II and III were obtained and characterized by X-ray diffraction. Compound I belongs to space group P2(1)/c, a = 12.6674(19) Å, b = 7.2173(11) Å, c = 11.5877(14) Å, b = 97.203(13)° and the asymmetric unit was Z = 4, whereas compound II was in the space group P2(1), with a = 3.85728(9) Å, b = 10.62375(19) Å, c = 12.8625(2) Å, b = 91.722 (2)° and the asymmetric unit was Z = 2. Compound III crystallized as single colorless needle crystals, belonging to the monoclinic system with space group P2(1), with Z = 2, with a = 3.89359(7) Å, b = 17.7014(3) Å, c = 8.04530(12) Å, b = 94.4030 (16)°. All compounds were completely characterized by IR, (1)H-NMR, EI-MS and UV-Vis.

  8. X-ray Structures of Precursors of Styrylpyridine-Derivatives Used to Obtain 4-((E-2-(Pyridin-2-ylvinylbenzamido-TEMPO: Synthesis and Characterization

    Directory of Open Access Journals (Sweden)

    Guillermo Soriano-Moro

    2015-04-01

    Full Text Available The synthesis and characterization of the precursor isomers trans-4-(2-(pyridin-2-ylvinylbenzaldehyde (I, trans-4-(2-(pyridin-4-ylvinylbenzaldehyde (II, trans-4-(2-(pyridin-2-ylvinylbenzoic acid (III and (E-4-(2-(pydridin-4-ylvinylbenzoic acid (IV are reported. These compounds were prepared in order to obtain trans-4-((E-2-(pyridin-2-ylvinylbenzamide-TEMPO (V. Compounds I and II were obtained by using a Knoevenagel reaction in the absence of a condensing agent and solvent. Oxidation of the aldehyde group using the Jones reagent afforded the corresponding acid forms III and IV. A condensation reaction with 4-amino-TEMPO using oxalyl chloride/DMF/CH2Cl2 provided the 4-((E-2-(pyridin-2-ylvinylbenzamide-TEMPO. Single crystals of compounds I, II and III were obtained and characterized by X-ray diffraction. Compound I belongs to space group P21/c, a = 12.6674(19 Å, b = 7.2173(11 Å, c = 11.5877(14 Å, b = 97.203(13° and the asymmetric unit was Z = 4, whereas compound II was in the space group P21, with a = 3.85728(9 Å, b = 10.62375(19 Å, c = 12.8625(2 Å, b = 91.722 (2° and the asymmetric unit was Z = 2. Compound III crystallized as single colorless needle crystals, belonging to the monoclinic system with space group P21, with Z = 2, with a = 3.89359(7 Å, b = 17.7014(3 Å, c = 8.04530(12 Å, b = 94.4030 (16°. All compounds were completely characterized by IR, 1H-NMR, EI-MS and UV-Vis.

  9. Penetration effect of prostaglandin E2 gel on oral mucosa of rats

    Directory of Open Access Journals (Sweden)

    Rafinus Arifin

    2012-09-01

    Full Text Available Background: Several researches reported that Prostaglandin E2 (PGE2 injection on buccal mucosa combined with orthodontic pressure can faster tooth movement but has disadvantages such as high alveolar bone and root resorption furthermore pain from injection needle. PGE2 gel was made to better replace the lacks of injectable PGE2. Purpose: This research was aimed to prove that PGE 2 gel can penetrate rat’s oral mucosa effecting the appearance of PMN cells. Methods: This research was an in vivo laboratory experiment using 36 Sprague Dawley rats which were divided into 3 groups: normal group, topical PGE2 gel group after 1, 2, 4, 8 hours (4 subgroups, and topical gel without PGE2 group after 1, 2, 4, 8 hours (4 subgroups. Each group consists of 4 rats, therefore the total sample for all research groups were 36 rats. Gel with 25 µg/mL of PGE2 and gel without PGE2 were applied on oral mucosa for 2 minutes. Then, the rats were sacrificed after 1 hour, 2 hours, 4 hours, and 8 hours application. After that, the samples were prepared for histological examination with Hematoxyllin and Eosin. The picture were taken with OptiLab View and PMN cells amount were counted with light microscope, set 400 times of magnification. Results: Penetration effect of PGE2 gel on rat’s oral mucosa result in PMN inflammation cells distribution. One-way ANOVA showed no significant difference on PMN cells count in rats’ lower jaws between groups of normal and gel without PGE2. There was significant difference between groups of PGE2 gel and gel without PGE2 (p=0,001. PGE2 gel application showed PGE2 as inflammatory media, even though administered topically. Conclusion: PGE2 gel can penetrate rat’s oral mucosa, effecting PMN cells 1, 2, 4 and 8 hours after application of PGE2 gel.Latar belakang: Beberapa penelitian melaporkan bahwa injeksi (Prostaglandin E2 PGE2pada mukosa bukal yang dikombinasikan dengan tekanan ortodonti dapat mempercepat pergerakan gigi, tapi

  10. Overexpression of the prostaglandin E2 receptor EP2 results in enhanced skin tumor development.

    Science.gov (United States)

    Sung, Y M; He, G; Hwang, D H; Fischer, S M

    2006-09-07

    We previously showed that the EP2 knockout mice were resistant to chemically induced skin carcinogenesis. The purpose of this study was to investigate the role of the overexpression of the EP2 receptor in mouse skin carcinogenesis. To determine the effect of overexpression of EP2, we used EP2 transgenic (TG) mice and wild-type (WT) mice in a DMBA (7,12-dimethylbenz[alpha]anthracene)/TPA (12-O-tetradecanoylphorbol-13-acetate) two-stage carcinogenesis protocol. EP2 TG mice developed significantly more tumors compared with WT mice. Overexpression of the EP2 receptor increased TPA-induced keratinocyte proliferation both in vivo and in vitro. In addition, the epidermis of EP2 TG mice 48 h after topical TPA treatment was significantly thicker compared to that of WT mice. EP2 TG mice showed significantly increased cyclic adenosine monophosphate levels in the epidermis after prostaglandin E2 (PGE2) treatment. The inflammatory response to TPA was increased in EP2 TG mice, as demonstrated by an increased number of macrophages in the dermis. Tumors and 7 x TPA-treated and DMBA-TPA-treated (6 weeks) skins from EP2 TG mice produced more blood vessels than those of WT mice as determined by CD-31 immunostaining. Vascular endothelial growth factor (VEGF) protein expression was significantly increased in squamous cell carcinoma (SCC) samples from EP2 TG mice compared that of WT mice. There was, however, no difference in the number of apoptotic cells in tumors from WT and EP2 TG mice. Together, our results suggest that the overexpression of the EP2 receptor plays a significant role in the protumorigenic action of PGE2 in mouse skin.

  11. Cloning, functional expression, and characterization of the human prostaglandin E2 receptor EP2 subtype.

    Science.gov (United States)

    Bastien, L; Sawyer, N; Grygorczyk, R; Metters, K M; Adam, M

    1994-04-22

    A cDNA clone encoding the human prostaglandin (PG) E2 receptor EP2 subtype has been isolated from a human lung cDNA library. The 1.9-kilobase pair cDNA, hEP2, encodes for a 488-amino acid protein with a predicted molecular mass of 53,115 and has the seven putative transmembrane domains characteristic of G protein-coupled receptors. The specific binding of [3H]PGE2 to COS cell membranes transfected with the hEP2 cDNA was of high affinity with an equilibrium dissociation constant (Kd) of 1 nM and the rank order of potency for prostaglandins in competition for [3H]PGE2 specific binding was PGE1 = PGE2 > iloprost > PGF2 alpha > PGD2. In competition studies using more selective prostanoid-receptor agonist and antagonists, the [3H]PGE2 specific binding was competed by MB28767, an EP3 agonist, but not by the EP1-preferring antagonists AH6809 and SC19220, or by the EP2 agonist butaprost. Electrophysiological studies of Xenopus oocytes co-injected with hEP2 and cystic fibrosis transmembrane conductance regulator (cAMP-activated Cl- channel) cDNAs detected PGE2-specific inward Cl- currents, demonstrating that the hEP2 cDNA encoded a functional receptor which produced an increase in cAMP levels. Thus, we have cloned the human EP2 receptor subtype which is functionally coupled to increase in cAMP. Northern blot analysis showed that hEP2 is expressed as a 3.8-kilobase mRNA in a number of human tissues with the highest expression levels present in the small intestine.

  12. The prostaglandin E2 receptor EP2 is required for cyclooxygenase 2-mediated mammary hyperplasia.

    Science.gov (United States)

    Chang, Sung-Hee; Ai, Youxi; Breyer, Richard M; Lane, Timothy F; Hla, Timothy

    2005-06-01

    Expression of cyclooxygenase 2 (COX-2) in breast cancer correlates with poor prognosis, and COX-2 enzyme inhibitors reduce breast cancer incidence in humans. We recently showed that COX-2 overexpression in the mammary gland of transgenic mice induced mammary cancer. Because prostaglandin E2 (PGE2) is the major eicosanoid and because the EP2 subtype of the PGE2 receptor is highly expressed in the mammary tumors, we tested if this G protein-coupled receptor is required for tumorigenesis. We crossed the MMTV-COX-2 transgenic mice with Ep2-/- mice and studied tumor development in bigenic mice. Lack of EP2 receptor strongly suppressed COX-2-induced effects such as precocious development of the mammary gland in virgins and the development of mammary hyperplasia in multiparous female mice. Interestingly, the expression of amphiregulin, a potent mammary epithelial cell growth factor was down regulated in mammary glands of Ep2-/- mice. Total cyclic AMP (cAMP) levels were reduced in Ep2-/- mammary glands suggesting that PGE2 signaling via the EP2 receptor activates the Gs/cAMP/protein kinase A pathway. In mammary tumor cell lines, expression of the EP2 receptor followed by treatment with CAY10399, an EP2-specific agonist, strongly induced amphiregulin mRNA levels in a protein kinase A-dependent manner. These data suggest that PGE2 signaling via the EP2 receptor in mammary epithelial cells regulate mammary gland hyperplasia by the cAMP-dependent induction of amphiregulin. Inhibition of the EP2 pathway in the mammary gland may be a novel approach in the prevention and/or treatment of mammary cancer.

  13. Prostaglandin E2 promotes endothelial differentiation from bone marrow-derived cells through AMPK activation.

    Directory of Open Access Journals (Sweden)

    Zhenjiu Zhu

    Full Text Available Prostaglandin E2 (PGE2 has been reported to modulate angiogenesis, the process of new blood vessel formation, by promoting proliferation, migration and tube formation of endothelial cells. Endothelial progenitor cells are known as a subset of circulating bone marrow mononuclear cells that have the capacity to differentiate into endothelial cells. However, the mechanism underlying the stimulatory effects of PGE2 and its specific receptors on bone marrow-derived cells (BMCs in angiogenesis has not been fully characterized. Treatment with PGE2 significantly increased the differentiation and migration of BMCs. Also, the markers of differentiation to endothelial cells, CD31 and von Willebrand factor, and the genes associated with migration, matrix metalloproteinases 2 and 9, were significantly upregulated. This upregulation was abolished by dominant-negative AMP-activated protein kinase (AMPK and AMPK inhibitor but not protein kinase, a inhibitor. As a functional consequence of differentiation and migration, the tube formation of BMCs was reinforced. Along with altered BMCs functions, phosphorylation and activation of AMPK and endothelial nitric oxide synthase, the target of activated AMPK, were both increased which could be blocked by EP4 blocking peptide and simulated by the agonist of EP4 but not EP1, EP2 or EP3. The pro-angiogenic role of PGE2 could be repressed by EP4 blocking peptide and retarded in EP4(+/- mice. Therefore, by promoting the differentiation and migration of BMCs, PGE2 reinforced their neovascularization by binding to the receptor of EP4 in an AMPK-dependent manner. PGE2 may have clinical value in ischemic heart disease.

  14. Perspective of microsomal prostaglandin E2 synthase-1 as drug target in inflammation-related disorders.

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    Koeberle, Andreas; Werz, Oliver

    2015-11-01

    Prostaglandin (PG)E2 encompasses crucial roles in pain, fever, inflammation and diseases with inflammatory component, such as cancer, but is also essential for gastric, renal, cardiovascular and immune homeostasis. Cyclooxygenases (COX) convert arachidonic acid to the intermediate PGH2 which is isomerized to PGE2 by at least three different PGE2 synthases. Inhibitors of COX - non-steroidal anti-inflammatory drugs (NSAIDs) - are currently the only available therapeutics that target PGE2 biosynthesis. Due to adverse effects of COX inhibitors on the cardiovascular system (COX-2-selective), stomach and kidney (COX-1/2-unselective), novel pharmacological strategies are in demand. The inducible microsomal PGE2 synthase (mPGES)-1 is considered mainly responsible for the excessive PGE2 synthesis during inflammation and was suggested as promising drug target for suppressing PGE2 biosynthesis. However, 15 years after intensive research on the biology and pharmacology of mPGES-1, the therapeutic value of mPGES-1 as drug target is still vague and mPGES-1 inhibitors did not enter the market so far. This commentary will first shed light on the structure, mechanism and regulation of mPGES-1 and will then discuss its biological function and the consequence of its inhibition for the dynamic network of eicosanoids. Moreover, we (i) present current strategies for interfering with mPGES-1-mediated PGE2 synthesis, (ii) summarize bioanalytical approaches for mPGES-1 drug discovery and (iii) describe preclinical test systems for the characterization of mPGES-1 inhibitors. The pharmacological potential of selective mPGES-1 inhibitor classes as well as dual mPGES-1/5-lipoxygenase inhibitors is reviewed and pitfalls in their development, including species discrepancies and loss of in vivo activity, are discussed.

  15. Presence of crevicular fluid Prostaglandin E2 in relation with clinical and radiographic periodontal status

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    Javier Elpidio Monzón

    2016-07-01

    Full Text Available Background and Objectives: Prostaglandin E2 (PGE2 is present in gingival crevicular fluid the (GCF and is evidenced in periodontal disease (PD. However, there are no enough reports to correlate the PGE2 concentrations in GCF in periodontal health and disease with clinical and radiographic indicators, age and gender. Hence, the present study is aimed to estimate the levels of PGE2 in GCF of subjects without periodontal disease (SEP and periodontal disease (CEP. Materials and Methods: 99 subjects were selected, 33 without PD (G1 and 66 with PD, 33 with gingivitis (G2 and 33 with periodontitis (G3, which were submitted to a clinical and radiographic diagnosis, registering samples FGC, being stored, centrifuged and refrigerated for preservation. Subsequently the concentration of crevicular PGE2 was measured by using the enzyme linked immunosorbent assay (ELISA, determining the concentration of each subject. Results: PGE2 was detected in all the samples. The G1 presented a concentration of 28.82 ± 2.88 pg / mL, G2 44.91 ± 4.37 pg / mL and G3 148.67 ± 74.74 pg / mL (0.0001. PGE2 levels were significantly correlated with bleeding on probing, probing depth, attachment loss and bone loss (0.05. PGE2 levels were modified by age, but not gender. Conclusion: It is well known that activated inflammatory cells produce inflammatory mediators that stimulate the production of PGE2. The findings of this study demonstrate an increased concentration of PGE2 in FCG according to the presence of greater severity of PD. PGE2 may be considered as a biomarker in PD progression. However, controlled, longitudinal studies are needed to confirm this possibility.

  16. Carnosol and carnosic acids from Salvia officinalis inhibit microsomal prostaglandin E2 synthase-1.

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    Bauer, Julia; Kuehnl, Susanne; Rollinger, Judith M; Scherer, Olga; Northoff, Hinnak; Stuppner, Hermann; Werz, Oliver; Koeberle, Andreas

    2012-07-01

    Prostaglandin E(2) (PGE(2)), the most relevant eicosanoid promoting inflammation and tumorigenesis, is formed by cyclooxygenases (COXs) and PGE(2) synthases from free arachidonic acid. Preparations of the leaves of Salvia officinalis are commonly used in folk medicine as an effective antiseptic and anti-inflammatory remedy and possess anticancer activity. Here, we demonstrate that a standard ethyl acetate extract of S. officinalis efficiently suppresses the formation of PGE(2) in a cell-free assay by direct interference with microsomal PGE(2) synthase (mPGES)-1. Bioactivity-guided fractionation of the extract yielded closely related fractions that potently suppressed mPGES-1 with IC(50) values between 1.9 and 3.5 μg/ml. Component analysis of these fractions revealed the diterpenes carnosol and carnosic acid as potential bioactive principles inhibiting mPGES-1 activity with IC(50) values of 5.0 μM. Using a human whole-blood assay as a robust cell-based model, carnosic acid, but not carnosol, blocked PGE(2) generation upon stimulation with lipopolysaccharide (IC(50) = 9.3 μM). Carnosic acid neither inhibited the concomitant biosynthesis of other prostanoids [6-keto PGF(1α), 12(S)-hydroxy-5-cis-8,10-trans-heptadecatrienoic acid, and thromboxane B(2)] in human whole blood nor affected the activities of COX-1/2 in a cell-free assay. Together, S. officinalis extracts and its ingredients carnosol and carnosic acid inhibit PGE(2) formation by selectively targeting mPGES-1. We conclude that the inhibitory effect of carnosic acid on PGE(2) formation, observed in the physiologically relevant whole-blood model, may critically contribute to the anti-inflammatory and anticarcinogenic properties of S. officinalis.

  17. Cyclic Mechanical Stretching Induces Autophagic Cell Death in Tenofibroblasts Through Activation of Prostaglandin E2 Production

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    Hua Chen

    2015-04-01

    Full Text Available Background/Aims: Autophagic cell death has recently been implicated in the pathophysiology of tendinopathy. Prostaglandin E2 (PGE2, a known inflammatory mediator of tendinitis, inhibits tenofibroblast proliferation in vitro; however, the underlying mechanism is unclear. The present study investigated the relationship between PGE2 production and autophagic cell death in mechanically loaded human patellar tendon fibroblasts (HPTFs in vitro. Methods: Cultured HPTFs were subjected to exogenous PGE2 treatment or repetitive cyclic mechanical stretching. Cell death was determined by flow cytometry with acridine orange/ethidium bromide staining. Induction of autophagy was assessed by autophagy markers including the formation of autophagosomes and autolysosomes (by electron microscopy, AO staining, and formation of GPF-LC3-labeled vacuoles and the expression of LC3-II and BECN1 (by western blot. Stretching-induced PGE2 release was determined by ELISA. Results: Exogenous PGE2 significantly induced cell death and autophagy in HPTFs in a dose-dependent manner. Blocking autophagy using inhibitors 3-methyladenine and chloroquine, or small interfering RNAs against autophagy genes Becn-1 and Atg-5 prevented PGE2-induced cell death. Cyclic mechanical stretching at 8% and 12% magnitudes for 24 h significantly stimulated PGE2 release by HPTFs in a magnitude-dependent manner. In addition, mechanical stretching induced autophagy and cell death. Blocking PGE2 production using COX inhibitors indomethacin and celecoxib significantly reduced stretching-induced autophagy and cell death. Conclusion: Taken together, cyclic mechanical stretching induces autophagic cell death in tenofibroblasts through activation of PGE2 production.

  18. Prostaglandin E2 regulates angiogenesis via activation of fibroblast growth factor receptor-1.

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    Finetti, Federica; Solito, Raffaella; Morbidelli, Lucia; Giachetti, Antonio; Ziche, Marina; Donnini, Sandra

    2008-01-25

    Prostaglandin E(2) (PGE(2)) behaves as a mitogen in epithelial tumor cells as well as in many other cell types. We investigated the actions of PGE(2) on microvascular endothelial cells (capillary venular endothelial cells) with the purpose of delineating the signaling pathway leading to the acquisition of the angiogenic phenotype and to new vessel formation. PGE(2) (100 nM) produced activation of the fibroblast growth factor receptor 1 (FGFR-1), as measured by its phosphorylation, but not of vascular endothelial growth factor receptor 2. PGE(2) stimulated the EP3 subtype receptor, as deduced by abrogation of EP3 Galpha(i) subunit activity through pertussis toxin. Consistent with this result, in human umbilical venular endothelial cells missing the EP3 receptor, PGE(2) did not phosphorylate FGFR-1. Upon binding to its receptor, PGE(2) initiated an autocrine/paracrine signaling cascade involving the intracellular activation of c-Src, activation of matrix metalloproteinase (predominantly MMP2), which in turn caused the mobilization of membrane-anchored fibroblast growth factor-2 (FGF-2). In fact, in cells unable to release FGF-2 the transfection with both FGFR-1 and EP3 did not result in FGFR-1 phosphorylation in response to PGE(2). Relevance for the FGF2-FGFR-1 system was highlighted by confocal analysis, showing receptor internalization after cell exposure to the prostanoid. ERK1/2 appeared to be the distal signal involved, its phosphorylation being sensitive to either cSrc inhibitor or FGFR-1 blocker. Finally, PGE(2) stimulated cell migration and capillary formation in aortic rings, which were severely reduced by inhibitors of signaling molecules or by receptor antagonist. In conclusion, this study provides evidence for the involvement of FGFR-1 through FGF2 in eliciting PGE(2) angiogenic responses. This signaling pattern is similar to the autocrine-paracrine mechanism which operates in endothelial cells to support neovascular growth.

  19. Asteroid (4179) Toutatis size determination via optical images observed by the Chang'e-2 probe

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    Liu, P.; Huang, J.; Zhao, W.; Wang, X.; Meng, L.; Tang, X.

    2014-07-01

    This work is a physical and statistical study of the asteroid (4179) Toutatis using the optical images obtained by a solar panel monitor of the Chang'e-2 probe on Dec. 13, 2012 [1]. In the imaging strategy, the camera is focused at infinity. This is specially designed for the probe with its solar panels monitor's principle axis pointing to the relative velocity direction of the probe and Toutatis. The imaging strategy provides a dedicated way to resolve the size by multi-frame optical images. The inherent features of the data are: (1) almost no rotation was recorded because of the 5.41-7.35 Earth-day rotation period and the small amount of elapsed imaging time, only minutes, make the object stay in the images in a fixed position and orientation; (2) the sharpness of the upper left boundary and the vagueness of lower right boundary resulting from the direction of SAP (Sun-Asteroid-Probe angle) cause a varying accuracy in locating points at different parts of Toutatis. A common view is that direct, accurate measurements of asteroid shapes, sizes, and pole positions are now possible for larger asteroids that can be spatially resolved using the Hubble Space Telescope or large ground-based telescopes equipped with adaptive optics. For a quite complex planetary/asteroid probe study, these measurements certainly need continuous validation via a variety of ways [2]. Based on engineering parameters of the probe during the fly-by, the target spatial resolving and measuring procedures are described in the paper. Results estimated are optical perceptible size on the flyby epoch under the solar phase angles during the imaging. It is found that the perceptible size measured using the optical observations and the size derived from the radar observations by Ostro et al.~in 1995 [3], are close to one another.

  20. Expression of prostaglandin E2 and EP receptors in human papillary thyroid carcinoma.

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    Sun, Liao; Wei, Xiaohong; Liu, Xueting; Zhou, Danli; Hu, Fang; Zeng, Yingjuan; Sun, Ying; Luo, Shunkui; Zhang, Yu; Yi, Xian Ping

    2016-04-01

    The objective of the present study is to determine the role of prostaglandin E2 (PGE2) and downstream EP receptors in the development of human papillary thyroid carcinoma (PTC). A total of 90 thyroid specimens excised from patients undergoing total or subtotal thyroidectomy in the Department of General Surgery, the Fifth Affiliated Hospital of Sun Yat-sen University, China, from August 2013 to September 2014, were analyzed. The quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemical analyses were employed to examine the messenger RNA (mRNA) and protein expression, respectively. The expressions and significances of cyclooxygenase-2 (COX-2), microsomal prostaglandin E synthase-1 (mPGES-1), PGE2, and EP receptors in PTC and nodular goiter were investigated. The COX-2 mRNA and protein expression level significantly increased in the PTC tissues than in the paired noncarcinoma tissues adjacent to the PTC or nodular goiter tissues. The mPGES-1 protein expression was also significantly upregulated in the PTC tissues. All the four subtypes of EP receptors (EP1-4) could express in the thyroid tissues, while only the EP4 mRNA and protein levels significantly increased in the PTC tissues. The local production of PGE2 had a higher-level expression in the PTC tissues than in the noncarcinoma thyroid tissues adjacent to the PTC lesion and the benign nodular goiter tissues. The induction of PGE2 biosynthesis as well as the overexpression of EP4 in PTC suggested that this pathway might play an important role in the carcinogenesis and progression of PTC. These observations raise the possibility that pharmacological inhibition of mPGES-1 and/or EP4 may hold therapeutic promise in this common cancer.