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Sample records for in-band e2 transitions

  1. M1 and E2 transitions in the ground-state configuration of atomic ...

    Indian Academy of Sciences (India)

    forbidden. The lowest-order metastable levels which radiatively decay correspond to magnetic dipole (M1) and electric quadrupole (E2) transitions [16]. M1 and E2 transi- tion rates are several orders of magnitude smaller than those for electric dipole (E1) tran- sitions with a similar energy level separation. These transitions ...

  2. M1 and E2 transitions in the ground-state configuration of atomic ...

    Indian Academy of Sciences (India)

    state configuration are particularly useful because their relatively long wavelengths make them convenient for spectroscopic studies [1]. Although the atomic kinetics depend on, in particular, optical allowed transitions (E1), the weak forbidden transitions (in particular, magnetic dipole, M1 and electric quadrupole, E2) have ...

  3. 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.

  4. The B(E2) value of the first-excited to ground-state transition in 49Ti

    International Nuclear Information System (INIS)

    Mando, P.A.; Sona, P.; Taccetti, N.; Liberati, G.

    1978-01-01

    The B(E2) value of the 1381 keV transition connecting the J=3/2 - first excited state to the J=7/2 - ground state in 49 Ti has been determined by means of Coulomb excitation measurements. The value obtained is B(E2)=(33.5+- 4.5) e 2 fm 4

  5. Inter-band B(E2) transitions strengths in 160-170Dy nuclei

    International Nuclear Information System (INIS)

    Vargas, Carlos E; Lerma, Sergio; Velázquez, Víctor

    2015-01-01

    The rare earth region of the nuclear landscape is characterized by a large collectivity observed. The microscopic studies are difficult to perform in the region due to the enormous size of the valence spaces. The use of symmetries based models avoids that problem, because the symmetry allows to choose the most relevant degrees of freedom for the system under consideration. We present theoretical results for electromagnetic properties in 160-168 Dy isotopes employing the pseudo-SU(3) model. In particular, we study the B(E2) inter-band transition strengths between the ground state, γ and, β-bands. The model succesfully describes in a systematic way rotational features in these nuclei and allows to extrapolate toward the midshell nucleus 170 Dy

  6. {E2}/{M1} ratio for the γN → Δ transition in the chiral quark soliton model

    Science.gov (United States)

    Watabe, T.; Christov, Chr. V.; Goeke, K.

    1995-02-01

    We calculate the electric quadrupole to magnetic dipole transition ratio {E2}/{M1} for the reaction γN → Δ (1232) in the chiral quark soliton model. The calculated {E2}/{M1} ratio is in a good agreement with the very new experimental data. We obtain non-zero negative value for the electric quadrupole N - Δ transition moment, which suggests an oblate deformed charge structure of the nucleon or/and the delta isobar. Other observables related to this quantity, namely the N - Δ mass splitting, the isovector charge radius, and isovector magnetic moment, are properly reproduced as well.

  7. 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.

  8. Systematics in band gaps and optical spectra of 3D transition metal compounds

    International Nuclear Information System (INIS)

    Zaanen, J.; Sawatzky, G.A.

    1990-01-01

    In this paper the authors discuss the systematics in the transition metal d-d Coulomb interactions and the anion to cation charge transfer energies, and relate these to systematics in observed band gaps. In addition, they discuss the nature of the optical thresholds and their dependence on the cation and anion electronegativity

  9. Synthesis, Characterization and Antimicrobial Activities of Transition Metal Complexes of methyl 2-(((E)-(2-hydroxyphenyl)methylidene)amino)benzoate

    International Nuclear Information System (INIS)

    Ikram, M.; Rehman, S.

    2016-01-01

    New metal complexes with Schiff base ligand methyl 2-(((E)-(2-hydroxyphenyl)methylidene)amino)benzoate, were synthesized and characterized. Elemental analyses, EI-MS, 1H and 13C(1H)-NMR were used for ligand characterization whereas elemental analyses, EI-MS, IR and UV-Visible spectroscopic techniques were used for the transition metal compounds. All these analyses reveal the bis arrangement of the ligand around the metal centres. The compounds were studied for their antimicrobial activities against different pathogenic microbial species. It was found that the Schiff base ligand was completely inactive in comparison to the transition metal compounds. It was also observed that nickel based metal complex shown good results against Candida albican (25 mm) and zinc based metal complex against Agrobacterium tumefaciens (16 mm). (author)

  10. Upregulation of E2F8 promotes cell proliferation and tumorigenicity in breast cancer by modulating G1/S phase transition

    Science.gov (United States)

    Wang, Xi; Lin, Chuyong; Zhang, Xin; Wu, Shu; Bao, Yong; Yang, Qi; Song, Libing; Lin, Huanxin

    2016-01-01

    E2F transcription factors are involved in cell cycle regulation and synthesis of DNA in mammalian cells, and simultaneously play important roles in the development and progression of cancer when dysregulated. E2F8, a novel identified E2F family member, was found to be associated with the progression of several human cancers; however, the biological role and clinical significance of E2F8 in breast cancer remain to be further elucidated. Herein, we report that E2F8 is robustly elevated in breast cancer cell lines and clinical breast cancer tissue samples, respectively. The high expression level of E2F8 significantly correlates with clinical progression (P = 0.001), poor patient survival (P Ki67 staining index (P = 0.008) in 187 human breast cancer specimens. Furthermore, we find that overexpressing E2F8 promotes, whereas silencing E2F8 suppresses, the proliferation and tumorigenicity of breast cancer cells both in vitro and in vivo. We further demonstrate that E2F8 transcriptionally upregulates CCNE1 and CCNE2 via directly interacting with their respective gene promoter, which accelerates the transition of G1 to S phase of breast cancer cells. Taken together, these findings uncover a novel biologic role and regulatory mechanism of E2F8 responsible for the progression of breast cancer, indicating E2F8 may represent a novel prognostic biomarker and therapeutic target against breast cancer. PMID:26992224

  11. Experimental study of muonic x-ray transitions in mercury isotopes. [Fermi distribution, B(E2)

    Energy Technology Data Exchange (ETDEWEB)

    Hahn, A.A.; Miller, J.P.; Powers, R.J.; Zehnder, A.; Rushton, A.M.; Welsh, R.E.; Kunselman, A.R.; Roberson, P.; Walter, H.K.

    1978-01-01

    Muonic x-ray spectra were measured for /sup 198/ /sup 199/ /sup 200/ /sup 201/ /sup 202/ and /sup 204/Hg. These data were interpreted in terms of a two parameter Fermi distribution for the charge density. The spectroscopic quadrupole moments (Q/sub s/) of some of the 2/sup +/ nuclear states were inferred. For /sup 199/Hg the spectroscopic quadrupole moments of the first two excited states and the B(E2)'s connecting these states to the ground state were determined. For /sup 201/Hg the ground state quadrupole moment was obtained as well as several other E2 moments but the interpretation of the data was hampered by a possible incomplete knowledge of the nuclear scheme of this nucleus. The muonic isotope shifts were measured and interpreted in terms of deltaR/sub k/ and are compared to electronic x-ray and optical isotope shift measurements. 41 references

  12. Selected properties of nuclei at the magic shell closures from the studies of E1, M1 and E2 transition rates

    International Nuclear Information System (INIS)

    Mach, H.; Baluyut, A.-M.; Smith, D.; Ruchowska, E.; Koester, U.; Fraile, L. M.; Penttilae, H.; Aeystoe, J.; Elomaa, V.-V.; Eronen, T.; Hakala, J.; Jokinen, A.; Karvonen, P.; Kessler, T.; Moore, I. D.; Rahaman, S.; Rissanen, J.; Ronkainen, J.; Ronkanen, P.; Saastamoinen, A.

    2009-01-01

    Using the Advanced Time-Delayed method we have studied transition rates in several neutron-rich nuclei at the magic shell closures. These include the heavy Co and Fe nuclei just below the Z = 28 shell closure at the point of transition from spherical to collective structures. Of particular interest is 63 Fe located exactly at the point of transition at N = 37. A substantial increase in the information on this nucleus was obtained from a brief fast timing study conducted at ISOLDE. The new results indicate that 63 Fe seems to depart from a simple shell model structure observed for heavier N = 37 isotones of 65 Ni and 67 Zn.Another region of interest are the heavy Cd and Sn nuclei at N = 72, 74 and the properties of negative parity quasi-particle excitations. These experiments, performed at the IGISOL separator at Jyvaeskylae, revealed interesting properties of the E2 rates in the sequence of E2 transitions connecting the 10 + , 8 + , 6 + , 4 + , 2 + and 0 + members of the multiplet of levels in 122 Sn due to neutrons in the h 11/2 orbit.

  13. A differential equation for the transition probability B(E2)↑ and the resulting recursion relations connecting even-even nuclei

    Science.gov (United States)

    Pattnaik, S.; Nayak, R. C.

    2014-04-01

    We obtain here a new relation for the reduced electric quadrupole transition probability B(E2)↑ of a given nucleus in terms of its derivatives with respect to neutron and proton numbers based on a similar local energy relation in the Infinite Nuclear Matter (INM) model of atomic nuclei, which is essentially built on the foundation of the Hugenholtz-Van Hove (HVH) theorem of many-body theory. Obviously, such a relation in the form of a differential equation is expected to be more powerful than the usual algebraic difference equations. Although the relation for B(E2)↑ has been perceived simply on the basis of a corresponding differential equation for the local energy in the INM model, its theoretical foundation otherwise has been clearly demonstrated. We further exploit the differential equation in using the very definitions of the derivatives to obtain two different recursion relations for B(E2)↑, connecting in each case three neighboring even-even nuclei from lower to higher mass numbers and vice versa. We demonstrate their numerical validity using available data throughout the nuclear chart and also explore their possible utility in predicting B(E2)↑ values.

  14. Spontaneous transition rates for electric dipole (E1), magnetic dipole (M1), electric quadrupole (E2) and magnetic quadrupole (M2) transitions for He-like calcium and sulfur ions

    International Nuclear Information System (INIS)

    Kingston, A.E.; Norrington, P.H.; Boone, A.W.

    2002-01-01

    The spontaneous decay rates for the electric dipole (E1), electric quadrupole (E2), magnetic dipole (M1) and magnetic quadrupole (M2) transitions between all of the 1s 2 , 1s2 l and 1s3 l states have been obtained for helium-like calcium and sulfur ions. To assess the accuracy of the calculations, the transition probabilities were calculated using two sets of configuration interaction wavefunctions. One set of wavefunctions was generated using the fully relativistic GRASP code and the other was obtained using CIV3, in which relativistic effects are introduced using the Breit-Pauli approximation. The transition rates, A values, oscillator strengths and line strengths from our two calculations are found to be similar and to compare very well with other recent results for Δn=1 or 2 transitions. For Δn=0 transitions the agreement is much less good; this is mainly due to differences in the calculated excitation energies. (author)

  15. Strain engineering a 4 a ×√ 3 a charge-density-wave phase in transition-metal dichalcogenide 1 T -VS e2

    Science.gov (United States)

    Zhang, Duming; Ha, Jeonghoon; Baek, Hongwoo; Chan, Yang-Hao; Natterer, Fabian D.; Myers, Alline F.; Schumacher, Joshua D.; Cullen, William G.; Davydov, Albert V.; Kuk, Young; Chou, M. Y.; Zhitenev, Nikolai B.; Stroscio, Joseph A.

    2017-07-01

    We report a rectangular charge density wave (CDW) phase in strained 1 T -VS e2 thin films synthesized by molecular beam epitaxy on c -sapphire substrates. The observed CDW structure exhibits an unconventional rectangular 4 a ×√ 3 a periodicity, as opposed to the previously reported hexagonal 4 a ×4 a structure in bulk crystals and exfoliated thin-layered samples. Tunneling spectroscopy shows a strong modulation of the local density of states of the same 4 a ×√ 3 a CDW periodicity and an energy gap of 2 ΔCDW=(9.1 ±0.1 ) meV . The CDW energy gap evolves into a full gap at temperatures below 500 mK, indicating a transition to an insulating phase at ultra-low temperatures. First-principles calculations confirm the stability of both 4 a ×4 a and 4 a ×√ 3 a structures arising from soft modes in the phonon dispersion. The unconventional structure becomes preferred in the presence of strain, in agreement with experimental findings.

  16. B (E2) values of transitions from kπ= 0+→ 2+ vibrational bands in some well deformed heavy nuclei

    International Nuclear Information System (INIS)

    Singh, M.; Varshney, Mani; Gupta, D.K.; Bihari, Chhail; Singh, Yuvraj; Varshney, A.K.; Gupta, K.K

    2009-01-01

    There is simultaneous reduced B (E2) values of low-lying K π= 0 + → 2 + states, indicating a beta vibration like structure as well as the two particle transfer cross-section which suggest a pairing vibration like character and interpreted that low-lying k π= 0 + → 2 + resonance are classical beta vibrations. Recently, similar doubts about the origin of beta vibrations from surface oscillation have also been published

  17. Tudor Staphylococcal Nuclease (Tudor-SN), a Novel Regulator Facilitating G1/S Phase Transition, Acting as a Co-activator of E2F-1 in Cell Cycle Regulation*

    Science.gov (United States)

    Su, Chao; Zhang, Chunyan; Tecle, Adiam; Fu, Xue; He, Jinyan; Song, Juan; Zhang, Wei; Sun, Xiaoming; Ren, Yuanyuan; Silvennoinen, Olli; Yao, Zhi; Yang, Xi; Wei, Minxin; Yang, Jie

    2015-01-01

    Tudor staphylococcal nuclease (Tudor-SN) is a multifunctional protein implicated in a variety of cellular processes. In the present study, we identified Tudor-SN as a novel regulator in cell cycle. Tudor-SN was abundant in proliferating cells whereas barely expressed in terminally differentiated cells. Functional analysis indicated that ectopic overexpression of Tudor-SN promoted the G1/S transition, whereas knockdown of Tudor-SN caused G1 arrest. Moreover, the live-cell time-lapse experiment demonstrated that the cell cycle of MEF−/− (knock-out of Tudor-SN in mouse embryonic fibroblasts) was prolonged compared with wild-type MEF+/+. We noticed that Tudor-SN was constantly expressed in every cell cycle phase, but was highly phosphorylated in the G1/S border. Further study revealed that Tudor-SN was a potential substrate of Cdk2/4/6, supportively, we found the physical interaction of endogenous Tudor-SN with Cdk4/6 in G1 and the G1/S border, and with Cdk2 in the G1/S border and S phase. In addition, roscovitine (Cdk1/2/5 inhibitor) or CINK4 (Cdk4/6 inhibitor) could inhibit the phosphorylation of Tudor-SN, whereas ectopic overexpression of Cdk2/4/6 increased the Tudor-SN phosphorylation. The underlying molecular mechanisms indicated that Tudor-SN could physically interact with E2F-1 in vivo, and could enhance the physical association of E2F-1 with GCN5 (a cofactor of E2F-1, which possesses histone acetyltransferase activity), and promote the binding ability of E2F-1 to the promoter region of its target genes CYCLIN A and E2F-1, and as a result, facilitate the gene transcriptional activation. Taken together, Tudor-SN is identified as a novel co-activator of E2F-1, which could facilitate E2F-1-mediated gene transcriptional activation of target genes, which play essential roles in G1/S transition. PMID:25627688

  18. Variation in band gap of lanthanum chromate by transition metals doping LaCr0.9A0.1O3 (A:Fe/Co/Ni)

    International Nuclear Information System (INIS)

    Naseem, Swaleha; Khan, Wasi; Saad, A. A.; Shoeb, M.; Ahmed, Hilal; Naqvi, A. H.; Husain, Shahid

    2014-01-01

    Transition metal (Fe, Co, Ni) doped lanthanum chromate (LaCrO 3 ) nanoparticles (NPs) were prepared by gel combustion method and calcinated at 800°C. Microstructural studies were carried by XRD and SEM/EDS techniques. The results of structural characterization show the formation of all samples in single phase without any impurity. Optical properties were studied by UV- visible and photoluminescence techniques. The energy band gap was calculated and the variation was observed with the doping of transition metal ions. Photoluminescence spectra show the emission peak maxima for the pure LaCrO 3 at about 315 nm. Influence of Fe, Co, Ni doping was studied and compared with pure lanthanum chromate nanoparticles

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

    International Nuclear Information System (INIS)

    Aggarwal, Kanti M.; Keenan, Francis P.

    2015-01-01

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

  20. TRANSIT

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. TRANSIT. SYSTEM: DETERMINE 2D-POSITION GLOBALLY BUT INTERMITTENT (POST-FACTO). IMPROVED ACCURACY. PRINCIPLE: POLAR SATELLITES WITH INNOVATIONS OF: GRAVITY-GRADIENT ATTITUDE CONTROL; DRAG COMPENSATION. WORKS ...

  1. Variation in band gap of lanthanum chromate by transition metals doping LaCr{sub 0.9}A{sub 0.1}O{sub 3} (A:Fe/Co/Ni)

    Energy Technology Data Exchange (ETDEWEB)

    Naseem, Swaleha, E-mail: wasiamu@gmail.com; Khan, Wasi, E-mail: wasiamu@gmail.com; Saad, A. A., E-mail: wasiamu@gmail.com; Shoeb, M., E-mail: wasiamu@gmail.com; Ahmed, Hilal, E-mail: wasiamu@gmail.com; Naqvi, A. H. [Centre of Excellence in Materials Science (Nanomaterials), Department of Applied Physics, Z.H. College of Engg. and Technology, Aligarh Muslim University, Aligarh-202002 (India); Husain, Shahid [Department of Physics, Aligarh Muslim University, Aligarh-202002 (India)

    2014-04-24

    Transition metal (Fe, Co, Ni) doped lanthanum chromate (LaCrO{sub 3}) nanoparticles (NPs) were prepared by gel combustion method and calcinated at 800°C. Microstructural studies were carried by XRD and SEM/EDS techniques. The results of structural characterization show the formation of all samples in single phase without any impurity. Optical properties were studied by UV- visible and photoluminescence techniques. The energy band gap was calculated and the variation was observed with the doping of transition metal ions. Photoluminescence spectra show the emission peak maxima for the pure LaCrO{sub 3} at about 315 nm. Influence of Fe, Co, Ni doping was studied and compared with pure lanthanum chromate nanoparticles.

  2. Loop 7 of E2 enzymes

    DEFF Research Database (Denmark)

    Papaleo, Elena; Casiraghi, Nicola; Arrigoni, Alberto

    2012-01-01

    , and influencing the ultimate fate of the substrates. Several E2s are characterized by an extended acidic insertion in loop 7 (L7), which if mutated is known to impair the proper E2-related functions. In the present contribution, we show that acidic loop is a conserved ancestral motif in E2s, relying...

  3. 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).

  4. 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).

  5. The cellular effects of E2F overexpression.

    Science.gov (United States)

    Adams, P D; Kaelin, W G

    1996-01-01

    The product of the retinoblastoma tumor-suppressor gene (RB) is a ubiquitously expressed, 105-kDa nuclear phosphoprotein (pRB). The pRB protein negatively regulates the cellular G1/S phase transition, and it is at this point in the cell cycle that it is thought to play its role as a tumor suppressor. The growth-inhibitory effects of pRB are exerted, at least in part, through the E2F family of transcription factors. This chapter reviews the insights into the mechanism of action of the E2F family members that have been obtained through overexpression studies. Studies in RB-/- SAOS-2 cells have provided evidence in support of the hypothesis that the E2F family members are negatively regulated by pRB and the related protein p130. In particular, the results obtained are consistent with the earlier biochemical data which suggested that E2F1 is regulated primarily by pRB, and E2F4 by p130. Results relating to p107 are also discussed. Consistent with the proposed role of pRB and E2F1 as coregulators of entry into S phase, experiments have demonstrated that overexpression of E2F1 is sufficient to override the cell cycle arrests caused by serum deprivation of fibroblasts or transforming growth factor-beta (TGF-beta) treatment of mink lung epithelial cells. However, at least in the case of the serum deprivation induced arrest, the ultimate result of E2F1 overexpression is death by p53-dependent apoptosis. In light of this and other data, a model is discussed as to how functional inactivation of pRB and p53 might cooperate to promote tumorigenesis. A number of studies have demonstrated the oncogenic potential of E2F family members, at least under certain conditions. This is, again, in keeping with the notion that these proteins play a critical role in controlling proliferation.

  6. Differential calculus on deformed E(2) group

    International Nuclear Information System (INIS)

    Giller, S.; Gonera, C.; Kosinski, P.; Maslanka, P.

    1997-01-01

    Four dimensional bi-covariant differential *-calculus on quantum E(2) group is constructed. The relevant Lie algebra is obtained and covariant differential calculus on quantum plane is found. (author)

  7. 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....

  8. Evolutionary variation of papillomavirus E2 protein and E2 binding sites

    Directory of Open Access Journals (Sweden)

    Angeletti Peter C

    2011-08-01

    Full Text Available Abstract Background In an effort to identify the evolutionary changes relevant to E2 function, within and between papillomavirus genera, we evaluated the E2 binding sites (E2BSs inside the long-control-region (LCR, and throughout the genomes. We identified E2BSs in the six largest genera of papillomaviruses: Alpha, Beta, Gamma, Delta, Lambda, and Xi-papillomaviruses (128 genomes, by comparing the sequences with a model consensus we created from known functional E2BSs (HPV16, HPV18, BPV1. We analyzed the sequence conservation and nucleotide content of the 4-nucleotide spacer within E2BSs. We determined that there is a statistically significant difference in GC content of the four-nucleotide E2BS spacer, between Alpha and Delta-papillomaviruses, as compared to each of the other groups. Additionally, we performed multiple alignments of E2 protein sequences using members of each genus in order to identify evolutionary changes within the E2 protein. Results When a phylogenetic tree was generated from E2 amino acid sequences, it was discovered that the alpha-papillomavirus genera segregates into two distinct subgroups (α1 and α2. When these subgroups were individually analyzed, it was determined that the subgroup α1 consensus E2BS favored a spacer of AAAA, whereas subgroup α2 favored the opposite orientation of the same spacer; TTTT. This observation suggests that these conserved inverted linkers could have functional importance.

  9. E2eUberIM

    DEFF Research Database (Denmark)

    Wac, Katarzyna; Cummings, Mark; Dey, Jayanta

    2016-01-01

    compose new innovative services, leads to high and exponentially growing integration expenses, and impairs the user experience for deployed services. All this is reducing long-term TNO profits. To meet this challenge, solutions employing network function virtualization (NFV) and software defined......, high-quality services, we propose an innovative end-to-end service management framework called e2eUberIM. This framework contains a scalable, flexible, and volatile information model (UberIM) and a real-time, "organic" communication and storage process (e2eUber). It leverages the proprietary interfaces...... of different vendors, enabling the resulting enhanced operations system environment to automatically and in real-time optimize operational overhead while maximizing the user experience, and quickly field new innovative, composed "any-services" (XaaS). We document the e2eUberIM requirements and its design...

  10. The (e,2e) reaction in molecules

    International Nuclear Information System (INIS)

    Dey, S.; Dixon, A.; Teubner, P.J.O.; Weigold, E.

    1975-01-01

    The aplication of the (e,2e) technique is discussed in the framework of (e,2e) on molecular hydrogen. It is shown that the technique is sufficiently sensitive to distinguish between simple wavefunctions and those containing configuration interactions. By comparing the data on H 2 and D 2 is shown that the Born-Oppenheimer approximation is confirmed to an accuracy of about 3 per cent. The data is also used to contrast other methods of determining electron momentum distributions in molecules. Data on methane, carbon monoxide and molecular nitrogen is also presented. (author)

  11. Universal EUV in-band intensity detector

    Science.gov (United States)

    Berger, Kurt W.

    2004-08-24

    Extreme ultraviolet light is detected using a universal in-band detector for detecting extreme ultraviolet radiation that includes: (a) an EUV sensitive photodiode having a diode active area that generates a current responsive to EUV radiation; (b) one or more mirrors that reflects EUV radiation having a defined wavelength(s) to the diode active area; and (c) a mask defining a pinhole that is positioned above the diode active area, wherein EUV radiation passing through the pinhole is restricted substantially to illuminating the diode active area.

  12. 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

    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......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...... 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...

  13. Unexpected structure in the E2 quasicontinuum spectrum of 154Dy

    International Nuclear Information System (INIS)

    Holzmann, R.; Khoo, T.L.; Ma, W.C.

    1988-01-01

    The evolution of the γ quasicontinuum spectrum with neutron number has been investigated in the sequence of dysprosium isotopes /sup 152,154,156/Dy. The three nuclei display a pronounced collective E2 component. In 154 Dy this component shows an unexpected splitting into two distinct parts, signifying a structural change along the γ cascade. The E2 and statistical components can be reproduced in simple γ cascade calculations; in 152 Dy and 156 Dy only rotational bands were included, whereas in 154 Dy additional vibration-like transitions were required to reproduce the two E2 peaks. 11 refs., 2 figs

  14. Prostaglandin E2 regulates hematopoietic stem cell

    International Nuclear Information System (INIS)

    Wang Yingying; Zhou Daohong; Meng Aimin

    2013-01-01

    Prostaglandin E2 (PGE2) is a bioactive lipid molecule produced by cyclooxygenase (COX), which plays an important role on hematopoiesis. While it can block differentiation of myeloid progenitors but enhance proliferation of erythroid progenitors. Recent research found that PGE2 have the effects on hematopoietic stem cell (HSC) function and these effects were independent from effects on progenitor cells. Exposure of HSC cells to PGE2 in vitro can increase homing efficiency of HSC to the murine bone marrow compartment and decrease HSC apoptosis, meanwhile increase long-term stem cell engraftment. In-vivo treatment with PGE2 expands short-term HSC and engraftment in murine bone marrow but not long-term HSC.In addition, PGE2 increases HSC survival after radiation injury and enhance hematopoietic recovery, resulting maintains hematopoietic homeostasis. PGE2 regulates HSC homeostasis by reactive oxygen species and Wnt pathway. Clinical beneficial of 16, 16-dimethyl-prostaglandin E2 treatment to enhance engraftment of umbilical cord blood suggest important improvements to therapeutic strategies. (authors)

  15. Shell evolution and E2 collectivity: new spectroscopic information

    Science.gov (United States)

    Pietralla, N.; Kremer, C.; Lettmann, M.; Aslanidou, S.; Krugmann, A.; Lizarazo, C.; von Neumann-Cosel, P.; Werner, V.; Witt, W.

    2018-02-01

    We report here on the first evidence for shape coexistence caused by Type II Shell Evolution which is firmly based on the measurement of absolute E2 transition rates. The data have been obtained in high-resolution inelastic electron scattering spectroscopy of the nucleus 96 Zr at the Superconducting Darmstadt Linear electron Accelerator (S-DALINAC). The data are presented and discussed. The neutron sub-shell closure at neutron number N = 56 plays a crucial role for the occurence of shape coexistence in 96,98Zr. We have studied the structure of exotic neutron-rich isotopes near the N = 56 neutron sub-shell closure using γ-ray spectroscopy and radioactive beams. We also present and discuss spectroscopic data on 84,86,88Ge taken recently at RIBF, RIKEN. The new data suggest the hitherto unknown existence of a region of pronounced nuclear triaxiality in neutron-rich Ge isotopes.

  16. 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

    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, a...

  17. 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

    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...

  18. E2F-7: a distinctive E2F family member with an unusual organization of DNA-binding domains

    NARCIS (Netherlands)

    Logan, N.; Delavaine, L.; Graham, A.; Reilly, C.; Wilson, J.; Brummelkamp, T.R.; Hijmans, E.M.; Bernards, R.A.; Thangue, N.B. La

    2004-01-01

    The E2F family of transcription factors play an important role in regulating cell cycle progression. We report here the characterization and functional properties of a new member of the human E2F family, referred to as E2F-7. E2F-7 has two separate DNA-binding domains, a feature that distinguishes

  19. Synergistic Function of E2F7 and E2F8 is Essential for Cell Survival and Embryonic Development

    OpenAIRE

    Li, Jing; Ran, Cong; Li, Edward; Gordon, Faye; Comstock, Grant; Siddiqui, Hasan; Cleghorn, Whitney; Chen, Hui-zi; Kornacker, Karl; Pandit, Shusil K.; Khanizadeh, Mehrbod; Weinstein, Michael; Leone, Gustavo; de Bruin, Alain

    2008-01-01

    The novel E2f7 and E2f8 family members are thought to function as transcriptional repressors important for the control of cell proliferation. Here we have analyzed the consequences of inactivating E2f7 and E2f8 in mice and show that their individual loss had no significant effect on development. Their combined ablation, however, resulted in massive apoptosis and dilation of blood vessels, culminating in lethality by embryonic day E11.5. A deficiency in E2f7 and E2f8 led to an increase in E2f1...

  20. Effect of closed shells on the multipole mixing parameter δ(E2/M1)

    International Nuclear Information System (INIS)

    Morozov, V.A.

    1992-01-01

    The behavior of the magnitude and sign of the mixing parameter δ(E2/M1) in even-even nuclei has been studied in a number of papers. The most extensive data has been given for transitions of the type 3 γ + , 2 γ + , 2 β + →2 g + . The data on δ are relatively scarce for mixed transitions in odd nuclei with magic or semimagic cores. However, certain conclusions can be drawn about the behavior of δ in transitions in odd nuclei near magic numbers, and also in transitions in even-even nuclei when passing through quasishells: (1) the absolute value of the reduced mixing parameter in transitions between particle and cluster-vibrational states in odd nuclei decreases as a closed shell is approached; (2) δ has the same sign for transitions between particle and cluster-vibrational levels in nuclei with Z=83 and 85 and N=83, 85, and 87; (3) in odd nuclei the sign of δ is positive for transitions between positive-parity states s 1/2 -d 3/2 in Cd, Sm, and Tl isotopes and is negative for transitions between negative-parity states f 7/2 π and h 9/2 π in Sm, Gd, Bi, and At isotopes, independently of whether these transitions are neutron or proton transitions; (4) the removal of ±2 nucleons in an even shell from a magic core (and in certain nuclei a larger number of pairs of nucleons) does not lead to a change in sign of δ in transitions producing an odd nucleus; (5) the closure of quasishells at N=96 and 104 in even-even nuclei is associated with an increase in the absolute value of δ(E2/M1)/E γ , but the sign of δ does not change

  1. Synergistic Function of E2F7 and E2F8 is Essential for Cell Survival and Embryonic Development

    Science.gov (United States)

    Li, Jing; Ran, Cong; Li, Edward; Gordon, Faye; Comstock, Grant; Siddiqui, Hasan; Cleghorn, Whitney; Chen, Hui-zi; Kornacker, Karl; Pandit, Shusil K.; Khanizadeh, Mehrbod; Weinstein, Michael; Leone, Gustavo; de Bruin, Alain

    2008-01-01

    Summary The novel E2f7 and E2f8 family members are thought to function as transcriptional repressors important for the control of cell proliferation. Here we have analyzed the consequences of inactivating E2f7 and E2f8 in mice and show that their individual loss had no significant effect on development. Their combined ablation, however, resulted in massive apoptosis and dilation of blood vessels, culminating in lethality by embryonic day E11.5. A deficiency in E2f7 and E2f8 led to an increase in E2f1 and p53, as well as in many stress-related genes. Homo- and hetero-dimers of E2F7 and E2F8 were found on target promoters, including E2f1. Importantly, loss of either E2f1 or p53 suppressed the massive apoptosis in double mutant embryos. These results identify E2F7 and E2F8 as a unique repressive arm of the E2F transcriptional network that is critical for embryonic development and control of the E2F1-p53 apoptotic axis. PMID:18194653

  2. 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......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...

  3. Cesium vacancy ordering in phase-separated C sxF e2 -yS e2

    Science.gov (United States)

    Taddei, K. M.; Sturza, M.; Chung, D. Y.; Cao, H. B.; Claus, H.; Kanatzidis, M. G.; Osborn, R.; Rosenkranz, S.; Chmaissem, O.

    2015-09-01

    By simultaneously displaying magnetism and superconductivity in a single phase, the iron-based superconductors provide a model system for the study of magnetism's role in superconductivity. The class of intercalated iron selenide superconductors is unique among these in having the additional property of phase separation and coexistence of two distinct phases—one majority phase with iron vacancy ordering and strong antiferromagnetism, and the other a poorly understood minority microscopic phase with a contested structure. Adding to the intrigue, the majority phase has never been found to show superconductivity on its own while the minority phase has never been successfully synthesized separate from the majority phase. In order to better understand this minority phase, a series of high-quality C sxF e2 -yS e2 single crystals with (0.8 ≤x ≤1 ; 0 ≤y ≤0.3 ) were grown and studied. Neutron and x-ray powder diffraction performed on ground crystals show that the average I 4 /m m m structure of the minority phase is distinctly different from the high-temperature I 4 /m m m parent structure. Moreover, single-crystal diffraction reveals the presence of discrete superlattice reflections that remove the degeneracy of the Cs sites in both the majority and minority phases and reduce their structural symmetries from body centered to primitive. Group theoretical analysis in conjunction with structural modeling shows that the observed superlattice reflections originate from three-dimensional Cs vacancy ordering. This model predicts a 25 % vacancy of the Cs site in the minority phase which is consistent with the site's refined occupancy. Magnetization measurements performed in tandem with neutron single-crystal diffraction provide evidence that the minority phase is the host of superconductivity. Our results also reveal a superconducting dome in which the superconducting transition temperature varies as a function of the nominal valence of iron.

  4. E2F6: a member of the E2F family that does not modulate squamous differentiation

    International Nuclear Information System (INIS)

    Wong, C.F.; Barnes, Liam M.; Smith, Louise; Popa, Claudia; Serewko-Auret, Magdalena M.; Saunders, Nicholas A.

    2004-01-01

    The inhibition of E2F has been demonstrated to be important in the initiation of squamous differentiation by two independent manners: promotion of growth arrest and the relief of the differentiation-suppressive properties of E2Fs. E2F6 is reported to behave as a transcriptional repressor of the E2F family. In this study, we examined the ability of E2F6 to act as the molecular switch required for E2F inhibition in order for keratinocytes to enter a terminal differentiation programme. Results demonstrated that whilst E2F6 was able to suppress E2F activity in proliferating keratinocytes, it did not modulate squamous differentiation in a differentiated keratinocyte. Furthermore, inhibition of E2F, by overexpressing E2F6, was not sufficient to sensitise either proliferating keratinocytes or the squamous cell carcinoma cell line, KJD-1/SV40, to differentiation-inducing agents. Significantly, although E2F6 could suppress E2F activity in proliferating cells, it could not inhibit proliferation of KJD-1/SV40 cells. These results demonstrate that E2F6 does not contain the domains required for modulation of squamous differentiation and imply isoform-specific functions for individual E2F family members

  5. Urinary prostaglandin E2 in the newborn and infant.

    Science.gov (United States)

    Antonucci, Roberto; Cuzzolin, Laura; Arceri, Augusta; Fanos, Vassilios

    2007-08-01

    Prostaglandin E(2) (PGE(2)) belongs to a family of biologically active lipids derived from the 20-carbon essential fatty acids. Renal PGE(2) is involved in the development of the kidney; it also contributes to regulate renal perfusion and glomerular filtration rate, and controls water and electrolyte balance. Furthermore, this mediator protects the kidney against excessive functional changes during the transition from fetal to extrauterine life, when it counteracts the vasoconstrictive effects of high levels of angiotensin II and other mediators. There is evidence that PGE(2) plays an important pathophysiological role in neonatal conditions of renal stress, and in congenital or acquired nephropaties. Thus, measurement of urinary PGE(2) as an index of renal synthesis of this primary prostaglandin may represent a non-invasive and sensitive method of investigating the homeostatic function of the kidney in early life. The aim of this literature review is to examine urinary PGE(2) as a non-invasive marker of renal homeostasis in the newborn and infant under both physiological and pathological conditions, or during treatments with widely used, potentially toxic drugs.

  6. Dosage-dependent copy number gains in E2f1 and E2f3 drive hepatocellular carcinoma.

    Science.gov (United States)

    Kent, Lindsey N; Bae, Sooin; Tsai, Shih-Yin; Tang, Xing; Srivastava, Arunima; Koivisto, Christopher; Martin, Chelsea K; Ridolfi, Elisa; Miller, Grace C; Zorko, Sarah M; Plevris, Emilia; Hadjiyannis, Yannis; Perez, Miguel; Nolan, Eric; Kladney, Raleigh; Westendorp, Bart; de Bruin, Alain; Fernandez, Soledad; Rosol, Thomas J; Pohar, Kamal S; Pipas, James M; Leone, Gustavo

    2017-03-01

    Disruption of the retinoblastoma (RB) tumor suppressor pathway, either through genetic mutation of upstream regulatory components or mutation of RB1 itself, is believed to be a required event in cancer. However, genetic alterations in the RB-regulated E2F family of transcription factors are infrequent, casting doubt on a direct role for E2Fs in driving cancer. In this work, a mutation analysis of human cancer revealed subtle but impactful copy number gains in E2F1 and E2F3 in hepatocellular carcinoma (HCC). Using a series of loss- and gain-of-function alleles to dial E2F transcriptional output, we have shown that copy number gains in E2f1 or E2f3b resulted in dosage-dependent spontaneous HCC in mice without the involvement of additional organs. Conversely, germ-line loss of E2f1 or E2f3b, but not E2f3a, protected mice against HCC. Combinatorial mapping of chromatin occupancy and transcriptome profiling identified an E2F1- and E2F3B-driven transcriptional program that was associated with development and progression of HCC. These findings demonstrate a direct and cell-autonomous role for E2F activators in human cancer.

  7. Functional characterization of E2F3b in human HepG2 liver cancer cell line.

    Science.gov (United States)

    Lu, Yujia; Li, Wei

    2018-04-01

    E2F3 is a transcription factor that has been shown to be overexpressed in hepatocellular carcinoma (HCC). It is well-known that the E2F3 gene encodes two proteins E2F3a and E2F3b. Therefore, the functions of the two distinct isoforms need to be clarified separately. To characterize the function of E2F3b in HCC, the effects of ectopic expression of E2F3b on cell proliferation, cell cycle, apoptosis and gene expression were investigated. E2F3b promoted G1/S phase transition and markedly increased cell proliferation, but had minor effect on apoptosis. Microarray analyses identified 366 differentially expressed genes (171 upregulated and 195 downregulated) in E2F3b- overexpressing cells. Differential expression of 16 genes relevant to cell cycle and cell proliferation were further verified by real-time PCR. Six genes, including CDC2, CCNE1, ARF, MAP4K2, MUSK, and PAX2 were confirmed to be upregulated by more than twofold; one gene, CCNA2 was validated to be downregulated by more than twofold. We also confirmed that E2F3b increased the protein levels of both cyclin E and Arf but did not affect cyclin D1 protein. These results suggest that E2F3b functions as an important promoter for cell proliferation and plays important roles in transcriptional regulation in HepG2 liver cancer cells. © 2017 Wiley Periodicals, Inc.

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

    DEFF Research Database (Denmark)

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

    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......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......-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...

  9. Gravitational Analysis of the In-Band Wormhole Phenomenon

    National Research Council Canada - National Science Library

    Gopaul, Richard; Kruus, Peter; Sterne, Dan; Rivera, Brian

    2006-01-01

    ...], for evaluating the effects of in-band wormhole attacks on OLSR routing. The gravitational analysis technique examines individual network topologies and results in the creation of a gravitational chart for each topology...

  10. 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/Gtf2...e2.1.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.bioscience...dbc.jp/kyushu-u/mm9/colo/Gtf2e2.Liver.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/colo/Blood.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Liver.gml ...

  11. PPARγ ligands suppress the feedback loop between E2F2 and cyclin-E1

    International Nuclear Information System (INIS)

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

    2008-01-01

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

  12. Evolving intricacies and implications of E2F1 regulation.

    Science.gov (United States)

    Mundle, Suneel D; Saberwal, Gurveen

    2003-04-01

    E2F transcription factors may play a pivotal role in the transcriptional regulation of several cellular processes far beyond the originally described cell cycle and proliferation. Among the six E2F family members, only E2F1 is noted for its role in apoptosis. The pocket protein family members Rb, p107, and p130 act as the main regulators of E2F activity. Nonetheless, in recent years other protein-protein interactions have been described for E2Fs. The post-translational modifications resulting from such protein interactions may have significant implications in the stability, half-life, and functional activity of E2Fs. In human diseases the significance of E2Fs is still under appreciated and is primarily recognized only as a consequence of the impairment in retinoblastoma gene product (Rb). However, with increasing knowledge of other protein interactions, the derailment of E2F activity could be anticipated to stem from an abnormality of any node in the complex network governing their availability and activity. The present review is intended to provide a perspective on the diversity of biochemical mechanisms underlying abnormal E2F expression and activity, understanding of which may have significant clinical implications.

  13. Unusual proliferation arrest and transcriptional control properties of a newly discovered E2F family member, E2F-6.

    Science.gov (United States)

    Gaubatz, S; Wood, J G; Livingston, D M

    1998-08-04

    E2F transcription factors play an important role in the regulation of cell cycle progression. We report here the cloning and characterization of an additional member of this family, E2F-6. E2F-6 lacks pocket protein binding and transactivation domains, and it is a potent transcriptional repressor that contains a modular repression domain at its carboxyl terminus. Overproduction of E2F-6 had no specific effect on cell cycle progression in asynchronously growing Saos2 and NIH 3T3 cells, but it inhibited entry into S phase of NIH 3T3 cells stimulated to exit G0. Taken together, these data suggest that E2F-6 can regulate a subset of E2F-dependent genes whose products are required for entry into the cell cycle but not for normal cell cycle progression.

  14. E2F-6, a member of the E2F family that can behave as a transcriptional repressor

    Science.gov (United States)

    Trimarchi, Jeffrey M.; Fairchild, Brian; Verona, Raluca; Moberg, Ken; Andon, Nancy; Lees, Jacqueline A.

    1998-01-01

    The E2F family of proteins is required to establish the correct cell-cycle-dependent transcription of genes that direct the process of cell division. All previously identified E2F proteins can act in a similar manner; depending on whether or not they are associated with the cell cycle inhibitors the retinoblastoma protein (pRB), p107, or p130, they can either repress or activate the transcription of E2F-responsive genes. We now report the cloning and characterization of another E2F family member, E2F-6, whose structure is reminiscent of the dominant inhibitors of other transcription factor families. The dimerization and DNA binding properties of E2F-6 are similar to those of the other E2F family members. However, it is not regulated by pRB, p107, or p130, and it is unable to activate transcription. Instead, it can act to repress the transcription of E2F responsive genes by countering the activity of the other E2F complexes via a pRB-, p107-, or p130-independent mechanism. PMID:9501179

  15. E2F-6, a member of the E2F family that can behave as a transcriptional repressor.

    Science.gov (United States)

    Trimarchi, J M; Fairchild, B; Verona, R; Moberg, K; Andon, N; Lees, J A

    1998-03-17

    The E2F family of proteins is required to establish the correct cell-cycle-dependent transcription of genes that direct the process of cell division. All previously identified E2F proteins can act in a similar manner; depending on whether or not they are associated with the cell cycle inhibitors the retinoblastoma protein (pRB), p107, or p130, they can either repress or activate the transcription of E2F-responsive genes. We now report the cloning and characterization of another E2F family member, E2F-6, whose structure is reminiscent of the dominant inhibitors of other transcription factor families. The dimerization and DNA binding properties of E2F-6 are similar to those of the other E2F family members. However, it is not regulated by pRB, p107, or p130, and it is unable to activate transcription. Instead, it can act to repress the transcription of E2F responsive genes by countering the activity of the other E2F complexes via a pRB-, p107-, or p130-independent mechanism.

  16. The biochemical basis of CDK phosphorylation-independent regulation of E2F1 by the retinoblastoma protein.

    Science.gov (United States)

    Cecchini, Matthew J; Dick, Frederick A

    2011-03-01

    The pRB (retinoblastoma protein) has a central role in the control of the G(1)-S phase transition of the cell cycle that is mediated in part through the regulation of E2F transcription factors. Upon S-phase entry pRB is phosphorylated extensively, which in turn releases bound E2Fs to drive the expression of the genes required for S-phase progression. In the present study, we demonstrate that E2F1-maintains the ability to interact with ppRB (hyperphosphorylated pRB). This interaction is dependent upon the 'specific' E2F1-binding site located in the C-terminal domain of pRB. A unique region of the marked box domain of E2F1 contacts the 'specific' site to mediate the interaction with ppRB. The mechanistic basis of the interaction between E2F1 and ppRB is subtle. A single substitution between valine and proline residues in the marked box distinguishes E2F1's ability to interact with ppRB from the inability of E2F3 to bind to the 'specific' site in ppRB. The E2F1-pRB interaction at the 'specific' site also maintains the ability to regulate the transcriptional activation of E2F1 target genes. These data reveal a mechanism by which E2F1 regulation by pRB can persist, when pRB is hyperphosphorylated and presumed to be inactive. © The Authors Journal compilation © 2011 Biochemical Society

  17. Molecular and functional characterisation of E2F-5, a new member of the E2F family

    NARCIS (Netherlands)

    Buck, V.; Allen, K.E.; Sørensen, T.; Bybee, A.; Hijmans, E.M.; Voorhoeve, P.M.; Bernards, R.A.; Thangue, N.B. La

    1995-01-01

    The transcription factor DRTF1/E2F is implicated in the control of cellular proliferation due to its interaction with key regulators of cell cycle progression, such as the retinoblastoma tumour suppressor gene product and related pocket proteins, cyclins and cyclin-dependent kinases. DRTF1/E2F DNA

  18. Effective Lagrangians, Watson's theorem and the E2/M1 mixing ratio in the excitation of the Delta resonance

    International Nuclear Information System (INIS)

    Davidson, R.M.

    1992-01-01

    The author investigates theoretical uncertainties and model dependence in the extraction of the nucleon-delta(1232) electromagnetic transition amplitudes from the multipole data base. The starting point is an effective Lagrangian incorporating chiral symmetry, which includes at the tree level the pseudovector Born terms, leading t-channel vector meson exchanges, and s and u channel delta exchanges. The nucleon-delta magnetic dipole (M1) and electric quadrupole (E2) transition amplitudes are expressed in terms of two independent gauge couplings at the γNΔ vertex. After unitarizing the tree level amplitude, the gauge couplings are fitted to various multipole data sets, thus determining E2 and M1. Although there is much sensitivity to the method used to unitarize the amplitude, the author extracts the E2/M1 ratio to be negative, with a magnitude around 1.5%. 11 refs., 3 figs

  19. Energy Efficiency Management Platform (E2MP), Phase I

    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...

  20. M1 transitions between superdeformed states in 195Tl

    International Nuclear Information System (INIS)

    Zheng Xing; Xingqu Chen; Xiaochun Wang

    1996-01-01

    Using a triaxial-particle-rotor model, the quadrupole and dipole transition energies, kinematic and dynamic moments of inertia, electromagnetic transition probabilities and the relative intensity of the E2 γ-transitions are calculated for superdeformed bands in 195 Tl. A strong perturbation effect of rotation on transition energies and M1 and E2 transitions of superdeformed states is investigated. The total M1 transitions, enhanced by internal conversion, are expected to compete strongly with the E2 γ-ray at low spins in the superdeformed 195 Tl nucleus. (author)

  1. Snail regulates p21WAF/CIP1 expression in cooperation with E2 A and Twist

    International Nuclear Information System (INIS)

    Takahashi, Eishi; Funato, Noriko; Higashihori, Norihisa; Hata, Yuiro; Gridley, Thomas; Nakamura, Masataka

    2004-01-01

    Snail, a zinc-finger transcriptional repressor, is essential for mesoderm and neural crest cell formation and epithelial-mesenchymal transition. The basic helix-loop-helix transcription factors E2A and Twist have been linked with Snail during embryonic development. In this study, we examined the role of Snail in cellular differentiation through regulation of p21 WAF/CIP1 expression. A reporter assay with the p21 promoter demonstrated that Snail inhibited expression of p21 induced by E2A. Co-expression of Snail with Twist showed additive inhibitory effects. Deletion mutants of the p21 promoter revealed that sequences between -270 and -264, which formed a complex with unidentified nuclear factor(s), were critical for E2A and Snail function. The E2A-dependent expression of the endogenous p21 gene was also inhibited by Snail

  2. A novel mechanism of E2F1 regulation via nucleocytoplasmic shuttling: determinants of nuclear import and export.

    Science.gov (United States)

    Ivanova, Iordanka A; Vespa, Alisa; Dagnino, Lina

    2007-09-01

    E2F1 is a transcription factor central for cell survival, proliferation, and repair following genomic insult. Depending on the cell type and conditions, E2F1 can induce apoptosis in transformed cells, behaving as a tumour suppressor, or impart growth advantages favouring tumour formation. The pleiotropic functions of E2F1 are a likely consequence of its ability to transcriptionally control a wide variety of target genes, and require tight regulation of its activity at multiple levels. Although sequestration of proteins to particular cellular compartments is a well-established regulatory mechanism, virtually nothing is known about its contribution to modulation of E2F1 target gene expression. We have examined the subcellular trafficking of E2F1 and, contrary to the widely held notion that this factor is constitutively nuclear, we now demonstrate that it is subjected to continuous nucleocytoplasmic shuttling. We have also defined two nuclear localization domains and a nuclear export region, which mediates CRM1-dependent transit out of the nucleus. The predominant subcellular location of E2F1 is likely determined by the balance between the activity of nuclear import and export domains, and can be modulated by differentiation stimuli in epidermal cells. Thus, we have identified a hitherto unrecognized mechanism to control E2F1 function through modulation of its subcellular localization.

  3. Pressure-induced magnetic collapse and metallization of TlF e1.6S e2

    Science.gov (United States)

    Naumov, P. G.; Filsinger, K.; Shylin, S. I.; Barkalov, O. I.; Ksenofontov, V.; Qi, Y.; Palasyuk, T.; Schnelle, W.; Medvedev, S. A.; Greenblatt, M.; Felser, C.

    2017-08-01

    The crystal structure, magnetic ordering, and electrical resistivity of TlF e1.6S e2 were studied at high pressures. Below ˜7 GPa , TlF e1.6S e2 is an antiferromagnetically ordered semiconductor with a ThC r2S i2 -type structure. The insulator-to-metal transformation observed at a pressure of ˜7 GPa is accompanied by a loss of magnetic ordering and an isostructural phase transition. In the pressure range ˜7.5 -11 GPa a remarkable downturn in resistivity, which resembles a superconducting transition, is observed below 15 K. We discuss this feature as the possible onset of superconductivity originating from a phase separation in a small fraction of the sample in the vicinity of the magnetic transition.

  4. 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...

  5. M1 and E2 transitions in the ground-state configuration of atomic ...

    Indian Academy of Sciences (India)

    Pramana – Journal of Physics. Current Issue : Vol. 90, Issue 4 · Current Issue Volume 90 | Issue 4. April 2018. Home · Volumes & Issues · Special Issues · Forthcoming Articles · Search · Editorial Board · Information for Authors · Subscription ...

  6. M1 and E2 transitions in the ground-state configuration of atomic ...

    Indian Academy of Sciences (India)

    2015-11-27

    Proceedings of the International Workshop/Conference on Computational Condensed Matter Physics and Materials Science (IWCCMP-2015). Posted on November 27, 2015. Guest Editors: Anurag Srivastava, C. S. Praveen, H. S. Tewari. © 2015 Indian Academy of Sciences, Bengaluru. Contact | Site index.

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

    Science.gov (United States)

    Muller, Mandy; Jacob, Yves; Jones, Louis; Weiss, Amélie; Brino, Laurent; Chantier, Thibault; Lotteau, Vincent; Favre, Michel; Demeret, Caroline

    2012-01-01

    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.

  8. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Ma, T., E-mail: matao@pmo.ac.cn [Purple Mountain Observatory, Chinese Academy of Sciences, Nanjing 210008 (China); Key Laboratory of dark matter and space astronomy, Chinese Academy of Sciences, Nanjing 210008 (China); 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. [Purple Mountain Observatory, Chinese Academy of Sciences, Nanjing 210008 (China); Key Laboratory of dark matter and space astronomy, Chinese Academy of Sciences, Nanjing 210008 (China); Xu, A.A.; Zhu, M.H. [MACAU University of Science and Technology, Avenida Wai Long, Taipa, Macau (China)

    2013-10-21

    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 LaBr{sub 3} for its main detector, and present its performance in this paper. Moreover, the initial result of Chang'E-2 GRS is reported.

  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. A new convenient access to highly functionalized (E)-2-arylvinyl ...

    Indian Academy of Sciences (India)

    Administrator

    The esterification of phenols using anhydrides or acyl halides as esterifying agent is one of the most routinely used transformation in organic synthesis. While this method was applied in the synthesis of. 4-acyloxy-(E)-2-arylvinyl bromides, the yield was poor mainly due to the formation of by-product un- der condition of acid ...

  12. Astro-E2 education and public outreach program

    Science.gov (United States)

    Mukai, K.; Boyce, K.; Lochner, J.; Harrus, I.; Jacob, B.; Mitchell, S.

    Astro-E2 is a joint Japanese-US X-ray astronomy mission to be launched in early 2005, concentrating on high resolution X-ray spectroscopy. The Astro-E2 team at NASA's Goddard Space Flight Center is implementing an interconnected set of educational activities for this mission, aimed primarily at high school students. The focus of Astro-E2, X-ray spectroscopy, is a challenge and an opportunity: how do we communicate the power of spectroscopy, rather than that of images? We also feature two key technology components of Astro-E2, X-ray optics and cryogenics, as well as the processes of building a satellite, including the cultural aspects of this international collaboration. We have developed a web-based learning center, are producing an educational video, and will host a student competition. We will present the status of, and the plans for, these activities, as well as the lessons we have learned in developing them.

  13. Theory of the (e,2e) reaction on molecules II

    International Nuclear Information System (INIS)

    McCarthy, I.E.

    1975-01-01

    The theory of (e,2e) reactions given in a previous publication is modified in the light of experience with fitting data for atoms and molecules. The molecular orbitals are linear combinations of atomic orbitals in spherical polar coordinates. The general formulation is greatly simplified by using closure over unresolved rotational and vibrational states. Concrete examples of interest are formulated and discussed. (author)

  14. A new convenient access to highly functionalized (E)-2-arylvinyl ...

    Indian Academy of Sciences (India)

    Administrator

    routinely used transformation in organic synthesis. While this method was applied in the synthesis of. 4-acyloxy-(E)-2-arylvinyl bromides, the yield was poor mainly due to the formation of by-product un- der condition of acid or high temperature. In order to avoid the formation of by-product, a mild reaction condition should be ...

  15. Synthesis and characterization of 4-[(E)-(-2,5 ...

    African Journals Online (AJOL)

    The synthesis of 4-[(E)-(-2,5- dimethoxybenzylidene)amino] benzoic acid. Schiff base, SBDAB was carried out inorder to determine its inhibitory efficiency at higher temperature using weight loss and gasometric techniques. The results showed that the inhibition efficiency of the studied Schiff base increased with increase in ...

  16. 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...

  17. 26 CFR 31.3231(e)-2 - Contribution base.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Contribution base. 31.3231(e)-2 Section 31.3231... Contribution base. The term compensation does not include any remuneration paid during any calendar year by an employer to an employee for services rendered in excess of the applicable contribution base. For rules...

  18. Regulation of the retinoblastoma-E2F pathway by the ubiquitin-proteasome system.

    Science.gov (United States)

    Sengupta, Satyaki; Henry, R William

    2015-10-01

    The retinoblastoma tumor suppressor (RB) and its related family members p107 and p130 regulate cell proliferation through the transcriptional repression of genes involved in cellular G1 to S phase transition. However, RB proteins are functionally versatile, and numerous genetic and biochemical studies point to expansive roles in cellular growth control, pluripotency, and apoptotic response. For the vast majority of genes, RB family members target the E2F family of transcriptional activators as an integral component of its gene regulatory mechanism. These interactions are regulated via reversible phosphorylation by Cyclin/Cyclin-dependent kinase (Cdk) complexes, a major molecular mechanism that regulates transcriptional output of RB/E2F target genes. Recent studies indicate an additional level of regulation involving the ubiquitin-proteasome system that renders pervasive control over each component of the RB pathway. Disruption of the genetic circuitry for proteasome-mediated targeting of the RB pathway has serious consequences on development and cellular transformation, and is associated with several forms of human cancer. In this review, we discuss the role of the ubiquitin-proteasome system in proteolytic control of RB-E2F pathway components, and recent data that points to surprising non-proteolytic roles for the ubiquitin-proteasome system in novel transcriptional regulatory mechanisms. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. 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...

  20. Analytical calculation of the vibrator-rotor transition in the sdg interacting boson model

    International Nuclear Information System (INIS)

    Wang Baolin

    1992-01-01

    Analytical calculation of the vibrator-rotor transition is given by utilizing the 1/N expansion technique in the sdg IBM. The phase transition of low-lying energy spectrum and E2 transition for Sm isotopes are calculated

  1. Dosage-dependent copy number gains in E2f1 and E2f3 drive hepatocellular carcinoma

    NARCIS (Netherlands)

    Kent, Lindsey N.; Bae, Sooin; Tsai, Shih-Yin; Tang, Xing; Srivastava, Arunima; Koivisto, Christopher; Martin, Chelsea K.; Ridolfi, Elisa; Miller, Grace C.; Zorko, Sarah M.; Plevris, Emilia; Hadjiyannis, Yannis; Perez, Miguel; Nolan, Eric; Kladney, Raleigh; Westendorp, Bart; de Bruin, Alain; Fernandez, Soledad; Rosol, Thomas J.; Pohar, Kamal S.; Pipas, James M.; Leone, Gustavo

    2017-01-01

    Disruption of the retinoblastoma (RB) tumor suppressor pathway, either through genetic mutation of upstream regulatory components or mutation of RB1 itself, is believed to be a required event in cancer. However, genetic alterations in the RB-regulated E2F family of transcription factors are

  2. Intracervical misoprostol and prostaglandin E2 for labor induction.

    Science.gov (United States)

    Chang, Y-K; Chen, W-H; Yu, M-H; Liu, H-S

    2003-01-01

    To compare the safety and efficacy of misoprostol with PGE(2) for induction of labor by intracervical administration. Eighty-six women with indications for labor induction at term were randomly assigned to two groups. Each woman received either 50 microg of misoprostol or 0.5 mg of prostaglandin E(2) intracervically. If labor was not initiated after 4 h, the same dose was repeated every 4 h to a maximum of 200 microg of misoprostol or 1.5 mg of PGE(2) until adequate labor was achieved. Forty-three women were allocated to the misoprostol group and 43 to the prostaglandin E(2) group. Misoprostol was more effective than PGE(2) in producing cervical changes (Pintracervical misoprostol is more effective in cervical ripening and labor induction at term. The higher frequency of uterine hypercontractility associated with the use of misoprostol did not increase the risk of adverse intrapartum and neonatal outcomes.

  3. 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.

  4. Investigation of generalized overlap amplitudes via (e,2e) spectroscopy

    International Nuclear Information System (INIS)

    Williams, G.R.J.; McCarthy, I.E.; Weigold, E.

    1976-11-01

    The (e,2e) reaction has previously been shown to be an extremely direct and accurate measure of the overlap of the wave function of a target molecule with that of different resolved electronic states of the positive ion resulting from electron knockout. The present paper discusses the reaction in relation to the direct computation of the structure overlaps for different ion states as the generalized overlap amplitudes appearing in the spectral resolution of the one-particle Green's function. The case of water is used to illustrate the effectiveness of the Green's function technique for calculating (e,2e) cross sections of the principal ion states and the use of the reaction as a very sensitive measure of the long-range charge density. (Author)

  5. Chimeric homeobox gene E2A-PBX1 induces proliferation, apoptosis, and malignant lymphomas in transgenic mice.

    Science.gov (United States)

    Dedera, D A; Waller, E K; LeBrun, D P; Sen-Majumdar, A; Stevens, M E; Barsh, G S; Cleary, M L

    1993-09-10

    Expression of the homeobox fusion gene E2A-PBX1 under control of the immunoglobulin heavy chain enhancer efficiently induced malignancies in transgenic mice. All animals died before 5 months of age with lymphomas that demonstrated phenotypes consistent with transitional intermediate thymocytes (CD4+/CD8+/CD3med). E2A-PBX1 also markedly altered lymphoid development in pretumorous animals, reducing the number of thymocytes and bone marrow B lineage progenitors to 20% of normal levels. In spite of the observed reductions in lymphoid cells, premalignant animals contained significantly increased numbers of cycling thymocytes, but a higher proportion was also undergoing apoptosis, suggesting that increased cell death resulted in the marked lymphopenias. These data indicate that the chimeric homeodomain protein E2A-PBX1 paradoxically induces both proliferation and apoptosis in lymphoid cells, suggesting an in vivo association between nuclear oncogene-induced cell cycle progression and programed cell death.

  6. Inhibition of Nitric Oxide and Prostaglandin E 2 Expression by ...

    African Journals Online (AJOL)

    Inhibition of Nitric Oxide and Prostaglandin E2 Expression by Methanol Extract of Polyopes affinis in Lipopolysaccharide-stimulated BV2 Microglial Cells through Suppression of Akt-dependent NF-kB Activity and MAPK Pathway. RGPT Jayasooriya, Y-J Jang, C-H Kang, MG Dilshara, D-O Moon, T-J Nam, YH Choi, G-Y Kim ...

  7. Irradiation And Papillomavirus E2 Proteins On Hela Cells

    International Nuclear Information System (INIS)

    Abderrafi, B.

    2005-01-01

    Exposure to relatively high doses ionizing radiation activates cellular responses that impair cell survival. These responses, for which the p53 protein plays a central role, form the basis for cancer radiotherapy. However, the efficacy of radiation treatments on cell killing is often reduced as a consequence of the frequent inactivation of the p53 protein in cancer cells. Loss of p53 protein is associated with later stages of most human tumors and resistance to anticancer agents. Carcinomas are frequent malignant tumors in humans. The majority of cervical carcinomas are etiologically linked to the presence of HPV virus (Human Papillomavirus). In carcinoma tumor cells, as well as in their derived-cell lines such as HeLa cells, the p53 protein is generally not detected due to its degradation by the product of the HPV-associated oncogenic E6 gene. Another characteristic of HPV-positive cervical cancer cells is the loss of the regulatory viral E2 gene expression as a consequence of viral DNA integration into the cellular genome. Reintroduction of E2 expression in HeLa cells reactivates p53, due to a negative effect on the expression of E6 protein, with a concomitant arrest of cell proliferation at the phase G1 of the cell cycle and delay in cell division via the repression of E2F-target genes. To elucidate whether reactivation of p53 would improve the cell killing effect of ionizing radiation in cancer cells, we studied the combined effects of radiation and E2 expression on the cell cycle distribution in HeLa cells

  8. Structural, vibrational, and electrical properties of 1 T -TiT e2 under hydrostatic pressure: Experiments and theory

    Science.gov (United States)

    Rajaji, V.; Dutta, Utpal; Sreeparvathy, P. C.; Sarma, Saurav Ch.; Sorb, Y. A.; Joseph, B.; Sahoo, Subodha; Peter, Sebastian C.; Kanchana, V.; Narayana, Chandrabhas

    2018-02-01

    We report the structural, vibrational, and electrical transport properties up to ˜16 GPa of 1 T -TiT e2 , a prominent layered 2D system. We clearly show signatures of two isostructural transitions at ˜2 GPa and ˜4 GPa obtained from the minima in c /a ratio concomitant with the phonon linewidth anomalies of Eg and A1 g modes around the same pressures, providing a strong indication of unusual electron-phonon coupling associated with these transitions. Resistance measurements present nonlinear behavior over similar pressure ranges shedding light on the electronic origin of these pressure-driven isostructural transitions. These multiple indirect signatures of an electronic transition at ˜2 GPa and ˜4 GPa are discussed in connection with the recent theoretical proposal for 1 T -TiT e2 and also the possibility of an electronic topological transition from our electronic Fermi surface calculations. Between 4 GPa and ˜8 GPa , the c /a ratio shows a plateau suggesting a transformation from an anisotropic 2D layer to a quasi-3D crystal network. First-principles calculations suggest that the 2D to quasi-3D evolution without any structural phase transitions is mainly due to the increased interlayer Te-Te interactions (bridging) via the charge density overlap. In addition, we observed a first-order structural phase transition from the trigonal (P 3 ¯m 1 ) to monoclinic (C 2 /m ) phase at higher pressure regions. We estimate the start of this structural phase transition to be ˜8 GPa and also the coexistence of two phases [trigonal (P 3 ¯m 1 ) and monoclinic (C 2 /m )] was observed from ˜8 GPa to ˜16 GPa .

  9. 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

  10. E2F-dependent accumulation of hEmi1 regulates S phase entry by inhibiting APC(Cdh1)

    DEFF Research Database (Denmark)

    Hsu, Jerry Y; Reimann, Julie D R; Sørensen, Claus S

    2002-01-01

    . At the G1-S transition, hEmi1 is transcriptionally induced by the E2F transcription factor, much like cyclin A. hEmi1 overexpression accelerates S phase entry and can override a G1 block caused by overexpression of Cdh1 or the E2F-inhibitor p105 retinoblastoma protein (pRb). Depleting cells of hEmi1...

  11. Towards a direct numerical solution of Schroedinger's equation for (e, 2e) reactions

    International Nuclear Information System (INIS)

    Jones, S.; Stelbovics, A.T.

    1999-01-01

    The finite-difference method for electron-hydrogen scattering is presented in a simple, easily understood form for a model collision problem in which all angular momentum is neglected. The model Schroedinger equation is integrated outwards from the atomic centre on a grid of fixed spacing h. The number of difference equations is reduced each step outwards using an algorithm due to Poet, resulting in a propagating solution of the partial-differential equation. By imposing correct asymptotic boundary conditions on this general, propagating solution, the particular solution that physically corresponds to scattering is obtained along with the scattering amplitudes. Previous works using finite differences (and finite elements) have extracted scattering amplitudes only for low-level transitions (elastic scattering and n = 2 excitation). If we are to eventually extract ionisation amplitudes, however, the numerical method must remain stable for higher-level transitions. Here we report converged cross sections for transitions up to n = 8, as a first step towards obtaining ionisation (e, 2e) results. Copyright (1999) CSIRO Australia

  12. 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...... of a family of proteins....

  13. High-precision B(E2) measurements of semi-magic 58,60,62,64Ni by Coulomb excitation

    Energy Technology Data Exchange (ETDEWEB)

    Allmond, James M [ORNL; Brown, Alex [National Superconducting Cyclotron Laboratory (NSCL), Michigan State University; Stuchbery, Andrew E [ORNL; Galindo-Uribarri, Alfredo {nmn} [ORNL; Padilla-Rodal, Elizabeth [Universidad Nacional Autonoma de Mexico (UNAM); Radford, David C [ORNL; Batchelder, J. C. [Oak Ridge Associated Universities (ORAU); Howard, Meredith E [ORNL; Liang, J Felix [ORNL; Manning, Brett M [ORNL; Varner Jr, Robert L [ORNL; Yu, Chang-Hong [ORNL

    2014-01-01

    High-precision reduced electric-quadrupole transition probabilities B(E2) have been measured from single-step Coulomb excitation of semi-magic 58,60,62,64 Ni (Z = 28) beams at 1.8 MeV per nucleon on a natural carbon target. The energy loss of the nickel beams through the carbon target were directly measured with a zero-degree Bragg detector and the absolute B(E2) values were normalized by Rutherford scattering. The B(E2) values disagree with recent lifetime studies that employed the Doppler-shift attenuation method. The present high-precision B(E2) values reveal an asymmetry about 62 Ni, midshell between N = 28 and 40, with larger values towards 56 Ni (Z = N = 28). The experimental B(E2) values are compared with shell-model calculations in the full pf model space and the results indicate a soft 56 Ni core.

  14. Critical role for a single leucine residue in leukemia induction by E2A-PBX1.

    Science.gov (United States)

    Bayly, Richard; Murase, Takayuki; Hyndman, Brandy D; Savage, Rachel; Nurmohamed, Salima; Munro, Kim; Casselman, Richard; Smith, Steven P; LeBrun, David P

    2006-09-01

    In roughly 5% of cases of acute lymphoblastic leukemia, a chromosomal translocation leads to expression of the oncogenic protein E2A-PBX1. The N-terminal portion of E2A-PBX1, encoded by the E2A gene, is identical in sequence to the corresponding portion of the E proteins E12/E47 and includes transcriptional activation domains. The C terminus consists of most of the HOX interacting transcription factor PBX1, including its DNA-binding homeodomain. Structure-function correlative experiments have suggested that oncogenesis by E2A-PBX1 requires an activation domain, called AD1, at the extreme N terminus. We recently demonstrated that a potentially helical portion of AD1 interacts directly with the transcriptional coactivator protein cyclic AMP response element-binding protein (CBP) and that this interaction is essential in the immortalization of primary bone marrow cells in tissue culture. Here we show that a conserved LXXLL motif within AD1 is required in the interaction between E2A-PBX1 and the KIX domain of CBP. We show by circular dichroism spectroscopy that the LXXLL-containing portion of AD1 undergoes a helical transition upon interacting with the KIX domain and that amino acid substitutions that prevent helix formation prevent both the KIX interaction and cell immortalization by E2A-PBX1. Perhaps most strikingly, substitution of a single, conserved leucine residue (L20) within the LXXLL motif impairs leukemia induction in mice after transplantation with E2A-PBX1-expressing bone marrow. The KIX domain of CBP mediates well-characterized interactions with several transcription factors of relevance to leukemia induction. Circumstantial evidence suggests that the side chain of L20 might interact with a deep hydrophobic pocket in the KIX domain. Therefore, our results serve to identify a potential new drug target.

  15. Transitional Justice

    DEFF Research Database (Denmark)

    Gissel, Line Engbo

    This presentation builds on an earlier published article, 'Contemporary Transitional Justice: Normalising a Politics of Exception'. It argues that the field of transitional justice has undergone a shift in conceptualisation and hence practice. Transitional justice is presently understood...... to be the provision of ordinary criminal justice in contexts of exceptional political transition....

  16. Transcription factors E2F1 and E2F3 are expressed in placenta but do not regulate MMP14.

    Science.gov (United States)

    Kaitu'u-Lino, T J; Hastie, R; Cannon, P; Nguyen, H; Lee, S; Hannan, N J; Tong, S

    2015-08-01

    Preeclampsia is a serious complication of pregnancy for which there are no efficacious medical treatments. Soluble endoglin is as an anti-angiogenic factor that contributes to the pathogenesis of the disease, however little is known about its molecular regulation in placenta. Recent data has demonstrated E2F transcription factors directly regulate MMPs in metastatic disease. Of particular interest was the capacity of E2F1 and E2F3 to up-regulate MMP14, a protease that cleaves and releases soluble endoglin from placenta. The aim of this study was to characterize E2F1 and E2F3 in preeclamptic placenta and assess whether silencing affects soluble endoglin release. E2F1 and E2F3 mRNA, protein expression and localization were assessed in severe early onset preeclamptic and preterm control placentas (delivered placentas, while E2F3 was unchanged. Silencing E2F1 did not decrease MMP14 expression in primary trophoblast or endothelial cells. However, E2F1 silencing resulted in a significant increase in soluble endoglin secretion from both cell types, and silencing of E2F3 also significantly increased soluble endoglin release from primary trophoblast. This study demonstrates that E2F1 and E2F3 are present within the syncytiotrophoblast of placenta and that E2F1 is reduced in preeclampsia. Although silencing of either E2F1 or E2F3 does not alter MMP14 expression, both appear to regulate soluble endoglin release. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. 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.

  18. Evaluation of E2 form factor = 24Mg

    International Nuclear Information System (INIS)

    Marinelli, J.R.; Moreira, J.R.

    1988-11-01

    Longitudinal and transverse electron scattering form factors for the 2 + state at 1.37 Mev of the 24 Mg nucleus was evaluated with rotational model wavefunctions. Four different approaches were used for the transverse E2 form factor: PHF, cranking model, ridig rotor and irrotational flow. For the nuclear intrinsic wavefunction, the Nilsson model was assumed in all approaches yielding the calculation of the form factor in PWBA and DWBA. The results are discussed and compared with a recent measurement performed with 180 0 electron scattered from this state. The DWBA calculation, taking into account first order corrections shows that PHF and irrotational flow models give the best agreements with the available data and compete in quality with more complex calculation performed under the 'shell model' approach. (author) [pt

  19. A novel alphaherpesvirus associated with fatal diseases in banded Penguins.

    Science.gov (United States)

    Pfaff, Florian; Schulze, Christoph; König, Patricia; Franzke, Kati; Bock, Sabine; Hlinak, Andreas; Kämmerling, Jens; Ochs, Andreas; Schüle, André; Mettenleiter, Thomas C; Höper, Dirk; Beer, Martin

    2017-01-01

    A novel avian alphaherpesvirus, preliminarily designated sphenicid alphaherpesvirus 1 (SpAHV-1), has been independently isolated from juvenile Humboldt and African penguins (Spheniscus humboldti and Spheniscus demersus) kept in German zoos suffering from diphtheroid oropharyngitis/laryngotracheitis and necrotizing enteritis (collectively designated as penguin-diphtheria-like disease). High-throughput sequencing was used to determine the complete genome sequences of the first two SpAHV-1 isolates. SpAHV-1 comprises a class D genome with a length of about 164 kbp, a G+C content of 45.6 mol% and encodes 86 predicted ORFs. Taxonomic association of SpAHV-1 to the genus Mardivirus was supported by gene content clustering and phylogenetic analysis of herpesvirus core genes. The presented results imply that SpAHV-1 could be the primary causative agent of penguin-diphtheria-like fatal diseases in banded penguins. These results may serve as a basis for the development of diagnostic tools in order to investigate similar cases of penguin diphtheria in wild and captive penguins.

  20. Compact Magic-T using microstrip-slotline transitions

    Science.gov (United States)

    U-Yen, Kongpop (Inventor); Wollack, Edward J. (Inventor); Doiron, Terence (Inventor); Moseley, Samuel H. (Inventor)

    2010-01-01

    The design of a compact low-loss Magic-T is described. The planar Magic-T incorporates a compact microstrip-slotline tee junction and small microstrip-slotline transition area to reduce slotline radiation. The Magic-T produces broadband in-phase and out-of-phase power combiner/divider responses, has low in-band insertion loss, and small in-band phase and amplitude imbalance.

  1. The evolution of B(E2) values around the doubly-magic nucleus {sup 132}Sn

    Energy Technology Data Exchange (ETDEWEB)

    Behrens, Thomas

    2009-08-24

    In this work the evolution of B(E2) values in nuclei around the N=82 shell closure has been studied. The reduced transition strength between ground state and rst excited 2{sup +} state is a good indicator for the collectivity in even-even nuclei. Former experimental and theoretical investigations of the region above N=82 indicated that the B(E2) values might be systematically lower than expected and questioned the current understanding of collective excitations. Since the experimental data concerning the proposed N=82 shell quenching for nuclei below {sup 132}Sn is not yet conclusive, a systematic investigation of neutron-rich nuclei both below and above this shell closure has been performed at the Radioactive Ion Beam Facility REX-ISOLDE at CERN. The B(E2) values of {sup 122-126}Cd (N<82) and {sup 138-144}Xe (N>82) have been measured by Coulomb excitation in inverse kinematics, applying the MINIBALL {gamma}-detector array. The values of {sup 124,126}Cd and {sup 138,142,144}Xe have been determined for the first time, whereas for {sup 140}Xe the ambiguity of the two contradicting published B(E2) values has been solved. The relative uncertainty of the B(E2) value of {sup 122}Cd could be reduced significantly. For {sup 140,142}Xe the Coulomb excitation cross section for the 2{sub 1}{sup +}{yields}4{sub 1}{sup +} transition has also been determined. Further, the deorientation e ect and the influence of the quadrupole deformation on the Coulomb excitation cross section have been taken into account for {sup 138-142}Xe. It could be shown that the latter plays an important role for the determination of the B(E2) values. Assuming only a small or even vanishing quadrupole moment, all measured B(E2) values agree with the expectations and no sign for a quenching of the N=82 gap could be seen. (orig.)

  2. Magnetic imaging of antiferromagnetic and superconducting phases in R bxF e2 -yS e2 crystals

    Science.gov (United States)

    Hazi, J.; Mousavi, T.; Dudin, P.; van der Laan, G.; Maccherozzi, F.; Krzton-Maziopa, A.; Pomjakushina, E.; Conder, K.; Speller, S. C.

    2018-02-01

    High-temperature superconducting (HTS) cuprate materials, with the ability to carry large electrical currents with no resistance at easily reachable temperatures, have stimulated enormous scientific and industrial interest since their discovery in the 1980's. However, technological applications of these promising compounds have been limited by their chemical and microstructural complexity and the challenging processing strategies required for the exploitation of their extraordinary properties. The lack of theoretical understanding of the mechanism for superconductivity in these HTS materials has also hindered the search for new superconducting systems with enhanced performance. The unexpected discovery in 2008 of HTS iron-based compounds has provided an entirely new family of materials for studying the crucial interplay between superconductivity and magnetism in unconventional superconductors. Alkali-metal-doped iron selenide (AxF e2 -yS e2 , A =alkali metal ) compounds are of particular interest owing to the coexistence of superconductivity at relatively high temperatures with antiferromagnetism. Intrinsic phase separation on the mesoscopic scale is also known to occur in what were intended to be single crystals of these compounds, making it difficult to interpret bulk property measurements. Here, we use a combination of two advanced microscopy techniques to provide direct evidence of the magnetic properties of the individual phases. First, x-ray linear dichroism studies in a photoelectron emission microscope, and supporting multiplet calculations, indicate that the matrix (majority) phase is antiferromagnetic whereas the minority phase is nonmagnetic at room temperature. Second, cryogenic magnetic force microscopy demonstrates unambiguously that superconductivity occurs only in the minority phase. The correlation of these findings with previous microstructural studies and bulk measurements paves the way for understanding the intriguing electronic and magnetic

  3. Cyclin E-induced S phase without activation of the pRb/E2F pathway

    DEFF Research Database (Denmark)

    Lukas, J; Herzinger, T; Hansen, Klaus

    1997-01-01

    In cells of higher eukaryotes, cyclin D-dependent kinases Cdk4 and Cdk6 and, possibly, cyclin E-dependent Cdk2 positively regulate the G1- to S-phase transition, by phosphorylating the retinoblastoma protein (pRb), thereby releasing E2F transcription factors that control S-phase genes. Here we...... performed microinjection and transfection experiments using rat R12 fibroblasts, their derivatives conditionally overexpressing cyclins D1 or E, and human U-2-OS cells, to explore the action of G1 cyclins and the relationship of E2F and cyclin E in S-phase induction. We demonstrate that ectopic expression...... that the cyclin E-induced S phase and completion of the cell division cycle can occur in the absence of E2F-mediated transactivation. Together with the ability of cyclin E to overcome a G1 block induced by expression of dominant-negative mutant DP-1, a heterodimeric partner of E2Fs, these results provide evidence...

  4. Darier disease mutation E917K/E918K of SERCA causes accumulation of the E2 form

    DEFF Research Database (Denmark)

    Mikkelsen, Stine; Holdensen, Anne Nyholm; Vilsen, Bente

    2011-01-01

    sensitivity as E918K, thus supporting the proposal that mutual repulsion between the side chains (now negative) in E1 causes accumulation of E2. Moreover the swop mutation E918R/R819E led to gain of function with respect to vanadate affinity. The Na+,K+-ATPase residue at the position corresponding to E917/E......918 of SERCA is an arginine, which interacts with the C-terminus. The effects of adding the Na+,K+-ATPase C-terminus to wild-type SERCA1a and E918R will also be presented....... of the E2 to E1 conformational transition. A comparison of the crystal structures of SERCA1a in E1 and E2 conformations indicate that E918 bonds to R819 of the L6-7 loop in E1 (2-3 Å distance), but not in E2 (9-10 Å distance), suggesting that the E918K mutation destabilizes the E1 conformation by mutual...

  5. 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

  6. Regulation of prostaglandin E2 synthesis after brain irradiation

    International Nuclear Information System (INIS)

    Moore, Amy H.; Olschowka, John A.; Williams, Jacqueline P.; Okunieff, Paul; O'Banion, M. Kerry

    2005-01-01

    Purpose: A local tissue reaction, termed neuroinflammation, occurs after irradiation of brain tissue. Previous work suggested that cyclooxygenase (COX)-2 activity was important for changes in gene expression associated with neuroinflammation as well as increased prostaglandin E 2 (PGE 2 ) levels seen after radiation treatment. Methods and materials: To begin to determine the contributions of other enzymes involved in PGE 2 production, we examined protein levels of COX-1 and COX-2 as well as 2 PGE synthases (membrane and cytosolic PGES) 4 h after 35 Gy single dose irradiation to the brains of C3HeN mice. We also evaluated the effects of specific COX inhibitors on PGE 2 production and PGES expression. Results: As expected, COX-2 expression increased after radiation exposure. Brain irradiation also increased tissue protein levels for both PGES isoforms. Specific COX-2 inhibition with NS398 lowered brain PGE 2 levels by about 60%. Surprisingly, COX-1 inhibition with SC560 completely prevented the elevation of PGE 2 seen after irradiation. Interestingly, NS398 reduced the membrane-associated PGES isoform, whereas SC560 treatment lowered cytosolic isoform levels below those seen in unirradiated controls. Conclusions: Taken together, these data indicate that both cyclooxygenases contribute to PGE 2 production in irradiated brain and reveal dependence of PGES isoforms expression on specific cyclooxygenase activities

  7. Prevotella intermedia induces prostaglandin E2 via multiple signaling pathways.

    Science.gov (United States)

    Guan, S-M; Fu, S-M; He, J-J; Zhang, M

    2011-01-01

    Prostaglandin E(2) (PGE(2)) plays important roles in the bone resorption of inflammatory diseases such as rheumatoid arthritis and periodontitis via specific prostaglandin receptors (i.e., EP1-EP4). In this study, the authors examined whether Prevotella intermedia regulates PGE(2) production and EP expression in human periodontal ligament fibroblasts (hPDLs); they also explored the potential signaling pathways involved in PGE(2) production. P. intermedia induced PGE(2) production and cyclooxygenase-2 (COX-2) expression in a dose- and time-dependent manner. Indomethacin and NS-398 completely abrogated the P. intermedia-induced PGE(2) production without modulating COX-2 expression. Specific inhibitors of extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38, phosphatidylinositol 3-kinase, and protein kinase C--but not c-AMP and protein kinase A--significantly attenuated the P. intermedia-induced COX-2 and PGE(2) expression. P. intermedia reduced EP1 expression in a concentration- and time-dependent manner. The results indicate that the COX-2-dependent induction of PGE(2) by P. intermedia in hPDLs is mediated by multiple signaling pathways.

  8. Epigenetic involvement of Alien/ESET complex in thyroid hormone-mediated repression of E2F1 gene expression and cell proliferation

    International Nuclear Information System (INIS)

    Hong, Wei; Li, Jinru; Wang, Bo; Chen, Linfeng; Niu, Wenyan; Yao, Zhi; Baniahmad, Aria

    2011-01-01

    Highlights: ► Corepressor Alien interacts with histone methyltransferase ESET in vivo. ► Alien/ESET complex is recruited to nTRE of T3-responsive gene by liganded TRβ1. ► ESET-mediated H3K9 methylation is required for liganded TRβ1-repressed transcription. ► ESET is involved in T3-repressed G1/S phase transition and proliferation. -- Abstract: The ligand-bound thyroid hormone receptor (TR) is known to repress via a negative TRE (nTRE) the expression of E2F1, a key transcription factor that controls the G1/S phase transition. Alien has been identified as a novel interacting factor of E2F1 and acts as a corepressor of E2F1. The detailed molecular mechanism by which Alien inhibits E2F1 gene expression remains unclear. Here, we report that the histone H3 lysine 9 (H3K9) methyltransferase (HMT) ESET is an integral component of the corepressor Alien complex and the Alien/ESET complex is recruited to both sites, the E2F1 and the nTRE site of the E2F1 gene while the recruitment to the negative thyroid hormone response element (nTRE) is induced by the ligand-bound TRβ1 within the E2F1 gene promoter. We show that, overexpression of ESET promotes, whereas knockdown of ESET releases, the inhibition of TRβ1-regulated gene transcription upon T3 stimulation; and H3K9 methylation is required for TRβ1-repressed transcription. Furthermore, depletion of ESET impairs thyroid hormone-repressed proliferation as well as the G1/S transition of the cell cycle. Taken together, our data indicate that ESET is involved in TRβ1-mediated transcription repression and provide a molecular basis of thyroid hormone-induced repression of proliferation.

  9. Supporting Transition

    Science.gov (United States)

    Qureshi, Asima; Petrucco, James

    2018-01-01

    Meadowbrook Primary School has explored the use of The Teacher Assessment in Primary Science (TAPS) to support transition, initially for transfer to secondary school and now for transition from Early Years Foundation Stage (EYFS) into Key Stage 1 (ages 5-7). This article will consider an example of a secondary transition project and discuss the…

  10. K-forbidden transition probabilities

    International Nuclear Information System (INIS)

    Saitoh, T.R.; Sletten, G.; Bark, R.A.; Hagemann, G.B.; Herskind, B.; Saitoh-Hashimoto, N.; Tsukuba Univ., Ibaraki

    2000-01-01

    Reduced hindrance factors of K-forbidden transitions are compiled for nuclei with A∝180 where γ-vibrational states are observed. Correlations between these reduced hindrance factors and Coriolis forces, statistical level mixing and γ-softness have been studied. It is demonstrated that the K-forbidden transition probabilities are related to γ-softness. The decay of the high-K bandheads has been studied by means of the two-state mixing, which would be induced by the γ-softness, with the use of a number of K-forbidden transitions compiled in the present work, where high-K bandheads are depopulated by both E2 and ΔI=1 transitions. The validity of the two-state mixing scheme has been examined by using the proposed identity of the B(M1)/B(E2) ratios of transitions depopulating high-K bandheads and levels of low-K bands. A break down of the identity might indicate that other levels would mediate transitions between high- and low-K states. (orig.)

  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. The First Human Epitope Map of the Alphaviral E1 and E2 Proteins Reveals a New E2 Epitope with Significant Virus Neutralizing Activity

    OpenAIRE

    Hunt, Ann R.; Frederickson, Shana; Maruyama, Toshiaki; Roehrig, John T.; Blair, Carol D.

    2010-01-01

    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 (E2c,d,e,f,g,h) bound VEEV-neutralizing antibody and mapped to amino acids (aa) 182–207. Nothing is ...

  14. 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...... binding domains. Acetylation of E2F-1 in vitro and in vivo markedly increases its binding affinity for a consensus E2F DNA-binding site, which is paralleled by enhanced transactivation of an E2F-responsive promoter. Acetylation of E2F-1 can be reversed by histone deacetylase-1, indicating that reversible...

  15. Intermediate-spin states of 92Zr and a large B (E 2 ) value between the 101+ and 81+ states

    Science.gov (United States)

    Sugawara, M.; Toh, Y.; Koizumi, M.; Oshima, M.; Kimura, A.; Kin, T.; Hatsukawa, Y.; Kusakari, H.

    2017-08-01

    This study investigated intermediate-spin states of 92Zr via the inverse reaction 9Be(3 n 76Kr)92Zr . Seven transitions were newly observed, and a lifetime was extracted for the 101+ state by analysis of Doppler-broadened line shapes of decay γ rays. A large B (E 2 ) value was obtained for the transition from 101+ to 81+, and the magnitude was comparable to that for the deformed excited configurations in 94Zr that have recently been established. A possible origin for such collectivity is discussed qualitatively based on a phenomenological deformed rotor model. Moreover, a multipletlike structure that fits into the systematics for N =52 even-A isotones is revealed for the negative-parity yrast states.

  16. Transition radiation and transition scattering

    International Nuclear Information System (INIS)

    Ginzburg, V.L.

    1982-01-01

    Transition radiation is a process of a rather general character. It occurs when some source, which does not have a proper frequency (for example, a charge) moves at a constant velocity in an inhomogeneous and (or) nonstationary medium or near such a medium. The simplest type of transition radiation takes place when a charge crosses a boundary between two media (the role of one of the media may be played by vacuum). In the case of periodic variation of the medium, transition radiation possesses some specific features (resonance transition radiation or transition scattering). Transition scattering occurs, in particular, when a permittivity wave falls onto an nonmoving (fixed) charge. Transition scattering is closely connected with transition bremsstrahlung radiation. All these transition processes are essential for plasma physics. Transition radiation and transition scattering have analogues outside the framework of electrodynamics (like in the case of Vavilov-Cherenkov radiation). In the present report the corresponding range of phenomena is elucidated, as far as possible, in a generally physical aspect. (Auth.)

  17. Transformation properties of the E2a-Pbx1 chimeric oncoprotein: fusion with E2a is essential, but the Pbx1 homeodomain is dispensable.

    Science.gov (United States)

    Monica, K; LeBrun, D P; Dedera, D A; Brown, R; Cleary, M L

    1994-12-01

    The t(1;19) chromosomal translocation in acute lymphoblastic leukemias creates chimeric E2a-Pbx1 oncoproteins that can act as DNA-binding activators of transcription. A structural analysis of the functional domains of E2a-Pbx1 showed that portions of both E2a and Pbx1 were essential for transformation of NIH 3T3 cells and transcriptional activation of synthetic reporter genes containing PBX1 consensus binding sites. Hyperexpression of wild-type or experimentally truncated Pbx1 proteins was insufficient for transformation, consistent with their inability to activate transcription. When fused with E2a, the Pbx-related proteins Pbx2 and Pbx3 were also transformation competent, demonstrating that all known members of this highly similar subfamily of homeodomain proteins have latent oncogenic potential. The oncogenic contributions of E2a to the chimeras were localized to transactivation motifs AD1 and AD2, as their mutation significantly impaired transformation. Either the homeodomain or Pbx1 amino acids flanking this region could mediate transformation when fused to E2a. However, the homeodomain was not essential for transformation, since a mutant E2a-Pbx1 protein (E2a-Pbx delta HD) lacking the homeodomain efficiently transformed fibroblasts and induced malignant lymphomas in transgenic mice. Thus, transformation mediated by the chimeric oncoprotein E2a-Pbx1 is absolutely dependent on motifs acquired from E2a but the Pbx1 homeodomain is optional. The latter finding suggests that E2a-Pbx1 may interact with cellular proteins that assist or mediate alterations in gene expression responsible for oncogenesis even in the absence of homeodomain-DNA interactions.

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

    International Nuclear Information System (INIS)

    Wang, Jimin; Li, Yue; Modis, Yorgo

    2014-01-01

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

  19. 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.

  20. Association of Human Papillomavirus 16 E2 with Rad50-Interacting Protein 1 Enhances Viral DNA Replication.

    Science.gov (United States)

    Campos-León, Karen; Wijendra, Kalpanee; Siddiqa, Abida; Pentland, Ieisha; Feeney, Katherine M; Knapman, Alison; Davies, Rachel; Androphy, Elliot J; Parish, Joanna L

    2017-03-01

    Rad50-interacting protein 1 (Rint1) associates with the DNA damage response protein Rad50 during the transition from the S phase to the G 2 /M phase and functions in radiation-induced G 2 checkpoint control. It has also been demonstrated that Rint1 is essential in vesicle trafficking from the Golgi apparatus to the endoplasmic reticulum (ER) through an interaction with Zeste-White 10 (ZW10). We have isolated a novel interaction between Rint1 and the human papillomavirus 16 (HPV16) transcription and replication factor E2. E2 binds to Rint1 within its ZW10 interaction domain, and we show that in the absence of E2, Rint1 is localized to the ER and associates with ZW10. E2 expression results in a disruption of the Rint1-ZW10 interaction and an accumulation of nuclear Rint1, coincident with a significant reduction in vesicle movement from the ER to the Golgi apparatus. Interestingly, nuclear Rint1 and members of the Mre11/Rad50/Nbs1 (MRN) complex were found in distinct E2 nuclear foci, which peaked during mid-S phase, indicating that the recruitment of Rint1 to E2 foci within the nucleus may also result in the recruitment of this DNA damage-sensing protein complex. We show that exogenous Rint1 expression enhances E2-dependent virus replication. Conversely, the overexpression of a truncated Rint1 protein that retains the E2 binding domain but not the Rad50 binding domain acts as a dominant negative inhibitor of E2-dependent HPV replication. Put together, these experiments demonstrate that the interaction between Rint1 and E2 has an important function in HPV replication. IMPORTANCE HPV infections are an important driver of many epithelial cancers, including those within the anogenital and oropharyngeal tracts. The HPV life cycle is tightly regulated and intimately linked to the differentiation of the epithelial cells that it infects. HPV replication factories formed in the nucleus are locations where viral DNA is copied to support virus persistence and amplification of

  1. Exact Solutions of an Extended Bose-Hubbard Model with E 2 Symmetry

    Science.gov (United States)

    Pan, Feng; Zhang, Ningyun; Wang, Qianyun; Draayer, J. P.

    2015-07-01

    An extended Bose-Hubbard (BH) model with number-dependent multi-site and infinite-range hopping is proposed, which, similar to the original BH model, describes a phase transition between the delocalized superfluid (SF) phase and localized Mott insulator (MI) phase. It is shown that this extended model with local Euclidean E 2 symmetry is exactly solvable when on-site local potentials are included, while the model without local potentials is quasi-exactly solvable, which means only a part of the excited states including the ground state being exactly solvable. As applications of the exact solution for the ground state, phase diagram of the model in 1D without local potential and on-site disorder for filling factor ρ = 1 with M = 6, M = 10, and M = 14 sites are obtained. The ground state probabilities to detect n particles on a single site, P n , for n = 0, 1, 2 as functions of the control parameter U/ t in these cases are also calculated. It is shown that the critical point in P n and in the entanglement measure is away from that of the SF-MI transition determined in the phase analysis. It is also shown that the model-independent entanglement measure is related with P n , which, therefore, may be practically useful because P n is measurable experimentally. The ground state expectation value of local particle numbers, the ground state local particle number fluctuations, the ground state probabilities to detect n particles on every site, and the entanglement measure have also been studied in the model for N = M = 4 with the two-body onsite repulsion and a local confining harmonic potential. The connection between these quantities and the entanglement observed previously is verified.

  2. Plasma lipoproteins in familial dysbetalipoproteinemia associated with apolipoproteins E2 (Arg158 -->Cys), E3-Leiden, and E2 (Lys146-->Gln), and effects of treatment with simvastatin

    NARCIS (Netherlands)

    Zhao, S.P.; Smelt, A.H.; Maagdenberg, A.M. van den; Tol, A. van; Vroom T.F.; Gevers Leuven, J.A.; Frants, R.R.; Havekes, L.M.; Laarse, A. van der; Hooft, F.M. van 't

    1994-01-01

    Using a density-gradient ultracentrifugation technique, we analyzed in detail the plasma lipoprotein profiles of 18 patients with familial dysbetalipoproteinemia (FD) who had apolipoprotein (apo) E2(Arg158-->Cys) homozygosity (the E2-158 variant, n = 6), apoE3-Leiden heterozygosity (the E3-Leiden

  3. E2F4 loss suppresses tumorigenesis in Rb mutant mice.

    Science.gov (United States)

    Lee, Eunice Y; Cam, Hieu; Ziebold, Ulrike; Rayman, Joseph B; Lees, Jacqueline A; Dynlacht, Brian David

    2002-12-01

    The E2F transcription factors mediate the activation or repression of key cell cycle regulatory genes under the control of the retinoblastoma protein (pRB) tumor suppressor and its relatives, p107 and p130. Here we investigate how E2F4, the major "repressive" E2F, contributes to pRB's tumor-suppressive properties. Remarkably, E2F4 loss suppresses the development of both pituitary and thyroid tumors in Rb(+/-) mice. Importantly, E2F4 loss also suppresses the inappropriate gene expression and proliferation of pRB-deficient cells. Biochemical analyses suggest that this tumor suppression occurs via a novel mechanism: E2F4 loss allows p107 and p130 to regulate the pRB-specific, activator E2Fs. We also detect these novel E2F complexes in pRB-deficient cells, suggesting that they play a significant role in the regulation of tumorigenesis in vivo.

  4. 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...

  5. 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

  6. 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...

  7. The chimeric oncoproteins E2A-PBX1 and E2A-HLF are concentrated within spherical nuclear domains.

    Science.gov (United States)

    LeBrun, D P; Matthews, B P; Feldman, B J; Cleary, M L

    1997-10-23

    Oncogenic mutation of nuclear transcription factors often is associated with altered patterns of subcellular localization that may be of functional importance. The leukemogenic transcription factor gene E2A-PBX1 is created through fusion of the genes E2A and PBX1 as a result of t(1;19) in acute lymphoblastic leukemia. We evaluated subcellular localization patterns of E2A-PBX1 protein in transfected cells using immunofluorescence. Full-length E2A-PBX1 was exclusively nuclear and was concentrated in spherical domains denoted chimeric-E2A oncoprotein domains (CODs). In contrast, nuclear fluorescence for wild-type E2A or PBX1 proteins was diffuse. Enhanced concentrations of RNA polymerase II within many CODs and the requirement for an E2A-encoded activation domain suggested transcriptional relevance. However, in situ co-detection of nascent transcripts labeled with bromouridine failed to confirm altered transcriptional activity in relation to CODs. CODs also failed to co-localize with other proteins known to occupy functional nuclear compartments, including the transcription factor PML, the spliceosome-associated protein SC-35 and the adenovirus replication factor DBP, or with foci of DNA replication. Co-transfection of Hoxb7, a homeodomain protein capable of enhancing DNA binding by PBX1, impaired COD formation, suggesting that CODs contain E2A-PBX1 protein not associated with DNA. We conclude that, as a 'gain of function' phenomenon requiring protein elements from both E2A and PBX1, COD formation may be relevant to the biology of E2A-PBX1 in leukemogenesis.

  8. Modification of the intestinal postirradiation proliferative response by intraabdominal H-4-II-E2 tumors

    International Nuclear Information System (INIS)

    Evans, M.J.; Kovacs, C.J.; Schenken, L.L.; Burholt, D.R.

    1981-01-01

    Intraperitoneal injection of H-4-II-E 2 tumor cells gave rise to a number of individually growing intraabdominal tumors concentrated at sites of high abdominal vascularization. During tumor growth, both tumor and intestinal crypt cell proliferative activity were progressively depressed. A linear reduction of [ 3 H]TdR incorporation occurred in individual tumors independent of tumor size, suggesting that total tumor burden determines the proliferative status of individual tumors. Cytokinetic jejunal crypt analyses indicated that both a reduction in crypt cellularity and an abbreviated cell cycle transit time were noted during the depression of proliferative activity in the jejunum. In tumor-bearing rats the migration rate of cells from the jejunal crypt through the villus was reduced in response to a reduction in total cell production in the crypt. The life span of the epithelial cell in both tumor-bearing and normal rats was similar due to a reduction in villus cellularity in the tumor-bearing animals. Following abdominal irradiation of the tumor, the magnitude, but not the time course of hyperproliferative intestinal recovery, was influenced by the tumor mass. For nontumor-bearing animals, maximal hyperproliferation (>200% of control) occurred 96 hr postradiation. With increasing tumor burden the compensatory proliferative response to radiation was progressively reduced

  9. Cyclin E-induced S phase without activation of the pRb/E2F pathway

    DEFF Research Database (Denmark)

    Lukas, J; Herzinger, T; Hansen, Klaus

    1997-01-01

    In cells of higher eukaryotes, cyclin D-dependent kinases Cdk4 and Cdk6 and, possibly, cyclin E-dependent Cdk2 positively regulate the G1- to S-phase transition, by phosphorylating the retinoblastoma protein (pRb), thereby releasing E2F transcription factors that control S-phase genes. Here we...... performed microinjection and transfection experiments using rat R12 fibroblasts, their derivatives conditionally overexpressing cyclins D1 or E, and human U-2-OS cells, to explore the action of G1 cyclins and the relationship of E2F and cyclin E in S-phase induction. We demonstrate that ectopic expression...... of cyclin E, but not cyclin D1, can override G1 arrest imposed by either the p16INK4a Cdk inhibitor specific for Cdk4 and Cdk6 or a novel phosphorylation-deficient mutant pRb. Several complementary approaches to assess E2F activation, including quantitative reporter assays in live cells, showed...

  10. DEPDC1 promotes cell proliferation and tumor growth via activation of E2F signaling in prostate cancer.

    Science.gov (United States)

    Huang, Lin; Chen, Keng; Cai, Zhao-Peng; Chen, Fu-Chao; Shen, Hui-Yong; Zhao, Wei-Hua; Yang, Song-Jie; Chen, Xu-Biao; Tang, Guo-Xue; Lin, Xi

    2017-08-26

    DEP domain containing 1 (DEPDC1) is recently reported to be overexpressed in several types of human cancer; however the role of DEPDC1 in prostate cancer remains to be investigated. Herein, we identified that the DEPDC1 mRNA and protein expression levels were dramatically increased in prostate cancer tissues and cell lines. Overexpression of DEPDC1 promoted, but depletion of DEPDC1 inhibited cell proliferation by regulating the G1-S phase cell cycle transition. Importantly, we found that DEPDC1 was essential for the tumor growth and formation of bone metastases of prostate cancer cells in vivo. Finally, we demonstrated that DEPDC1 interacted with E2F1 and increased its transcriptional activity, leading to hyper-activation of E2F signaling in prostate cancer cells. Our findings reveal an oncogenic role of DEPDC1 in prostate cancer progression via activation of E2F signaling, and suggest DEPDC1 might be a potential therapeutic target against the disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Regulation of cell proliferation by the E2F transcription factors

    DEFF Research Database (Denmark)

    Helin, K

    1998-01-01

    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...

  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 669...

  13. 26 CFR 1.860E-2 - Tax on transfers of residual interests to certain organizations.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 9 2010-04-01 2010-04-01 false Tax on transfers of residual interests to certain organizations. 1.860E-2 Section 1.860E-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Real Estate Investment Trusts § 1.860E-2...

  14. Phase transitions

    CERN Document Server

    Sole, Ricard V; Solé, Ricard V; Solé, Ricard V; Sol, Ricard V; Solé, Ricard V

    2011-01-01

    Phase transitions--changes between different states of organization in a complex system--have long helped to explain physics concepts, such as why water freezes into a solid or boils to become a gas. How might phase transitions shed light on important problems in biological and ecological complex systems? Exploring the origins and implications of sudden changes in nature and society, Phase Transitions examines different dynamical behaviors in a broad range of complex systems. Using a compelling set of examples, from gene networks and ant colonies to human language and the degradation of diverse ecosystems, the book illustrates the power of simple models to reveal how phase transitions occur. Introductory chapters provide the critical concepts and the simplest mathematical techniques required to study phase transitions. In a series of example-driven chapters, Ricard Solé shows how such concepts and techniques can be applied to the analysis and prediction of complex system behavior, including the origins of ...

  15. Labeling of 40 Gbit/s DPSK payload using in-band subcarrier multiplexing

    DEFF Research Database (Denmark)

    Flarup, Thomas; Peucheret, Christophe; Olmos, J. J. Vegas

    2005-01-01

    The transmission feasibility of a 40 Gbit/s DPSK payload with in-band SCM (subcarrier multiplexing) labeling at 3 GHz subcarrier frequency is experimentally verified over 80 km NZDSF (nonzero dispersion shifted fiber).......The transmission feasibility of a 40 Gbit/s DPSK payload with in-band SCM (subcarrier multiplexing) labeling at 3 GHz subcarrier frequency is experimentally verified over 80 km NZDSF (nonzero dispersion shifted fiber)....

  16. Pressure-induced superconductivity up to 13.1 K in the pyrite phase of palladium diselenide PdS e2

    Science.gov (United States)

    ElGhazali, Moaz A.; Naumov, Pavel G.; Mirhosseini, Hossein; Süß, Vicky; Müchler, Lukas; Schnelle, Walter; Felser, Claudia; Medvedev, Sergey A.

    2017-08-01

    The evolution of electrical transport properties, the electronic band structure, and lattice dynamics of PdS e2 is studied under high pressure. The emergence of superconductivity is reported in the high-pressure pyrite-type phase of PdS e2 . In this transition-metal dichalcogenide, the critical temperature of superconductivity rapidly increases with pressure up to 13.1 K. Ab initio electronic band structure calculations indicate the presence of Dirac and nodal-line fermions in the vicinity of the Fermi energy protected by the pyrite structure symmetry, which can lead to interesting superconducting states. Raman spectroscopy shows a direct correlation between critical temperature and bonding strength of Se-Se dumbbells in PdS e2 , underlining the crucial role of bonding for tuning the superconductivity.

  17. Estradiol-17β, prostaglandin E2 (PGE2) and the prostaglandin E2 receptor are involved in PGE2 positive feedback loop in the porcine endometrium

    OpenAIRE

    Waclawik, Agnieszka; Jabbour, Henry N.; Blitek, Agnieszka; Ziecik, Adam J.

    2009-01-01

    Before implantation, the porcine endometrium and trophoblast synthesize elevated amounts of luteoprotective prostaglandin E2 (PGE2). We hypothesized that embryo signal, estradiol-17β (E2) and PGE2 modulate expression of key enzymes in PG synthesis: prostaglandin-endoperoxide synthase-2 (PTGS2), PGE synthase (mPGES-1), PGF synthase (PGFS), and prostaglandin 9-ketoreductase (CBR1); as well as PGE2 receptor (PTGER2 and 4) expression and signaling within the endometrium. We determinated the site ...

  18. Defensive roles of (E)-2-alkenals and related compounds in heteroptera.

    Science.gov (United States)

    Noge, Koji; Prudic, Kathleen L; Becerra, Judith X

    2012-08-01

    We examined whether shared volatiles found in various heteropteran species and developmental stages function to repel predators. The nymphal dorsal abdominal gland secretions of Riptortus pedestris (Heteroptera: Alydidae) and Thasus acutangulus (Heteroptera: Coreidae), and the metathoracic scent gland secretion of Euschistus biformis (Heteroptera: Pentatomidae) adults were identified by gas chromatography/mass spectrometry (GC/MS). (E)-2-Hexenal, 4-oxo-(E)-2-hexenal (4-OHE), and (E)-2-octenal were found in all three species and deemed likely candidates for repelling predators. In addition to (E)-2-alkenals, the adult E. biformis secreted (E)-2-hexenyl acetate, (E)-2-octenyl acetate, and four hydrocarbons. We evaluated the potential predator repellent properties of these compounds and compound blends against a generalist, cosmopolitan insect predator, the Chinese praying mantid (Mantodea: Mantidae: Tenodera aridifolia sinensis). Mantids that experienced (E)-2-hexenal, (E)-2-octenal, and (E)-2-octenyl acetate moved away from the site of interaction, while 4-OHE and (E)-2-hexenyl acetate did not affect mantid behavior. The compound blends did not have additive or synergistic repellency effects on predator behavior. Compound repellency was not related to compound volatility. Instead, the repellent effect is likely related to predator olfaction, and the affinity of each compound to receptors on the antennae. Our results also suggest the repellents might intensify the visual defensive signals of aposematism (T. acutangulus nymphs) and mimicry (R. pedestris nymphs) in heteropteran bugs.

  19. Transcriptional regulation of human RANK ligand gene expression by E2F1

    International Nuclear Information System (INIS)

    Hu Yan; Sun Meng; Nadiminty, Nagalakshmi; Lou Wei; Pinder, Elaine; Gao, Allen C.

    2008-01-01

    Receptor activator of nuclear factor kappa B ligand (RANKL) is a critical osteoclastogenic factor involved in the regulation of bone resorption, immune function, the development of mammary gland and cardiovascular system. To understand the transcriptional regulation of RANKL, we amplified and characterized a 1890 bp 5'-flanking sequence of human RANKL gene (-1782 bp to +108 bp relative to the transcription start site). Using a series of deletion mutations of the 1890 bp RANKL promoter, we identified a 72 bp region (-172 to -100 bp) mediating RANKL basal transcriptional activity. Sequence analysis revealed a putative E2F binding site within this 72 bp region in the human RANKL promoter. Overexpression of E2F1 increased RANKL promoter activity, while down-regulation of E2F1 expression by small interfering RNA decreased RANKL promoter activity. RT-PCR and enzyme linked immunosorbent assays (ELISA) further demonstrated that E2F1 induced the expression of RANKL. Electrophoretic gel mobility shift assays (EMSA) and antibody competition assays confirmed that E2F1 proteins bind to the consensus E2F binding site in the RANKL promoter. Mutation of the E2F consensus binding site in the RANKL promoter profoundly reduced the basal promoter activity and abolished the transcriptional modulation of RANKL by E2F1. These results suggest that E2F1 plays an important role in regulating RANKL transcription through binding to the E2F consensus binding site

  20. Quantum phase transitional patterns of nuclei

    International Nuclear Information System (INIS)

    Dai Lianrong; Wang Lixing; Pan Feng; Zhong Weiwei; Liu Qi

    2013-01-01

    With the framework of Interacting Boson Model (IBM), transitional patterns from the spherical to the axially deformed limit of the IBM with a schematic Hamiltonian are studied by replacing the SU (3) quadrupole-quadrupole term with O (6) cubic interaction. But, we use the two schemes to investigate some energy ratios and B (E2) ratios for different bosons N = 8 and N = 20. The results show that with the increasing of the numbers of bosons, the transitional behaviors can be enhanced; the transitional behaviors are very similar in the two schemes. However, there are some distinctive differences for some quantities across the entire transitional region, such as energy levels and ratios, B (E2) values and ratios, and expectation values of the shape variables. Generally speaking, the transition is smoother and the nuclear shape is less well defined in the new scheme. Then we apply the two schemes to the critical point symmetry candidate, such as 152 Sm, and find the overall fitting quality of the UQ scheme is better than that of the U (5)-SU (3) scheme, especially for the inter-band E2 transitions in 152 Sm. (authors)

  1. Transit transparency.

    Science.gov (United States)

    2012-07-01

    Public transit agencies have employed intelligent systems for determining : schedules and routes and for monitoring the real-time location and status of their : vehicle fleets for nearly two decades. But until recently, the data generated by : daily ...

  2. Differential involvement of E2A-corepressor interactions in distinct leukemogenic pathways.

    Science.gov (United States)

    Gow, Chien-Hung; Guo, Chun; Wang, David; Hu, Qiande; Zhang, Jinsong

    2014-01-01

    E2A is a member of the E-protein family of transcription factors. Previous studies have reported context-dependent regulation of E2A-dependent transcription. For example, whereas the E2A portion of the E2A-Pbx1 leukemia fusion protein mediates robust transcriptional activation in t(1;19) acute lymphoblastic leukemia, the transcriptional activity of wild-type E2A is silenced by high levels of corepressors, such as the AML1-ETO fusion protein in t(8;21) acute myeloid leukemia and ETO-2 in hematopoietic cells. Here, we show that, unlike the HEB E-protein, the activation domain 1 (AD1) of E2A has specifically reduced corepressor interaction due to E2A-specific amino acid changes in the p300/CBP and ETO target motif. Replacing E2A-AD1 with HEB-AD1 abolished the ability of E2A-Pbx1 to activate target genes and to induce cell transformation. On the other hand, the weak E2A-AD1-corepressor interaction imposes a critical importance on another ETO-interacting domain, downstream ETO-interacting sequence (DES), for corepressor-mediated repression. Deletion of DES abrogates silencing of E2A activity by AML1-ETO in t(8;21) leukemia cells or by ETO-2 in normal hematopoietic cells. Our results reveal an E2A-specific mechanism important for its context-dependent activation and repression function, and provide the first evidence for the differential involvement of E2A-corepressor interactions in distinct leukemogenic pathways.

  3. miR-99a reveals two novel oncogenic proteins E2F2 and EMR2 and represses stemness in lung cancer

    Science.gov (United States)

    Feliciano, Andrea; Garcia-Mayea, Yoelsis; Jubierre, Luz; Mir, Cristina; Hummel, Manuela; Castellvi, Josep; Hernández-Losa, Javier; Paciucci, Rosanna; Sansano, Irene; Sun, Yilin; Ramón y Cajal, Santiago; Kondon, Hiroshi; Soriano, Aroa; Segura, Miguel; Lyakhovich, Alex; LLeonart, Matilde E

    2017-01-01

    Lung cancer is one of the most aggressive tumours with very low life expectancy. Altered microRNA expression is found in human tumours because it is involved in tumour growth, progression and metastasis. In this study, we analysed microRNA expression in 47 lung cancer biopsies. Among the most downregulated microRNAs we focussed on the miR-99a characterisation. In vitro experiments showed that miR-99a expression decreases the proliferation of H1650, H1975 and H1299 lung cancer cells causing cell cycle arrest and apoptosis. We identified two novel proteins, E2F2 (E2F transcription factor 2) and EMR2 (EGF-like module-containing, mucin-like, hormone receptor-like 2), downregulated by miR-99a by its direct binding to their 3′-UTR. Moreover, miR-99a expression prevented cancer cell epithelial-to-mesenchymal transition (EMT) and repressed the tumourigenic potential of the cancer stem cell (CSC) population in both these cell lines and mice tumours originated from H1975 cells. The expression of E2F2 and EMR2 at protein level was studied in 119 lung cancer biopsies. E2F2 and EMR2 are preferentially expressed in adenocarcinomas subtypes versus other tumour types (squamous and others). Interestingly, the expression of E2F2 correlates with the presence of vimentin and both E2F2 and EMR2 correlate with the presence of β-catenin. Moreover, miR-99a expression correlates inversely with E2F2 and directly with β-catenin expression in lung cancer biopsies. In conclusion, miR-99a reveals two novel targets E2F2 and EMR2 that play a key role in lung tumourigenesis. By inhibiting E2F2 and EMR2, miR-99a represses in vivo the transition of epithelial cells through an EMT process concomitantly with the inhibition of stemness features and consequently decreasing the CSC population. PMID:29072692

  4. Improved energy of the 21.5 keV M1+E2 nuclear transition in Eu-151

    Czech Academy of Sciences Publication Activity Database

    Inoyatov, A. K.; Kovalík, Alojz; Filosofov, D. V.; Ryšavý, Miloš; Perevoshchikov, L. L.; Baimukhanova, A.

    2016-01-01

    Roč. 52, č. 5 (2016), s. 133 ISSN 1434-6001 R&D Projects: GA ČR(CZ) GAP203/12/1896; GA MŠk LG14004 Institutional support: RVO:61389005 Keywords : electron binding energies * internal conversion * Gd-151 Subject RIV: BG - Nuclear, Atomic and Molecular Physics, Colliders Impact factor: 2.833, year: 2016

  5. Direct fluorescence detection of VirE2 secretion by Agrobacterium tumefaciens.

    Science.gov (United States)

    Yaakov, Noga; Barak, Yoav; Pereman, Idan; Christie, Peter J; Elbaum, Michael

    2017-01-01

    VirE2 is a ssDNA binding protein essential for virulence in Agrobacterium tumefaciens. A tetracysteine mutant (VirE2-TC) was prepared for in vitro and in vivo fluorescence imaging based on the ReAsH reagent. VirE2-TC was found to be biochemically active as it binds both ssDNA and the acidic secretion chaperone VirE1. It was also biologically functional in complementing virE2 null strains transforming Arabidopsis thaliana roots and Nicotiana tabacum leaves. In vitro experiments demonstrated a two-color fluorescent complex using VirE2-TC/ReAsH and Alexa Fluor 488 labeled ssDNA. In vivo, fluorescent VirE2-TC/ReAsH was detected in bacteria and in plant cells at time frames relevant to transformation.

  6. Direct fluorescence detection of VirE2 secretion by Agrobacterium tumefaciens

    Science.gov (United States)

    Yaakov, Noga; Barak, Yoav; Pereman, Idan; Christie, Peter J.; Elbaum, Michael

    2017-01-01

    VirE2 is a ssDNA binding protein essential for virulence in Agrobacterium tumefaciens. A tetracysteine mutant (VirE2-TC) was prepared for in vitro and in vivo fluorescence imaging based on the ReAsH reagent. VirE2-TC was found to be biochemically active as it binds both ssDNA and the acidic secretion chaperone VirE1. It was also biologically functional in complementing virE2 null strains transforming Arabidopsis thaliana roots and Nicotiana tabacum leaves. In vitro experiments demonstrated a two-color fluorescent complex using VirE2-TC/ReAsH and Alexa Fluor 488 labeled ssDNA. In vivo, fluorescent VirE2-TC/ReAsH was detected in bacteria and in plant cells at time frames relevant to transformation. PMID:28403156

  7. Identification of novel target genes specifically activated by deregulated E2F in human normal fibroblasts.

    Science.gov (United States)

    Kitamura, Hodaka; Ozono, Eiko; Iwanaga, Ritsuko; Bradford, Andrew P; Okuno, Junko; Shimizu, Emi; Kurayoshi, Kenta; Kugawa, Kazuyuki; Toh, Hiroyuki; Ohtani, Kiyoshi

    2015-09-01

    The transcription factor E2F is the principal target of the tumor suppressor pRB. E2F plays crucial roles not only in cell proliferation by activating growth-related genes but also in tumor suppression by activating pro-apoptotic and growth-suppressive genes. We previously reported that, in human normal fibroblasts, the tumor suppressor genes ARF, p27(Kip1) and TAp73 are activated by deregulated E2F activity induced by forced inactivation of pRB, but not by physiological E2F activity induced by growth stimulation. In contrast, growth-related E2F targets are activated by both E2F activities, underscoring the roles of deregulated E2F in tumor suppression in the context of dysfunctional pRB. In this study, to further understand the roles of deregulated E2F, we explored new targets that are specifically activated by deregulated E2F using DNA microarray. The analysis identified nine novel targets (BIM, RASSF1, PPP1R13B, JMY, MOAP1, RBM38, ABTB1, RBBP4 and RBBP7), many of which are involved in the p53 and RB tumor suppressor pathways. Among these genes, the BIM gene was shown to be activated via atypical E2F-responsive promoter elements and to contribute to E2F1-mediated apoptosis. Our results underscore crucial roles of deregulated E2F in growth suppression to counteract loss of pRB function. © 2015 The Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.

  8. Version E2 from Dimco-System for the statistical calculation of components

    International Nuclear Information System (INIS)

    Moreno Gonzalez, A.

    1981-01-01

    A short description of the general system Dimco, together with a detailed description of E2 version are presented. E2 version is a two-dimensional finite element structural code. To illustrate the posibilities of E2 version, some results obtained with this new version are presented. These results are related with the following behaviour of the material: a) elastic, b) thermo-elastic, c) Plastic and d) creep. (author)

  9. p15(PAF) is an Rb/E2F-regulated S-phase protein essential for DNA synthesis and cell cycle progression.

    Science.gov (United States)

    Chang, Chih-Ning; Feng, Mow-Jung; Chen, Yu-Ling; Yuan, Ray-Hwang; Jeng, Yung-Ming

    2013-01-01

    The p15(PAF)/KIAA0101 protein is a proliferating cell nuclear antigen (PCNA)-associated protein overexpressed in multiple types of cancer. Attenuation of p15(PAF) expression leads to modifications in the DNA repair process, rendering cells more sensitive to ultraviolet-induced cell death. In this study, we identified that p15(PAF) expression peaks during the S phase of the cell cycle. We observed that p15(PAF) knockdown markedly inhibited cell proliferation, S-phase progression, and DNA synthesis. Depletion of p15(PAF) resulted in p21 upregulation, especially chromatin-bound p21. We further identified that the p15(PAF) promoter contains 3 E2F-binding motifs. Loss of Rb-mediated transcriptional repression resulted in upregulated p15(PAF) expression. Binding of E2F4 and E2F6 to the p15(PAF) promoter caused transcriptional repression. Overall, these results indicate that p15(PAF) is tightly regulated by the Rb/E2F complex. Loss of Rb/E2F-mediated repression during the G1/S transition phase leads to p15(PAF) upregulation, which facilitates DNA synthesis and S-phase progression.

  10. Next Generation Weather Radar (NEXRAD) Initial Operational Test and Evaluation. Phase 2. (IOT&E(2))

    Science.gov (United States)

    1989-12-01

    11 [ IOT &E(2)] FINAL REPORT (U) 00 DECEMBER 1989 Approved for public release; Dis ~ distribution is unlimited. gvaluakon peli.Dssmcopoii FR8 4 DE7TA iid...RADAR (NEXRAD) INITIAL OPERATIONAL TEST AND EVALUATION PHASE II ( IOT &E(2)) FINAL REPORT DECEMBER 1989 Prepared by: JAMES C. WEYMAN, Lt Colonel, USAF...Evaluation Phase II ( IOT &E(2)) of the Next Generation Weather Radar (NEXRAD) system. The test team conducted IOT &E(2) between 6 March and 6 August 1989 at

  11. 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...... of this gene is dependent on E2F. In vivo footprinting data demonstrate that the identified E2F sites are occupied in resting cells and in exponentially growing cells, suggesting that E2F is responsible for downregulating the promoter in early phases of the cell cycle and the subsequent upregulation when cells...

  12. E2F-1 induces melanoma cell apoptosis via PUMA up-regulation and Bax translocation

    International Nuclear Information System (INIS)

    Hao, Hongying; Dong, Yanbin; Bowling, Maria T; Gomez-Gutierrez, Jorge G; Zhou, H Sam; McMasters, Kelly M

    2007-01-01

    PUMA is a pro-apoptotic Bcl-2 family member that has been shown to be involved in apoptosis in many cell types. We sought to ascertain whether induction of PUMA plays a crucial role in E2F-1-induced apoptosis in melanoma cells. PUMA gene and protein expression levels were detected by real-time PCR and Western blot in SK-MEL-2 and HCT116 cell lines after Ad-E2F-1 infection. Activation of the PUMA promoter by E2F-1 overexpression was detected by dual luciferase reporter assay. E2F-1-induced Bax translocation was shown by immunocytochemistry. The induction of caspase-9 activity was measured by caspase-9 colorimetric assay kit. Up-regulation of the PUMA gene and protein by E2F-1 overexpression was detected by real-time PCR and Western blot analysis in the SK-MEL-2 melanoma cell line. In support of this finding, we found six putative E2F-1 binding sites within the PUMA promoter. Subsequent dual luciferase reporter assay showed that E2F-1 expression could increase the PUMA gene promoter activity 9.3 fold in SK-MEL-2 cells. The role of PUMA in E2F-1-induced apoptosis was further investigated in a PUMA knockout cell line. Cell viability assay showed that the HCT116 PUMA-/- cell line was more resistant to Ad-E2F-1-mediated cell death than the HCT116 PUMA+/+ cell line. Moreover, a 2.2-fold induction of the PUMA promoter was also noted in the HCT116 PUMA+/+ colon cancer cell line after Ad-E2F-1 infection. Overexpression of a truncated E2F-1 protein that lacks the transactivation domain failed to up-regulate PUMA promoter, suggesting that PUMA may be a transcriptional target of E2F-1. E2F-1-induced cancer cell apoptosis was accompanied by Bax translocation from the cytosol to mitochondria and the induction of caspase-9 activity, suggesting that E2F-1-induced apoptosis is mediated by PUMA through the cytochrome C/Apaf-1-dependent pathway. Our studies strongly demonstrated that E2F-1 induces melanoma cell apoptosis via PUMA up-regulation and Bax translocation. The signaling

  13. New insight into HCV E1/E2 region of genotype 4a

    OpenAIRE

    Hussein, Nehal; Zekri, Abdel-Rahman N; Abouelhoda, Mohamed; Alam El-din, Hanaa M; Ghamry, Ahmed Abdelwahab; Amer, Mahmoud A; sherif, Ghada M; Bahnassy, Abeer A

    2014-01-01

    Introduction Hepatitis C virus (HCV) genome contains two envelope proteins (E1 and E2) responsible for the virus entry into the cell. There is a substantial lack of sequences covering the full length of E1/E2 region for genotype 4. Our study aims at providing new sequences as well as characterizing the genetic divergence of the E1/E2 region of HCV 4a using our new sequences along with all publicly available datasets. Methods The genomic segments covering the whole E1/E2 region were isolated f...

  14. Odorant Receptor 51E2 Agonist β-ionone Regulates RPE Cell Migration and Proliferation

    Directory of Open Access Journals (Sweden)

    Nikolina Jovancevic

    2017-11-01

    Full Text Available The odorant receptor 51E2 (OR51E2, which is well-characterized in prostate cancer cells and epidermal pigment cells, was identified for the first time as the most highly expressed OR in human fetal and adult retinal pigment epithelial (RPE cells. Immunofluorescence staining and Western blot analysis revealed OR51E2 localization throughout the cytosol and in the plasma membrane. Additionally, immunohistochemical staining of diverse layers of the eye showed that the expression of OR51E2 is restricted to the pigment cells of the RPE and choroid. The results of Ca2+-imaging experiments demonstrate that activation of OR51E2 triggers a Ca2+ dependent signal pathway in RPE cells. Downstream signaling of OR51E2 involves the activation of adenylyl cyclase, ERK1/2 and AKT. The activity of these protein kinases likely accounts for the demonstrated increase in the migration and proliferation of RPE cells upon stimulation with the OR51E2 ligand β-ionone. These findings suggest that OR51E2 is involved in the regulation of RPE cell growth. Thus, OR51E2 represents a potential target for the treatment of proliferative disorders.

  15. An interaction between human papillomavirus 16 E2 and TopBP1 is required for optimum viral DNA replication and episomal genome establishment.

    Science.gov (United States)

    Donaldson, Mary M; Mackintosh, Lorna J; Bodily, Jason M; Dornan, Edward S; Laimins, Laimonis A; Morgan, Iain M

    2012-12-01

    In human papillomavirus DNA replication, the viral protein E2 forms homodimers and binds to 12-bp palindromic DNA sequences surrounding the origin of DNA replication. Via a protein-protein interaction, it then recruits the viral helicase E1 to an A/T-rich origin of replication, whereupon a dihexamer forms, resulting in DNA replication initiation. In order to carry out DNA replication, the viral proteins must interact with host factors that are currently not all known. An attractive cellular candidate for regulating viral replication is TopBP1, a known interactor of the E2 protein. In mammalian DNA replication, TopBP1 loads DNA polymerases onto the replicative helicase after the G(1)-to-S transition, and this process is tightly cell cycle controlled. The direct interaction between E2 and TopBP1 would allow E2 to bypass this cell cycle control, resulting in DNA replication more than once per cell cycle, which is a requirement for the viral life cycle. We report here the generation of an HPV16 E2 mutant compromised in TopBP1 interaction in vivo and demonstrate that this mutant retains transcriptional activation and repression functions but has suboptimal DNA replication potential. Introduction of this mutant into a viral life cycle model results in the failure to establish viral episomes. The results present a potential new antiviral target, the E2-TopBP1 interaction, and increase our understanding of the viral life cycle, suggesting that the E2-TopBP1 interaction is essential.

  16. 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

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

    Science.gov (United States)

    Hunt, Ann R; Frederickson, Shana; Maruyama, Toshiaki; Roehrig, John T; Blair, Carol D

    2010-07-13

    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 of a

  18. E2F transcription factors and digestive system malignancies: how much do we know?

    Science.gov (United States)

    Xanthoulis, Athanasios; Tiniakos, Dina G

    2013-06-07

    E2F family of transcription factors regulates various cellular functions related to cell cycle and apoptosis. Its individual members have traditionally been classified into activators and repressors, based on in vitro studies. However their contribution in human cancer is more complicated and difficult to predict. We review current knowledge on the expression of E2Fs in digestive system malignancies and its clinical implications for patient prognosis and treatment. E2F1, the most extensively studied member and the only one with prognostic value, exhibits a tumor-suppressing activity in esophageal, gastric and colorectal adenocarcinoma, and in hepatocellular carcinoma (HCC), whereas in pancreatic ductal adenocarcinoma and esophageal squamous cell carcinoma may function as a tumor-promoter. In the latter malignancies, E2F1 immunohistochemical expression has been correlated with higher tumor grade and worse patient survival, whereas in esophageal, gastric and colorectal adenocarcinomas is a marker of increased patient survival. E2F2 has only been studied in colorectal cancer, where its role is not considered significant. E2F4's role in colorectal, gastric and hepatic carcinogenesis is tumor-promoting. E2F8 is strongly upregulated in human HCC, thus possibly contributing to hepatocarcinogenesis. Adenoviral transfer of E2F as gene therapy to sensitize pancreatic cancer cells for chemotherapeutic agents has been used in experimental studies. Other therapeutic strategies are yet to be developed, but it appears that targeted approaches using E2F-agonists or antagonists should take into account the tissue-dependent function of each E2F member. Further understanding of E2Fs' contribution in cellular functions in vivo would help clarify their role in carcinogenesis.

  19. E2F1 enhances glycolysis through suppressing Sirt6 transcription in cancer cells.

    Science.gov (United States)

    Wu, Minghui; Seto, Edward; Zhang, Jingsong

    2015-05-10

    The fast proliferation of cancer cells requires reprogramming of its energy metabolism with aerobic glycolysis as a major energy source. Sirt6, a class III histone deacetylase, has been shown to down regulate glycolysis by inhibiting the expression of several key glycolytic genes. Based on the published study on the metabolic phenotype of E2F1 -/- mice and SIRT6 -/- mice, we hypothesize that E2F1 enhances glycolysis and inhibits the expression of Sirt6. Indeed, over-expressing of E2F1, but not its DNA binding deficient mutant, significantly enhanced glucose uptake and lactate production in bladder and prostate cancer cell lines. E2F1 over-expression also suppressed Sirt6 expression and function. Moreover, E2F1 directly bound to Sirt6 promoter and suppressed Sirt6 promoter activity under both normoxic and hypoxic culture conditions. E2F1 siRNA blocked the up-regulation of E2F1 under hypoxia, increased Sirt6 expression and decreased glycolysis compared to those of scrambled siRNA transected cells. Furthermore, HDAC1 deacetylated E2F1 and diminished its transcription suppression of Sirt6 promoter. Treatment with the HDAC inhibitor, trichostatin A (TSA), suppressed Sirt6 promoter activity with increased binding of acetylated E2F1 to Sirt6 promoter. Mutating the E2F1 binding site on the proximal Sirt6 promoter abolished the suppression of Sirt6 transcription by TSA. These data indicate a novel oncogenic role of E2F1, i.e. enhancing glycolysis by suppressing Sirt6 transcription.

  20. A role for E2F activities in determining the fate of Myc-induced lymphomagenesis.

    Directory of Open Access Journals (Sweden)

    Rachel E Rempel

    2009-09-01

    Full Text Available The phenotypic heterogeneity that characterizes human cancers reflects the enormous genetic complexity of the oncogenic process. This complexity can also be seen in mouse models where it is frequently observed that in addition to the initiating genetic alteration, the resulting tumor harbors additional, somatically acquired mutations that affect the tumor phenotype. To investigate the role of genetic interactions in the development of tumors, we have made use of the Emu-myc model of pre-B and B cell lymphoma. Since various studies point to a functional interaction between Myc and the Rb/E2F pathway, we have investigated the role of E2F activities in the process of Myc-induced lymphomagenesis. Whereas the absence of E2F1 and E2F3 function has no impact on Myc-mediated tumor development, the absence of E2F2 substantially accelerates the time of tumor onset. Conversely, tumor development is delayed by the absence of E2F4. The enhanced early onset of tumors seen in the absence of E2F2 coincides with an expansion of immature B lineage cells that are likely to be the target for Myc oncogenesis. In contrast, the absence of E2F4 mutes the response of the lineage to Myc and there is no expansion of immature B lineage cells. We also find that distinct types of tumors emerge from the Emu-myc mice, distinguished by different patterns of gene expression, and that the relative proportions of these tumor types are affected by the absence of either E2F2 or E2F4. From these results, we conclude that there are several populations of tumors that arise from the Emu-myc model, reflecting distinct populations of cells that are susceptible to Myc-mediated oncogenesis and that the proportion of these cell populations is affected by the presence or absence of E2F activities.

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

    Science.gov (United States)

    von Rosen, Tanya; Rangelova, Desislava; Nielsen, Jens; Rasmussen, Thomas Bruun; Uttenthal, Åse

    2014-06-04

    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, together with archival samples from pigs vaccinated with CP7_E2gif and subsequently CSFV challenged, were analysed for specific antibodies using ELISAs and for homologous neutralising antibodies. In animals vaccinated with CP7_E2gif, neutralising antibodies were detected from day 10. However, the sera remained negative for anti-CSFV E2-specific antibodies whereas pigs vaccinated with C-strain seroconverted against CSFV by 14 days after vaccination, as determined by a CSFV-E2 specific blocking ELISA. One week after subsequent CSFV challenge, a strong anti-CSFV E2 reaction was detected in CP7_E2gif vaccinated pigs and anti-E(rns) antibodies were detected from 10 days after infection. In conclusion, CP7_E2gif has the potential to be used as a DIVA vaccine in combination with detection of anti-CSFV E2-specific antibodies. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Activation of B-Myb by E2F1 in hepatocellular carcinoma.

    Science.gov (United States)

    Nakajima, Tomoaki; Yasui, Kohichiroh; Zen, Keika; Inagaki, Yoshikazu; Fujii, Hideki; Minami, Masahito; Tanaka, Shinji; Taniwaki, Masafumi; Itoh, Yoshito; Arii, Shigeki; Inazawa, Johji; Okanoue, Takeshi

    2008-09-01

    Deregulation of E2F1 transcriptional activity is observed in a variety of cancers, including hepatocellular carcinoma (HCC). The aim of the present study is to identify transcriptional target genes of E2F1 in HCC. We determined expression levels for E2F1 and ten candidate genes thought to be targets of E2F1 in primary HCCs using a real-time quantitative reverse transcription-PCR assay. Following small interfering RNA (siRNA)-mediated knockdown of E2F1 in HCC cell lines, we quantified mRNA levels of the candidate E2F1 target genes. E2F1 was significantly over-expressed in 41 primary HCCs as compared to non-tumorous liver tissues. Among the candidates, MYBL2, whose product is the transcriptional factor B-Myb, which is involved in controlling cell-cycle progression and apoptosis, was significantly over-expressed in primary HCCs. Additionally, expression levels of MYBL2 correlated with those of E2F1. Knockdown of E2F1 resulted in a decrease in expression of MYBL2. A copy-number gain for MYBL2 was observed in 36 of 66 primary HCCs, suggesting that MYBL2 expression is up-regulated by amplification in addition to being regulated by E2F1. Moreover, siRNA-mediated knockdown of MYBL2 led to reduced expression of CDC2 (which encodes CDC2), cyclin A2 (CCNA2), and topoisomerase II alpha (TOP2A), implicating these genes in the cell cycle and suggesting that they may be downstream targets of B-Myb. MYBL2 is a probable transcriptional target of E2F1 in HCC and may therefore be a useful biomarker for diagnosis and an attractive target for molecular therapies useful to treat HCC.

  3. HP-41CV Flight Performance Advisory System (FPAS) for the E-2C, E-2B, and C-2A Aircraft

    Science.gov (United States)

    1982-06-01

    Grumman engineers have assured E-2 flight crew that the microwave enerqy field that sweeps through the cockpit is not a health Razard. The transitory nature ...bandy, however, such parameters can easily be computed assuming the linear fuel consumption nature of the E-2 and C-2. 136 10. 2 iU.Uu ATo IS", 1. It is...F Pr1N~ Di~5~iCiiirv 1 ~e7-T-- 4- i_-jr !ATIQ F i ht Aanual NAVAIR 01-E2AAA-1: aSN, 1977. 5. Nr2 IA.TO P ligtht Maua 1AVAIR O1-85V5A-1: UJSN, 1973. 6

  4. Estradiol-17β, prostaglandin E2 (PGE2) and the prostaglandin E2 receptor are involved in PGE2 positive feedback loop in the porcine endometrium

    Science.gov (United States)

    Waclawik, Agnieszka; Jabbour, Henry N.; Blitek, Agnieszka; Ziecik, Adam J.

    2009-01-01

    Before implantation, the porcine endometrium and trophoblast synthesize elevated amounts of luteoprotective prostaglandin E2 (PGE2). We hypothesized that embryo signal, estradiol-17β (E2) and PGE2 modulate expression of key enzymes in PG synthesis: prostaglandin-endoperoxide synthase-2 (PTGS2), PGE synthase (mPGES-1), PGF synthase (PGFS), and prostaglandin 9-ketoreductase (CBR1); as well as PGE2 receptor (PTGER2 and 4) expression and signaling within the endometrium. We determinated the site of action of PGE2 in endometrium during the estrous cycle and pregnancy. Endometrial tissue explants obtained from gilts (n=6) on days 11-12 of the estrous cycle were treated with vehicle (control), PGE2 (100 nM), E2 (1-100 nM) or phorbol 12-myristate 13-acetate (100 nM, positive control). E2 increased PGE2 secretion through elevating expression of mPGES-1 mRNA and PTGS2 and mPGES-1 protein in endometrial explants. By contrast, E2 decreased PGFS and CBR1 protein expression. E2 also stimulated PTGER2 but not PTGER4 protein content. PGE2 enhanced mPGES-1 and PTGER2 mRNA as well as PTGS2, mPGES-1 and PTGER2 protein expression. PGE2 had no effect on PGFS, CBR1 and PTGER4 expression and PGF2α release. Treatment of endometrial tissue with PGE2 increased cAMP production. Co-treatment with PTGER2 antagonist (AH6809) but not PTGER4 antagonist (GW 627368X) inhibited significantly PGE2-mediated cAMP production. PTGER2 protein was localized in luminal and glandular epithelium and blood vessels of endometrium, and was significantly up-regulated on days 11-12 of pregnancy. Our results suggest that E2, prevents luteolysis through enzymatic modification of PG synthesis and that E2, PGE2 and endometrial PTGER2 are involved in PGE2 positive feedback loop in porcine endometrium. PMID:19359378

  5. 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.

  6. Data of evolutionary structure change: 1RAAC-3E2PN [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1RAAC-3E2PN 1RAA 3E2P C N ANPLYQKHIISINDLSRDDLNLVLATAAKLKANPQ----...Chain> 1RAA C 1RAAC KANPQ----PELL...pdbID> C 1RAAC KERLD-... 1RAAC FSDSANTSLGK E C 1RAAC TEFSGNVPVLN

  7. Transcriptional activation of the human CD2AP promoter by E2F1.

    Directory of Open Access Journals (Sweden)

    Li Zou

    Full Text Available CD2-associated protein (CD2AP is an adaptor molecule involved in T cell receptor signaling and podocyte homeostasis. CD2AP-deficient mice develop nephritic syndrome and renal failure caused by glomerulosclerosis. Transcription factor E2F1 is a key regulator of cell proliferation and apoptosis. Here we report that E2F1 up-regulates the human CD2AP promoter and further increases the mRNA and protein levels of the human CD2AP in human embryonic kidney (HEK 293 cells. By semi-quantitative RT-PCR and Western blot analysis we demonstrate that ectopic expression of E2F1 elevates the mRNA and protein levels of CD2AP. Consistently, transient transfection assays prove that overexpression of E2F1 transactivates the CD2AP promoter while knocking-down of endogenous E2F1 by a shRNA strategy results in reduction of the CD2AP promoter activity. Toward understanding the underlying mechanism of this regulation, we performed chromatin immunoprecipitation and mutations of the putative Sp1 binding sites, demonstrating that E2F1 can bind to Sp1 binding site and overexpression of E2F1 is capable of increasing the binding of E2F1 and decreasing the binding of Sp1 to Sp1 binding sites.

  8. 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...... cells were cotransfected with an ARHI/luciferase reporter and E2F-expression vectors, E2F1 and 4 reduced ARHI promoter activity 2-3-fold, and this reduction could be reversed by TSA treatment. The negative regulation by E2F-HDAC complexes could also be reduced by small interfering RNA of E2F1 and 4...

  9. 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.

  10. 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...

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

    Science.gov (United States)

    Wang, Jimin; Li, Yue; Modis, Yorgo

    2014-01-01

    The membrane anchors of viral envelope proteins play essential roles in cell entry. Recent crystal structures of the ectodomain of envelope protein E2 from a pestivirus suggest that E2 belongs to a novel structural class of membrane fusion machinery. Based on geometric constraints from the E2 structures, we generated atomic models of the E1 and E2 membrane anchors using computational approaches. The E1 anchor contains two amphipathic perimembrane helices and one transmembrane helix; the E2 anchor contains a short helical hairpin stabilized in the membrane by an arginine residue, similar to flaviviruses. A pair of histidine residues in the E2 ectodomain may participate in pH sensing. The proposed atomic models point to Cys987 in E2 as the site of disulfide bond linkage with E1 to form E1–E2 heterodimers. The membrane anchor models provide structural constraints for the disulfide bonding pattern and overall backbone conformation of the E1 ectodomain. PMID:24725935

  12. 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...

  13. Clinical value of combined determining leptin, T and E2 in male teenager obesity patients

    International Nuclear Information System (INIS)

    Bai Zhenlian; Lv Tongqin; Wu Qiuhua

    2006-01-01

    To study clinical significance of combined detection of leptin, T and E 2 for teenager obesity patients, levels of leptin, T and E 2 in male teenagers obesity patients and male adult obesity patients were determined by RIA. The result showed that in all obesity patients, the levels of leptin and E 2 were much higher than those in normal controls and T was lower than that in normal controls. After treatment, leptin and E 2 were decreased and T was increased significantly in teenager obesity patients, but only leptin was decreased in adult obesity patients. All results indicate that combined detection of leptin, T and E 2 could find endocrine and metabolism disorder of obese teenagers at early stage, instituting prevention and treatment without delay.(authors)

  14. Transit space

    DEFF Research Database (Denmark)

    Raahauge, Kirsten Marie

    2008-01-01

    and the interaction of cultural, social, and spatial organizations, as seen from the point of view of people living in Skåde Bakker and Fedet. The focus is on the city dwellers’ representations of the central district of Århus with specific reference to the concept of transit space. When applied to various Århusian...

  15. In-Band Interference Effects on UTRA LTE Uplink Resource Block Allocation

    DEFF Research Database (Denmark)

    Priyanto, Basuki Endah; Sørensen, Troels Bundgaard; Jensen, Ole Kiel

    2008-01-01

    In this paper we investigate the impact of in-band interference on the uplink multiple access of UMTS Terrestrial Radio Access, long term evolution (UTRA LTE). In- band and out-of-band interference arise as a result of transmitter imperfections. Out-of- band, or adjacent channel, interference can......, and when the interfering signal is received at higher power spectral density (PSD). The effect of frequency offset and different PSD level from the UE interferers to a victim UE is studied. The impact on different UE resource block size allocation is also investigated. The results are obtained from an LTE...

  16. 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

  17. 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.

  18. Direct visualization of Agrobacterium-delivered VirE2 in recipient cells

    Science.gov (United States)

    Li, Xiaoyang; Yang, Qinghua; Tu, Haitao; Lim, Zijie; Pan, Shen Q

    2014-01-01

    Agrobacterium tumefaciens is a natural genetic engineer widely used to deliver DNA into various recipients, including plant, yeast and fungal cells. The bacterium can transfer single-stranded DNA molecules (T–DNAs) and bacterial virulence proteins, including VirE2. However, neither the DNA nor the protein molecules have ever been directly visualized after the delivery. In this report, we adopted a split-GFP approach: the small GFP fragment (GFP11) was inserted into VirE2 at a permissive site to create the VirE2-GFP11 fusion, which was expressed in A. tumefaciens; and the large fragment (GFP1–10) was expressed in recipient cells. Upon delivery of VirE2-GFP11 into the recipient cells, GFP fluorescence signals were visualized. VirE2-GFP11 was functional like VirE2; the GFP fusion movement could indicate the trafficking of Agrobacterium-delivered VirE2. As the natural host, all plant cells seen under a microscope received the VirE2 protein in a leaf-infiltration assay; most of VirE2 moved at a speed of 1.3–3.1 μm sec−1 in a nearly linear direction, suggesting an active trafficking process. Inside plant cells, VirE2-GFP formed filamentous structures of different lengths, even in the absence of T-DNA. As a non-natural host recipient, 51% of yeast cells received VirE2, which did not move inside yeast. All plant cells seen under a microscope transiently expressed the Agrobacterium-delivered transgene, but only 0.2% yeast cells expressed the transgene. This indicates that Agrobacterium is a more efficient vector for protein delivery than T-DNA transformation for a non-natural host recipient: VirE2 trafficking is a limiting factor for the genetic transformation of a non-natural host recipient. The split-GFP approach could enable the real-time visualization of VirE2 trafficking inside recipient cells. PMID:24299048

  19. Genome-wide identification and expression analysis of E2 ubiquitin-conjugating enzymes in tomato.

    Science.gov (United States)

    Sharma, Bhaskar; Bhatt, Tarun Kumar

    2017-08-17

    The ubiquitin-proteasomal degradation mechanism has gained the attention over the past decade. The E2 ubiquitin conjugating enzymes are the crucial part of ubiquitination mechanism and they are believed to hold imperative association for plant development. It accepts ubiquitin from the E1 enzyme and interacts with the E3 ligase to transfer ubiquitin or directly transfers ubiquitin to the substrate. The functional aspects of E2 ubiquitin enzymes in plant systems are unclear. Tomato is being used as a model plant and rarely explored to study E2 ubiquitin enzyme. We have utilized in-silico methods to analyze E2 enzymes in Solanum lycopersicum and 59 genes were identified with UBC family domains. The physio-chemical properties, chromosomal localization, structural organization, gene duplication, promoter analysis, gene ontology and conserved motifs were investigated along with phylogenetic analysis of tomato E2 genes exploring evolutionary relations. The gene expression analysis of RNA sequencing data revealed expression profile of tomato E2 genes in seedling, root, leaf, seed, fruit, and flower tissues. Our study aid in the understanding of distribution, expansion, evolutionary relation and probable participation in plant biological processes of tomato E2 enzymes that will facilitate strong base for future research on ubiquitin-mediated regulations in tomato and other plant systems.

  20. 5 CFR 9901.355 - Setting pay upon reduction in band.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Setting pay upon reduction in band. 9901.355 Section 9901.355 Administrative Personnel DEPARTMENT OF DEFENSE HUMAN RESOURCES MANAGEMENT AND... NATIONAL SECURITY PERSONNEL SYSTEM (NSPS) Pay and Pay Administration Pay Administration § 9901.355 Setting...

  1. Scalable In-Band Optical Notch-Filter Labeling for Ultrahigh Bit Rate Optical Packet Switching

    DEFF Research Database (Denmark)

    Medhin, Ashenafi Kiros; Galili, Michael; Oxenløwe, Leif Katsuo

    2014-01-01

    We propose a scalable in-band optical notch-filter labeling scheme for optical packet switching of high-bit-rate data packets. A detailed characterization of the notch-filter labeling scheme and its effect on the quality of the data packet is carried out in simulation and verified by experimental...

  2. CMOS front-end techniques for in-band full-duplex radio

    NARCIS (Netherlands)

    van den Broek, Dirk-Jan

    2017-01-01

    In-band full-duplex wireless communication (FD), i.e. transmission and reception at the same time at the same frequency, is an emerging research topic, driven by the increasing demand for mobile data traffic in the crowded radio spectrum. Besides promising up to twice the spectral efficiency,

  3. In-Band full-duplex transceiver technology for 5G mobile networks

    NARCIS (Netherlands)

    Deballie, B.; van Liempd, B.; Hershberg, B.; Craninckx, J.; Rikkinen, K.; van den Broek, Dirk-Jan; Klumperink, Eric A.M.; Nauta, Bram

    2015-01-01

    In-band full-duplex is a promising air interface technique to tackle several of the key challenges of next generation (5G)mobile networks. Simultaneous transmission and reception in the same frequency band increases the throughput and spectral efficiency, and reduces the air interface delay. Its

  4. Sustainable Transition

    DEFF Research Database (Denmark)

    Hansen, Ole Erik; Søndergård, Bent

    2014-01-01

    What. The chapter addresses designing for sustainability as interventions in socio-technical systems and social practices of users and communities. It calls for reflexive design practices challenging dominant regimes and shaping alternative design spaces. The specific case is the reconfiguration...... of agendas/vision, technologies, actors and institutions in the emergent design of an urban mobility system based on an electric car sharing system. Why. Designing for sustainability is a fundamental challenge for future design practices; designers have to obtain an ability to contribute to sustainable...... transition processes. Where. Addresses design processes aimed at sustainable transition enacted in complex social settings, socio-technical systems involving many different actors and agendas. How. The chapter outlines a conceptual and analytic framework for a reflexive design practice for sustainability...

  5. Presidential Transitions

    Science.gov (United States)

    2006-06-09

    done to facilitate the transition.52 CRS-12 53 David T. Stanley, Changing Administrations (Washington: Brookings Institution, 1965), p. 6. 54 “Pre...Conference of Mayors; Sharleen Hirsch, an educational administrator; and Jule Sugarman , a public administrator. Staff members were assigned to task forces...Issues,” Washington Post, Nov. 13, 1980, p. Al. 77 David Hoffman, “Bush Names Baker Secretary of State,” Washington Post, Nov. 10, 1988, pp. Al and

  6. Acute Hemoperitoneum after Administration of Prostaglandin E2 for Induction of Labour

    Directory of Open Access Journals (Sweden)

    Zhenyu Zhang

    2015-01-01

    Full Text Available Prostaglandin E2 is widely used in obstetrics and is thought to be relatively safe for cervical ripening and induction of labour. Here we present a case in which acute hemoperitoneum was observed after administration of prostaglandin E2 in a pregnant woman. The patient had a history of endometriosis, and a severe pelvic adhesion (ASRM stage IV was found during her last laparoscopic surgery 3 years previously. In cases with endometriosis, use of prostaglandin E2 for induction of labour in pregnant women must be done cautiously.

  7. Identification of cooperative genes for E2A-PBX1 to develop acute lymphoblastic leukemia.

    Science.gov (United States)

    Sera, Yasuyuki; Yamasaki, Norimasa; Oda, Hideaki; Nagamachi, Akiko; Wolff, Linda; Inukai, Takeshi; Inaba, Toshiya; Honda, Hiroaki

    2016-07-01

    E2A-PBX1 is a chimeric gene product detected in t(1;19)-bearing acute lymphoblastic leukemia (ALL) with B-cell lineage. To investigate the leukemogenic process, we generated conditional knock-in (cKI) mice for E2A-PBX1, in which E2A-PBX1 is inducibly expressed under the control of the endogenous E2A promoter. Despite the induced expression of E2A-PBX1, no hematopoietic disease was observed, strongly suggesting that additional genetic alterations are required to develop leukemia. To address this possibility, retroviral insertional mutagenesis was used. Virus infection efficiently induced T-cell, B-cell, and biphenotypic ALL in E2A-PBX1 cKI mice. Inverse PCR identified eight retroviral common integration sites, in which enhanced expression was observed in the Gfi1, Mycn, and Pim1 genes. In addition, it is of note that viral integration and overexpression of the Zfp521 gene was detected in one tumor with B-cell lineage; we previously identified Zfp521 as a cooperative gene with E2A-HLF, another E2A-involving fusion gene with B-lineage ALL. The cooperative oncogenicity of E2A-PBX1 with overexpressed Zfp521 in B-cell tumorigenesis was indicated by the finding that E2A-PBX1 cKI, Zfp521 transgenic compound mice developed B-lineage ALL. Moreover, upregulation of ZNF521, the human counterpart of Zfp521, was found in several human leukemic cell lines bearing t(1;19). These results indicate that E2A-PBX1 cooperates with additional gene alterations to develop ALL. Among them, enhanced expression of ZNF521 may play a clinically relevant role in E2A fusion genes to develop B-lineage ALL. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  8. Prostaglandins E1 and E2 inhibit lipopolysaccharide-induced interleukin-18 production in monocytes.

    Science.gov (United States)

    Takahashi, Hideo K; Iwagaki, Hiromi; Mori, Shuji; Yoshino, Tadashi; Tanaka, Noriaki; Nishibori, Masahiro

    2005-07-11

    The purpose of this present study was to explore the therapeutic potential of prostaglandins E1 and E2 on the systemic inflammatory response evoked by endotoxin. Since interleukin-18, a monocyte-derived cytokine, is increased during sepsis, decreasing the production of interleukin-18 is important in treating this condition. Prostaglandin E1 and E2 inhibited interleukin-18 production in human monocytes treated with lipopolysaccharide and prostanoid IP-, EP2- and EP4-receptor agonists mimicked the effects of prostaglandins E1 and E2. Therefore, prostanoid IP, EP2- and EP4-receptors might be involved in the decrease in interleukin-18 production during sepsis.

  9. 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

    RB or the deregulation of E2F activity occurs via both p53-dependent and p53-independent mechanisms. The mechanism by which E2F induces apoptosis is still unclear. Here we show that E2F1 directly regulates the expression of Apaf-1, the gene for apoptosis protease-activating factor 1. These results provide a direct link......, 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....

  10. Strengths of gamma-ray transitions in A = 45–90 nuclei

    NARCIS (Netherlands)

    Endt, P.M.

    The present tables list the strengths (in Weisskopf units) of over 1200 gamma-ray transitions in A = 45–90 nuclei, classified according to character (electric or magnetic, multipolarity). It appears that E1, M1, and M2 transitions are weaker here than in the A = 6–44 region, whereas E2 transitions

  11. miR-302b enhances breast cancer cell sensitivity to cisplatin by regulating E2F1 and the cellular DNA damage response.

    Science.gov (United States)

    Cataldo, Alessandra; Cheung, Douglas G; Balsari, Andrea; Tagliabue, Elda; Coppola, Vincenzo; Iorio, Marilena V; Palmieri, Dario; Croce, Carlo M

    2016-01-05

    The identification of the molecular mechanisms involved in the establishment of the resistant phenotype represents a critical need for the development of new strategies to prevent or overcome cancer resistance to anti-neoplastic treatments.Breast cancer is the leading cause of cancer-related deaths in women, and resistance to chemotherapy negatively affects patient outcomes. Here, we investigated the potential role of miR-302b in the modulation of breast cancer cell resistance to cisplatin.miR-302b overexpression enhances sensitivity to cisplatin in breast cancer cell lines, reducing cell viability and proliferation in response to the treatment. We also identified E2F1, a master regulator of the G1/S transition, as a direct target gene of miR-302b. E2F1 transcriptionally activates ATM, the main cellular sensor of DNA damage. Through the negative regulation of E2F1, miR-302b indirectly affects ATM expression, abrogating cell-cycle progression upon cisplatin treatment. Moreover miR-302b, impairs the ability of breast cancer cells to repair damaged DNA, enhancing apoptosis activation following cisplatin treatment.These findings indicate that miR-302b plays a relevant role in breast cancer cell response to cisplatin through the modulation of the E2F1/ATM axis, representing a valid candidate as therapeutic tool to overcome chemotherapy resistance.

  12. 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.

  13. 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

    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

  14. Atomic Transition Probabilities Scandium through Manganese

    International Nuclear Information System (INIS)

    Martin, G.A.; Fuhr, J.R.; Wiese, W.L.

    1988-01-01

    Atomic transition probabilities for about 8,800 spectral lines of five iron-group elements, Sc(Z = 21) to Mn(Z = 25), are critically compiled, based on all available literature sources. The data are presented in separate tables for each element and stage of ionization and are further subdivided into allowed (i.e., electric dipole-E1) and forbidden (magnetic dipole-M1, electric quadrupole-E2, and magnetic quadrupole-M2) transitions. Within each data table the spectral lines are grouped into multiplets, which are in turn arranged according to parent configurations, transition arrays, and ascending quantum numbers. For each line the transition probability for spontaneous emission and the line strength are given, along with the spectroscopic designation, the wavelength, the statistical weights, and the energy levels of the upper and lower states. For allowed lines the absorption oscillator strength is listed, while for forbidden transitions the type of transition is identified (M1, E2, etc.). In addition, the estimated accuracy and the source are indicated. In short introductions, which precede the tables for each ion, the main justifications for the choice of the adopted data and for the accuracy rating are discussed. A general introduction contains a discussion of our method of evaluation and the principal criteria for our judgements

  15. Dual inhibition of nitric oxide and prostaglandin E-2 production by polysubstituted 2-aminopyrimidines

    Czech Academy of Sciences Publication Activity Database

    Zídek, Z.; Kverka, Miloslav; Dusilová, Adéla; Kmoníčková, E.; Jansa, P.

    2016-01-01

    Roč. 57, July 1 (2016), s. 48-56 ISSN 1089-8603 Institutional support: RVO:61388971 Keywords : Pyrimidines * Nitric oxide * Prostaglandin E-2 Subject RIV: EE - Microbiology, Virology Impact factor: 4.181, year: 2016

  16. The Possible Role of E2F in Rat Mammary Carcinogenesis

    National Research Council Canada - National Science Library

    Lee, Traci

    1998-01-01

    My project, as described in the last annual report, was to coexpress E2F wild type and mutant proteins, ras, and GFP from the same viral vector and infuse the viruses into rat mammary glands to see...

  17. The E2F transcription factor is a cellular target for the RB protein.

    Science.gov (United States)

    Chellappan, S P; Hiebert, S; Mudryj, M; Horowitz, J M; Nevins, J R

    1991-06-14

    Although it is generally believed that the product of the retinoblastoma susceptibility gene (RB1) is an important regulator of cell proliferation, the biochemical mechanism for its action is unclear. We now show that the RB protein is found in a complex with the E2F transcription factor and that only the under phosphorylated form of RB is in the E2F complex. Moreover, the adenovirus E1A protein can dissociate the E2F-RB complex, dependent on E1A sequence also critical for E1A to bind to RB. These sequences are also critical for E1A to immortalize primary cell cultures and to transform in conjunction with other oncogenes. Taken together, these results suggest that the interaction of RB with E2F is an important event in the control of cellular proliferation and that the dissociation of the complex is part of the mechanism by which E1A inactivates RB function.

  18. 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

    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...... 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...... progenitors may stimulate abnormal cell proliferation by overriding negative regulatory signals mediated by tumor suppressor proteins such as pRb....

  19. Prostaglandins E1 and E2 prevent bronchoconstriction in the guinea-pig

    Science.gov (United States)

    Herxheimer, H.

    1974-01-01

    Prostaglandin E1 and E2 aerosols protected the guinea-pig against bronchoconstriction caused by anaphylactic microshock, 1% histamine, 4% acetylcholine and 1% 5-hydroxytryptamine aerosols. PMID:4425768

  20. The pestivirus Erns glycoprotein interacts with E2 in both infected cells and mature virions

    International Nuclear Information System (INIS)

    Lazar, Catalin; Zitzmann, Nicole; Dwek, Raymond A.; Branza-Nichita, Norica

    2003-01-01

    E rns is a pestivirus envelope glycoprotein indispensable for virus attachment and infection of target cells. Unlike the other two envelope proteins E1 and E2, E rns lacks a transmembrane domain and a vast quantity is secreted into the medium of infected cells. The protein is also present in fractions of pure pestivirus virions, raising the important and intriguing question regarding the mechanism of its attachment to the pestivirus envelope. In this study a direct interaction between E rns and E2 glycoproteins was demonstrated in both pestivirus-infected cells and mature virions. By co- and sequential immunoprecipitation we showed that an E rns -E2 heterodimer is assembled very early after translation of the viral polyprotein and before its processing is completed. Our results suggest that E rns is attached to the pestivirus envelope via a direct interaction with E2 and explain the role of E rns in the initial virus-target cell interaction

  1. 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.

  2. Design and Synthesis of Cyclopropane Congeners of Resolvin E2, an Endogenous Proresolving Lipid Mediator, as Its Stable Equivalents.

    Science.gov (United States)

    Fukuda, Hayato; Muromoto, Ryuta; Takakura, Yuuki; Ishimura, Kohei; Kanada, Ryutaro; Fushihara, Daichi; Tanabe, Makoto; Matsubara, Kotaro; Hirao, Toru; Hirashima, Koki; Abe, Hiroshi; Arisawa, Mitsuhiro; Matsuda, Tadashi; Shuto, Satoshi

    2016-12-16

    Lipid chemical mediator resolvins with highly potent anti-inflammatory activity can be leads to develop novel anti-inflammatory drugs; however, they are unstable in oxygen due to their characteristic polyunsaturated structures. To solve the problem, CP-RvE2 has been designed and synthesized in which the cis-olefin of RvE2 was replaced with a cyclopropane. CP-RvE2s were much more stable than RvE2 against autoxidation and equipotent or more potent than RvE2. CP-RvE2s were successfully identified as stable equivalents of RvE2.

  3. Role for Homodimerization in Growth Deregulation by E2a Fusion Proteins

    Science.gov (United States)

    Bayly, Richard; LeBrun, David P.

    2000-01-01

    The oncogenic transcription factor E2a-Pbx1 is expressed in some cases of acute lymphoblastic leukemia as a result of chromosomal translocation 1;19. The early observation that E2a-Pbx1 incorporates transcriptional activation domains from E2a and a DNA-binding homeodomain from Pbx1 inspired a model in which E2a-Pbx1 promotes leukemogenic transformation of lymphoid progenitor cells through transcriptional induction of target genes defined by the Pbx1 portion of the molecule. However, the subsequent demonstration that the only known DNA-binding module on the molecule, the Pbx1 homeodomain, is dispensable for the induction of lymphoblastic lymphoma in transgenic mice called into question the contribution made by the Pbx1 portion. In this study, we have used a domain swap approach coupled with a fibroblast-based focus formation assay to evaluate further the requirement for PBX1-encoded peptide elements in growth deregulation by E2a-Pbx1. No impairment of focus formation was observed when the entire Pbx1 portion was replaced with DNA-binding/dimerization domains derived from yeast transcription factor GAL4 or GCN4. Furthermore, replacement of Pbx1 with tandem FKBP domains that mediate homodimerization in the presence of a synthetic ligand led to striking growth deregulation exclusively in the presence of the dimerizing agent. N-terminal elements encoded by E2A, including the AD1 transcriptional activation domain, were required for dimerization-induced focus formation. We conclude that transcriptional target genes defined by heterologous C-terminal DNA-binding modules are not required in growth deregulation by E2a fusion proteins. We speculate that interactions between N-terminal E2a elements and undefined proteins that could function as components of a transcriptional coactivator complex may be more important. PMID:10913162

  4. 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.

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

    Science.gov (United States)

    Schultz, Peter A

    2015-02-25

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

  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. E2F8 confers cisplatin resistance to ER+ breast cancer cells via transcriptionally activating MASTL.

    Science.gov (United States)

    Tian, Jianjun; Lin, Yuting; Yu, Jianhua

    2017-08-01

    MASTL (microtubule-associated serine/threonine kinase-like) is a critical kinase modulating mitotic entry. In this study, we investigated the mechanism of its dysregulation in breast cancer and its involvement in cisplatin resistance in ER+ breast cancer cells. Data mining in Kaplan-Meier Plotter showed that high MASTL expression was associated with worse distant metastasis free survival (DMFS) and relapse free survival (RFS) in ER+ breast cancer patients. In TCGA breast cancer cohort (TCGA-BRCA), MASTL was strongly co-upregulated with E2F8. High E2F8 expression was also strongly associated with unfavorable DMFS and RFS in ER+ breast cancer patients. Promoter scanning in JASPAR Database showed that the MASTL promoter region has a highly possible E2F8 binding site upstream the TSS site. The following western blot, dual luciferase assay and ChIP-qPCR validated this binding site. In MCF-7 cells, E2F8 overexpression alleviated cisplatin induced cell apoptosis by shortening G2/M arrest and promoting mitotic entry, the effect of which was largely canceled by inhibiting MASTL. Therefore, we infer that E2F8 can shorten cisplatin induced G2/M arrest by promoting MASTL mediated mitotic progression in ER+ breast cancer cells. These findings might help to explain why high MASTL or high E2F8 expression is associated with worse RFS in ER+ breast cancer. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  8. 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.

  9. 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 (vflc36 BVDVII 684–796 seemed to be reduced compared to vflc9 (with the complete antigenic region of BVDVII.

  10. Rapid transitions

    Energy Technology Data Exchange (ETDEWEB)

    Hamrin, J.G.

    1980-01-01

    Solar energy programs are entering a critical transitional period as we move from the initial marketing of solar technologies into a phase of widespread commercialization. We face the dual challenge of trying to get enough solar systems in place fast enough to prove solar is a viable alternative, while trying to ensure the systems are designed and installed properly, proving the energy savings as promised. This is a period of both great opportunity and high risk as the field becomes crowded with new solar cheerleaders and supporters but seldom enough competent players. The status of existing and proposed programs for the accelerated commercialization of solar energy in California is described.

  11. Transit space

    DEFF Research Database (Denmark)

    Raahauge, Kirsten Marie

    2008-01-01

    This article deals with representations of one specific city, Århus, Denmark, especially its central district. The analysis is based on anthropological fieldwork conducted in Skåde Bakker and Fedet, two well-off neighborhoods. The overall purpose of the project is to study perceptions of space...... and the interaction of cultural, social, and spatial organizations, as seen from the point of view of people living in Skåde Bakker and Fedet. The focus is on the city dwellers’ representations of the central district of Århus with specific reference to the concept of transit space. When applied to various Århusian...

  12. Differential Effects of E2 on MAPK Activity in the Brain and Heart of Aged Female Rats.

    Directory of Open Access Journals (Sweden)

    Elena Pinceti

    Full Text Available Aging and the coincident loss of circulating estrogens at menopause lead to increased risks for neurological and cardiovascular pathologies. Clinical studies show that estrogen therapy (ET can be beneficial in mitigating these negative effects, in both the brain and heart, when it is initiated shortly after the perimenopausal transition. However, this same therapy is detrimental when initiated >10 years postmenopause. Importantly, the molecular mechanisms underlying this age-related switch in ET efficacy are unknown. Estrogen receptors (ERs mediate the neuroprotective and cardioprotective functions of estrogens by modulating gene transcription or, non-genomically, by activating second messenger signaling pathways, such as mitogen activated protein kinases (MAPK. These kinases are critical regulators of cell signaling pathways and have widespread downstream effects. Our hypothesis is that age and estrogen deprivation following menopause alters the expression and activation of the MAPK family members p38 and ERK in the brain and heart. To test this hypothesis, we used a surgically induced model of menopause in 18 month old rats through bilateral ovariectomy (OVX followed by an acute dose of 17β-estradiol (E2 administered at varying time points post-OVX (1 week, 4 weeks, 8 weeks, or 12 weeks. Age and E2 treatment differentially regulated kinase activity in both the brain and heart, and the effects were also brain region specific. MAPK signaling plays an integral role in aging, and the aberrant regulation of those signaling pathways might be involved in age-related disorders. Clinical studies show benefits of ET during early menopause but detrimental effects later, which might be reflective of changes in kinase expression and activation status.

  13. Reduction of the In-Band RCS of Microstrip Patch Antenna by Using Offset Feeding Technique

    Directory of Open Access Journals (Sweden)

    Weiwei Xu

    2014-01-01

    Full Text Available This paper presents a method for implementing a low in-band scattering design for microstrip patch antennas based on the analysis of structural mode scattering and radiation characteristics. The antenna structure is first designed to have the lowest structural mode scattering in a desired frequency band. The operating frequency band of the antenna is then changed to coincide with that of the lowest structural mode scattering by adjusting the feed position on the antenna (offset feeding to achieve an antenna with low in-band radar cross section (RCS. In order to reduce the level of cross polarization of the antenna caused by offset feeding, symmetry feeding structures for both single patch antennas and two-patch arrays are proposed. Examples that show the efficiency of the method are given, and the results illustrate that the in-band RCS of the proposed antennas can be reduced by as much as 17 dBsm for plane waves impinging from the normal direction compared to patch antennas fed by conventional methods.

  14. Detergent-resistant membrane association of NS2 and E2 during hepatitis C virus replication.

    Science.gov (United States)

    Shanmugam, Saravanabalaji; Saravanabalaji, Dhanaranjani; Yi, MinKyung

    2015-04-01

    Previously, we demonstrated that the efficiency of hepatitis C virus (HCV) E2-p7 processing regulates p7-dependent NS2 localization to putative virus assembly sites near lipid droplets (LD). In this study, we have employed subcellular fractionations and membrane flotation assays to demonstrate that NS2 associates with detergent-resistant membranes (DRM) in a p7-dependent manner. However, p7 likely plays an indirect role in this process, since only the background level of p7 was detectable in the DRM fractions. Our data also suggest that the p7-NS2 precursor is not involved in NS2 recruitment to the DRM, despite its apparent targeting to this location. Deletion of NS2 specifically inhibited E2 localization to the DRM, indicating that NS2 regulates this process. Treatment of cells with methyl-β-cyclodextrin (MβCD) significantly reduced the DRM association of Core, NS2, and E2 and reduced infectious HCV production. Since disruption of the DRM localization of NS2 and E2, either due to p7 and NS2 defects, respectively, or by MβCD treatment, inhibited infectious HCV production, these proteins' associations with the DRM likely play an important role during HCV assembly. Interestingly, we detected the HCV replication-dependent accumulation of ApoE in the DRM fractions. Taking into consideration the facts that ApoE was shown to be a major determinant for infectious HCV particle production at the postenvelopment step and that the HCV Core protein strongly associates with the DRM, recruitment of E2 and ApoE to the DRM may allow the efficient coordination of Core particle envelopment and postenvelopment events at the DRM to generate infectious HCV production. The biochemical nature of HCV assembly sites is currently unknown. In this study, we investigated the correlation between NS2 and E2 localization to the detergent-resistant membranes (DRM) and HCV particle assembly. We determined that although NS2's DRM localization is dependent on p7, p7 was not targeted to these

  15. Energy transition

    International Nuclear Information System (INIS)

    Anon.

    2013-01-01

    The yearly environmental conference will hold on September 2013 to evaluate the negotiations led at the national and local levels for december 2012. The government will have then to decide of an energy programming bill which will be submitted to the Parliament at the beginning of the year 2014. 30 main propositions have emerged of the decentralised debates. One of them is the ecological taxation which raise the question of the gas oil and petrol taxation. The current environmental taxes are for almost three quarters of them taxes on energy consumptions and mainly on fossil energies. The Economic, Social and Environmental Council, gives his opinion on the way to find resources to ensure the ecological and energy transition while reducing the public deficit of the State. (O.M.)

  16. Identification of E2F1 as a positive transcriptional regulator for δ-catenin

    International Nuclear Information System (INIS)

    Kim, Kwonseop; Oh, Minsoo; Ki, Hyunkyoung; Wang Tao; Bareiss, Sonja; Fini, M. Elizabeth.; Li Dawei; Lu Qun

    2008-01-01

    δ-Catenin is upregulated in human carcinomas. However, little is known about the potential transcriptional factors that regulate δ-catenin expression in cancer. Using a human δ-catenin reporter system, we have screened several nuclear signaling modulators to test whether they can affect δ-catenin transcription. Among β-catenin/LEF-1, Notch1, and E2F1, E2F1 dramatically increased δ-catenin-luciferase activities while β-catenin/LEF-1 induced only a marginal increase. Rb suppressed the upregulation of δ-catenin-luciferase activities induced by E2F1 but did not interact with δ-catenin. RT-PCR and Western blot analyses in 4 different prostate cancer cell lines revealed that regulation of δ-catenin expression is controlled mainly at the transcriptional level. Interestingly, the effects of E2F1 on δ-catenin expression were observed only in human cancer cells expressing abundant endogenous δ-catenin. These studies identify E2F1 as a positive transcriptional regulator for δ-catenin, but further suggest the presence of strong negative regulator(s) for δ-catenin in prostate cancer cells with minimal endogenous δ-catenin expression

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

    International Nuclear Information System (INIS)

    Kasim, Vivi; Huang, Can; Zhang, Jing; Jia, Huizhen; Wang, Yunxia; Yang, Li; Miyagishi, Makoto; Wu, Shourong

    2014-01-01

    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

  18. 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

    Gene expression of the plasminogen activation system is cell-cycle dependent. Previously, we showed that ectopic expression of E2F1 repressed the plasminogen activator inhibitor type 1 (PAI-1) promoter in a manner dependent on the presence of DNA-binding and transactivation domains of E2F1....... These results all indicate that endogenous E2F can directly repress the PAI-1 gene. DNase I hypersensitive-site analysis of the PAI-1 promoter suggested the involvement of conformation changes in chromatin structure of the PAI-1 promoter. 5' deletion analysis of the PAI-1 promoter showed that multiple sites......-regulation of PAI-1 gene expression correlates with an increase in endogenous E2F activity. When cells were treated with a cdk2/4-specific inhibitor, which maintains E2F in an inactive state, the decline of serum-induced PAI-1 mRNA levels was suppressed. In mutant U2OS cells expressing a temperature...

  19. [Variant fusion transcript in ALL children with E2A-PBX1 fusion gene positive].

    Science.gov (United States)

    Li, Zhi-Gang; Zhao, Wei; Wu, Min-Yuan; Hu, Ya-Mei

    2006-06-01

    The study was aimed to investigate the expression of E2A-PBX1 fusion gene in children with acute lymphoblastic leukemia (ALL). The primers located at different sites of E2A and PBX1 gene were used to screen for the fusion gene in 410 children with ALL, including 362 cases of B cell ALL and 48 cases of T cell ALL. The results showed that 17 children carried the fusion gene. The positive rate was 4.1%. Furthermore, all the positive cases expressed a variant type of fusion transcript. It resulted from different splicing of the 13th exon (159 bp) of E2A gene. Analyses with BLASTn indicated that the variant type of transcript retained the open reading frame. However, the loss of 53 amino acid residues which were located at the 2nd activation domain resulted in the partial deletion of the putative loop-helix (LH) structure as well as the complete deletion of the heptad leucine repeat. It is concluded that all the children with ALL positive for the E2A-PBX1 fusion gene express typical and variant fusion transcripts. The latter resulted from different splicing of the 13th exon (159 bp) of E2A gene. The loss of 53aa would lead to the partial deletion of the putative loop-helix (LH) structure as well as the complete deletion of the heptad leucine repeat.

  20. The Cellular Bromodomain Protein Brd4 has Multiple Functions in E2-Mediated Papillomavirus Transcription Activation

    Directory of Open Access Journals (Sweden)

    Christine M. Helfer

    2014-08-01

    Full Text Available The cellular bromodomain protein Brd4 functions in multiple processes of the papillomavirus life cycle, including viral replication, genome maintenance, and gene transcription through its interaction with the viral protein, E2. However, the mechanisms by which E2 and Brd4 activate viral transcription are still not completely understood. In this study, we show that recruitment of positive transcription elongation factor b (P-TEFb, a functional interaction partner of Brd4 in transcription activation, is important for E2’s transcription activation activity. Furthermore, chromatin immunoprecipitation (ChIP analyses demonstrate that P-TEFb is recruited to the actual papillomavirus episomes. We also show that E2’s interaction with cellular chromatin through Brd4 correlates with its papillomavirus transcription activation function since JQ1(+, a bromodomain inhibitor that efficiently dissociates E2-Brd4 complexes from chromatin, potently reduces papillomavirus transcription. Our study identifies a specific function of Brd4 in papillomavirus gene transcription and highlights the potential use of bromodomain inhibitors as a method to disrupt the human papillomavirus (HPV life cycle.

  1. PTEN Physically Interacts with and Regulates E2F1-mediated Transcription in Lung Cancer.

    Science.gov (United States)

    Malaney, Prerna; Palumbo, Emily; Semidey-Hurtado, Jonathan; Hardee, Jamaal; Stanford, Katherine; Kathiriya, Jaymin J; Patel, Deepal; Tian, Zhi; Allen-Gipson, Diane; Davé, Vrushank

    2017-11-06

    PTEN phosphorylation at its C-terminal (C-tail) serine/threonine cluster negatively regulates its tumor suppressor function. However, the consequence of such inhibition and its downstream effects in driving lung cancer remain unexplored. Herein, we ascertain the molecular mechanisms by which phosphorylation compromises PTEN function, contributing to lung cancer. Replacement of the serine/threonine residues with alanine generated PTEN-4A, a phosphorylation-deficient PTEN mutant, which suppressed lung cancer cell proliferation and migration. PTEN-4A preferentially localized to the nucleus where it suppressed E2F1-mediated transcription of cell cycle genes. PTEN-4A physically interacted with the transcription factor E2F1 and associated with chromatin at gene promoters with E2F1 DNA-binding sites, a likely mechanism for its transcriptional suppression function. Deletion analysis revealed that the C2 domain of PTEN was indispensable for suppression of E2F1-mediated transcription. Further, we uncovered cancer-associated C2 domain mutant proteins that had lost their ability to suppress E2F1-mediated transcription, supporting the concept that these mutations are oncogenic in patients. Consistent with these findings, we observed increased PTEN phosphorylation and reduced nuclear PTEN levels in lung cancer patient samples establishing phosphorylation as a bona fide inactivation mechanism for PTEN in lung cancer. Thus, use of small molecule inhibitors that hinder PTEN phosphorylation is a plausible approach to activate PTEN function in the treatment of lung cancer.

  2. 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

    2016-08-01

    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. 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. 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. It was observed that FF Hcy level was significantly higher in PCOS patients compared with non PCOSs (pPCOS 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. 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).

  3. Anomalous DNA binding by E2 regulatory protein driven by spacer sequence TATA.

    Science.gov (United States)

    Xi, Zhiqun; Zhang, Yongli; Hegde, Rashmi S; Shakked, Zippora; Crothers, Donald M

    2010-06-01

    We have investigated the anomalously weak binding of human papillomavirus (HPV) regulatory protein E2 to a DNA target containing the spacer sequence TATA. Experiments in magnesium (Mg(2+)) and calcium (Ca(2+)) ion buffers revealed a marked reduction in cutting by DNase I at the CpG sequence in the protein-binding site 3' to the TATA spacer sequence, Studies of the cation dependence of DNA-E2 affinities showed that upon E2 binding the TATA sequence releases approximately twice as many Mg(2+) ions as the average of the other spacer sequences. Binding experiments for TATA spacer relative to ATAT showed that in potassium ion (K(+)) the E2 affinity of the two sequences is nearly equal, but the relative dissociation constant (K(d)) for TATA increases in the order K(+ )TATA relative to ATAT is independent of ion concentration, whereas for Mg(2+) the affinity for TATA drops sharply as ion concentration increases. Thus, ions of increasing positive charge density increasingly distort the E2 binding site, weakening the affinity for protein. In the case of Mg(2+), additional ions are bound to TATA that require displacement for protein binding. We suggest that the TATA sequence may bias the DNA structure towards a conformation that binds the protein relatively weakly.

  4. 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.

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

    Science.gov (United States)

    El Omari, Kamel; Iourin, Oleg; Harlos, Karl; Grimes, Jonathan M.; Stuart, David I.

    2013-01-01

    Summary 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. PMID:23273918

  6. Synthesis, characterization and computational studies of (E)-2-{[(2-aminopyridine-3-yl)imino]-methyl}-4,6-di-tert-butylphenol

    Energy Technology Data Exchange (ETDEWEB)

    Carreno, Alexander; Vega, Andres, E-mail: ichavez@uc.cl [Departamento de Ciencias Quimicas, Facultad de Ciencias Exactas, Universidad Andres Bello, Santiago (Chile); Zarate, Ximena; Schott, Eduardo [Lab. Bionanotecnologia, Departamento de Ciencias Quimico-Biologicas, Universidad Bernardo O' Higgins, Santiago (Chile); Gacitua, Manuel; Valenzuela, Ninnette; Manriquez, Juan M.; Chavez, Ivonne [Departamento de Quimica Inorganica, Facultad de Quimica, Pontificia Universidad Catolica de Chile, Santiago (Chile); Preite, Marcelo [Departamento de Quimica Inorganica, Facultad de Quimica, Pontificia Universidad Catolica de Chile, Santiago (Chile)

    2014-07-01

    (E)-2-{[(2-Aminopyridine-3-yl)imino]-methyl}-4,6-di-tert-butyl-phenol ( 3: ), a ligand containing an intramolecular hydrogen bond, was prepared according to a previous literature report, with modifications, and was characterized by UV-vis, FTIR, {sup 1}H-NMR, {sup 13}C-NMR, HHCOSY, TOCSY and cyclic voltammetry. Computational analyses at the level of DFT and TD-DFT were performed to study its electronic and molecular structures. The results of these analyses elucidated the behaviors of the UV-vis and electrochemical data. Analysis of the transitions in the computed spectrum showed that the most important band is primarily composed of a HOMO→LUMO transition, designated as an intraligand (IL) charge transfer. (author)

  7. 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.

  8. 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

    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......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...

  9. LISA Pathfinder E2E performance simulation: optical and self-gravity stability analysis

    Science.gov (United States)

    Brandt, N.; Fichter, W.; Kersten, M.; Lucarelli, S.; Montemurro, F.

    2005-05-01

    End-to-end (E2E) modelling and simulation, i.e. verifying the science performance of LISA Pathfinder (spacecraft and payload), is mandatory in order to minimize mission risks. In this paper, focus is on two particular applications of the E2E performance simulator currently being developed at EADS Astrium GmbH: the opto-dynamical stability and the self-gravity disturbance stability analysis. The E2E models applied here comprise the opto-dynamical modelling of the optical metrology systems (OMS) laser interferometry, the thermo-elastic distortion modelling of the OMS optical elements and the self-gravity disturbance model accounting for structural distortions. Preliminary analysis results are presented in detail, identifying shortcomings of the current LISA technology package (LTP) mounting baseline. As a consequence, the design is now being revised.

  10. LISA Pathfinder E2E performance simulation: optical and self-gravity stability analysis

    International Nuclear Information System (INIS)

    Brandt, N; Fichter, W; Kersten, M; Lucarelli, S; Montemurro, F

    2005-01-01

    End-to-end (E2E) modelling and simulation, i.e. verifying the science performance of LISA Pathfinder (spacecraft and payload), is mandatory in order to minimize mission risks. In this paper, focus is on two particular applications of the E2E performance simulator currently being developed at EADS Astrium GmbH: the opto-dynamical stability and the self-gravity disturbance stability analysis. The E2E models applied here comprise the opto-dynamical modelling of the optical metrology systems (OMS) laser interferometry, the thermo-elastic distortion modelling of the OMS optical elements and the self-gravity disturbance model accounting for structural distortions. Preliminary analysis results are presented in detail, identifying shortcomings of the current LISA technology package (LTP) mounting baseline. As a consequence, the design is now being revised

  11. Regulation of E2F1 Transcription Factor by Ubiquitin Conjugation

    Directory of Open Access Journals (Sweden)

    Laurence Dubrez

    2017-10-01

    Full Text Available Ubiquitination is a post-translational modification that defines the cellular fate of intracellular proteins. It can modify their stability, their activity, their subcellular location, and even their interacting pattern. This modification is a reversible event whose implementation is easy and fast. It contributes to the rapid adaptation of the cells to physiological intracellular variations and to intracellular or environmental stresses. E2F1 (E2 promoter binding factor 1 transcription factor is a potent cell cycle regulator. It displays contradictory functions able to regulate both cell proliferation and cell death. Its expression and activity are tightly regulated over the course of the cell cycle progression and in response to genotoxic stress. I discuss here the most recent evidence demonstrating the role of ubiquitination in E2F1’s regulation.

  12. ApoE2 Exaggerates PTSD-Related Behavioral, Cognitive, and Neuroendocrine Alterations.

    Science.gov (United States)

    Johnson, Lance A; Zuloaga, Damian G; Bidiman, Erin; Marzulla, Tessa; Weber, Sydney; Wahbeh, Helane; Raber, Jacob

    2015-09-01

    Apolipoprotein E (apoE) is an essential component of lipoprotein particles in both the brain and periphery, and exists in three isoforms in the human population: E2, E3, and E4. ApoE has numerous, well-established roles in neurobiology. Most notably, E4 is associated with earlier onset and increased risk of Alzheimer's disease (AD). Although possession of E2 is protective in the context of AD, E2 appears to confer an increased incidence and severity of posttraumatic stress disorder (PTSD). However, the biological processes underlying this link remain unclear. In this study, we began to elucidate these associations by examining the effects of apoE on PTSD severity in combat veterans, and on PTSD-like behavior in mice with human apoE. In a group of 92 veterans with PTSD, we observed significantly higher Clinician-Administered PTSD Scale and PTSD Checklist scores in E2+ individuals, as well as alterations in salivary cortisol levels. Furthermore, we measured behavioral and biological outcomes in mice expressing human apoE after a single stressful event as well as following a period of chronic variable stress, a model of combat-related trauma. Mice with E2 showed impairments in fear extinction, and behavioral, cognitive, and neuroendocrine alterations following trauma. To the best of our knowledge, these data constitute the first translational demonstration of PTSD severity in men and PTSD-like symptoms in mice with E2, and point to apoE as a novel biomarker of susceptibility, and potential therapeutic target, for PTSD.

  13. Comparative genomics reveals multistep pathogenesis of E2A-PBX1 acute lymphoblastic leukemia.

    Science.gov (United States)

    Duque-Afonso, Jesús; Feng, Jue; Scherer, Florian; Lin, Chiou-Hong; Wong, Stephen H K; Wang, Zhong; Iwasaki, Masayuki; Cleary, Michael L

    2015-09-01

    Acute lymphoblastic leukemia (ALL) is the most common childhood cancer; however, its genetic diversity limits investigation into the molecular pathogenesis of disease and development of therapeutic strategies. Here, we engineered mice that conditionally express the E2A-PBX1 fusion oncogene, which results from chromosomal translocation t(1;19) and is present in 5% to 7% of pediatric ALL cases. The incidence of leukemia in these mice varied from 5% to 50%, dependent on the Cre-driving promoter (Cd19, Mb1, or Mx1) used to induce E2A-PBX1 expression. Two distinct but highly similar subtypes of B cell precursor ALLs that differed by their pre-B cell receptor (pre-BCR) status were induced and displayed maturation arrest at the pro-B/large pre-B II stages of differentiation, similar to human E2A-PBX1 ALL. Somatic activation of E2A-PBX1 in B cell progenitors enhanced self-renewal and led to acquisition of multiple secondary genomic aberrations, including prominent spontaneous loss of Pax5. In preleukemic mice, conditional Pax5 deletion cooperated with E2A-PBX1 to expand progenitor B cell subpopulations, increasing penetrance and shortening leukemia latency. Recurrent secondary activating mutations were detected in key signaling pathways, most notably JAK/STAT, that leukemia cells require for proliferation. These data support conditional E2A-PBX1 mice as a model of human ALL and suggest targeting pre-BCR signaling and JAK kinases as potential therapeutic strategies.

  14. GCN5 acetylates and regulates the stability of the oncoprotein E2A-PBX1 in acute lymphoblastic leukemia.

    Science.gov (United States)

    Holmlund, T; Lindberg, M J; Grander, D; Wallberg, A E

    2013-03-01

    The t(1;19) translocation in pediatric pre-B-cell acute lymphoblastic leukemia (ALL) fuses the genes, which encode the transcriptional activator E2A and homeobox pre-B-cell leukemia transcription factor 1 (PBX1), resulting in expression of the chimeric transcription factor E2A-PBX1. E2A-PBX1 can promote cell transformation both in vitro and in vivo; however, the mechanisms by which E2A-PBX1 contributes to malignancy merit further investigation. In the current work we report, for the first time, a physical and functional interaction between the SPT3-TAFII31-GCN5L acetylase (STAGA) complex and E2A-PBX1. STAGA, and its acetyltransferase subunit GCN5, directly interacted with the E2A portion of E2A-PBX1. GCN5 acetylated E2A-PBX1 and increased the stability of E2A-PBX1 protein in cells. Moreover, the GCN5 inhibitor α-methylene-γ-butyrolactone 3 (MB-3) decreased E2A-PBX1 acetylation and E2A-PBX1 protein levels in leukemic cells, indicating that GCN5 inhibitors have potential value as therapeutic agents for ALL. In addition, we show that the E3 ubiquitin ligase HDM2 potentiates the degradation of E2A-PBX1. We suggest that dynamic regulation of E2A-PBX1 protein levels in vivo has a fundamental role in ALL.

  15. Brd4-Mediated Nuclear Retention of the Papillomavirus E2 Protein Contributes to Its Stabilization in Host Cells

    Directory of Open Access Journals (Sweden)

    Jing Li

    2014-01-01

    Full Text Available Papillomavirus E2 is a multifunctional viral protein that regulates many aspects of the viral life cycle including viral episome maintenance, transcriptional activation, and repression. E2 is degraded by the ubiquitin-proteasome pathway. Cellular bromodomain protein Brd4 has been implicated in the stabilization of the E2 protein. E2 normally shuttles between the cytoplasm and the nucleus. In this study, we demonstrate that E2 ubiquitylation mostly occurs in the cytoplasm. We also find that the interaction with Brd4 promotes nuclear retention of papillomavirus E2 proteins and contributes to their stabilization in the nucleus. Compared to wild type E2 proteins, nuclear-localization-defective mutants are rapidly degraded by the ubiquitin-proteasome pathway; however, co-expression of Brd4 redirects these mutants into the nucleus and significantly increases their stability. We further demonstrate that tethering E2 proteins to chromatin as either double-bromodomain fusion proteins or histone 2B (H2B fusion proteins significantly stabilizes the E2 proteins. Our studies suggest that chromatin recruitment of the E2 protein via interaction with Brd4 prevents E2 ubiquitylation and proteasomal degradation in the cytoplasm, leading to its stabilization in the nucleus. These studies bring new insights for understanding Brd4-mediated E2 stabilization, and provide an additional mechanism by which the chromatin-associated Brd4 regulates E2 functions.

  16. 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

  17. E2F repression by C/EBPalpha is required for adipogenesis and granulopoiesis in vivo

    DEFF Research Database (Denmark)

    Porse, B T; Pedersen TA; Xu, X

    2001-01-01

    -dependent transcription and found them to be impaired in their ability to suppress cellular proliferation, and to induce adipocyte differentiation in vitro. Using targeted mutagenesis of the mouse germline, we show that E2F repression-deficient C/EBPalpha alleles failed to support adipocyte and granulocyte...... differentiation in vivo. These results indicate that E2F repression by C/EBPalpha is critical for its ability to induce terminal differentiation, and thus provide genetic evidence that direct cell cycle control by a mammalian lineage-instructive transcription factor couples cellular growth arrest...

  18. 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).

  19. 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

  20. 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.

  1. The Mechanism of E2F/P130 Mediated Repression and Its Potential Tumor Suppressor Function in Breast Cancer

    National Research Council Canada - National Science Library

    Meloni, Alison

    1999-01-01

    .... Previous work has shown the importance of E2F-Rb and E2F-p13O complexes in promoting this transcriptional silencing, however, the mechanisms of action of these complexes has yet to be thoroughly elucidated...

  2. Branching ratios of radiative transitions in O VI

    International Nuclear Information System (INIS)

    Sur, Chiranjib; Chaudhuri, Rajat K

    2007-01-01

    We study the branching ratios of the allowed and forbidden radiative transitions among the first few (9) fine structure levels of O VI using relativistic coupled-cluster theory. We find irregular patterns for a number of transitions within n-complexes with n ≤ 4. We have used the existing values of the allowed electric dipole (E1) transition as a benchmark of our theory. Good agreement with the existing values establish accuracies of not only the theoretical method but the basis function as well. In general, the electric quadrupole (E2) transition probabilities are greater in magnitude than magnetic dipole (M1) transition probabilities, whereas for medium atomic transition frequencies they are of the same order of magnitude. On the other hand, if the transitions involved are in between two fine-structure components of the same term, then the M1 transition probability is more probable than that of E2. The results presented here in tabular and graphical form are compared with the available theoretical and observed data. Graphical analysis helps to understand the trends of electric and magnetic transitions for the decay channels presented here. Our calculated values of the lifetimes of the excited states are in very good agreement with the available results

  3. 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...

  4. 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...

  5. Changes in Gene Expression and Estrogen Receptor Cistrome in Mouse Liver Upon Acute E2 Treatment

    Science.gov (United States)

    Palierne, Gaëlle; Fabre, Aurélie; Solinhac, Romain; Le Péron, Christine; Avner, Stéphane; Lenfant, Françoise; Fontaine, Coralie; Salbert, Gilles; Flouriot, Gilles; Arnal, Jean-François

    2016-01-01

    Transcriptional regulation by the estrogen receptor-α (ER) has been investigated mainly in breast cancer cell lines, but estrogens such as 17β-estradiol (E2) exert numerous extrareproductive effects, particularly in the liver, where E2 exhibits both protective metabolic and deleterious thrombotic actions. To analyze the direct and early transcriptional effects of estrogens in the liver, we determined the E2-sensitive transcriptome and ER cistrome in mice after acute administration of E2 or placebo. These analyses revealed the early induction of genes involved in lipid metabolism, which fits with the crucial role of ER in the prevention of liver steatosis. Characterization of the chromatin state of ER binding sites (BSs) in mice expressing or not ER demonstrated that ER is not required per se for the establishment and/or maintenance of chromatin modifications at the majority of its BSs. This is presumably a consequence of a strong overlap between ER and hepatocyte nuclear factor 4α BSs. In contrast, 40% of the BSs of the pioneer factor forkhead box protein a (Foxa2) were dependent upon ER expression, and ER expression also affected the distribution of nucleosomes harboring dimethylated lysine 4 of Histone H3 around Foxa2 BSs. We finally show that, in addition to a network of liver-specific transcription factors including CCAAT/enhancer-binding protein and hepatocyte nuclear factor 4α, ER might be required for proper Foxa2 function in this tissue. PMID:27164166

  6. 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

  7. Stages of Change – Continuous Measure (URICA-E2): psychometrics of a Norwegian version

    Science.gov (United States)

    Lerdal, Anners; Moe, Britt; Digre, Elin; Harding, Thomas; Kristensen, Frode; Grov, Ellen K; Bakken, Linda N; Eklund, Marthe L; Ruud, Ireen; Rossi, Joseph S

    2009-01-01

    Title Stages of Change – Continuous Measure (URICA-E2): psychometrics of a Norwegian version. Aim This paper is a report of research to translate the English version of the Stages of Change continuous measure questionnaire (URICA-E2) into Norwegian and to test the validity of the questionnaire and its usefulness in predicting behavioural change. Background While the psychometric properties of the Stages of Change categorical measure have been tested extensively, evaluation of the psychometric properties of the continuous questionnaire has not been described elsewhere in the literature. Method Cross-sectional data were collected with a convenience sample of 198 undergraduate nursing students in 2005 and 2006. The English version of URICA-E2 was translated into Norwegian according to standardized procedures. Findings Principal components analysis clearly confirmed five of the dimensions of readiness to change (Precontemplation Non-Believers, Precontemplation Believers, Contemplation, Preparation and Maintenance), while the sixth dimension, Action, showed the lowest Eigenvalue (0·93). Findings from the cluster analysis indicate distinct profiles among the respondents in terms of readiness to change their exercise behaviour. Conclusion The URICA-E2 was for the most part replicated from Reed’s original work. The result of the cluster analysis of the items associated with the factor ‘Action’ suggests that these do not adequately measure the factor. PMID:19032513

  8. Protein kinase A-dependent transactivation by the E2A-Pbx1 fusion protein.

    Science.gov (United States)

    Ogo, A; Waterman, M R; Kamps, M P; Kagawa, N

    1995-10-27

    The chimeric gene E2A-PBX1 is formed by the t(1;19) chromosomal translocation exclusively associated with pediatric pre-B cell acute lymphoblastic leukemia (pre-B ALL). The resultant fusion protein from this chimeric gene contains the DNA-binding homeodomain of Pbx1. The first and only functional Pbx1 binding site has been localized in bovine CYP17 to a sequence (CRS1) that participates in cAMP-dependent transcription of this gene encoding the steroid hydroxylase, 17 alpha-hydroxylase cytochrome P450. Because Pbx1 is not expressed in pre-B cells, it may be possible that the E2a-Pbx1 fusion protein expressed in pre-B cells having this translocation will activate, in response to cAMP, transcription of genes not normally expressed in these cells leading to arrest of differentiation at the pre-B cell stage. We have now shown that reporter genes comprising CRS1 are activated transcriptionally by protein kinase A (PKA) in the pre-B cell line 697, which endogenously expresses the fusion protein, and that overexpression of E2A-Pbx1 in additional cell lines enhances transcription of reporter genes in a PKA-dependent fashion. Thus, it seems plausible that arrest in the pre-B stage leading to pre-B ALL includes cAMP-dependent activation of E2A-Pbx1.

  9. Controlling Depth of Cellular Quiescence by an Rb-E2F Network Switch

    Directory of Open Access Journals (Sweden)

    Jungeun Sarah Kwon

    2017-09-01

    Full Text Available Quiescence is a non-proliferative cellular state that is critical to tissue repair and regeneration. Although often described as the G0 phase, quiescence is not a single homogeneous state. As cells remain quiescent for longer durations, they move progressively deeper and display a reduced sensitivity to growth signals. Deep quiescent cells, unlike senescent cells, can still re-enter the cell cycle under physiological conditions. Mechanisms controlling quiescence depth are poorly understood, representing a currently underappreciated layer of complexity in growth control. Here, we show that the activation threshold of a Retinoblastoma (Rb-E2F network switch controls quiescence depth. Particularly, deeper quiescent cells feature a higher E2F-switching threshold and exhibit a delayed traverse through the restriction point (R-point. We further show that different components of the Rb-E2F network can be experimentally perturbed, following computer model predictions, to coarse- or fine-tune the E2F-switching threshold and drive cells into varying quiescence depths.

  10. "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…

  11. Inhibition of in vitro myogenic differentiation by cellular transcription factor E2F1

    DEFF Research Database (Denmark)

    Wang, J; Helin, K; Jin, P

    1995-01-01

    expression is irreversibly down-regulated during differentiation of C2C12 myocytes. Furthermore, deregulated E2F1 expression in C2C12 cells prevented myogenic differentiation. This inhibition of myogenesis was associated with the repression of myogenin expression and an elevated cyclin D1 expression...

  12. 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...

  13. 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 activation...

  14. 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

    The "pocket proteins" pRb (retinoblastoma tumor suppressor protein), p107, and p130 regulate cell proliferation via phosphorylation-sensitive interactions with E2F transcription factors and other proteins. We previously identified 22 in vivo phosphorylation sites in human p130, including three...

  15. Gingival inflammation assessed by histology, 3H-estrone metabolism and prostaglandin E2 levels

    International Nuclear Information System (INIS)

    Holmes, L.G.; ElAttar, T.M.A.

    1977-01-01

    Gingival samples were histologically evaluated and placed in two groups, 7 samples each. Group 1 was normal gingiva with no or very few inflammatory cells and group 2 was inflamed gingiva with moderately dense accumulation of imflammatory cells in isolated areas, and sparse distribution in other areas. One hundred to three hundred mg gingival tissue samples were separately homogenized in 7 ml of 0.1 M potasssium phosphate buffer (pH 7.4) and incubated with 1.51 x 10 -4 μM of 3 H-estrone in the presence of NADPH at 37 deg for three hours. Organic solvent extracts of the homogenates were separated by silica gel thin layer chromatography and the radioactivity incorporated in estrone (E 1 ) and estradiol-17 β (E 2 ) zones was extracted with methanol and measured by liquid scintillation spectrometry. The rate conversion of (E 1 ) to (E 2 ) in normal and inflamed gingiva was 4.4 and 8.3 x 10 -7 μM/g/min respectively. Prostaglandin E 2 in 3 normal and 2 inflamed gingival samples were 37.8 and 448.7 pmole/g respectively. The significant increase in the biosynthesis of (E 2 ) and PGE 2 in inflamed as compared with normal gingiva could be a systemic factor in aggravating gingival inflammation due to the hyperemic effects of these hormones. (author)

  16. [Foley catheter versus prostaglandin E2 gel for induction of labour at term: the PROBAAT study

    NARCIS (Netherlands)

    Jozwiak, M.; Oude Rengerink, K.; Leeuw, J.W. de; Mol, B.W.; Bloemenkamp, K.W.; Benthem, M.; Beek, E. van; Dijksterhuis, M.G.; Graaf, I.M. de; Huizen, M.E. van; Oudijk, M.A.; Papatsonis, D.N.; Perquin, D.A.; Porath, M.; Post, J.A. van der; Rijnders, R.J.; Scheepers, H.C.; Spaanderman, M.E.A.; Pampus, M.G. van

    2012-01-01

    Objective To study the effectiveness and safety of induction of labour with a Foley catheter compared with vaginal prostaglandin E2 gel in full term pregnant women. Design Multicentre, randomised, open-label trial in 12 hospitals in the Netherlands between February 2009 and May 2010. Methods Women

  17. Foleykatheter versus prostaglandine E2-gel voor inleiden van aterme baring

    NARCIS (Netherlands)

    Jozwiak, M.; Oude Rengerink, K.; de Leeuw, J. W.; Mol, B. W. J.; Bloemenkamp, K. W. M.; Benthem, M.; van Beek, E.; Dijksterhuis, M. G. K.; de Graaf, I. M.; van Huizen, M. E.; Oudijk, M. A.; Papatsonis, D. N. M.; Perquin, D. A. M.; Porath, M.; van der Post, J. A. M.; Rijnders, R. J. P.; Scheepers, H. C. J.; Spaanderman, M. E. A.; van Pampus, M. G.

    2012-01-01

    OBJECTIVE : To study the effectiveness and safety of induction of labour with a Foley catheter compared with vaginal prostaglandin E2 gel in full term pregnant women. DESIGN : Multicentre, randomised, open-label trial in 12 hospitals in the Netherlands between February 2009 and May 2010. METHODS :

  18. Dual inhibition of nitric oxide and prostaglandin E2 production by polysubstituted 2-aminopyrimidines

    Czech Academy of Sciences Publication Activity Database

    Zídek, Zdeněk; Kverka, Miloslav; Dusilová, Adéla; Kmoníčková, Eva; Jansa, Petr

    2016-01-01

    Roč. 57, jul (2016), s. 48-56 ISSN 1089-8603 R&D Projects: GA ČR(CZ) GAP303/12/0172 Institutional support: RVO:68378041 ; RVO:61388963 Keywords : pyrimidines * nitric oxide * prostaglandin E-2 Subject RIV: FR - Pharmacology ; Medidal Chemistry; CC - Organic Chemistry (UOCHB-X) Impact factor: 4.181, year: 2016

  19. 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...

  20. 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...

  1. Human TFDP3, a novel DP protein, inhibits DNA binding and transactivation by E2F

    DEFF Research Database (Denmark)

    Qiao, Huan; Di Stefano, Luisa; Tian, Chan

    2006-01-01

    The two known DP proteins, TFDP1 and -2, bind E2Fs to form heterodimers essential for high affinity DNA binding and efficient transcriptional activation/repression. Here we report the identification of a new member of the DP family, human TFDP3. Despite the high degree of sequence similarity, TFD...

  2. Scaling of triple differential cross-sections for asymmetric (e,2e ...

    Indian Academy of Sciences (India)

    A simple scaling law is obtained for asymmetric (e, 2e) process on helium isoelectronic ions by ... the process. Several studies were carried out thereafter on various neutral atomic targets to measure and calculate the triple differential cross-sections (TDCS) for .... metric kinematics for ionization by fast electrons. Figures 1 ...

  3. Direct and indirect targets of the E2A-PBX1 leukemia-specific fusion protein

    OpenAIRE

    Wiemels, Joseph; Diakos, C; Xiao, Y; Zheng, S; Kager, L; Dworzak, M; Wiemels, JL

    2014-01-01

    E2A-PBX1 is expressed as a result of the t(1;19) chromosomal translocation in nearly 5% of cases of childhood acute lymphoblastic leukemia. The E2A-PBX1 chimeric transcription factor contains the N-terminal transactivation domain of E2A (TCF3) fused to the

  4. E2A proteins are required for proper B cell development and initiation of immunoglobulin gene rearrangements

    NARCIS (Netherlands)

    Bain, G.; Maandag, E. C.; Izon, D. J.; Amsen, D.; Kruisbeek, A. M.; Weintraub, B. C.; Krop, I.; Schlissel, M. S.; Feeney, A. J.; van Roon, M.

    1994-01-01

    E12 and E47 are two helix-loop-helix transcription factors that arise by alternative splicing of the E2A gene. Both have been implicated in the regulation of immunoglobulin gene expression. We have now generated E2A (-/-) mice by gene targeting. E2A-null mutant mice fail to generate mature B cells.

  5. 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...

  6. An intronic microRNA links Rb/E2F and EGFR signaling.

    Directory of Open Access Journals (Sweden)

    Mary Truscott

    2014-07-01

    Full Text Available The importance of microRNAs in the regulation of various aspects of biology and disease is well recognized. However, what remains largely unappreciated is that a significant number of miRNAs are embedded within and are often co-expressed with protein-coding host genes. Such a configuration raises the possibility of a functional interaction between a miRNA and the gene it resides in. This is exemplified by the Drosophila melanogaster dE2f1 gene that harbors two miRNAs, mir-11 and mir-998, within its last intron. miR-11 was demonstrated to limit the proapoptotic function of dE2F1 by repressing cell death genes that are directly regulated by dE2F1, however the biological role of miR-998 was unknown. Here we show that one of the functions of miR-998 is to suppress dE2F1-dependent cell death specifically in rbf mutants by elevating EGFR signaling. Mechanistically, miR-998 operates by repressing dCbl, a negative regulator of EGFR signaling. Significantly, dCbl is a critical target of miR-998 since dCbl phenocopies the effects of miR-998 on dE2f1-dependent apoptosis in rbf mutants. Importantly, this regulation is conserved, as the miR-998 seed family member miR-29 repressed c-Cbl, and enhanced MAPK activity and wound healing in mammalian cells. Therefore, the two intronic miRNAs embedded in the dE2f1 gene limit the apoptotic function of dE2f1, but operate in different contexts and act through distinct mechanisms. These results also illustrate that examining an intronic miRNA in the context of its host's function can be valuable in elucidating the biological function of the miRNA, and provide new information about the regulation of the host gene itself.

  7. 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

    . In conclusion, PGE2 and PGI2 may protect renal perfusion by activating cognate IP and EP4 receptors associated with smooth muscle cells and endothelium in human intrarenal arteries and contribute to increased renal vascular resistance at high pathological concentrations mediated by noncognate TP receptor.......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...... and PGI2 induced concentration-dependent relaxation (-log EC50: PGE2=7.1±0.3 and PGI2=7.7). The response to PGE2 displayed endothelium dependence and desensitization. Relaxation by PGE2 was mimicked by an EP4 receptor agonist (CAY10598, EC50=6.7±0.2). The relaxation after PGI2 was abolished by an IP...

  8. Neutralizing activities of caprine antibodies towards conserved regions of the HCV envelope glycoprotein E2

    Directory of Open Access Journals (Sweden)

    El-Shenawy Reem

    2011-08-01

    Full Text Available Abstract Anti HCV vaccine is not currently available and the present antiviral therapies fail to cure approximately half of the treated HCV patients. This study was designed to assess the immunogenic properties of genetically conserved peptides derived from the C-terminal region of HVR-1 and test their neutralizing activities in a step towards developing therapeutic and/or prophylactic immunogens against HCV infection. Antibodies were generated by vaccination of goats with synthetic peptides derived from HCV E2. Viral neutralizing capacity of the generated anti E2 antibodies was tested using in vitro assays. Goats immunized with E2 synthetic peptides termed p412 [a.a 412-419], p430 [a.a 430-447] and p517 [a.a 517-531] generated high titers of antibody responses 2 to 4.5 fold higher than comparable titers of antibodies to the same epitopes in chronic HCV patients. In post infection experiments of native HCV into cultured Huh7.5 cells anti p412 and anti p 517 were proven to be neutralizing to HCV genotype 4a from patients' sera (87.5% and 75% respectively. On the contrary anti p430 exhibited weak viral neutralization capacity on the same samples (31.25%. Furthermore Ab mixes containing anti p430 exhibited reduced viral neutralization properties. From these experiments one could predict that neutralization by Abs towards different E2-epitopes varies considerably and success in the enrichment of neutralization epitope-specific antibodies may be accompanied by favorable results in combating HCV infection. Also, E2 conserved peptides p517 and p412 represent potential components of a candidate peptide vaccine against HCV infection.

  9. VirE2: a unique ssDNA-compacting molecular machine.

    Directory of Open Access Journals (Sweden)

    Wilfried Grange

    2008-02-01

    Full Text Available The translocation of single-stranded DNA (ssDNA across membranes of two cells is a fundamental biological process occurring in both bacterial conjugation and Agrobacterium pathogenesis. Whereas bacterial conjugation spreads antibiotic resistance, Agrobacterium facilitates efficient interkingdom transfer of ssDNA from its cytoplasm to the host plant cell nucleus. These processes rely on the Type IV secretion system (T4SS, an active multiprotein channel spanning the bacterial inner and outer membranes. T4SSs export specific proteins, among them relaxases, which covalently bind to the 5' end of the translocated ssDNA and mediate ssDNA export. In Agrobacterium tumefaciens, another exported protein-VirE2-enhances ssDNA transfer efficiency 2000-fold. VirE2 binds cooperatively to the transferred ssDNA (T-DNA and forms a compact helical structure, mediating T-DNA import into the host cell nucleus. We demonstrated-using single-molecule techniques-that by cooperatively binding to ssDNA, VirE2 proteins act as a powerful molecular machine. VirE2 actively pulls ssDNA and is capable of working against 50-pN loads without the need for external energy sources. Combining biochemical and cell biology data, we suggest that, in vivo, VirE2 binding to ssDNA allows an efficient import and pulling of ssDNA into the host. These findings provide a new insight into the ssDNA translocation mechanism from the recipient cell perspective. Efficient translocation only relies on the presence of ssDNA binding proteins in the recipient cell that compacts ssDNA upon binding. This facilitated transfer could hence be a more general ssDNA import mechanism also occurring in bacterial conjugation and DNA uptake processes.

  10. An Alphavirus E2 Membrane-Proximal Domain Promotes Envelope Protein Lateral Interactions and Virus Budding

    Directory of Open Access Journals (Sweden)

    Emily A. Byrd

    2017-11-01

    Full Text Available Alphaviruses are members of a group of small enveloped RNA viruses that includes important human pathogens such as Chikungunya virus and the equine encephalitis viruses. The virus membrane is covered by a lattice composed of 80 spikes, each a trimer of heterodimers of the E2 and E1 transmembrane proteins. During virus endocytic entry, the E1 glycoprotein mediates the low-pH-dependent fusion of the virus membrane with the endosome membrane, thus initiating virus infection. While much is known about E1 structural rearrangements during membrane fusion, it is unclear how the E1/E2 dimer dissociates, a step required for the fusion reaction. A recent Alphavirus cryo-electron microscopy reconstruction revealed a previously unidentified D subdomain in the E2 ectodomain, close to the virus membrane. A loop within this region, here referred to as the D-loop, contains two highly conserved histidines, H348 and H352, which were hypothesized to play a role in dimer dissociation. We generated Semliki Forest virus mutants containing the single and double alanine substitutions H348A, H352A, and H348/352A. The three D-loop mutations caused a reduction in virus growth ranging from 1.6 to 2 log but did not significantly affect structural protein biosynthesis or transport, dimer stability, virus fusion, or specific infectivity. Instead, growth reduction was due to inhibition of a late stage of virus assembly at the plasma membrane. The virus particles that are produced show reduced thermostability compared to the wild type. We propose the E2 D-loop as a key region in establishing the E1-E2 contacts that drive glycoprotein lattice formation and promote Alphavirus budding from the plasma membrane.

  11. Efficient in-band diode-pumped Q-switched solid state laser for methane detection, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — We propose to develop an efficient, tunable Q-switched SSL operating at a wavelength of 1651 nm with pulse energy >1 mJ at 2000 Hz repetition rate with in-band...

  12. Prostaglandin synthesis and catabolism in the gastric mucosa: studies in normal rabbits and rabbits immunized with prostaglandin E2

    International Nuclear Information System (INIS)

    Redfern, J.S.

    1988-01-01

    Antral and fundic mucosal homogenates obtained from prostaglandin E2-immunized rabbits converted 14C-arachidonic acid to prostaglandin E2, 6-keto prostaglandin F1 alpha, prostaglandin F2 alpha, and prostaglandin D2. Percentage conversion of 14C-arachidonic acid to these prostaglandin products was not significantly different in prostaglandin E2-immunized rabbits compared with control rabbits (thyroglobulin-immunized and unimmunized rabbits combined). Synthesis of 6-keto prostaglandin F1 alpha, prostaglandin E2 and 13,14-dihydro 15-keto prostaglandin E2 from endogenous arachidonic acid after vortex mixing fundic mucosal homogenates was similar in prostaglandin E2 immunized rabbits and control rabbits. Both in prostaglandin E2-immunized rabbits and controls, 3H-prostaglandin E2 was catabolized extensively by the fundic mucosa, whereas 3H-6-keto prostaglandin F1 alpha, 3H-prostaglandin F2 alpha, and 3H-prostaglandin D2 were not catabolized to any appreciable extent. The rate of catabolism of PGs was not significantly different in prostaglandin E2-immunized rabbits and control rabbits, with the exception of prostaglandin F2 alpha which was catabolized slightly more rapidly in prostaglandin E2-immunized rabbits. These results indicate that development of gastric ulcers in prostaglandin E2-immunized rabbits is not associated with an alteration in the capacity of the gastric mucosa to synthesize or catabolize prostaglandins

  13. 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

    suppressor protein or neutralizing antibodies to cyclin D1, E2F-4 and -5 do not. Using E2F-1 and E2F-4 as representatives of the two subgroups, we showed here, by constructing a set of chimeric proteins, that the amino terminus of E2F-1 is sufficient to confer S-phase-inducing potential as well...... 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...

  14. COMPARISON OF INTRACERVICAL PROSTAGLANDIN E2 AND INTRAVENOUS OXYTOCIN IN INDUCTION OF LABOUR.

    Science.gov (United States)

    Bhattacharyya, T K; Shandil, M S

    1998-07-01

    154 patients requiring induction with unfavourable cervix at varying period of gestation were studied. Patients were distributed into two groups. 76 patients were induced with 0.5 mgm single dose intracervical application of Prostaglandin E2 gel and remaining 78 patients with Oxytocin and efficacy of the two methods of induction was compared. Labour was established within 24 hours in 71.4% of primigravidas and 91.7% of multigravidas in the prostaglandin treated group compared to 65.6% of primigravidas and 89.1% of multigravidas in the oxytocin group. The study found substantial improvement in cervical score 12 hours after application of intracervical prostaglandin E2 gel and decrease in Caesarean section rate with no major adverse effect to mother or neonate.

  15. Sweeping of membranes vs. intracervical prostaglandin E2 gel for cervical ripening. Randomized trial.

    Science.gov (United States)

    Gemer, O; Kapustian, V; Harari, D; Sassoon, E; Segal, S

    2001-08-01

    To compare intracervical prostaglandin E2 gel and membrane sweeping for cervical ripening. Fifty patients were randomized to either intracervical prostaglandin E2 or membrane sweeping. A Bishop score was assigned by a blinded examiner prior to and 24 hours following the procedure. The Bishop scores assigned 24 hours after prostaglandin instillation and membrane sweeping were not significantly different (3.4, SE 0.42, vs. 3.3, SE 0.37, respectively; P > .05). The proportions of women entering active labor or delivering within 24 hours were similar in the prostaglandin and membrane groups (21% and 19%, respectively; P > .05). When both intracervical prostaglandin insertion and membrane sweeping are feasible, their salutary effects are comparable.

  16. E2A-PBX1 fusion in adult acute lymphoblastic leukaemia: biological and clinical features.

    Science.gov (United States)

    Foa, Robin; Vitale, Antonella; Mancini, Marco; Cuneo, Antonio; Mecucci, Cristina; Elia, Loredana; Lombardo, Romina; Saglio, Giuseppe; Torelli, Giuseppe; Annino, Luciana; Specchia, Giorgina; Damasio, Eugenio; Recchia, Anna; Di Raimondo, Francesco; Morra, Enrica; Volpe, Ettore; Tafuri, Agostino; Fazi, Paola; Hunger, Stephen P; Mandelli, Franco

    2003-02-01

    Molecular and cytogenetic studies performed in 305 adult acute lymphoblastic leukaemia (ALL) patients enrolled in the gimema (Gruppo Italiano Malattie EMatologiche dell'Adulto) multicentric protocols identified an E2A-PBX1 fusion and/or t(1;19) in 10 patients (3.3%). All had common ALL, were mostly CyIg+ and were CD34/CD13/CD33-. Nine patients achieved a complete remission (CR); five patients showed a haematological relapse after 7 months (median). Four patients are alive in first CR with a median follow-up of 29 months; three patients are molecularly negative. This abnormality is frequently associated with early treatment failure. E2A-PBX1+ adult ALL should be considered for intensified treatment strategies and monitoring of minimal residual disease.

  17. E2 enzyme inhibition by stabilization of a low-affinity interface with ubiquitin.

    Science.gov (United States)

    Huang, Hao; Ceccarelli, Derek F; Orlicky, Stephen; St-Cyr, Daniel J; Ziemba, Amy; Garg, Pankaj; Plamondon, Serge; Auer, Manfred; Sidhu, Sachdev; Marinier, Anne; Kleiger, Gary; Tyers, Mike; Sicheri, Frank

    2014-02-01

    Weak protein interactions between ubiquitin and the ubiquitin-proteasome system (UPS) enzymes that mediate its covalent attachment to substrates serve to position ubiquitin for optimal catalytic transfer. We show that a small-molecule inhibitor of the E2 ubiquitin-conjugating enzyme Cdc34A, called CC0651, acts by trapping a weak interaction between ubiquitin and the E2 donor ubiquitin-binding site. A structure of the ternary CC0651-Cdc34A-ubiquitin complex reveals that the inhibitor engages a composite binding pocket formed from Cdc34A and ubiquitin. CC0651 also suppresses the spontaneous hydrolysis rate of the Cdc34A-ubiquitin thioester without decreasing the interaction between Cdc34A and the RING domain subunit of the E3 enzyme. Stabilization of the numerous other weak interactions between ubiquitin and UPS enzymes by small molecules may be a feasible strategy to selectively inhibit different UPS activities.

  18. Concomitant sensitization to legumin, Fag e 2 and Fag e 5 predicts buckwheat allergy

    DEFF Research Database (Denmark)

    Geiselhart, S; Nagl, C; Dubiela, P

    2018-01-01

    pattern in sera from allergic patients when compared to sensitized individuals. Several IgE-reactive proteins were purified from crude buckwheat extract, namely legumin (Fag e 1 plus its large subunit), Fag e 2 (2S albumin), and newly identified Fag e 5 (vicilin-like) as well as hevein-like antimicrobial...... vicilin-like protein as a new relevant marker allergen, designated Fag e 5. Additionally, another new allergen, Fag e 4, potentially important for cross-reactivity to latex was added to the allergen panel of buckwheat. Further, our data show that the full-length legumin comprising both, large and small...... subunit should be applied for component resolved diagnosis. Our data indicate that concomitant sensitization to legumin, Fag e 2 and Fag e 5 predicts buckwheat allergy. This article is protected by copyright. All rights reserved....

  19. 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.

  20. 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

    functions similar to those of E2F proteins in higher eukaryotes, by regulating the timed expression of genes implicated in cell cycle progression and DNA synthesis. The CDC6 gene is a target for MBF and SBF-regulated transcription. S. cerevisiae Cdc6p induces the formation of the prereplication complex......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...... and is essential for initiation of DNA replication. Interestingly, the Cdc6p homolog in Schizosaccharomyces pombe, Cdc18p, is regulated by DSC1, the S. pombe homolog of MBF. By cloning the promoter for the human homolog of Cdc6p and Cdc18p, we demonstrate here that the cell cycle-regulated transcription...

  1. Vitexin inhibits polyubiquitin synthesis by the ubiquitin-conjugating enzyme E2-25K.

    Science.gov (United States)

    Helms, Kimberli M; Wilson, Randall C; Ogungbe, Ifedayo V; Setzer, William N; Twigg, Pamela D

    2011-10-01

    An extract of bark from the tropical rainforest plant Byrsonima crassifolia was screened for inhibition of diubiquitin formation by the human ubiquitin-conjugating enzyme E2-25K. Activity assays with both the full-length enzyme and a truncated, active catalytic UBC domain revealed that the extract contained inhibitory properties. Separation of the extract into individual components and additional screens identified vitexin as the active inhibitor. An IC50 for vitexin was calculated to be approximately 0.5 mM. Molecular modeling simulations were used to predict the mode of inhibition and NMR spectra were used to confirm the binding site of vitexin to E2-25K.

  2. Effect of Aspirin and Indomethacin on Prostaglandin E2 Synthesis in C6 Glioma Cells

    OpenAIRE

    Hwang, Shiuh-Lin; Lee, Kung-Shing; Lin, Chih-Lung; Lieu, Ann-Shung; Cheng, Chi-Yun; Loh, Joon-Khim; Hwang, Yan-Fen; Su, Yu-Feng; Howng, Shen-Long

    2004-01-01

    Prostaglandin E2 (PGE2) plays an important role in immunosuppression and tumor growth. PGE2 inhibitors such as aspirin and indomethacin suppress experimental tumor growth. Little is known of the relationship between PGE2 synthesis in brain tumors and the dose of aspirin or indomethacin. The present study was undertaken to evaluate the effect of different doses of aspirin and indomethacin on PGE2 synthesis in C6 glioma cells. C6 glioma cells were incubated with different concentrations (2, 4, ...

  3. Comparative genomics reveals multistep pathogenesis of E2A-PBX1 acute lymphoblastic leukemia

    OpenAIRE

    Duque-Afonso, Jesús; Feng, Jue; Scherer, Florian; Lin, Chiou-Hong; Wong, Stephen H.K.; Wang, Zhong; Iwasaki, Masayuki; Cleary, Michael L.

    2015-01-01

    Acute lymphoblastic leukemia (ALL) is the most common childhood cancer; however, its genetic diversity limits investigation into the molecular pathogenesis of disease and development of therapeutic strategies. Here, we engineered mice that conditionally express the E2A-PBX1 fusion oncogene, which results from chromosomal translocation t(1;19) and is present in 5% to 7% of pediatric ALL cases. The incidence of leukemia in these mice varied from 5% to 50%, dependent on the Cre-driving promoter ...

  4. Low energy (e,2e) measurements of Xe in the symmetric non-coplanar geometry

    International Nuclear Information System (INIS)

    Nixon, K L; Murray, A J

    2012-01-01

    Low energy (e,2e) measurements from the valence state of xenon will be presented. Symmetric non-coplanar kinematics were utilized. Incident energies range from 5 to 40eV above the ionization potential with outgoing electron angles from 30-140°. Geometries from coplanar to perpendicular were investigated for each energy regime. These measurements show significant difference to those from helium and other noble gases, particularly at high incident electron angles.

  5. Electron momentum spectroscopy of solids by the (e,2e) reaction

    International Nuclear Information System (INIS)

    Kheifets, A.S.; Vos, M.; Canney, S.A.; Guo, X.; McCarthy, I.E.

    1996-08-01

    Recent developments in (e,2e) momentum spectroscopy have resulted in the study of a diverse range of solid targets. These studies have revealed the electronic structure of solids in much more detail that was previously available using this technique. The method is now capable of producing quantitative data on energy-resolved momentum density of solids. A summary of these results is presented, in particular for aluminium, aluminium oxides and graphite. 26 refs., 9 figs

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

    Science.gov (United States)

    Seabroke, George; Holland, Andrew; Burt, David; Robbins, Mark

    2010-07-01

    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 μm offset to the nominal widths. These offsets appear to be uncalibrated systematic offsets in e2v photolithography, which could either be due to systematic stitch alignment offsets or lateral ABD shield doping diffusion. The range of SBC capacities were used to derive the worst-case random stitch error between two pixel features within a stitch block to be +/-0.25 μm, which cannot explain the systematic offsets. It is beyond the scope of our pixel model to provide the manufacturing reason for the range of SBC capacities, so it does not allow us to predict how representative the tested CCD is. This open question has implications for Gaia's radiation damage and geometric calibration models.

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

    International Nuclear Information System (INIS)

    Carroll, P. Brandon; McGuire, Brett A.; Blake, Geoffrey A.; Apponi, A. J.; Ziurys, L. M.; Remijan, Anthony

    2015-01-01

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

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

    DEFF Research Database (Denmark)

    Müller, H; Helin, K

    2000-01-01

    Ever since its discovery, the RB-1 gene and the corresponding protein, pRB, have been a focal point of cancer research. The isolation of E2F transcription factors provided the key to our current understanding of RB-1 function in the regulation of the cell cycle and in tumor suppression. It is bec......Ever since its discovery, the RB-1 gene and the corresponding protein, pRB, have been a focal point of cancer research. The isolation of E2F transcription factors provided the key to our current understanding of RB-1 function in the regulation of the cell cycle and in tumor suppression....... 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...

  9. 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.

  10. 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.

  11. 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.

  12. Selection and characterization of specific nanobody against bovine virus diarrhea virus (BVDV E2 protein.

    Directory of Open Access Journals (Sweden)

    Tiansen Li

    Full Text Available Bovine viral diarrhea-mucosal disease (BVD-MD is caused by bovine viral diarrhea virus (BVDV, and results in abortion, stillbirth, and fetal malformation in cows. Here, we constructed the phage display vector pCANTAB 5E-VHH and then transformed it into Escherichia coli TG1-competent cells, to construct an initial anti-BVDV nanobody gene library. We obtained a BVDV-E2 antigen epitope bait protein by prokaryotic expression using the nucleotide sequence of the E2 gene of the BVDV-NADL strain published in GenBank. Phage display was used to screen the anti-BVDV nanobody gene library. We successfully constructed a high quality phage display nanobody library, with an initial library capacity of 4.32×105. After the rescue of helper phage, the titer of the phage display nanobody library was 1.3×1011. The BVDV-E2 protein was then expressed in Escherichia coli (DE3, and a 49.5 kDa band was observed with SDS-PAGE analysis that was consistent with the expected nanobody size. Thus, we were able to isolate one nanobody that exhibits high affinity and specificity against BVDV using phage display techniques. This isolated nanobody was then used in Enzyme Linked Immunosorbent Assay and qRT-PCR, and ELISA analyses of BVDV infection of MDBK cells indicated that the nanobodies exhibited good antiviral effect.

  13. Selection and characterization of specific nanobody against bovine virus diarrhea virus (BVDV) E2 protein.

    Science.gov (United States)

    Li, Tiansen; Huang, Meiling; Xiao, Hongran; Zhang, Guoqi; Ding, Jinhua; Wu, Peng; Zhang, Hui; Sheng, Jinliang; Chen, Chuangfu

    2017-01-01

    Bovine viral diarrhea-mucosal disease (BVD-MD) is caused by bovine viral diarrhea virus (BVDV), and results in abortion, stillbirth, and fetal malformation in cows. Here, we constructed the phage display vector pCANTAB 5E-VHH and then transformed it into Escherichia coli TG1-competent cells, to construct an initial anti-BVDV nanobody gene library. We obtained a BVDV-E2 antigen epitope bait protein by prokaryotic expression using the nucleotide sequence of the E2 gene of the BVDV-NADL strain published in GenBank. Phage display was used to screen the anti-BVDV nanobody gene library. We successfully constructed a high quality phage display nanobody library, with an initial library capacity of 4.32×105. After the rescue of helper phage, the titer of the phage display nanobody library was 1.3×1011. The BVDV-E2 protein was then expressed in Escherichia coli (DE3), and a 49.5 kDa band was observed with SDS-PAGE analysis that was consistent with the expected nanobody size. Thus, we were able to isolate one nanobody that exhibits high affinity and specificity against BVDV using phage display techniques. This isolated nanobody was then used in Enzyme Linked Immunosorbent Assay and qRT-PCR, and ELISA analyses of BVDV infection of MDBK cells indicated that the nanobodies exhibited good antiviral effect.

  14. Calculation of the N to $\\Delta$ electromagnetic transition matrix element

    CERN Document Server

    Alexandrou, C; Lippert, T; Neff, H; Negele, J W; Schilling, K; Tsapalis, A; Forcrand, Ph. de; Lippert, Th.

    2003-01-01

    We present results on the ratio of electric quadrupole to magnetic dipole amplitudes, $R_{EM}={\\cal G}_{E2}/{\\cal G}_{M1}$, for the transition $\\gamma N\\to \\Delta$ from lattice QCD. We consider both the quenched and the 2-flavor theory.

  15. 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.

  16. 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

  17. Polynomial expansions and transition strengths

    International Nuclear Information System (INIS)

    Draayer, J.P.

    1980-01-01

    The subject is statistical spectroscopy applied to determining strengths and strength sums of excitation processes in nuclei. The focus will be on a ds-shell isoscalar E2 study with detailed shell-model results providing the standard for comparison; similar results are available for isovector E2 and M1 and E4 transitions as well as for single-particle transfer and ν +- decay. The present study is intended to serve as a tutorial for applications where shell-model calculations are not feasible. The problem is posed and a schematic theory for strengths and sums is presented. The theory is extended to include the effect of correlations between H, the system Hamiltonian, and theta, the excitation operator. Associated with correlation measures is a geometry that can be used to anticipate the goodness of a symmetry. This is illustrated for pseudo SU(3) in the fp-shell. Some conclusions about fluctuations and collectivity that one can deduce from the statistical results for strengths are presented

  18. 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.

  19. How does (E-2-(acetamidomethylenesuccinate bind to its hydrolase? From the binding process to the final result.

    Directory of Open Access Journals (Sweden)

    Ji-Long Zhang

    Full Text Available The binding of (E-2-(acetamidomethylenesuccinate (E-2AMS to E-2AMS hydrolase is crucial for biological function of the enzyme and the last step reaction of vitamin B(6 biological degradation. In the present study, several molecular simulation methods, including molecular docking, conventional molecular dynamics (MD, steered MD (SMD, and free energy calculation methods, were properly integrated to investigate the detailed binding process of E-2AMS to its hydrolase and to assign the optimal enzyme-substrate complex conformation. It was demonstrated that the substrate binding conformation with trans-form amide bond is energetically preferred conformation, in which E-2AMS's pose not only ensures hydrogen bond formation of its amide oxygen atom with the vicinal oxyanion hole but also provides probability of the hydrophobic interaction between its methyl moiety and the related enzyme's hydrophobic cavity. Several key residues, Arg146, Arg167, Tyr168, Arg179, and Tyr259, orientate the E-2AMS's pose and stabilize its conformation in the active site via the hydrogen bond interaction with E-2AMS. Sequentially, the binding process of E-2AMS to E-2AMS hydrolase was studied by SMD simulation, which shows the surprising conformational reversal of E-2AMS. Several important intermediate structures and some significant residues were identified in the simulation. It is stressed that Arg146 and Arg167 are two pivotal residues responsible for the conformational reversal of E-2AMS in the binding or unbinding. Our research has shed light onto the full binding process of the substrate to E-2AMS hydrolase, which could provide more penetrating insight into the interaction of E-2AMS with the enzyme and would help in the further exploration on the catalysis mechanism.

  20. Timing of transcription during the cell cycle: Protein complexes binding to E2F, E2F/CLE, CDE/CHR, or CHR promoter elements define early and late cell cycle gene expression

    Science.gov (United States)

    Müller, Gerd A.; Stangner, Konstanze; Schmitt, Thomas; Wintsche, Axel; Engeland, Kurt

    2017-01-01

    A central question in cell cycle control is how differential gene expression is regulated. Timing of expression is important for correct progression through the cell cycle. E2F, CDE, and CHR promoter sites have been linked to transcriptional repression in resting cells and activation during the cell cycle. Further, the DREAM complex binds CHR or CDE/CHR elements of G2/M genes resulting in repression during G0/G1. Here, we show that DREAM also binds to E2F sites of S phase genes in quiescence and upon p53 activation. Furthermore, we describe a novel class of promoter sites, the CHR-like elements (CLE), which can support binding of DREAM to E2F elements. Activation of such S phase genes is achieved through binding of E2F1-3/DP complexes to E2F sites. In contrast, the activating MuvB complexes MMB and FOXM1-MuvB bind to CHR elements and mediate peak expression in G2/M. In conclusion, data presented here in combination with earlier results leads us to propose a model that explains how DREAM can repress early cell cycle genes through E2F or E2F/CLE sites and late genes through CHR or CDE/CHR elements. Also p53-dependent indirect transcriptional repression through the p53-p21-Cyclin/CDK-DREAM-E2F/CLE/CDE/CHR pathway requires DREAM binding to E2F or E2F/CLE sites in early cell cycle genes and binding of DREAM to CHR or CDE/CHR elements of late cell cycle genes. Specific timing of activation is achieved through binding of E2F1-3/DP to E2F sites and MMB or FOXM1-MuvB complexes to CHR elements. PMID:29228647

  1. M1 transitions between collective levels and F-spin purity

    International Nuclear Information System (INIS)

    von Brentano, P.; Frank, W.; Gelberg, A.; Harter, H.; Krips, W.; Casten, R.F.; Boerner, H.G.; Krusche, B.

    1987-01-01

    M1 transitions between low-lying collective levels in deformed nuclei are described within the IBM-2 framework. This is done by a special choice of the Hamiltonian which allows a simultaneous fit of energies, E2 and M1 transitions. Finally, the results are interpreted using the F-spin concept. 12 refs., 4 tabs

  2. 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...

  3. Lung Myofibroblasts Are Characterized by Down-Regulated Cyclooxygenase-2 and Its Main Metabolite, Prostaglandin E2

    Science.gov (United States)

    Gabasa, Marta; Royo, Dolores; Molina-Molina, Maria; Roca-Ferrer, Jordi; Pujols, Laura; Picado, Cesar

    2013-01-01

    Background Prostaglandin E2 (PGE2), the main metabolite of cyclooxygenase (COX), is a well-known anti-fibrotic agent. Moreover, myofibroblasts expressing α-smooth muscle actin (α-SMA), fibroblast expansion and epithelial-mesenchymal transition (EMT) are critical to the pathogenesis of idiopathic pulmonary fibrosis (IPF). Our aim was to investigate the expression of COX-2 and PGE2 in human lung myofibroblasts and establish whether fibroblast-myofibroblast transition (FMT) and EMT are associated with COX-2 and PGE2 down-regulation. Methods Fibroblasts obtained from IPF patients (n = 6) and patients undergoing spontaneous pneumothorax (control, n = 6) and alveolar epithelial cell line A549 were incubated with TGF-β1 and FMT and EMT markers were evaluated. COX-2 and α-SMA expression, PGE2 secretion and cell proliferation were measured after IL-1β and PGE2 incubation. Results Myofibroblasts from both control and IPF fibroblast cultures stimulated with IL-1β showed no COX-2 expression. IPF fibroblasts showed increased myofibroblast population and reduced COX-2 expression in response to IL-1β. TGF-β1 increased the number of myofibroblasts in a time-dependent manner. In contrast, TGF-β1 induced slight COX-2 expression at 4 h (without increase in myofibroblasts) and 24 h, but not at 72 h. Both IPF and control cultures incubated with TGF-β1 for 72 h showed diminished COX-2 induction, PGE2 secretion and α-SMA expression after IL-1β addition. The latter decreased proliferation in fibroblasts but not in myofibroblasts. A549 cells incubated with TGF-β1 for 72 h showed down-regulated COX-2 expression and low basal PGE2 secretion in response to IL-1β. Immuno-histochemical analysis of IPF lung tissue showed no COX-2 immuno-reactivity in myofibroblast foci. Conclusions Myofibroblasts are associated with COX-2 down-regulation and reduced PGE2 production, which could be crucial in IPF development and progression. PMID:23755232

  4. In-Band Full-Duplex Communications for Cellular Networks with Partial Uplink/Downlink Overlap

    KAUST Repository

    AlAmmouri, Ahmad

    2015-12-06

    In-band full-duplex (FD) communications have been optimistically promoted to improve the spectrum utilization in cellular networks. However, the explicit impact of spatial interference, imposed by FD communications, on uplink and downlink transmissions has been overlooked in the literature. This paper presents an extensive study of the explicit effect of FD communications on the uplink and downlink performances. For the sake of rigorous analysis, we develop a tractable framework based on stochastic geometry toolset. The developed model accounts for uplink truncated channel inversion power control in FD cellular networks. The study shows that FD communications improve the downlink throughput at the expense of significant degradation in the uplink throughput. Therefore, we propose a novel fine-grained duplexing scheme, denoted as α-duplex scheme, which allows a partial overlap between uplink and downlink frequency bands. To this end, we show that the amount of the overlap can be optimized via adjusting α to achieve a certain design objective.

  5. First observation of E2 coherent phonon modes in CdS using a noncollinear optical parametric amplifier

    Science.gov (United States)

    Suzuki, Daisuke; Kunugita, Hideyuki; Ema, Kazuhiro

    2009-11-01

    We report the first observation of E2 coherent phonon modes in CdS using a noncollinear optical parametric amplifier. We studied the intensity, temperature and excitation energy dependences of the high- and low-frequency E2 modes. We obtain that generation mechanism under non- and near resonant regions is impulsive stimulated Raman scattering (ISRS) and E2 modes are barely affected by Fröhlich interaction. As temperature increases, E2 modes are affected by anharmonic effect. The observed phonon lifetime of the low- and high-E2 modes in CdS is 243 ± 37 and 11.4 ± 0.4 ps, respectively, at 83 K. From fitting, we can estimate the lifetime of the high-E2 mode at the low-temperature limit to be 49.3 ps.

  6. A global network of transcription factors, involving E2A, EBF1 and Foxo1, that orchestrates B cell fate.

    Science.gov (United States)

    Lin, Yin C; Jhunjhunwala, Suchit; Benner, Christopher; Heinz, Sven; Welinder, Eva; Mansson, Robert; Sigvardsson, Mikael; Hagman, James; Espinoza, Celso A; Dutkowski, Janusz; Ideker, Trey; Glass, Christopher K; Murre, Cornelis

    2010-07-01

    It is now established that the transcription factors E2A, EBF1 and Foxo1 have critical roles in B cell development. Here we show that E2A and EBF1 bound regulatory elements present in the Foxo1 locus. E2A and EBF1, as well as E2A and Foxo1, in turn, were wired together by a vast spectrum of cis-regulatory sequences. These associations were dynamic during developmental progression. Occupancy by the E2A isoform E47 directly resulted in greater abundance, as well as a pattern of monomethylation of histone H3 at lysine 4 (H3K4) across putative enhancer regions. Finally, we divided the pro-B cell epigenome into clusters of loci with occupancy by E2A, EBF and Foxo1. From this analysis we constructed a global network consisting of transcriptional regulators, signaling and survival factors that we propose orchestrates B cell fate.

  7. 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

    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......, a candidate repressor, from the MT2 site in late G1 may be essential for S phase-dependent transcription of the mouse TK gene....

  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...

  9. 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 for...

  10. The Hox cooperativity motif of the chimeric oncoprotein E2a-Pbx1 is necessary and sufficient for oncogenesis.

    OpenAIRE

    Chang, C P; de Vivo, I; Cleary, M L

    1997-01-01

    E2a-Pbx1 chimeric oncoproteins result from fusion of the E2A and PBX1 genes at the sites of t(1;19) chromosomal translocations in a subset acute lymphoblastic leukemias. Experimentally, E2a-Pbx1 transforms a variety of cell types, including fibroblasts, myeloid progenitors, and lymphoblasts. Structure-function studies have shown that contributions from both E2a and Pbx1 are necessary for oncogenesis, but the Pbx1 homeodomain is dispensable and the required portion of Pbx1 has not been delinea...

  11. The Oncoprotein E2A-Pbx1a Collaborates with Hoxa9 To Acutely Transform Primary Bone Marrow Cells

    OpenAIRE

    Thorsteinsdottir, Unnur; Krosl, Jana; Kroon, Evert; Haman, André; Hoang, Trang; Sauvageau, Guy

    1999-01-01

    A recurrent translocation between chromosome 1 (Pbx1) and 19 (E2A) leading to the expression of the E2A-Pbx1 fusion oncoprotein occurs in ∼5 to 10% of acute leukemias in humans. It has been proposed that some of the oncogenic potential of E2A-Pbx1 could be mediated through heterocomplex formation with Hox proteins, which are also involved in human and mouse leukemias. To directly test this possibility, mouse bone marrow cells were engineered by retroviral gene transfer to overexpress E2A-Pbx1...

  12. Detection of E2A-PBX1 fusion transcripts in human non-small-cell lung cancer

    OpenAIRE

    Mo, Min-Li; Chen, Zhao; Zhou, Hai-Meng; Li, Hui; Hirata, Tomomi; Jablons, David M; He, Biao

    2013-01-01

    Background E2A-PBX1 fusion gene caused by t(1;19)(q23;p13), has been well characterized in acute lymphoid leukemia (ALL). There is no report on E2A-PBX1 fusion transcripts in non-small-cell lung cancer (NSCLC). Methods We used polymerase chain reaction (PCR) to detect E2A-PBX1 fusion transcripts in human NSCLC tissue specimens and cell lines. We analyzed correlation of E2A-PBX1 fusion transcripts with clinical outcomes in 76 patients with adenocarcinoma in situ (AIS) and other subgroups. We c...

  13. Enhancing expression of the classical swine fever virus glycoprotein E2 in yeast and its application to a blocking ELISA.

    Science.gov (United States)

    Cheng, Chih-Yuan; Wu, Ching-Wei; Lin, Guang-Jan; Lee, Wei-Cheng; Chien, Maw-Sheng; Huang, Chienjin

    2014-03-20

    Classical swine fever virus (CSFV) infection is a severe swine disease, often causing large economic losses. A Pichia pastoris yeast-expressed CSFV glycoprotein E2 (yE2) has been shown to induce a protective immune response against the virus. To improve the expression level of yE2, the first codon of E2 gene, Arg (CGG), which is the least used in P. pastoris, was optimized to the most favorite codon AGA. The yield of E2 protein was remarkably increased in the codon optimized strain (N342). Three truncated E2 subunits encoding the N-terminal 330 (N330), 301 (N301), and 190 (N190) residues, respectively, were also constructed. The immunogenicity of each recombinant E2 subunits was confirmed by immunization of pigs, and all immunized groups demonstrated high neutralizing antibody titers after boost immunization, which lasted for a long period of time. In addition, a monoclonal antibody (MAb), 1B6, specific to yE2, was generated and shown to recognize CSFV-infected cells. A panel of swine sera were tested by peroxidase-conjugated MAb 1B6-based blocking enzyme-linked immunosorbent assay (ELISA) using N330 as coated antigen, and the assay demonstrated high sensitivity and specificity. The recombinant yE2 subunits may provide potential subunit vaccine candidates and useful diagnostic reagents for CSFV with easy manipulation and low cost. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Serpin E2 promotes breast cancer metastasis by remodeling the tumor matrix and polarizing tumor associated macrophages

    OpenAIRE

    Smirnova, Tatiana; Bonapace, Laura; MacDonald, Gwen; Kondo, Shunya; Ebersbach, Hilmar; Fayard, Bérengère; Doelemeyer, Arno; Coissieux, Marie-May; Heideman, Marinus R.; Bentires-Alj, Mohamed; Hynes, Nancy E.; Wyckoff, Jeffrey

    2016-01-01

    The extracellular serine protease inhibitor serpinE2 is overexpressed in breast cancer and has been shown to foster metastatic spread. Here, we investigated the hypothesis that serpinE2 creates tumor-promoting conditions in the tumor microenvironment (TME) by affecting extracellular matrix remodeling. Using two different breast cancer models, we show that blocking serpinE2, either by knock-down (KD) in tumor cells or in response to a serpinE2 binding antibody, decreases metastatic disseminati...

  15. Functional interrelationship between TFII-I and E2F transcription factors at specific cell cycle gene loci.

    Science.gov (United States)

    Shen, Yong; Nar, Rukiye; Fan, Alex X; Aryan, Mahmoud; Hossain, Mir A; Gurumurthy, Aishwarya; Wassel, Paul C; Tang, Ming; Lu, Jianrong; Strouboulis, John; Bungert, Jörg

    2018-01-01

    Transcription factor TFII-I is a multifunctional protein implicated in the regulation of cell cycle and stress-response genes. Previous studies have shown that a subset of TFII-I associated genomic sites contained DNA-binding motifs for E2F family transcription factors. We analyzed the co-association of TFII-I and E2Fs in more detail using bioinformatics, chromatin immunoprecipitation, and co-immunoprecipitation experiments. The data show that TFII-I interacts with E2F transcription factors. Furthermore, TFII-I, E2F4, and E2F6 interact with DNA-regulatory elements of several genes implicated in the regulation of the cell cycle, including DNMT1, HDAC1, CDKN1C, and CDC27. Inhibition of TFII-I expression led to a decrease in gene expression and in the association of E2F4 and E2F6 with these gene loci in human erythroleukemia K562 cells. Finally, TFII-I deficiency reduced the proliferation of K562 cells and increased the sensitivity toward doxorubicin toxicity. The results uncover novel interactions between TFII-I and E2Fs and suggest that TFII-I mediates E2F function at specific cell cycle genes. © 2017 Wiley Periodicals, Inc.

  16. E2F1 Hinders Skin Wound Healing by Repressing Vascular Endothelial Growth Factor (VEGF Expression, Neovascularization, and Macrophage Recruitment.

    Directory of Open Access Journals (Sweden)

    Ningning Wang

    Full Text Available Refractory surface of wound and dermal chronic ulcer are largely attributed to poor neovascularization. We have previously shown that E2F1 suppresses VEGF expression in the ischemic heart, and that genetic deletion of E2F1 leads to better cardiac recovery. However, whether E2F1 has a role in dermal wound healing is currently not known.Skin wounds were surgically induced in E2F1-null (E2F1-/- mice and WT littermates. E2F1-/- displayed an accelerated wound healing including wound closure, dermal thickening and collagen deposition, which was associated with an increased endothelial cell proliferation and greater vessel density in the border zone of the wound. Furthermore, more macrophages were recruited to the skin lesions and the level of VEGF expression was markedly higher in E2F1-/- than in WT mice.E2F1 hinders skin wound healing by suppressing VEGF expression, neovascularization, and macrophage recruitment. Strategies that target E2F1 may enhance wound healing.

  17. Rb-mediated neuronal differentiation through cell-cycle-independent regulation of E2f3a.

    Directory of Open Access Journals (Sweden)

    Danian Chen

    2007-07-01

    Full Text Available It has long been known that loss of the retinoblastoma protein (Rb perturbs neural differentiation, but the underlying mechanism has never been solved. Rb absence impairs cell cycle exit and triggers death of some neurons, so differentiation defects may well be indirect. Indeed, we show that abnormalities in both differentiation and light-evoked electrophysiological responses in Rb-deficient retinal cells are rescued when ectopic division and apoptosis are blocked specifically by deleting E2f transcription factor (E2f 1. However, comprehensive cell-type analysis of the rescued double-null retina exposed cell-cycle-independent differentiation defects specifically in starburst amacrine cells (SACs, cholinergic interneurons critical in direction selectivity and developmentally important rhythmic bursts. Typically, Rb is thought to block division by repressing E2fs, but to promote differentiation by potentiating tissue-specific factors. Remarkably, however, Rb promotes SAC differentiation by inhibiting E2f3 activity. Two E2f3 isoforms exist, and we find both in the developing retina, although intriguingly they show distinct subcellular distribution. E2f3b is thought to mediate Rb function in quiescent cells. However, in what is to our knowledge the first work to dissect E2f isoform function in vivo we show that Rb promotes SAC differentiation through E2f3a. These data reveal a mechanism through which Rb regulates neural differentiation directly, and, unexpectedly, it involves inhibition of E2f3a, not potentiation of tissue-specific factors.

  18. Factorized distorted wave approximation for the (e,2e) reaction on atoms : coplanar symmetric

    International Nuclear Information System (INIS)

    Fuss, I.; McCarthy, I.E.; Noble, C.J.; Weigold, E.

    1977-02-01

    The coplanar symmetric (e,2e) cross section has been studied in the intermediate energy region for the valence states of the inert gases He, Ar and Ne. Experimental measurements at 200, 400, 800, and 1200eV for He, and at 400, 800 and 1200eV for Ne and Ar, are compared with calculations based on the factorized half-off-shell distorted-wave impulse approximation. Calculations are carried out using partial wave expanded optical model wave functions which describe elastic scattering for the distorted waves, the eikonal approximation, and the plane wave approximation. (Author)

  19. COMPARISON OF INTRACERVICAL PROSTAGLANDIN E2 AND INTRAVENOUS OXYTOCIN IN INDUCTION OF LABOUR

    OpenAIRE

    BHATTACHARYYA, TK; SHANDIL, MS

    1998-01-01

    154 patients requiring induction with unfavourable cervix at varying period of gestation were studied. Patients were distributed into two groups. 76 patients were induced with 0.5 mgm single dose intracervical application of Prostaglandin E2 gel and remaining 78 patients with Oxytocin and efficacy of the two methods of induction was compared. Labour was established within 24 hours in 71.4% of primigravidas and 91.7% of multigravidas in the prostaglandin treated group compared to 65.6% of prim...

  20. Correlated ground state and E2 giant resonance built on it

    International Nuclear Information System (INIS)

    Tohyama, Mitsuru

    1995-01-01

    Taking 16 O as an example of realistic nuclei, we demonstrate that a correlated ground state can be obtained as a long time solution of a time-dependent density-matrix formalism (TDDM) when the residual interaction is adiabatically treated. We also study in TDDM the E2 giant resonance of 16 O built on the correlated ground state and compare it with that built on the Hartree-Fock ground state. It is found that a spurious mixing of low frequency components seen in the latter is eliminated by using the correlated ground state. (author)

  1. Actions of prostaglandins e1, e2 and e3 on the central nervous system

    Science.gov (United States)

    Horton, E. W.

    1964-01-01

    Prostaglandins E1, E2 and E3, injected into the cerebral ventricles of unanaesthetized cats, produced sedation, stupor and signs of catatonia. The threshold dose was 3 μg/kg. Slight sedation was also observed following an intravenous injection, but a dose of 20 μg/kg was required. In chicks, intravenous injections of prostaglandins (10 to 400 μg/kg) caused respiratory depression, profound sedation, loss of normal posture and, with the higher doses, loss of the righting reflex. PMID:14126050

  2. The effect of protons on E2V Technologies L3Vision CCDs

    International Nuclear Information System (INIS)

    Smith, D.R.; Holland, A.D.; Robbins, M.S.

    2003-01-01

    The effect of different 10 MeV equivalent proton fluences on the performance of E2V Technologies (formerly Marconi applied technologies, formerly EEV) L3Vision Charge Coupled Devices (CCDs) was investigated. The first experimental radiation damage results of the L3Vision device are presented, with emphasis given to the analysis of damage to the gain register of the device. Changes in dark current and generation of bright pixels in the CCD image, store, readout register and gain register as a result of proton irradiation are reported and viewed in light of the potential use of the device in space-based applications

  3. The nature of the background in transmission (e,2e) experiments

    International Nuclear Information System (INIS)

    Vos, M.; Storer, P.; Kheifets, A.S.; McCarthy, I.E.; Weigold, E.

    1995-08-01

    The authors present (e,2e) data of a graphitic carbon film over a large energy range (from 0 to 330 eV binding energy). This range contains both the valence band and the C 1s core level. Below the valence band there is always intensity, due to inelastic scattering effects. The momentum characteristics of this background are discussed. Finally, the intensity-ratio of the valence band features and the core level are compared with the theoretically calculated one. 9 refs., 4 figs

  4. 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.

  5. Interband B (E2) ratios in the rigid triaxial model, a review

    International Nuclear Information System (INIS)

    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 γ 0 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. (orig.)

  6. Butyrate attenuates lipolysis in adipocytes co-cultured with macrophages through non-prostaglandin E2-mediated and prostaglandin E2-mediated pathways.

    Science.gov (United States)

    Ohira, Hideo; Tsutsui, Wao; Mamoto, Rie; Yamaguchi, Sayaka; Nishida, Masako; Ito, Miki; Fujioka, Yoshio

    2016-12-09

    Interactions between adipocytes and macrophages are associated with metabolic disorders. Production of pro-inflammatory mediators and the release of free fatty acids (FFAs) increase when these cells are co-cultured; butyrate significantly diminishes these effects by suppressing both the macrophage inflammatory and adipocyte lipolysis pathways. Butyrate is known to up-regulate the expression of prostaglandin E2 (PGE2). Therefore, we hypothesized that PGE2 is associated with the suppression of lipolysis by butyrate in co-culture. Using contact or transwell co-culture methods with differentiated 3T3-L1 adipocytes and RAW264.7 macrophages, we investigated the effects of butyrate on the release of PGE2 into the medium and on lipolysis in adipocytes. To elucidate the underlying mechanism, we examined the effects of butyrate on cyclooxygenase-2 (COX2) and phospholipase A2 (PLA2) in co-cultured cells, and cyclic adenine monophosphate (cAMP) and protein kinase A type 1-α regulatory subunit (PRKAR1A) in co-cultured adipocytes. Silent interfering (si)RNA targeting of G-protein-coupled receptor (GPR)41 and 109A was employed to examine the effect on lipolysis in TNF-α-stimulated adipocytes. Co-culture increased PGE2 release into the medium, compared with cells cultured separately. Butyrate significantly increased PGE2 production. Co-culture elevated COX2 expression in macrophages and adipocytes, and butyrate further enhanced this effect. Co-culture enhanced cytosolic PLA2 activity in macrophages, which was further enhanced by butyrate. As for lipolysis, co-culture increased the release of FFAs and free glycerol into the medium, whereas butyrate (and to a lesser extent, PGE2) suppressed FFAs and free glycerol release. An inhibition study using a prostaglandin E receptor 3-selective antagonist suggested that approximately 40% of the suppressive effect of butyrate depends on the PGE2-mediated pathway, whereas 60% depends on a non-PGE2-mediated pathway. Co-culture increased c

  7. The Spt-Ada-Gcn5-acetyltransferase complex interaction motif of E2a is essential for a subset of transcriptional and oncogenic properties of E2a-Pbx1.

    Science.gov (United States)

    Scheele, Jürgen S; Kolanczyk, Mateusz; Gantert, Melanie; Zemojtel, Tomasz; Dorn, Annette; Sykes, David B; Sykes, David P; Möbest, Dietrich C C; Kamps, Mark P; Räpple, Daniel; Duchniewicz, Marlena

    2009-05-01

    The oncogene E2a-Pbx1 is formed by the t(1;19) translocation, which joins the N-terminal transactivation domain of E2a with the C-terminal homeodomain of PBX1. The goal of this work was to elucidate the mechanisms by which E2a-Pbx1 can lead to deregulated target gene expression. For reporter constructs it was shown that E2a-Pbx1 can activate transcription through homodimer elements (TGATTGAT) or through heterodimer elements with Hox proteins (e.g. TGATTAAT). We show a novel mechanism by which E2a-Pbx1 activates transcription of EF-9 using a promoter in intron 1 of the EF-9 gene, resulting in an aminoterminal truncated transcript. Our results indicate that the LDFS motif of E2a is essential for the transactivation of EF-9, but dispensable for transactivation of fibroblast growth factor 15. The E2a LDFS motif was also essential for proliferation of NIH3T3 fibroblasts but was dispensable for the E2a-Pbx1-induced differentiation arrest of myeloid progenitors.

  8. 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...... core-NS2, we exchanged E2 with functional isolate sequences of genotypes 1a (alternative isolate), 1b, and 2a. While the 1a-E2 exchange did not impact virus viability, the 2a-E2 recombinant was nonviable. After E2 exchange from three 1b isolates, long delays were observed before spread of infection....... For recovered 1b-E2 recombinants, single E2 stem region amino acid changes were identified at residues 706, 707, and 710. In reverse genetic studies, these mutations increased infectivity titers by ~100-fold, apparently without influencing particle stability or cell binding although introducing slight decrease...

  9. 0(gs)+ -->2(1)+ transition strengths in 106Sn and 108Sn.

    Science.gov (United States)

    Ekström, A; Cederkäll, J; Fahlander, C; Hjorth-Jensen, M; Ames, F; Butler, P A; Davinson, T; Eberth, J; Fincke, F; Görgen, A; Górska, M; Habs, D; Hurst, A M; Huyse, M; Ivanov, O; Iwanicki, J; Kester, O; Köster, U; Marsh, B A; Mierzejewski, J; Reiter, P; Scheit, H; Schwalm, D; Siem, S; Sletten, G; Stefanescu, I; Tveten, G M; Van de Walle, J; Van Duppen, P; Voulot, D; Warr, N; Weisshaar, D; Wenander, F; Zielińska, M

    2008-07-04

    The reduced transition probabilities, B(E2; 0(gs)+ -->2(1)+), have been measured in the radioactive isotopes (108,106)Sn using subbarrier Coulomb excitation at the REX-ISOLDE facility at CERN. Deexcitation gamma rays were detected by the highly segmented MINIBALL Ge-detector array. The results, B(E2;0(gs)+ -->2(1)+)=0.222(19)e2b2 for 108Sn and B(E2; 0(gs)+-->2(1)+)=0.195(39)e2b2 for 106Sn were determined relative to a stable 58Ni target. The resulting B(E2) values are approximately 30% larger than shell-model predictions and deviate from the generalized seniority model. This experimental result may point towards a weakening of the N=Z=50 shell closure.

  10. E2A proteins enhance the histone acetyltransferase activity of the transcriptional co-activators CBP and p300.

    Science.gov (United States)

    Hyndman, Brandy D; Thompson, Patrick; Bayly, Richard; Côté, Graham P; LeBrun, David P

    2012-05-01

    The E2A gene encodes the E-protein transcription factors E12 and E47 that play critical roles in B-lymphopoiesis. A somatic chromosomal translocation detectable in 5% of cases of acute lymphoblastic leukemia (ALL) involves E2A and results in expression of the oncogenic transcription factor E2A-PBX1. CREB binding protein (CBP) and its close paralog p300 are transcriptional co-activators with intrinsic histone acetyltransferase (HAT) activity. We and others have shown that direct binding of an N-terminal transcriptional activation domain present in E12/E47 and E2A-PBX1 to the KIX domain of CBP/p300 contributes to E2A protein function. In the current work we show for the first time that the catalytic HAT activity of CBP/p300 is increased in the presence of residues 1-483 of E2A (i.e., the portion present in E2A-PBX1). The addition of purified, recombinant E2A protein to in vitro assays results in a two-fold augmentation of CBP/p300 HAT activity, whereas in vivo assays show a ten-fold augmentation of HAT-dependent transcriptional induction and a five-fold augmentation of acetylation of reporter plasmid-associated histone by CBP in response to co-transfected E2A. Our results indicate that the HAT-enhancing effect is independent of the well-documented E2A-CBP interaction involving the KIX domain and suggest a role for direct, perhaps low affinity binding of E2A to a portion of CBP that includes the HAT domain and flanking elements. Our findings add to a growing body of literature indicating that interactions between CBP/p300 and transcription factors can function in a specific manner to modulate HAT catalytic activity. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Direct and indirect targets of the E2A-PBX1 leukemia-specific fusion protein.

    Directory of Open Access Journals (Sweden)

    Christofer Diakos

    Full Text Available E2A-PBX1 is expressed as a result of the t(1;19 chromosomal translocation in nearly 5% of cases of childhood acute lymphoblastic leukemia. The E2A-PBX1 chimeric transcription factor contains the N-terminal transactivation domain of E2A (TCF3 fused to the C-terminal DNA-binding homeodomain of PBX1. While there is no doubt of its oncogenic potential, the mechanisms of E2A-PBX1-mediated pre-B cell transformation and the nature of direct E2A-PBX1 target genes and pathways remain largely unknown. Herein we used chromatin immunoprecipitation assays (ChIP-chip to identify direct targets of E2A-PBX1, and we used gene expression arrays of siRNA E2A-PBX1-silenced cells to evaluate changes in expression induced by the fusion protein. Combined ChIP-chip and expression data analysis gave rise to direct and functional targets of E2A-PBX1. Further we observe that the set of ChIP-chip identified E2A-PBX1 targets show a collective down-regulation trend in the E2A-PBX1 silenced samples compared to controls suggesting an activating role of this fusion transcription factor. Our data suggest that the expression of the E2A-PBX1 fusion gene interferes with key regulatory pathways and functions of hematopoietic biology. Among these are members of the WNT and apoptosis/cell cycle control pathways, and thus may comprise an essential driving force for the propagation and maintenance of the leukemic phenotype. These findings may also provide evidence of potentially attractive therapeutic targets.

  12. Direct and indirect targets of the E2A-PBX1 leukemia-specific fusion protein.

    Science.gov (United States)

    Diakos, Christofer; Xiao, Yuanyuan; Zheng, Shichun; Kager, Leo; Dworzak, Michael; Wiemels, Joseph L

    2014-01-01

    E2A-PBX1 is expressed as a result of the t(1;19) chromosomal translocation in nearly 5% of cases of childhood acute lymphoblastic leukemia. The E2A-PBX1 chimeric transcription factor contains the N-terminal transactivation domain of E2A (TCF3) fused to the C-terminal DNA-binding homeodomain of PBX1. While there is no doubt of its oncogenic potential, the mechanisms of E2A-PBX1-mediated pre-B cell transformation and the nature of direct E2A-PBX1 target genes and pathways remain largely unknown. Herein we used chromatin immunoprecipitation assays (ChIP-chip) to identify direct targets of E2A-PBX1, and we used gene expression arrays of siRNA E2A-PBX1-silenced cells to evaluate changes in expression induced by the fusion protein. Combined ChIP-chip and expression data analysis gave rise to direct and functional targets of E2A-PBX1. Further we observe that the set of ChIP-chip identified E2A-PBX1 targets show a collective down-regulation trend in the E2A-PBX1 silenced samples compared to controls suggesting an activating role of this fusion transcription factor. Our data suggest that the expression of the E2A-PBX1 fusion gene interferes with key regulatory pathways and functions of hematopoietic biology. Among these are members of the WNT and apoptosis/cell cycle control pathways, and thus may comprise an essential driving force for the propagation and maintenance of the leukemic phenotype. These findings may also provide evidence of potentially attractive therapeutic targets.

  13. 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).

  14. Classification of new BVDV isolates from Philippine water buffalo using the viral E2 region.

    Science.gov (United States)

    Mingala, Claro N; Konnai, Satoru; Tajima, Motoshi; Onuma, Misao; Ohashi, Kazuhiko

    2009-10-01

    Characterization of bovine viral diarrhea virus (BVDV) isolates has been focused of several studies this last decade. Until now lots of new strains are being unfolded maybe due to the viral fast mutation ability. As we focused our research on water buffalo immunology, we were able to identify a probable new BVDV isolates. RNA was extracted from water buffalo blood in the Philippines. The extracted RNA was reverse-transcribed and synthesized cDNA. Oligonucleotide primers from the viral E2 region were used to amplify the target viral gene and later purified, cloned and sequenced. The E2 region with 420 bp nucleotides long was compared with existing published sequences in the GenBank. Based on the constructed phylogenetic tree, the isolated strain showed to be a BVDV type 1b along with Osloss and CP7 strains. Further classification of the new isolates was done within the BVDV type 1b1 group, which was compared with other strains in the sub-group. The analysis revealed that Lamspringe/738, KE9 and 2543/87 were the closest with 92% homology. Additional study is being done to further qualify and quantify the extent of the existence of this new BVDV isolates in water buffalo in the Philippines. This is the first report of BVDV in the Philippines and first concerning BVDV in Philippine water buffalo. Copyright 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Cooperative and Integrated Vehicle and Intersection Control for Energy Efficiency (CIVIC-E2)

    Energy Technology Data Exchange (ETDEWEB)

    Gonder, Jeffrey D [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Wood, Eric W [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Hou, Yunfei [State University of New York at Buffalo; Seliman, Salaheldeen M. S. [State University of New York at Buffalo; Wang, Enshu [State University of New York at Buffalo; He, Qing [State University of New York at Buffalo; Sadek, Adel W. [State University of New York at Buffalo; Su, Lu [State University of New York at Buffalo; Qiao, Chunming [State University of New York at Buffalo

    2018-02-15

    Recent advances in connected vehicle technologies enable vehicles and signal controllers to cooperate and improve the traffic management at intersections. This paper explores the opportunity for cooperative and integrated vehicle and intersection control for energy efficiency (CIVIC-E2) to contribute to a more sustainable transportation system. We propose a two-level approach that jointly optimizes the traffic signal timing and vehicles' approach speed, with the objective being to minimize total energy consumption for all vehicles passing through an isolated intersection. More specifically, at the intersection level, a dynamic programming algorithm is designed to find the optimal signal timing by explicitly considering the arrival time and energy profile of each vehicle. At the vehicle level, a model predictive control strategy is adopted to ensure that vehicles pass through the intersection in a timely fashion. Our simulation study has shown that the proposed CIVIC-E2 system can significantly improve intersection performance under various traffic conditions. Compared with conventional fixed-time and actuated signal control strategies, the proposed algorithm can reduce energy consumption and queue length by up to 31% and 95%, respectively.

  16. 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.

  17. Design, synthesis, and anti-melanogenic effects of (E-2-benzoyl-3-(substituted phenylacrylonitriles

    Directory of Open Access Journals (Sweden)

    Yun HY

    2015-08-01

    Full Text Available Hwi Young Yun,1 Do Hyun Kim,1 Sujin Son,1 Sultan Ullah,1 Seong Jin Kim,1 Yeon-Jeong Kim,2 Jin-Wook Yoo,1 Yunjin Jung,1 Pusoon Chun,2 Hyung Ryong Moon1 1College of Pharmacy, Pusan National University, Busan, 2College of Pharmacy, Inje University, Gimhae, Republic of Korea Background: Tyrosinase is the most prominent target for inhibitors of hyperpigmentation because it plays a critical role in melaninogenesis. Although many tyrosinase inhibitors have been identified, from both natural and synthetic sources, there remains a considerable demand for novel tyrosinase inhibitors that are safer and more effective. Methods: (E-2-Benzoyl-3-(substituted phenylacrylonitriles (BPA analogs with a linear β-phenyl-α,β-unsaturated carbonyl scaffold were designed and synthesized as potential tyrosinase inhibitors. We evaluated their effects on cellular tyrosinase activity and melanin biosynthesis in murine B16F10 melanoma cells and their ability to inhibit mushroom tyrosinase activity. Results: BPA analogs exhibited inhibitory activity against mushroom tyrosinase. In particular, BPA13 significantly suppressed melanin biosynthesis and inhibited cellular tyrosinase activity in B16F10 cells in a dose-dependent manner. A docking study revealed that BPA13 had higher binding affinity for tyrosinase than kojic acid. Conclusion: BPA13, which possesses a linear β-phenyl-α,β-unsaturated carbonyl scaffold, is a potential candidate skin-whitening agent and treatment for diseases associated with hyperpigmentation. Keywords: (E-2-benzoyl-3-(substituted phenylacrylonitriles, melanogenesis, tyrosinase inhibitor

  18. Interband transitions in 106Pd, 152Sm, 152Gd and 182W

    International Nuclear Information System (INIS)

    Kartashov, V.M.; Oborovskij, A.I.; Troitskaya, A.G.

    1990-01-01

    Internal transitions in 106 Pd, 152 Sm, 152 Gd, 182 W nuclei, observed during decay of 152,152m Eu, 182,183 Ta, 106m Ag, are studied. The experimental characteristics of E0-transitions and E0-components of E0+M1+E2 type transitions in the studied nuclei, relative intensities of internal conversion electron lines during 182 Ta decay, multipolar composition and forbidden factor for 182 W and 183 W low-energy transitions, characteristics of transitions are presented

  19. Theoretical and experimental investigation of (E)-2-([3,4-dimethylphenyl)imino]methyl)-3-methoxyphenol: Enol-keto tautomerism, spectroscopic properties, NLO, NBO and NPA analysis

    Science.gov (United States)

    Demircioğlu, Zeynep; Albayrak, Çiğdem; Büyükgüngör, Orhan

    2014-05-01

    The molecular structure and spectroscopic properties of (E)-2-([3,4-dimethylphenyl)imino]methyl)-3-methoxyphenol were investigated by X-ray diffraction, FT-IR and UV-vis spectroscopy. The vibrational frequencies calculatedusing DFT/B3LYP/6-31G(d,p) method. Results showed better agreement with the experimental values. The electronic properties was studied and the most prominent transition corresponds to π → π* and n → π*. Two types of intramolecular hydrogen bonds are strong OH⋯N interactions in enol-imine form and NH⋯O interactions in keto-amine form are compared by using density functional theory (DFT) method with B3LYP applying 6-31G(d,p) basis set. Both enol-keto tautomers engender six-membered ring due to intramolecular hydrogen bonded interactions.

  20. Design of LD in-band direct-pumping side surface polished micro-rod Nd:YVO4 laser

    International Nuclear Information System (INIS)

    Zhang Wen-Qi; Wang Fei; Liu Qiang; Gong Ma-Li

    2016-01-01

    To diminish the thermal load, two ways, that is, in-band direct pumping and micro-rod crystal, could be adopted at the same time. The efficiency of LD in-band direct-pumping side surface polished micro-rod Nd:YVO 4 laser is numerically analyzed. By optimizing parameters such as crystal length, laser mode radius, pump beam radius, doping concentration and crystal cross-section size, the overall efficiency can reach over 50%. It is found that with micro-rod crystal implemented in the laser oscillator, high overall efficiency LD in-band direct-pumping Nd:YVO 4 laser could be realized. High efficiency combined with low thermal load makes this laser an outstanding scheme for building high-power Nd:YVO 4 lasers. (paper)

  1. A prospective, randomized comparison of Foley catheter insertion versus intracervical prostaglandin E2 gel for preinduction cervical ripening.

    Science.gov (United States)

    Sciscione, A C; McCullough, H; Manley, J S; Shlossman, P A; Pollock, M; Colmorgen, G H

    1999-01-01

    The objective of this study was to compare intracervical prostaglandin E2 gel with insertion of a Foley bulb for efficacy in preinduction cervical ripening. Women who came to the hospital for induction of labor with a Bishop score intracervical prostaglandin E2 gel.

  2. Integration, viral charge and E2 mRNA levels in the progresion of intraepitelial cervical lesions

    Directory of Open Access Journals (Sweden)

    Esperanza Trujillo

    2018-01-01

    Full Text Available It is important to distinguish among squamous intraepithelial lesions (SIL those associated with increased risk cervical cancer. Our aim was to evaluate if the expression level of gen E2 in women with SIL and evidence of viral integration is associated to the grade of lesion. Cervical scrapes HPV16 positive from 19 women with normal histology, 45 women with low-grade SIL (LSIL and 45 women with high-grade SIL (HSIL were analyzed. Real-time PCR was used to quantify the mRNA of E2 and E2 and E6 genes to calculate viral load (E6 and the ratio E2/E6 to assess viral integration. Similar frequencies of E2 expression were found in LSIL and HSIL15/45 (33 %, the frequency in women without SIL was lower 3/19 (15.8 %, and all cases with E2 gene expression had mixed episomal and integrated viral DNA. The viral load increased significantly with the grade of SIL (p= 0.049, while E2/E6 ratio decreased (p=0.049. The ROC analysis showed low capacity of the three viral parameters analyzed to distinguish between low and high grade SIL. In conclusion although SIL with mixed and integrated viral DNA with E2 expression could be at lower risk of progression, and viral load and integration were associated with higher severity of the lesion, its clinical value as biomarkers of HSIL is limited.

  3. 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.

  4. 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.

  5. Instructive role of the transcription factor E2A in early B lymphopoiesis and germinal center B cell development.

    Science.gov (United States)

    Kwon, Kyongrim; Hutter, Caroline; Sun, Qiong; Bilic, Ivan; Cobaleda, César; Malin, Stephen; Busslinger, Meinrad

    2008-06-01

    The transcription factor E2A controls the initiation of B lymphopoiesis, which is arrested at the pre-pro-B cell stage in E2A-deficient mice. Here, we demonstrate by conditional mutagenesis that E2A is essential for the development of pro-B, pre-B, and immature B cells in the bone marrow. E2A is, however, dispensable for the generation of mature B cells and plasma cells in peripheral lymphoid organs. In contrast, germinal center B cell development is impaired in the absence of E2A despite normal AID expression and class-switch recombination. Molecular analysis revealed that E2A is required not only for initiating but also for maintaining the expression of Ebf1, Pax5, and the B cell gene program in pro-B cells. Notably, precocious Pax5 transcription from the Ikzf1 locus promotes pro-B cell development in E2A-deficient mice, demonstrating that ectopic Pax5 expression is sufficient to activate the B lymphoid transcription program in vivo in the absence of E2A.

  6. 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...

  7. 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 Exchanges...

  8. 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

    The E2F transcription factors are essential for regulating the correct timing of activation of several genes whose products are implicated in cell proliferation and DNA replication. The E2Fs are targets for negative regulation by the retinoblastoma protein family, which includes pRB, p107, and p130...

  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 tumors...

  10. 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...

  11. Recombinant pestivirus E2 glycoproteins prevent viral attachment to permissive and non permissive cells with different efficiency.

    Science.gov (United States)

    Asfor, A S; Wakeley, P R; Drew, T W; Paton, D J

    2014-08-30

    Bovine viral diarrhoea virus (BVDV) is an economically important animal pathogen, which like other pestiviruses has similar molecular biological features to hepaciviruses, including human Hepatitis C virus. The pestivirus E2 glycoproteins are the major target for virus-neutralising antibodies, as well as playing a role in receptor binding and host range restriction. In this study, recombinant E2 glycoproteins (rE2) derived from three different pestivirus species were examined for their inhibitory effects on pestivirus infectivity in cell culture. Histidine-tagged rE2 glycoproteins of BVDV type 2 strain 178003, BVDV type 1 strain Oregon C24V and CSFV strain Alfort 187 were produced in Spodoptera frugiperda insect cells and purified under native conditions. The ability of rE2 glycoprotein to inhibit the infection of permissive cells by both homologous and heterologous virus was compared, revealing that the inhibitory effects of rE2 glycoproteins correlated with the predicted similarity of the E2 structures in the recombinant protein and the test virus. This result suggests that the sequence and structure of E2 are likely to be involved in the host specificity of pestiviruses at their point of uptake into cells. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. 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...

  13. Allowed and forbidden transition parameters for Fe XV

    International Nuclear Information System (INIS)

    Nahar, Sultana N.

    2009-01-01

    A comprehensive set of fine structure energy levels, oscillator strengths (f), line strengths (S), and radiative decay rates (A) for bound-bound transitions in Fe XV is presented. The allowed electric dipole (E1) transitions were obtained from the relativistic Breit-Pauli R-matrix method which is based on the close coupling approximation. A total of 507 fine structure energy levels with n ≤ 10, l ≤ 9, and 0 ≤ J ≤ 10 are found. They agree within 1% with the available observed energies. These energy levels yield a total of 27,812 E1, same-spin multiplets and intercombination transitions. The A values are in good agreement with those compiled by NIST and other existing values for most transitions. Forbidden transitions are obtained from a set of 20 configurations with orbitals ranging from 1s to 5f using the relativistic code SUPERSTRUCTURE (SS) in the Breit-Pauli approximation. From a set of 123 fine structure levels, a total of 6962 S and A values are presented for forbidden electric quadrupole (E2), electric octupole (E3), magnetic dipole (M1), and magnetic quadrupole (M2) transitions. The energies from SS calculations agree with observed energies to within 1-3%. A values for E2, M1 transitions agree very well with the available values for most transitions while those for M2 transitions show variable agreement. The large set of transition parameters presented should be applicable for both diagnostics and spectral modeling in the X-ray, ultraviolet, and optical regions of astrophysical plasmas.

  14. Biodiesel Mass Transit Demonstration

    Science.gov (United States)

    2010-04-01

    The Biodiesel Mass Transit Demonstration report is intended for mass transit decision makers and fleet managers considering biodiesel use. This is the final report for the demonstration project implemented by the National Biodiesel Board under a gran...

  15. Public Transit Stations

    Data.gov (United States)

    Department of Homeland Security — fixed rail transit stations within the Continental United States, Alaska, Hawaii, the District of Columbia, and Puerto Rico. The modes of transit that are serviced...

  16. Transition Matrix Cluster Algorithms

    OpenAIRE

    Yevick, David; Lee, Yong Hwan

    2018-01-01

    We demonstrate that a series of simple procedures for increasing the efficiency of transition matrix calculations can be realized by integrating the standard single-spin reversal transition matrix method with global cluster inversion techniques.

  17. Transit operator absenteeism.

    Science.gov (United States)

    1985-01-01

    A nationwide survey of transit operators indicated that absenteeism among transit operators is a significant problem and that the associated costs are substantial. The objective of the research reported here was to determine the scope of operator abs...

  18. Exploring diurnal and seasonal characteristics of global carbon cycle with GISS Model E2 GCM

    Science.gov (United States)

    Aleinov, I. D.; Kiang, N. Y.; Romanou, A.

    2017-12-01

    The ability to properly model surface carbon fluxes on the diurnal and seasonal time scale is a necessary requirement for understanding of the global carbon cycle. It is also one of the most challenging tasks faced by modern General Circulation Models (GCMs) due to complexity of the algorithms and variety of relevant spatial and temporal scales. The observational data, though abundant, is difficult to interpret at the global scale, because flux tower observations are very sparse for large impact areas (such as Amazon and African rainforest and most of Siberia) and satellite missions often struggle to produce sufficiently high confidence data over the land and may be missing CO2 amounts near the surface due to the nature of the method. In this work we use the GISS Model E2 GCM to perform a subset of experiments proposed by the Coupled Climate-Carbon Cycle Model Intercomparison Project (C4MIP) and relate the results to available observations.The GISS Model E2 GCM is currently equipped with a complete global carbon cycle algorithm. Its surface carbon fluxes are computed by the Ent Terrestrial Biosphere Model (Ent TBM) over the land with observed leaf area index of the Moderate Resolution Imaging Spectrometer (MODIS) and by the NASA Ocean Biogeochemistry Model (NOBM) over the ocean. The propagation of atmospheric CO2 is performed by a generic Model E2 tracer algorithm, which is based on a quadratic upstream method (Prather 1986). We perform a series spin-up experiments for preindustrial climate conditions and fixed preindustrial atmospheric CO2 concentration. First, we perform separate spin-up simulations each for terrestrial and ocean carbon. We then combine the spun-up states and perform a coupled spin-up simulation until the model reaches a sufficient equilibrium. We then release restrictions on CO2 concentration and allow it evolve freely, driven only by simulated surface fluxes. We then study the results of the unforced run, comparing the amplitude and the phase

  19. The Hox cooperativity motif of the chimeric oncoprotein E2a-Pbx1 is necessary and sufficient for oncogenesis.

    Science.gov (United States)

    Chang, C P; de Vivo, I; Cleary, M L

    1997-01-01

    E2a-Pbx1 chimeric oncoproteins result from fusion of the E2A and PBX1 genes at the sites of t(1;19) chromosomal translocations in a subset acute lymphoblastic leukemias. Experimentally, E2a-Pbx1 transforms a variety of cell types, including fibroblasts, myeloid progenitors, and lymphoblasts. Structure-function studies have shown that contributions from both E2a and Pbx1 are necessary for oncogenesis, but the Pbx1 homeodomain is dispensable and the required portion of Pbx1 has not been delineated. In this study, we used deletional and site-directed mutagenesis to identify portions of Pbx1 necessary for oncogenic and transcriptional activities of E2a-Pbx1. These studies defined a motif (named the Hox cooperativity motif [HCM]) carboxy terminal to the Pbx homeodomain that is required for cooperative DNA binding, cellular transcriptional activity, and the oncogenic potential of E2a-Pbx1. The HCM is highly conserved throughout the Pbx/exd subfamily of divergent homeodomain proteins and functions in DNA-binding assays as a potential contact site for Hox dimerization. E2a-Pbx1 proteins with interstitial deletion or single-point mutations in the HCM could neither activate transcription in cellular assays nor transform NIH 3T3 cells. An E2a-Pbx1 mutant containing 50 amino acids of Pbx1b spanning the HCM but lacking the homeodomain was capable of inducing fibroblast transformation. Thus, the HCM is a necessary and sufficient contribution of Pbx1 for oncogenesis induced by E2a-Pbx1 and accounts for its homeodomain-independent transforming properties. Since subtle alterations of the Pbx HCM result in complete abrogation of transforming activity whereas the homeodomain is entirely dispensable, we conclude that interactions mediated by the HCM are more important for transformation by E2a-Pbx1 than interactions with cognate Pbx DNA sites.

  20. Forbidden Transition Probabilities of Astrophysical Interest among ...

    Indian Academy of Sciences (India)

    astrophysical plasma densities are very low, the probability of collisions is small and many states decay by M1 or E2 ..... ences were computed according to the formula [gf (l) − gf (v)] ×100/max{gf(l), gf(v)}. Transition gf (l) gf (v). Diff. (%). 3d a 2G. −. 3d a 2D. 1.518E−11. 1.683E−11. 9.8. 3d a 2G. −. 3d a 2G. 5.290E−07.

  1. Quantum phase transitions

    International Nuclear Information System (INIS)

    Sachdev, S.

    1999-01-01

    Phase transitions are normally associated with changes of temperature but a new type of transition - caused by quantum fluctuations near absolute zero - is possible, and can tell us more about the properties of a wide range of systems in condensed-matter physics. Nature abounds with phase transitions. The boiling and freezing of water are everyday examples of phase transitions, as are more exotic processes such as superconductivity and superfluidity. The universe itself is thought to have passed through several phase transitions as the high-temperature plasma formed by the big bang cooled to form the world as we know it today. Phase transitions are traditionally classified as first or second order. In first-order transitions the two phases co-exist at the transition temperature - e.g. ice and water at 0 deg., or water and steam at 100 deg. In second-order transitions the two phases do not co-exist. In the last decade, attention has focused on phase transitions that are qualitatively different from the examples noted above: these are quantum phase transitions and they occur only at the absolute zero of temperature. The transition takes place at the ''quantum critical'' value of some other parameter such as pressure, composition or magnetic field strength. A quantum phase transition takes place when co-operative ordering of the system disappears, but this loss of order is driven solely by the quantum fluctuations demanded by Heisenberg's uncertainty principle. The physical properties of these quantum fluctuations are quite distinct from those of the thermal fluctuations responsible for traditional, finite-temperature phase transitions. In particular, the quantum system is described by a complex-valued wavefunction, and the dynamics of its phase near the quantum critical point requires novel theories that have no analogue in the traditional framework of phase transitions. In this article the author describes the history of quantum phase transitions. (UK)

  2. Origins of evolutionary transitions

    Indian Academy of Sciences (India)

    An `evolutionary transition in individuality' or `major transition' is a transformation in the hierarchical level at which natural selection operates on a population. In this article I give an abstract (i.e. level-neutral and substrate-neutral) articulation of the transition process in order to precisely understand how such processes can ...

  3. Microwave stability at transition

    International Nuclear Information System (INIS)

    Holt, J.A.; Colestock, P.L.

    1995-05-01

    The question of microwave stability at transition is revisited using a Vlasov approach retaining higher order terms in the particle dynamics near the transition energy. A dispersion relation is derived which can be solved numerically for the complex frequency in terms of the longitudinal impedance and other beam parameters. Stability near transition is examined and compared with simulation results

  4. Transit manager's handbook.

    Science.gov (United States)

    2011-09-01

    This handbook provides an overview of public transit in Iowa and how to do business with the Iowa Department of Transportation (Iowa DOT) Office of Public Transit (OPT). It is intended to be a tool to assist transit managers navigate through the many...

  5. Modeling for Transition Management

    NARCIS (Netherlands)

    Chappin, Emile J L; Dijkema, Gerard P.J.

    2015-01-01

    A framework for the modeling and simulation of transitions is presented. A transition, “substantial change in the state of a socio-technical system”, typically unfolds over a long timespan. We therefore suggest to use simulation to inform transition managers on the effect of their decisions.

  6. Transit labor relations guide

    Science.gov (United States)

    2001-09-01

    This report is designed as a guide for those involved in labor relations in the transit industry. It begins with a history of transit labor relations. The economic, political, and legal environment of transit relations is then discussed. A section fo...

  7. E2-quasi-exact solvability for non-Hermitian models

    International Nuclear Information System (INIS)

    Fring, Andreas

    2015-01-01

    We propose the notion of E 2 -quasi-exact solvability and apply this idea to find explicit solutions to the eigenvalue problem for a non-Hermitian Hamiltonian system depending on two parameters. The model considered reduces to the complex Mathieu Hamiltonian in a double scaling limit, which enables us to compute the exceptional points in the energy spectrum of the latter as a limiting process of the zeros for some algebraic equations. The coefficient functions in the quasi-exact eigenfunctions are univariate polynomials in the energy obeying a three-term recurrence relation. The latter property guarantees the existence of a linear functional such that the polynomials become orthogonal. The polynomials are shown to factorize for all levels above the quantization condition leading to vanishing norms rendering them to be weakly orthogonal. In two concrete examples we compute the explicit expressions for the Stieltjes measure. (paper)

  8. E2-quasi-exact solvability for non-Hermitian models

    Science.gov (United States)

    Fring, Andreas

    2015-04-01

    We propose the notion of E2-quasi-exact solvability and apply this idea to find explicit solutions to the eigenvalue problem for a non-Hermitian Hamiltonian system depending on two parameters. The model considered reduces to the complex Mathieu Hamiltonian in a double scaling limit, which enables us to compute the exceptional points in the energy spectrum of the latter as a limiting process of the zeros for some algebraic equations. The coefficient functions in the quasi-exact eigenfunctions are univariate polynomials in the energy obeying a three-term recurrence relation. The latter property guarantees the existence of a linear functional such that the polynomials become orthogonal. The polynomials are shown to factorize for all levels above the quantization condition leading to vanishing norms rendering them to be weakly orthogonal. In two concrete examples we compute the explicit expressions for the Stieltjes measure.

  9. [Molecular biology and childhood leukemia: E2A-PBX1 and central nervous system relapse].

    Science.gov (United States)

    Núñez-Enríquez, Juan Carlos; Mejía-Aranguré, Juan Manuel

    2015-01-01

    Acute lymphoblastic leukemia (ALL) is the most common cancer in children. The inclusion of molecular biology techniques in the diagnosis and prognostic stratification of these patients has allowed major treatment achievements in developed countries. One of the best studied gene rearrangements is E2A-PBX1, which predicts isolated central nervous system relapse in patients with ALL. However, further research on the search for new molecular markers related to prognosis of patients with childhood leukemia is required. Such studies need the integration of different disciplines, including epidemiology. Epidemiological studies are needed not only to accelerate the discovery of new molecular markers and new biological signals as to the etiology and pathophysiology of cancer, but also to evaluate the clinical impact of these findings in well-defined populations.

  10. 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.

  11. 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.

  12. 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.

  13. Reproductive control via eviction (but not the threat of eviction) in banded mongooses.

    Science.gov (United States)

    Cant, Michael A; Hodge, Sarah J; Bell, Matthew B V; Gilchrist, Jason S; Nichols, Hazel J

    2010-07-22

    Considerable research has focused on understanding variation in reproductive skew in cooperative animal societies, but the pace of theoretical development has far outstripped empirical testing of the models. One major class of model suggests that dominant individuals can use the threat of eviction to deter subordinate reproduction (the 'restraint' model), but this idea remains untested. Here, we use long-term behavioural and genetic data to test the assumptions of the restraint model in banded mongooses (Mungos mungo), a species in which subordinates breed regularly and evictions are common. We found that dominant females suffer reproductive costs when subordinates breed, and respond to these costs by evicting breeding subordinates from the group en masse, in agreement with the assumptions of the model. We found no evidence, however, that subordinate females exercise reproductive restraint to avoid being evicted in the first place. This means that the pattern of reproduction is not the result of a reproductive 'transaction' to avert the threat of eviction. We present a simple game theoretical analysis that suggests that eviction threats may often be ineffective to induce pre-emptive restraint among multiple subordinates and predicts that threats of eviction (or departure) will be much more effective in dyadic relationships and linear hierarchies. Transactional models may be more applicable to these systems. Greater focus on testing the assumptions rather than predictions of skew models can lead to a better understanding of how animals control each other's reproduction, and the extent to which behaviour is shaped by overt acts versus hidden threats.

  14. Limits on the Capacity of In-Band Full Duplex Communication in Uplink Cellular Networks

    KAUST Repository

    Randrianantenaina, Itsikiantsoa

    2016-02-26

    Simultaneous co-channel transmission and reception, denoted as in-band full duplex (FD) communication, has been promoted as an attractive solution to improve the spectral efficiency of cellular networks. However, in addition to the selfinterference problem, cross-mode interference (i.e., between uplink and downlink) imposes a major obstacle for the deployment of FD communication in cellular networks. More specifically, the downlink to uplink interference represents the performance bottleneck for FD operation due to the uplink limited transmission power and venerable operation when compared to the downlink counterpart. While the positive impact of FD communication to the downlink performance has been proved in the literature, its effect on the uplink transmission has been neglected. This paper focuses on the effect of downlink interference on the uplink transmission in FD cellular networks in order to see whether FD communication is beneficial for the uplink transmission or not, and if yes for which type of network. To quantify the expected performance gains, we derive a closed form expression of the maximum achievable uplink capacity in FD cellular networks. In contrast to the downlink capacity which always improves with FD communication, our results show that the uplink performance may improves or degrades depending on the associated network parameters. Particularly, we show that the intensity of base stations (BSs) has a more prominent effect on the uplink performance than their transmission power.

  15. In-Band α-Duplex Scheme for Cellular Networks: A Stochastic Geometry Approach

    KAUST Repository

    Alammouri, Ahmad

    2016-07-13

    In-band full-duplex (FD) communications have been optimistically promoted to improve the spectrum utilization and efficiency. However, the penetration of FD communications to the cellular networks domain is challenging due to the imposed uplink/downlink interference. This paper presents a tractable framework, based on stochastic geometry, to study FD communications in cellular networks. Particularly, we assess the FD communications effect on the network performance and quantify the associated gains. The study proves the vulnerability of the uplink to the downlink interference and shows that FD rate gains harvested in the downlink (up to 97%) come at the expense of a significant degradation in the uplink rate (up to 94%). Therefore, we propose a novel fine-grained duplexing scheme, denoted as -duplex scheme, which allows a partial overlap between the uplink and the downlink frequency bands. We derive the required conditions to harvest rate gains from the -duplex scheme and show its superiority to both the FD and half-duplex (HD) schemes. In particular, we show that the -duplex scheme provides a simultaneous improvement of 28% for the downlink rate and 56% for the uplink rate. Finally, we show that the amount of the overlap can be optimized based on the network design objective.

  16. Underlay Spectrum Sharing Techniques with In-Band Full-Duplex Systems using Improper Gaussian Signaling

    KAUST Repository

    Gaafar, Mohamed

    2016-10-26

    Sharing the spectrum with in-band full-duplex (FD) primary users (PUs) is a challenging and interesting problem in the underlay cognitive radio (CR) systems. The self-interference introduced at the primary network may dramatically impede the secondary user (SU) opportunity to access the spectrum. To tackle this problem, we use the so-called improper Gaussian signaling. Particularly, we assume the downlink transmission of a SU that uses improper Gaussian signaling while the FD PU pair implements the regular proper Gaussian signaling. First, we derive a closed form expression and an upper bound for the SU and PUs outage probabilities, respectively. Second, we optimize the SU signal parameters to minimize its outage probability while maintaining the required PUs quality-of-service based on the average channel state information (CSI). Moreover, we provide the conditions to reap merits from employing improper Gaussian signaling at the SU. Third, we design the SU signal parameters based on perfect knowledge of its direct link instantaneous CSI and investigate all benefits that can be achieved at both the SU and PUs. Finally, we provide some numerical results that demonstrate the advantages of using improper Gaussian signaling to access the spectrum of the FD PUs.

  17. Prostaglandin E2 facilitates neurite outgrowth in a motor neuron-like cell line, NSC-34

    Directory of Open Access Journals (Sweden)

    Hiroshi Nango

    2017-10-01

    Full Text Available Prostaglandin E2 (PGE2 exerts various biological effects by binding to E-prostanoid receptors (EP1-4. Although recent studies have shown that PGE2 induces cell differentiation in some neuronal cells such as mouse DRG neurons and sensory neuron-like ND7/23 cells, it is unclear whether PGE2 plays a role in differentiation of motor neurons. In the present study, we investigated the mechanism of PGE2-induced differentiation of motor neurons using NSC-34, a mouse motor neuron-like cell line. Exposure of undifferentiated NSC-34 cells to PGE2 and butaprost, an EP2-selective agonist, resulted in a reduction of MTT reduction activity without increase the number of propidium iodide-positive cells and in an increase in the number of neurite-bearing cells. Sulprostone, an EP1/3 agonist, also significantly lowered MTT reduction activity by 20%; however, no increase in the number of neurite-bearing cells was observed within the concentration range tested. PGE2-induced neurite outgrowth was attenuated significantly in the presence of PF-0441848, an EP2-selective antagonist. Treatment of these cells with dibutyryl-cAMP increased the number of neurite-bearing cells with no effect on cell proliferation. These results suggest that PGE2 promotes neurite outgrowth and suppresses cell proliferation by activating the EP2 subtype, and that the cAMP-signaling pathway is involved in PGE2-induced differentiation of NSC-34 cells. Keywords: Prostaglandin E2, E-prostanoid receptors, Motor neuron, Neurite outgrowth, cAMP

  18. A Digital Hydrologic Network Supporting NAWQA MRB SPARROW Modeling--MRB_E2RF1WS

    Science.gov (United States)

    Brakebill, J.W.; Terziotti, S.E.

    2011-01-01

    A digital hydrologic network was developed to support SPAtially Referenced Regression on Watershed attributes (SPARROW) models within selected regions of the United States. These regions correspond with the U.S. Geological Survey's National Water Quality Assessment (NAWQA) Program Major River Basin (MRB) study units 2, 3, 4, 5, and 7 (Preston and others, 2009). MRB2, covers the South Atlantic-Gulf and Tennessee River basins. MRB3, covers the Great Lakes, Ohio, Upper Mississippi, and Souris-Red-Rainy River basins. MRB4, covers the Missouri River basins. MRB5, covers the Lower Mississippi, Arkansas-White-Red, and Texas-Gulf River basins. MRB7, covers the Pacific Northwest River basins. The digital hydrologic network described here represents surface-water pathways (MRB_E2RF1) and associated catchments (MRB_E2RF1WS). It serves as the fundamental framework to spatially reference and summarize explanatory information supporting nutrient SPARROW models (Brakebill and others, 2011; Wieczorek and LaMotte, 2011). The principal geospatial dataset used to support this regional effort was based on an enhanced version of a 1:500,000 scale digital stream-reach network (ERF1_2) (Nolan et al., 2002). Enhancements included associating over 3,500 water-quality monitoring sites to the reach network, improving physical locations of stream reaches at or near monitoring locations, and generating drainage catchments based on 100m elevation data. A unique number (MRB_ID) identifies each reach as a single unit. This unique number is also shared by the catchment area drained by the reach, thus spatially linking the hydrologically connected streams and the respective drainage area characteristics. In addition, other relevant physical, environmental, and monitoring information can be associated to the common network and accessed using the unique identification number.

  19. A Digital Hydrologic Network Supporting NAWQA MRB SPARROW Modeling--MRB_E2RF1

    Science.gov (United States)

    Brakebill, J.W.; Terziotti, S.E.

    2011-01-01

    A digital hydrologic network was developed to support SPAtially Referenced Regression on Watershed attributes (SPARROW) models within selected regions of the United States. These regions correspond with the U.S. Geological Survey's National Water Quality Assessment (NAWQA) Program Major River Basin (MRB) study units 2, 3, 4, 5, and 7 (Preston and others, 2009). MRB2, covers the South Atlantic-Gulf and Tennessee River basins. MRB3, covers the Great Lakes, Ohio, Upper Mississippi, and Souris-Red-Rainy River basins. MRB4, covers the Missouri River basins. MRB5, covers the Lower Mississippi, Arkansas-White-Red, and Texas-Gulf River basins. MRB7, covers the Pacific Northwest River basins. The digital hydrologic network described here represents surface-water pathways (MRB_E2RF1) and associated catchments (MRB_E2RF1WS). It serves as the fundamental framework to spatially reference and summarize explanatory information supporting nutrient SPARROW models (Brakebill and others, 2011; Wieczorek and LaMotte, 2011). The principal geospatial dataset used to support this regional effort was based on an enhanced version of a 1:500,000 scale digital stream-reach network (ERF1_2) (Nolan et al., 2002). Enhancements included associating over 3,500 water-quality monitoring sites to the reach network, improving physical locations of stream reaches at or near monitoring locations, and generating drainage catchments based on 100m elevation data. A unique number (MRB_ID) identifies each reach as a single unit. This unique number is also shared by the catchment area drained by the reach, thus spatially linking the hydrologically connected streams and the respective drainage area characteristics. In addition, other relevant physical, environmental, and monitoring information can be associated to the common network and accessed using the unique identification number.

  20. 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

  1. 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

  2. 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.

  3. The Oncoprotein E2A-Pbx1a Collaborates with Hoxa9 To Acutely Transform Primary Bone Marrow Cells

    Science.gov (United States)

    Thorsteinsdottir, Unnur; Krosl, Jana; Kroon, Evert; Haman, André; Hoang, Trang; Sauvageau, Guy

    1999-01-01

    A recurrent translocation between chromosome 1 (Pbx1) and 19 (E2A) leading to the expression of the E2A-Pbx1 fusion oncoprotein occurs in ∼5 to 10% of acute leukemias in humans. It has been proposed that some of the oncogenic potential of E2A-Pbx1 could be mediated through heterocomplex formation with Hox proteins, which are also involved in human and mouse leukemias. To directly test this possibility, mouse bone marrow cells were engineered by retroviral gene transfer to overexpress E2A-Pbx1a together with Hoxa9. The results obtained demonstrated a strong synergistic interaction between E2A-Pbx1a and Hoxa9 in inducing growth factor-independent proliferation of transduced bone marrow cells in vitro and leukemic growth in vivo in only 39 ± 2 days. The leukemic blasts which coexpress E2A-Pbx1a and Hoxa9 showed little differentiation and produced cytokines such as interleukin-3, granulocyte colony-stimulating factor, and Steel. Together, these studies demonstrate that the Hoxa9 and E2A-Pbx1a gene products collaborate to produce a highly aggressive acute leukemic disease. PMID:10454582

  4. Study on the changes of serum GH, T and E2 levels in elderly patients with coronary heart disease

    International Nuclear Information System (INIS)

    Wu Shaoqin; Ji Naijun; Mei Yibin; Fan Bifu; Chen Donghai; Tong Lijun; Wang Chengyao; Li Fuyuan; Kao Yan

    2005-01-01

    Objective: To investigate the clinical significance of changes of serum growth hormone (GH), testosterone (T) and estradiol (E 2 ) levels in elderly patients with coronary heart disease (CHD). Methods: Serum GH, T and E 2 levels were determined with RIA in 112 elderly patients with CHD and 40 controls. Results: The serum levels of GH and E2 in the elderly patients with CHD were significantly lower than those in controls (P 0.05). Levels of GH and E 2 were mutually positively correlated (P 0.05). The serum levels of GH, T, and E 2 decreased gradually with the advancement of cardiac function impairment from grade I to grade IV (P 0.05). Serum levels of GH, T and E 2 were significantly lower in the patients succumbed in hospital (n=8) than those in patients discharged. Conclusion: The serum GH, T and E 2 levels were much lower in the patients with more advanced coronary heart disease, with least changes in T levels. (authors)

  5. Sites of disruption within E1 and E2 genes of HPV16 and association with cervical dysplasia.

    Science.gov (United States)

    Tsakogiannis, D; Gortsilas, P; Kyriakopoulou, Z; Ruether, I G A; Dimitriou, T G; Orfanoudakis, G; Markoulatos, P

    2015-11-01

    Integration of HPV16 DNA into the host chromosome usually disrupts the E1 and/or E2 genes. The present study investigated the disruption of E1, E2 genes in a total of eighty four HPV16-positive precancerous and cervical cancer specimens derived from Greek women (seventeen paraffin-embedded cervical biopsies and sixty seven Thin Prep samples). Complete E2 and E1 genes were amplified using three and nine overlapping primer sets respectively, in order to define the sites of disruption. Extensive mapping analysis revealed that disruption/deletion events within E2 gene occurred in high grade and cervical cancer samples (x(2) test, P disruption was documented among low grade cervical intraepithelial neoplasias. In addition, disruptions within the E1 gene occur both in high and low grade cervical intraepithelial neoplasia. This leads to the assumption that in low grade cervical intraepithelial neoplasias only E1 gene disruption was involved (Fisher's exact test, P disruption of E1 gene was located between nucleotides 1059 and 1323, while the most prevalent deleted region of the E2 gene was located between nucleotides 3172 and 3649 (E2 hinge region). Therefore, it is proposed that each population has its own profile of frequencies and sites of disruptions and extensive mapping analysis of E1 and E2 genes is mandatory in order to determine suitable markers for HPV16 DNA integration analysis in distinct populations. © 2015 Wiley Periodicals, Inc.

  6. Interaction of CSFV E2 protein with swine host factors as detected by yeast two-hybrid system.

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    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.

  7. Transition Theory – Sustainable Transition of Socio-Technical Systems

    DEFF Research Database (Denmark)

    Søndergård, Bent; Holm, Jesper; Stauning, Inger

    2015-01-01

    Theories of transition management, transition studies and social practise theory Applied to studies of hosuing and construction......Theories of transition management, transition studies and social practise theory Applied to studies of hosuing and construction...

  8. Evidence for Hox and E2A-PBX1 collaboration in mouse T-cell leukemia.

    Science.gov (United States)

    Bijl, J; Krosl, J; Lebert-Ghali, C-E; Vacher, J; Mayotte, N; Sauvageau, G

    2008-10-23

    Using murine Moloney leukemia virus (MMLV)-based proviral insertional mutagenesis, we previously showed a preferential targeting of a small region in the Hoxa gene locus in E2A-PBX1-induced lymphoid leukemia resulting in the overexpression of several Hoxa genes including Hoxa10, Hoxa9 and Hoxa7. This observation suggested a functional interaction between Hox gene overexpression and E2A-PBX1 in lymphoid tumors. To further explore this possibility, we generated a series of compound E2A-PBX1 x Hox transgenic mice and tested the genetic interaction between these genes in the generation of lymphoid leukemia in vivo. Results presented in this report show that the onset of T-cell leukemia is significantly accelerated in E2A-PBX1 x Hoxb4 compound transgenic animals when compared with control E2A-PBX1 or Hoxb4 littermates. Hoxa9 appears less potent than Hoxb4 to accelerate E2A-PBX1-induced T-cell leukemia in mice. E2A-PBX1-induced T-cell leukemias express much higher levels of Hoxa genes than MMLV-induced counterparts, possibly suggesting a contribution of these genes to T-cell transformation by E2A-PBX1. Collectively, these data provide the first genetic evidence showing oncogenic collaboration between E2A-PBX1 and a Hox gene in lymphoid malignancies in vivo and document the specific deregulation of a subgroup of Hoxa genes in these leukemias.

  9. Detection of E2A-PBX1 fusion transcripts in human non-small-cell lung cancer.

    Science.gov (United States)

    Mo, Min-Li; Chen, Zhao; Zhou, Hai-Meng; Li, Hui; Hirata, Tomomi; Jablons, David M; He, Biao

    2013-05-20

    E2A-PBX1 fusion gene caused by t(1;19)(q23;p13), has been well characterized in acute lymphoid leukemia (ALL). There is no report on E2A-PBX1 fusion transcripts in non-small-cell lung cancer (NSCLC). We used polymerase chain reaction (PCR) to detect E2A-PBX1 fusion transcripts in human NSCLC tissue specimens and cell lines. We analyzed correlation of E2A-PBX1 fusion transcripts with clinical outcomes in 76 patients with adenocarcinoma in situ (AIS) and other subgroups. We compared mutation status of k-ras, p53 and EGFR in 22 patients with E2A-PBX1 fusion transcripts. We detected E2A-PBX1 transcripts in 23 of 184 (12.5%) NSCLC tissue specimens and 3 of 13 (23.1%) NSCLC cell lines. Presence of E2A-PBX1 fusion transcripts correlated with smoking status in female patients (P=0.048), AIS histology (P=0.006) and tumor size (P=0.026). The overall survival was associated with gender among AIS patients (P=0.0378) and AIS patients without E2A-PBX1 fusion transcripts (P=0.0345), but not among AIS patients with E2A-PBX1 fusion transcripts (P=0.6401). The overall survival was also associated with status of E2A-PBX1 fusion transcripts among AIS stage IA patients (P=0.0363) and AIS stage IA female patients (P=0.0174). In addition, among the 22 patients with E2A-PBX1 fusion transcripts, 12 (54.5%) patients including all four non-smokers, showed no common mutations in k-ras, p53 and EGFR. E2A-PBX1 fusion gene caused by t(1;19)(q23;p13) may be a common genetic change in AIS and a survival determinant for female AIS patients at early stage.

  10. 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

  11. Clinical significance of determination of changes of serum leptin and E2 levels in females children with simple obesity

    International Nuclear Information System (INIS)

    Bai Hua; Qian Mingzhu

    2007-01-01

    Objective: To investigate the clinical significance of changes of serum leptin and E 2 levels in females children with simple obesity. Methods: Serum levels of leptin and E 2 were detected with RIA in 32 females children with simple obesity and 35 controls. Results: In the children with simple obesity the serum leptin and E 2 levels were significantly higher than those in controls (P 2 levels is of help for judgement of severity of obesity as well as outcome prediction in female children. (authors)

  12. Efficacy of marker vaccine candidate CP7 E2alf in piglets with maternally derived C-strain antibodies

    DEFF Research Database (Denmark)

    Rangelova, Desislava Yordanova; Nielsen, Jens; Strandbygaard, Bertel

    2012-01-01

    Marker vaccines offer the possibility to differentiate classical swine fever (CSF) infected from CSF vaccinated animals based on serology and their implementation will ensure free trade with pigs. Therefore, new generations of promising marker vaccines have been developed, among them the chimeric...... vaccine CP7_E2alf. However, in populations previously vaccinated with live attenuated vaccines like the C-strain, passive immunity through maternal antibodies can interfere with efficacy of CP7_E2alf vaccination. Therefore, the efficacy of CP7_E2alf was examined in piglets from sows vaccinated once...

  13. 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.

  14. Abscinazole-E2B, a practical and selective inhibitor of ABA 8'-hydroxylase CYP707A.

    Science.gov (United States)

    Okazaki, Mariko; Kittikorn, Monrudee; Ueno, Kotomi; Mizutani, Masaharu; Hirai, Nobuhiro; Kondo, Satoru; Ohnishi, Toshiyuki; Todoroki, Yasushi

    2012-05-15

    We developed abscinazole-E2B (Abz-E2B), a practical and specific inhibitor of abscisic acid (ABA) 8'-hydroxylase (CYP707A), by structural modification of abscinazole-E1 (Abz-E1), another compound we developed. A butoxy group was introduced to Abz-E2B instead of the tosylate group of Abz-E1, in expectation of better water solubility, because the calculated logP value of Abz-E2B is 3.47, which is smaller than that of Abz-E1 (4.02). The water solubility of Abz-E2B was greater than 90% at a concentration of 100 μM, at which the solubility of Abz-E1 was 20%. The enzyme specificity was improved significantly. In in vitro assays constructed using recombinant enzymes, (±)-Abz-E2B was a considerably weaker inhibitor than (±)-Abz-E1 for CYP701A, a GA biosynthetic enzyme, which is a target of S-uniconazole (S-UNI), a lead compound of Abz-E1. (±)-Abz-E2B application to plants resulted in improved desiccation tolerance and an increase in endogenous ABA, with little retardation of growth. We also prepared optically pure Abz-E2B and determined its absolute configuration. The R-enantiomer of Abz-E2B was the more potent inhibitor of CYP707A, unlike UNI, whereas both enantiomers were markedly less effective than S-UNI in inhibiting CYP701A. Because S-Abz-E2B arrested the growth of rice seedlings at 100 μM, probably because of off-target effects, R-Abz-E2B should be used as a chemical tool for research focusing on CYP707A when 100 μM or higher concentration is required, although (±)-Abz-E2B may be useful as an alternative option at a lower concentration. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Modulation of afferent nerve activity by prostaglandin E2 upon urinary bladder distension in rats.

    Science.gov (United States)

    Kuga, Nahoko; Tanioka, Asao; Hagihara, Koichiro; Kawai, Tomoyuki

    2016-05-01

    What is the central question of this study? It has been widely assumed that C fibres innervating the bladder are mainly excited in overactive bladder syndrome. However, it remains unclear whether Aδ fibres are also activated in pathological conditions. What is the main finding and its importance? We found that a certain population of Aδ fibres, which become active specifically at a bladder pressure of more than 15 cmH2 O in normal conditions, showed increased excitability in conditions of prostaglandin E2 -induced overactive bladder. This result suggests that a certain population of Aδ fibres, together with C fibres, triggers pathophysiological activity. In overactive bladder syndrome, afferent C fibres innervating the bladder show an increased activity level. However, it remains unclear whether all C fibres are highly activated and whether Aδ fibres, the other type of bladder afferent fibre, are also involved in pathological conditions. To address these questions, we analysed the relationship between bladder pressure and single-unit firing patterns of afferent nerves in the left L6 dorsal roots in living rats. The recorded fibres were classified as Aδ fibres or C fibres based on the response to 0.3 μm tetrodotoxin. Certain populations of both Aδ fibres and C fibres were activated at bladder pressures below 15 cmH2 O (classified as low-threshold fibres), indicating their potential contribution to detection of normal bladder filling. Intravesical administration of prostaglandin E2 (PGE2 ) induced hyperexcitation in approximately half of such C fibres, whereas the activity patterns of low-threshold Aδ fibres were unchanged. All fibres, regardless of type, which were almost silent in control conditions (classified as high-threshold fibres), were activated by application of PGE2 . Notably, the firing patterns of Aδ fibres, rather than C fibres, were highly time locked to PGE2 -induced micro-oscillation of bladder pressure. These modulatory effects

  16. 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

  17. 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

  18. Transition sum rules in the shell model

    Science.gov (United States)

    Lu, Yi; Johnson, Calvin W.

    2018-03-01

    An important characterization of electromagnetic and weak transitions in atomic nuclei are sum rules. We focus on the non-energy-weighted sum rule (NEWSR), or total strength, and the energy-weighted sum rule (EWSR); the ratio of the EWSR to the NEWSR is the centroid or average energy of transition strengths from an nuclear initial state to all allowed final states. These sum rules can be expressed as expectation values of operators, which in the case of the EWSR is a double commutator. While most prior applications of the double commutator have been to special cases, we derive general formulas for matrix elements of both operators in a shell model framework (occupation space), given the input matrix elements for the nuclear Hamiltonian and for the transition operator. With these new formulas, we easily evaluate centroids of transition strength functions, with no need to calculate daughter states. We apply this simple tool to a number of nuclides and demonstrate the sum rules follow smooth secular behavior as a function of initial energy, as well as compare the electric dipole (E 1 ) sum rule against the famous Thomas-Reiche-Kuhn version. We also find surprising systematic behaviors for ground-state electric quadrupole (E 2 ) centroids in the s d shell.

  19. Obtaining classical swine fever virus E2 recombinant protein and DNA-vaccine on the basis of one subunit

    International Nuclear Information System (INIS)

    Deryabin, O.; Deryabina, O.; Verbitskiy, P.; Kordyum, V.

    2005-01-01

    Three forms of E2 recombinant protein were expressed in E. coli. Swine sera obtained against different forms of the recombinant protein were cross-studied with indirect ELISA. Using individual proteins as an antigen, only 15% of sera against other forms of protein reacted positively, while 100% of heterologous sera showed positive reaction with fused protein. Challenge experiments showed the existence of protective action only from the individual protein. Specificity and activity of sera obtained from the animals after control challenge was confirmed in a blocking variant of ELISA. Genetic construction used a eukaryotic vector that contained the E2 protein gene. Immunization of mice with the resulting DNA induced synthesis of specific antibodies, the titre of which increased considerably after additional single immunization with the E2 recombinant protein, expressed in E. coli. This demonstrated the effectiveness of animal priming by DNA vaccine, and the possibility of using the E2 recombinant protein in E. coli for booster vaccination. (author)

  20. Allelic exclusion of IgH through inhibition of E2A in a VDJ recombination complex.

    Science.gov (United States)

    Hauser, Jannek; Grundström, Christine; Grundström, Thomas

    2014-03-01

    A key feature of the immune system is the paradigm that one lymphocyte has only one Ag specificity that can be selected for or against. This requires that only one of the alleles of genes for AgR chains is made functional. However, the molecular mechanism of this allelic exclusion has been an enigma. In this study, we show that B lymphocytes with E2A that cannot be inhibited by calmodulin are dramatically defective in allelic exclusion of the IgH locus. Furthermore, we provide data supporting that E2A, PAX5, and the RAGs are in a VDJ recombination complex bound to key sequences on the Igh gene. We show that pre-BCR activation releases the VDJ recombination complex through calmodulin binding to E2A. We also show that pre-BCR signaling downregulates several components of the recombination machinery, including RAG1, RAG2, and PAX5, through calmodulin inhibition of E2A.

  1. Cell cycle regulation of the cyclin A gene promoter is mediated by a variant E2F site

    DEFF Research Database (Denmark)

    Schulze, A; Zerfass, K; Spitkovsky, D

    1995-01-01

    Cyclin A is involved in the control of S phase and mitosis in mammalian cells. Expression of the cyclin A gene in nontransformed cells is characterized by repression of its promoter during the G1 phase of the cell cycle and its induction at S-phase entry. We show that this mode of regulation...... is mediated by the transcription factor E2F, which binds to a specific site in the cyclin A promoter. It differs from the prototype E2F site in nucleotide sequence and protein binding; it is bound by E2F complexes containing cyclin E and p107 but not pRB. Ectopic expression of cyclin D1 triggers premature...... activation of the cyclin A promoter by E2F, and this effect is blocked by the tumor suppressor protein p16INK4....

  2. [Identification of proteins associated with transcription factors HOXA9 and E2A-PBX1 by tandem affinity purification].

    Science.gov (United States)

    Shestakova, E A; Boutin, M; Bourassa, S; Bonneil, E; Bijl, J J

    2017-01-01

    Chimeric transcription factor E2A-PBX1 induces the development of acute lymphoblastic B-cell leukemia in children. Using a transgenic mouse model, we previously demonstrated that homeobox (HOX) gene HOXA9 genetically interact with E2A-PBX1 gene in the development of B-cell leukemia in mice. HOXA9 itself is a potent oncogene resulting in myeloid leukemia when overexpressed, which is strongly accelerated by its collaborator Meis1. HOX, PBX1 and MEIS1 proteins have been shown to form hetero dimeric or trimeric complexes in different combinations. Cooperative interaction between PBX1 and HOX proteins enhances their DNA binding specificity, essential for HOX dependent developmental programs. PBX1 is retained in E2A-PBX1, and thus the strong transcriptional activator properties of E2A-PBX1 may lead to aberrant activation of normally repressed targets of HOX-PBX complexes. However, although there is evidence that E2A-PBX1 could bind to HOX and MEIS1 proteins it is still unclear whether such complexes are actually required for leukemic transformation or whether E2A-PBX1 and HOXA9 are each part of larger protein complexes acting in independent complementing oncogenic pathways. In this study we aim to search for other HOXA9 and E2A-PBX1 interacting proteins. To identify novel proteins interacting with human E2A-PBX1 or HOXA9 we used tandem affinity purification (TAP) of protein complexes from 697 pre-B leukemic and HeLa cell lines transduced to express E2A-PBX1 or HOXA9, respectively, with covalently attached FLAG/HA peptides. The protein composition of each complex was determined using tandem mass-spectrometry. In the E2A-PBX1 containing complex we identified lymphoid transcription factor IKAROS, chromatin remodeling factors of SWI/SNF family while multiple subunits of translation initiation factor eIF3, E3 ubiquitin ligase UBR5 emerged from the HOXA9 complex as potential critical protein partners. This is the first time the protein partners of either E2A-PBX1 or HOXA9

  3. Pigs immunized with a novel E2 subunit vaccine are protected from subgenotype heterologous classical swine fever virus challenge.

    Science.gov (United States)

    Madera, Rachel; Gong, Wenjie; Wang, Lihua; Burakova, Yulia; Lleellish, Karen; Galliher-Beckley, Amy; Nietfeld, Jerome; Henningson, Jamie; Jia, Kaimin; Li, Ping; Bai, Jianfa; Schlup, John; McVey, Scott; Tu, Changchun; Shi, Jishu

    2016-09-09

    Classical swine fever (CSF) or hog cholera is a highly contagious swine viral disease. CSF endemic countries have to use routine vaccination with modified live virus (MLV) vaccines to prevent and control CSF. However, it is impossible to serologically differentiate MLV vaccinated pigs from those infected with CSF virus (CSFV). The aim of this study is to develop a one-dose E2-subunit vaccine that can provide protection against CSFV challenge. We hypothesize that a vaccine consisting of a suitable adjuvant and recombinant E2 with natural conformation may induce a similar level of protection as the MLV vaccine. Our experimental vaccine KNB-E2 was formulated with the recombinant E2 protein (Genotype 1.1) expressed by insect cells and an oil-in-water emulsion based adjuvant. 10 pigs (3 weeks old, 5 pigs/group) were immunized intramuscularly with one dose or two doses (3 weeks apart) KNB-E2, and 10 more control pigs were administered normal saline solution only. Two weeks after the second vaccination, all KNB-E2 vaccinated pigs and 5 control pigs were challenged with 5 × 10(5) TCID50 CSFV Honduras/1997 (Genotype 1.3, 1 ml intramuscular, 1 ml intranasal). It was found that while control pigs infected with CSFV stopped growing and developed high fever (>40 °C), high level CSFV load in blood and nasal fluid, and severe leukopenia 3-14 days post challenge, all KNB-E2 vaccinated pigs continued to grow as control pigs without CSFV exposure, did not show any fever, had low or undetectable level of CSFV in blood and nasal fluid. At the time of CSFV challenge, only pigs immunized with KNB-E2 developed high levels of E2-specific antibodies and anti-CSFV neutralizing antibodies. Our studies provide direct evidence that pigs immunized with one dose KNB-E2 can be protected clinically from CSFV challenge. This protection is likely mediated by high levels of E2-specific and anti-CSFV neutralizing antibodies.

  4. [Clinical significance of monitoring E2A- PBX1 fusion gene expression in patients with allogeneic hematopoietic stem cell transplantation].

    Science.gov (United States)

    Zhao, Xiaosu; Qin, Yazhen; Zhang, Yanling; Xu, Yongyan; Wang, Yu; Chen, Huan; Wang, Fengrong; Wang, Jingzhi; Huang, Xiaojun

    2015-12-01

    To investigate the clinical characteristics of E2A-PBX1(immunoglobulin enhancer binding factor-pre-B leukemia)fusion gene in patients with acute lymphoblastic leukemia(ALL) after allogeneic stem cell transplantation(allo-HSCT). Clinical data of 10 patients received allo- HSCT in Peking University Institute of Hematology from December 2010 to January 2015 were retrospectively collected. The E2A-PBX1 gene was examined by real-time quantitative polymerase chain reaction(RQ- PCR). The correlation between its expression level and the disease status was analyzed. Among 10 cases of enrolled ALL, the E2A-PBX1 expression of six patients converted to positive after transplant at a median time of 90 days(range, 75-180 days). The expression level of the first positive sample was 25.200%(range, 0.022%-353.600%). The duration from E2A-PBX1 positive to hematological relapse was 30 days(range, 0-74 days). Finally, 4 patients underwent relapse at a median time of 164 days (range, 75- 240 days) after allo- HSCT. The expression of E2A- PBX1 and minimal residual disease (MRD)level examined by flow cytometry were positive correlated(Spearman r=0.743, P=0.002). Once E2A-PBX1 expression converted to positive after transplant, MRD would increase rapidly. Patients with this type of ALL would have little response to the current intervention towards relapse. Monitoring E2A-PBX1 by RQ-PCR could be used to evaluate MRD status after allo-HSCT. Patients with positive E2A-PBX1 at early stage of transplant will have a poor prognosis.

  5. The Effect of Thyroid Hormone, Prostaglandin E2, and Calcium Gluconate on Orthodontic Tooth Movement and Root Resorption in Rats.

    Science.gov (United States)

    Seifi, Massoud; Hamedi, Roya; Khavandegar, Zohre

    2015-03-01

    A major objective of investigators is to clarify the role of metabolites in achievement of maximum tooth movement with minimal root damage during orthodontic tooth movement (OTM). The aim of this study was to determine the effect of administration of thyroid hormone, prostaglandin E2, and calcium on orthodontic tooth movement and root resorption in rats. Sixty four male Wistar rats were randomly divided into 8 groups of eight rats each: 1- 20µg/kg thyroxine was injected in traperitoneally after installation of the orthodontic appliance.  2- 0.1 ml of 1 mg/ml prostaglandin E2 was injected submucosally.  3- 10% (200 mg/kg) calcium gluconate was injected.  4- Prostaglandin E2 was injected submucosally and 10% calcium was injected intraperitoneally.  5- Thyroxine was injected intraperitoneally and prostaglandin E2 was injected submucosally.  6- 20µg/kg thyroxine with calcium was injected. 7- Prostaglandin E2 was injected submucosally with calcium and thyroxine.  8- Distilled water was used in control group. The orthodontic appliances comprised of a NiTi closed coil were posteriorly connected to the right first molar and anteriorly to the upper right incisor. OTM was measured with a feeler gauge. The mid-mesial root of the first molar and the adjacent tissues were histologically evaluated. The Data were analyzed by one-way ANOVA and Student-Newman-Keuls test. The highest mean OTM was observed in the thyroxine and prostaglandin E2 group (Mean±SD = 0.7375±0.1359 mm) that was significantly different (pprostaglandin E2 (0.0192±0.0198 mm(2)) and the other groups. It seems that the combination of thyroxine and prostaglandin E2, with a synergistic effect, would decrease the root resorption and increase the rate of orthodontic tooth movement in rats.

  6. Prostaglandin E2 receptor EP4 contributes to inflammatory pain hypersensitivity.

    Science.gov (United States)

    Lin, Chung-Ren; Amaya, Fumimasa; Barrett, Lee; Wang, Haibin; Takada, Junji; Samad, Tarek A; Woolf, Clifford J

    2006-12-01

    Prostaglandin E(2) (PGE(2)) is both an inflammatory mediator released at the site of tissue inflammation and a neuromodulator that alters neuronal excitability and synaptic processing. The effects of PGE(2) are mediated by four G-protein-coupled EP receptors (EP1-EP4). Here we show that the EP4 receptor subtype is expressed by a subset of primary sensory dorsal root ganglion (DRG) neurons, and that its levels, but not that of the other EP1-3 subtypes, increase in the DRG after complete Freund' adjuvant-induced peripheral inflammation. Administration of both an EP4 antagonist [AH23848, (4Z)-7-[(rel-1S,2S,5R)-5-((1,1'-biphenyl-4-yl)methoxy)-2-(4-morpholinyl)-3-oxocyclopentyl]-4-heptenoic acid] and EP4 knockdown with intrathecally delivered short hairpin RNA attenuates inflammation-induced thermal and mechanical behavioral hypersensitivity, without changing basal pain sensitivity. AH23848 also reduces the PGE(2)-mediated sensitization of capsaicin-evoked currents in DRG neurons in vitro. These data suggest that EP4 is a potential target for the pharmacological treatment of inflammatory pain.

  7. Hadronic atoms and ticklish nuclei: the E2 nuclear resonance effect

    International Nuclear Information System (INIS)

    Leon, M.

    1975-06-01

    The E2 nuclear resonance effect in hadronic atoms offers a way to increase the hadronic information that can be obtained from hadronic x-ray experiments. The effect occurs when an atomic deexcitation energy closely matches a nuclear excitation energy, so that some configuration mixing occurs. It shows up as an attenuation of some of the hadronic x-ray lines from a resonant versus a normal isotope target. The effect was observed very clearly in pionic cadmium in a recent LAMPF experiment. A planned LAMPF experiment will use the nuclear resonance effect to determine whether the p-wave π-nucleus interaction does indeed become repulsive for Z greater than or equal to 35 as predicted. The effect also appears in the kaonic molybdenum data taken at LBL because several of the stable molybdenum isotopes are resonant. A number of promising cases for π - , K - , anti p, and Σ - atoms are discussed and a spectacular and potentially very informative experiment on anti p- 100 Mo is proposed. (9 figures, 9 tables) (U.S.)

  8. Effect of Aspirin and Indomethacin on Prostaglandin E2 Synthesis in C6 Glioma Cells

    Directory of Open Access Journals (Sweden)

    Shiuh-Lin Hwang

    2004-01-01

    Full Text Available Prostaglandin E2 (PGE2 plays an important role in immunosuppression and tumor growth. PGE2 inhibitors such as aspirin and indomethacin suppress experimental tumor growth. Little is known of the relationship between PGE2 synthesis in brain tumors and the dose of aspirin or indomethacin. The present study was undertaken to evaluate the effect of different doses of aspirin and indomethacin on PGE2 synthesis in C6 glioma cells. C6 glioma cells were incubated with different concentrations (2, 4, and 8 μM of aspirin and indomethacin for 1, 2, 4, 6, 8, 12, and 24 hours. Intracellular PGE2 concentration was measured by enzyme immunoassay. Each concentration of aspirin and indomethacin effectively inhibited PGE2 synthesis. Concentrations of 2, 4, and 8 μM of aspirin significantly inhibited PGE2 production at 6, 4, and 1 hours, respectively, and the inhibition persisted for more than 24 hours (p 0.05. Indomethacin 8 μM was effective at 1 hour and the inhibition persisted beyond 24 hours (p < 0.05. Our study demonstrates that aspirin and indomethacin inhibit PGE2 synthesis in C6 glioma cells and that low-dose aspirin is as effective as high-dose aspirin. This study may encourage future clinical use of low-dose aspirin in the prevention or treatment of brain tumors.

  9. 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.

  10. Effect of probenecid on breathing movements and cerebral clearance of prostaglandin E2 in fetal sheep

    Science.gov (United States)

    Walker, David W; Pratt, Naomi

    1998-01-01

    Intravenous infusion of probencid (79-160 mg kg−1) into unanaesthetized fetal sheep (127-143 days gestation) in utero significantly decreased the incidence and amplitude of spontaneous breathing movements, but did not change the incidence of low voltage electrocortical (ECoG) activity, plasma prostaglandin E2 (PGE2) concentrations, blood gases or pH. In fetuses pretreated with paracetamol (350 mg kg−1) to inhibit PG synthase activity, infusion of probenecid did not change the mean incidence or amplitude of breathing movements, indicating that the inhibitory effect of probenecid on breathing movements required the presence of active PG synthesis. Probenecid infusion in four unanaesthetized fetuses significantly increased the PGE2 concentrations in cisternal cerebrospinal fluid (CSF) by 6.6 ± 1.5-fold (P probenecid infusion decreased the clearance of [3H]PGE2 from CSF during ventriculo-cisternal perfusion of artificial CSF containing [3H]PGE2. These results suggest that there is active transport of PGs from CSF to blood in fetal sheep from at least 127 days gestation. Inhibition of this transport results in the accumulation of PGs within interstitial fluid of the brain, one effect of which is to suppress the spontaneous activity of the respiratory centres. PMID:9481686

  11. Epidermal growth factor and prostaglandin E2 levels in Helicobacter pylori-positive gastric intraepithelial neoplasia

    Science.gov (United States)

    Chen, Zhitao; Xu, Dan; Huang, Manling; Sun, Shengbin; Zhang, Heng; Huang, Xiaodong; Wang, Ping

    2016-01-01

    Objective To investigate levels of epidermal growth factor (EGF) and prostaglandin E2 (PGE2) in Han Chinese patients with Helicobacter pylori-positive gastric low-grade intraepithelial neoplasia (LGIN). Methods In this prospective, observational study, gastric specimens from patients with LGIN were collected by gastroscopy with consecutive biopsy. EGF and PGE2 concentrations in serum and gastric juice from patients with LGIN were measured by enzyme-linked immunosorbent assay. Presence of H. pylori infection was assessed in patients with LGIN and healthy controls. Results Out of 5 638 patients and 548 controls, H. pylori infection in patients with chronic gastritis was associated with disease type (endoscopic classification) and disease severity. Patients with H. pylori-positive LGIN had significantly higher concentrations of serum EGF and lower concentrations of serum PGE2 versus patients with H. pylori-negative LGIN. Serum EGF and PGE2 levels in patients with LGIN were not significantly associated with disease type, but were significantly associated with disease severity. Conclusions H. pylori infection was associated with chronic gastritis type (endoscopic classification) and disease severity. Abnormal EGF and PGE2 levels may be associated with H. pylori-positive LGIN in Han Chinese patients in central China. PMID:26880792

  12. 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.

  13. Inhibition of mouse osteoblast proliferation and prostaglandin E2 synthesis by Ulmus davidiana Planch (Ulmaceae).

    Science.gov (United States)

    Jin, Un-Ho; Suh, Seok-Jong; Park, Sang-Dong; Kim, Kap-Sung; Kwon, Dae Young; Kim, Cheorl-Ho

    2008-06-01

    Ulmus davidiana Planch (Ulmaceae) (UD) is a widely used Korean herbal medicine that has been used historically in anti-inflammatory and anticancer therapy. Since UD has been known to have anti-inflammatory and protective effects on damaged tissue, inflammation and bone among other functions, this study was undertaken to address whether the water extract of the bark of UD could modulate proliferation of mouse osteoblasts in vitro and to investigate its effect on cyclooxygenase-2 (COX-2), which converts arachidonic acid to prostaglandin E2 (PGE2). Mouse osteoblasts were tested in vitro for growth inhibition, proliferating cell nuclear antigen (PCNA) expression, and COX-2 activity and expression after treatment with UD extract. Its effects were compared with those of indomethacin (a nonselective COX inhibitor) and celecoxib (a selective COX-2 inhibitor). UD demonstrated a strong growth inhibition in tested mouse osteoblasts. The IC50s were 10microg/ml for UD, 6microM for celecoxib and 42microM for indomethacin. UD, as well as celecoxib and indomethacin, suppressed PCNA expression and PGE2 synthesis in osteoblasts. UD inhibited COX-2 expression, whereas celecoxib inhibited COX-2 activity directly. UD selectively and effectively inhibits osteoblasts cell growth in vitro. Inhibition of PGE2 synthesis via suppression of COX-2 expression may be responsible for its anti-inflammatory activity.

  14. Effects of prostaglandin E2 and prostaglandin inhibitors on adrenal regeneration hypertension.

    Science.gov (United States)

    Paulson, D J; Eversole, W J

    1977-02-01

    The effects of prostaglandin E2 (PGE2) and a prostaglandin inhibitor, indomethacin, on the development of adrenal regeneration hypertension (ARH) were investigated. Weanling female rats underwent right adrenonephrectomy and left adrenal enucleation. PGE2 was injected subcutaneously daily in dosages of 0, 20, 40 and 80 mug/day. Indomethacin, 1 mg/kg, was administered twice daily by gavage. Blood pressures were determined by a tail and cuff plethysmographic method at 3, 5, and 7 wk after surgery. Increases in dosage of PGE2 produced a progressive reduction in mean blood pressures, heart, and kidney weights. Indomethacin produced significant increases in mean blood pressure, heart, kidney, and adrenal weights. The effects of aspirin and indomethacin on the blood pressures of rats with right adrenalectomy, left adrenal enucleation, and intact kidneys were studied. Administration of asprin twice daily (25 or 50 mg/kg) produced a fall in blood pressure, body and heart weight. Administration of 1 mg/kg twice daily of indomethacin resulted in a significant increase in blood pressure at 3 wk, and 0.1 or 1 mg/kg caused significant increases at 5 wk. The heart, kidney, and adrenal weights also showed increases with indomethacin administration. This study suggests that a deficiency of renal PGE2 may be involved in the etiology of ARH.

  15. Lateral Load Testing of the Advanced Stirling Convertor (ASC-E2) Heater Head

    Science.gov (United States)

    Cornell, Peggy A.; Krause, David L.; Davis, Glen; Robbie, Malcolm G.; Gubics, David A.

    2011-01-01

    Free-piston Stirling convertors are fundamental to the development of NASA s next generation of radioisotope power system, the Advanced Stirling Radioisotope Generator (ASRG). The ASRG will use General Purpose Heat Source (GPHS) modules as the energy source and Advanced Stirling Convertors (ASCs) to convert heat into electrical energy, and is being developed by Lockheed Martin under contract to the Department of Energy. Achieving flight status mandates that the ASCs satisfy design as well as flight requirements to ensure reliable operation during launch. To meet these launch requirements, GRC performed a series of quasi-static mechanical tests simulating the pressure, thermal, and external loading conditions that will be experienced by an ASC-E2 heater head assembly. These mechanical tests were collectively referred to as "lateral load tests" since a primary external load lateral to the heater head longitudinal axis was applied in combination with the other loading conditions. The heater head was subjected to the operational pressure, axial mounting force, thermal conditions, and axial and lateral launch vehicle acceleration loadings. To permit reliable prediction of the heater head s structural performance, GRC completed Finite Element Analysis (FEA) computer modeling for the stress, strain, and deformation that will result during launch. The heater head lateral load test directly supported evaluation of the analysis and validation of the design to meet launch requirements. This paper provides an overview of each element within the test and presents assessment of the modeling as well as experimental results of this task.

  16. Root resorption after local injection of prostaglandin E2 during experimental tooth movement.

    Science.gov (United States)

    Brudvik, P; Rygh, P

    1991-08-01

    The purpose of this study was to investigate the occurrence of orthodontic root resorption in connection with local injection of prostaglandin E2 (PGE2). The material consisted of 25 male Wistar rats. The control group comprised six animals where no force was applied. In five animals 0.1 ml of 0.1 micrograms/microliter PGE2 was injected in the gingival area of the upper right first molar. In one animal no PGE2 was injected. The animals were killed after 3 days. The experimental tooth movement groups consisted of 19 animals. Duration of experiments was 3 days, 7 days, and 10 days. The maxillary first molars on both sides were each moved mesially by means of a coil spring. On the right side 0.1 ml of PGE2 0.1 micrograms/microliters was injected in the gingiva on the buccal side of the upper first molar on days 0, 3, 5, and 7. On the left side no injection of PGE2 was performed. In three animals in the 7-day group the vehicle (Waymouth medium) was injected. There was no significant difference in root resorption between the experimentally moved teeth with and without local injection of PGE2, but a trend towards more root resorption was registered on the teeth where such injections had been performed.

  17. Dietary lipids, prostaglandin E2 levels, and tooth movement in alveolar bone of rats.

    Science.gov (United States)

    Kokkinos, P P; Shaye, R; Alam, B S; Alam, S Q

    1993-11-01

    A previous study showed that certain dietary lipids can alter arachidonic acid concentrations in alveolar bone. Because arachidonic acid is a precursor of prostaglandin (PG) E2, which is known to play an important role in orthodontic tooth movement, the purpose of the present study was to determine the effect of dietary lipids on PGE2 levels and tooth movement. Two groups of male Sprague-Dawley rats (20/group) were fed nutritionally adequate purified diets containing 10% corn oil (group I, rich in n-6 fatty acids) or 9% ethyl ester concentrate of n-3 fatty acids + 1% corn oil (group II rich in n-3 fatty acids). After 5 weeks of feeding the diets, orthodontic force of 56 g was applied to the maxillary incisors to tip them distally. Prior to killing the rats at day 4 and 8 of orthodontic force application, tooth movement was measured by computerized image analysis. Premaxillae were dissected out free of soft tissue and incisors. The alveolar bone was frozen in liquid nitrogen, pulverized, and lipids were extracted. The concentrations of arachidonic acid and fatty acid composition of total phospholipids were measured by gas chromatography. PGE2 levels were measured by enzyme immunoassay. Arachidonic acid and PGE2 concentration were significantly lower (P orthodontic tooth movement can be affected by the type of dietary fat.

  18. 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.

  19. Cell cycle transcription control: DREAM/MuvB and RB-E2F complexes.

    Science.gov (United States)

    Fischer, Martin; Müller, Gerd A

    2017-12-01

    The precise timing of cell cycle gene expression is critical for the control of cell proliferation; de-regulation of this timing promotes the formation of cancer and leads to defects during differentiation and development. Entry into and progression through S phase requires expression of genes coding for proteins that function in DNA replication. Expression of a distinct set of genes is essential to pass through mitosis and cytokinesis. Expression of these groups of cell cycle-dependent genes is regulated by the RB pocket protein family, the E2F transcription factor family, and MuvB complexes together with B-MYB and FOXM1. Distinct combinations of these transcription factors promote the transcription of the two major groups of cell cycle genes that are maximally expressed either in S phase (G1/S) or in mitosis (G2/M). In this review, we discuss recent work that has started to uncover the molecular mechanisms controlling the precisely timed expression of these genes at specific cell cycle phases, as well as the repression of the genes when a cell exits the cell cycle.

  20. Prostaglandin E2/leukotriene B4 balance induced by Lutzomyia longipalpis saliva favors Leishmania infantum infection.

    Science.gov (United States)

    Araújo-Santos, Théo; Prates, Deboraci Brito; França-Costa, Jaqueline; Luz, Nívea F; Andrade, Bruno B; Miranda, José Carlos; Brodskyn, Claudia I; Barral, Aldina; Bozza, Patrícia T; Borges, Valéria Matos

    2014-12-20

    Eicosanoids and sand fly saliva have a critical role in the Leishmania infection. Here, we evaluated the effect of Lutzomyia longipalpis salivary gland sonicate (SGS) on neutrophil and monocyte recruitment and activation of eicosanoid production in a murine model of inflammation. C57BL/6 mice were inoculated intraperitonealy with Lutzomyia longipalpis SGS or Leishmania infantum or both, followed by analyses of cell recruitment, parasite load and eicosanoid production. Intraperitoneal injection of Lutzomyia longipalpis SGS together with Leishmania infantum induced an early increased parasite viability in monocytes and neutrophils. L. longipalpis SGS increased prostaglandin E2 (PGE2), but reduced leukotriene B4 (LTB4) production ex vivo in peritoneal leukocytes. In addition, the pharmacological inhibition of cyclooxygenase 2 (COX-2) with NS-398 decreased parasite viability inside macrophages during Leishmania infection in the presence of L. longipalpis SGS arguing that PGE2 production is associated with diminished parasite killing. These findings indicate that L. longipalpis SGS is a critical factor driving immune evasion of Leishmania through modulation of PGE2/LTB4 axis, which may represent an important mechanism on establishment of the infection.

  1. Prostaglandin E2 production during neonatal respiratory infection with mouse adenovirus type 1.

    Science.gov (United States)

    Procario, Megan C; McCarthy, Mary K; Levine, Rachael E; Molloy, Caitlyn T; Weinberg, Jason B

    2016-03-02

    Neonatal mice are more susceptible than adults to mouse adenovirus type 1 (MAV1) respiratory infection. In adult mice, MAV-1 respiratory infection induces production of prostaglandin E2 (PGE2), a lipid mediator that exerts suppressive effects on a variety of host immune functions. We tested the hypothesis that exaggerated PGE2 production in neonatal mice contributes to increased susceptibility to MAV-1. PGE2 concentrations were lower in lungs of uninfected neonatal mice than in adults. PGE2 production was induced by both MAV-1 and a nonspecific stimulus to a greater degree in neonatal mice than in adults, but only in adults was PGE2 induced in a virus-specific manner. Lung viral loads were equivalent in PGE2-deficient neonatal mice and wild type controls, as was virus-induced expression of IFN-γ, IL-17A, and CCL5 in the lungs. PGE2 deficiency had minimal effect on production of virus-specific IgG or establishment of protective immunity in neonatal mice. Collectively, our data indicate that lung PGE2 production is exaggerated early in life, but this effect does not mediate increased susceptibility to MAV-1 infection. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. The construction of recombinant Lactobacillus casei expressing BVDV E2 protein and its immune response in mice.

    Science.gov (United States)

    Bhuyan, Anjuman Ara; Memon, Atta Muhammad; Bhuiyan, Ali Akbar; Zhonghua, Li; Zhang, Bingzhou; Ye, Shiyi; Mengying, Li; He, Qi-Gai

    2018-03-20

    Bovine viral diarrhea virus (BVDV) is the etiological agent of BVD causes substantial economic losses and endemic in world-wide cattle population. Mucosal immunity plays an important role in protection against BVDV infection and Lactobacillus casei is believed as an excellent live vaccine vector for expressing foreign genes. In this study, we have constructed a novel recombinant L. casei/pELX1-E2 strain expressing the most immunogenic E2 antigen of BVDV; using growth phage dependent surface expression system pELX1. The expression of E2 protein was verified by SDS-PAGE, Western blotting, and Immunofluorescence microscopic analysis. The immune responses triggered by the E2 producing recombinant L. casei were evaluated in BALB/c mice revealed that oral and intranasal (IN) administration of the recombinant strain was able to induce a significantly higher level of specific anti-E2 mucosal IgA and serum IgG as well as the greater level of cellular response by IFN-γ and IL-12 than those of intramuscular (IM) and control groups of mice. However, IN inoculation was found the most potent route of immunization. The ability of the recombinant strain to induce serum neutralizing antibody against BVDV and reduced viral load after viral challenge indicated better protection of BVDV infection. Therefore, this recombinant L. casei expressing E2 could be a safe and promising mucosal vaccine candidate against BVD. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. 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.

  4. S-phase checkpoint elements of the E2F-1 family increase radiosensitivity in fibrosarcoma cells lacking p53

    International Nuclear Information System (INIS)

    Bodis, Stephan; Pruschy, Martin; Wirbelauer, Christiane; Glanzmann, Christoph; Krek, Wilhelm

    1997-01-01

    Purpose: Correct advance of cells through the S-phase of the mammalian cell cycle depends on the timely controlled activity of the E2F-1 transcription factor by cyclin A-cdk2. We are studying the reproductive integrity and radiosensitation of isogenic mouse fibrosarcoma cells, differing only in their p53 status, after expression of E2F-1 wildtype (wt) and specific E2F-1 mutants (mt) lacking the cyclin-A-binding domain. In this tumor model system only p53 wild-type expressing tumor cells are sensitive to ionizing radiation in vitro and in vivo. Material and Methods: Either wild-type p53 or genetically engineered p53 'null' mouse embryo fibroblasts were transfected with the oncogenes E1A and ras. These otherwise isogenic fibrosarcoma cells, with a malignant phenotype and tumorigenic in nude mice, were transfected with retroviruses containing either E2F-1 wild-type or specific E2F-1 mutants lacking the cyclin-A binding domain. Reproductive integrity after E2F-1 transfection with or without ionizing radiation (RT) was tested using the clonogenic assay. Tumor cell morphology of treated cells is analyzed for cell death mechanism. Results: E2F-1 wild-type expression in fibrosarcoma cells induced a clear p53 dependent cell death. While clonogenic survival of p53 'null' tumor cells was only slightly reduced with the expression of E2F-1 wild type (survival fraction of 0.5), the clonogenic survival of p53 wild-type fibrosarcoma tumor cells was reduced by at least one logarithm (survival fraction of 0.05). However, expression of the specific E2F-1 mutant lacking the cyclin-A binding domain reduced clonogenic survival in both the p53 'null' and the p53 wild-type fibrosarcoma cells by at least 2 logarithms (survival fraction 0.01 for p53 'null' and 0.002 for p53 wild-type). The mean values of the survival fractions after 2 and 5 Gy radiation alone in p53 'null' fibrosarcoma cells (SF 2 and SF 5) were SF 2 0.7, SF 5 = 0.15, respectively. The combination of ionizing RT in the p53

  5. Transition and Social networks

    OpenAIRE

    Raghavan, Raghu; Pawson, N.

    2011-01-01

    School leavers with learning disabilities often face difficulties in making a smooth transition from school to college, employment or more broadly, to adult life. The transition phase is traumatic for the young person with learning disabilities and their families as it often results in the loss of friendships, relationships and social networks. The aim of this chapter is to explore the issues of transition from adolescence to adulthood for young people with learning disabilities and its effe...

  6. Deletion of the p107/p130-binding domain of Mip130/LIN-9 bypasses the requirement for CDK4 activity for the dissociation of Mip130/LIN-9 from p107/p130-E2F4 complex.

    Science.gov (United States)

    Sandoval, Raudel; Pilkinton, Mark; Colamonici, Oscar R

    2009-10-15

    Mip130/LIN-9 is part of a large complex that includes homologs of the Drosophila dREAM (drosophila RB-like, E2F, and Myb) and C. elegans DRM complexes. This complex also includes proteins such as Mip40/LIN-37, Mip120/LIN-54, and LIN-52. In mammalian cells, Mip130/LIN-9 specifically associates with the p107/p130-E2F4 repressor complex in G0/G1 and with B-Myb in S-phase. However, little is known about how the transition occurs and whether Mip130/LIN-9 contributes to the repressor effect of p107/p130. In this report, we demonstrate that Mip130/LIN-9, Mip40/LIN-37, Mip120/LIN-54, and Sin3b form a core complex, the Mip Core Complex or LIN Complex (MCC/LINC), which is detectable in all phases of the cell cycle. This complex specifically recruits transcriptional repressors such as p107, p130, E2F4 and HDAC1 in G0/G1, and B-Myb in S-phase. Importantly, we provide strong evidence that the transition between repressors and activators of transcription is mediated by CDK4, through the phosphorylation of the pocket proteins, p107 and p130. The requirement for CDK4 activity is bypassed by the deletion of the first 84 amino acids (Mip130/LIN-9(Delta84)), since this mutant is unable to interact with p107/p130 in G0/G1, while maintaining its association with B-Myb. Importantly, the Mip130/LIN-9(Delta84) allele rescues the low expression of G1/S genes observed in CDK4(-/-) MEFs demonstrating that Mip130/LIN-9 contributes to the repression of these E2F-regulated genes in G0/G1.

  7. The Energy Transition Chronicles

    International Nuclear Information System (INIS)

    Cappelletti, Floriane; Vallar, Jean-Pierre; Wyssling, Julia

    2015-01-01

    Energy Cities provides local authorities with support for implementing their own energy transition process. The Proposals for the energy transition of cities and towns (www.energy-cities.eu/30proposals) are illustrated with around a hundred of inspirational examples from all over Europe. In this document composed of five case reports, Energy Cities goes further and tells the tale of energy transition success stories. Because it is important to show that energy transition is 'possible'. Why, how, with whom, for what results? We interviewed local players and decision-makers to find out more. Here are their stories

  8. Transit Benefit Program Data -

    Data.gov (United States)

    Department of Transportation — This data set contains information about any US government agency participating in the transit benefits program, funding agreements, individual participating Federal...

  9. Lifetimes and electromagnetic transition strengths in 155Dy

    Science.gov (United States)

    Petkov, P.; Yavahchova, M. S.; Möller, O.; Dewald, A.; Tonev, D.; Saha, B.; Fitzler, A.; Jessen, K.; Klug, T.; Heinze, S.; Jolie, J.; von Brentano, P.; Goutev, N.; Bazzacco, D.; Ur, C. A.; Farnea, E.; Axiotis, M.; Lunardi, S.; de Angelis, G.; Napoli, D. R.; Marginean, N.; Martinez, T.; Caprio, M. A.

    2013-09-01

    Recoil distance Doppler-shift and Doppler-shift attenuation lifetime measurements were carried out for levels in 155Dy through the coincident detection of γ rays. Twenty-six lifetimes, most of them for the first time, were determined using the differential decay curve method for the analysis of the data. At low and medium spins, particle-plus-triaxial-rotor calculations reveal different quadrupole deformations for the one-quasineutron bands in this transitional nucleus. At high spin, the reduced B(E2) transition probabilities confirm with a better precision the results of a previous study implying decreased collectivity with increasing spin.

  10. The role of quasiparticles in rotating transitional nuclei

    International Nuclear Information System (INIS)

    Frauendorf, Stefan

    1984-01-01

    The yrast sequency of nuclei rotating about the symmetry axis is classified in analogy to class I and II superconductors, where the quasiparticles play the role of the quantized flux in metals. The experimental spectra show a class I behaviour. The ω-dependence of the quasiparticle excitation energy in collectively rotating nuclei is used as evidence for magnitude of the pair correlations and the occurrence of triaxial shapes. A transition from triaxial to oblate shape explains the experimental spectra and E2-transition probabilities in the N=88-90 nuclei. (author)

  11. Adenovirus E2F1 Overexpression Sensitizes LNCaP and PC3 Prostate Tumor Cells to Radiation In Vivo

    International Nuclear Information System (INIS)

    Udayakumar, Thirupandiyur S.; Stoyanova, Radka; Hachem, Paul; Ahmed, Mansoor M.; Pollack, Alan

    2011-01-01

    Purpose: We previously showed that E2F1 overexpression radiosensitizes prostate cancer cells in vitro. Here, we demonstrate the radiosensitization efficacy of adenovirus (Ad)-E2F1 infection in growing (orthotopic) LNCaP and (subcutaneous) PC3 nude mice xenograft tumors. Methods and Materials: Ad-E2F1 was injected intratumorally in LNCaP (3 x 10 8 plaque-forming units [PFU]) and PC3 (5 x 10 8 PFU) tumors treated with or without radiation. LNCaP tumor volumes (TV) were measured by magnetic resonance imaging, caliper were used to measure PC3 tumors, and serum prostate-specific antigen (PSA) levels were determined by enzyme-linked immunosorbent assay. Apoptosis was measured by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling, and key proteins involved in cell death signaling were analyzed by Western blotting. Results: Intracellular overexpression of Ad-E2F1 had a significant effect on the regression of TV and reduction of PSA levels relative to that of adenoviral luciferase (Ad-Luc)-infected control. The in vivo regressing effect of Ad-E2F1 on LNCaP tumor growth was significant (PSA, 34 ng/ml; TV, 142 mm 3 ) compared to that of Ad-Luc control (PSA, 59 ng/ml; TV, 218 mm 3 ; p 3 to Ad-Luc+RT/PSA, 42 ng/ml, and TV, 174 mm 3 , respectively; p <0.05). For PC3 tumors, the greatest effect was observed with Ad-E2F1 infection alone; there was little or no effect when radiotherapy (RT) was combined. However, addition of RT enhanced the level of in situ apoptosis in PC3 tumors. Molecularly, addition of Ad-E2F1 in a combination treatment abrogated radiation-induced BCL-2 protein expression and was associated with an increase in activated BAX, and together they caused a potent radiosensitizing effect, irrespective of p53 and androgen receptor functional status. Conclusions: We show here for the first time that ectopic overexpression of E2F1 in vivo, using an adenoviral vector, significantly inhibits orthotopic p53 wild-type LNCaP tumors and subcutaneous

  12. 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

  13. Heterodimerization of the prostaglandin E2 receptor EP2 and the calcitonin receptor CTR.

    Directory of Open Access Journals (Sweden)

    Shin Matsubara

    Full Text Available G protein-coupled receptors (GPCRs have been found to form heterodimers and modulate or fine-tune the functions of GPCRs. However, the involvement of GPCR heterodimerization and its functional consequences in gonadal tissues, including granulosa cells, have been poorly investigated, mainly due to the lack of efficient method for identification of novel GPCR heterodimers. In this paper, we identified a novel GPCR heterodimer between prostaglandin E2 (PGE2 receptor 2 (EP2 and calcitonin (CT receptor (CTR. High-resolution liquid chromatography (LC-tandem mass spectrometry (MS/MS of protease-digested EP2-coimmunoprecipitates detected protein fragments of CTR in an ovarian granulosa cell line, OV3121. Western blotting of EP2- and CTR-coimmunoprecipitates detected a specific band for EP2-CTR heterodimer. Specific heterodimerization between EP2 and CTR was also observed by fluorescence resonance energy transfer analysis in HEK293MSR cells expressing cyan- and yellow-fluorescent protein-fused EP2 and CTR, respectively. Collectively, these results provided evidence for heterodimerization between EP2 and CTR. Moreover, Ca2+ mobilization by CT was approximately 40% less potent in HEK293MSR cells expressing an EP2-CTR heterodimer, whereas cAMP production by EP2 or CT was not significantly altered compared with cells expressing EP2- or CTR alone. These functional analyses verified that CTR-mediated Ca2+ mobilization is specifically decreased via heterodimerization with EP2. Altogether, the present study suggests that a novel GPCR heterodimer, EP2-CTR, is involved in some functional regulation, and paves the way for investigation of novel biological roles of CTR and EP2 in various tissues.

  14. Prostaglandin E2 promotes features of replicative senescence in chronically activated human CD8+ T cells.

    Directory of Open Access Journals (Sweden)

    Jennifer P Chou

    Full Text Available Prostaglandin E2 (PGE2, a pleiotropic immunomodulatory molecule, and its free radical catalyzed isoform, iso-PGE2, are frequently elevated in the context of cancer and chronic infection. Previous studies have documented the effects of PGE2 on the various CD4+ T cell functions, but little is known about its impact on cytotoxic CD8+ T lymphocytes, the immune cells responsible for eliminating virally infected and tumor cells. Here we provide the first demonstration of the dramatic effects of PGE2 on the progression of human CD8+ T cells toward replicative senescence, a terminal dysfunctional state associated multiple pathologies during aging and chronic HIV-1 infection. Our data show that exposure of chronically activated CD8+ T cells to physiological levels of PGE2 and iso-PGE2 promotes accelerated acquisition of markers of senescence, including loss of CD28 expression, increased expression of p16 cell cycle inhibitor, reduced telomerase activity, telomere shortening and diminished production of key cytotoxic and survival cytokines. Moreover, the CD8+ T cells also produced higher levels of reactive oxygen species, suggesting that the resultant oxidative stress may have further enhanced telomere loss. Interestingly, we observed that even chronic activation per se resulted in increased CD8+ T cell production of PGE2, mediated by higher COX-2 activity, thus inducing a negative feedback loop that further inhibits effector function. Collectively, our data suggest that the elevated levels of PGE2 and iso-PGE2, seen in various cancers and HIV-1 infection, may accelerate progression of CD8+ T cells towards replicative senescence in vivo. Inhibition of COX-2 activity may, therefore, provide a strategy to counteract this effect.

  15. Cyclic Mechanical Stretching Induces Autophagic Cell Death in Tenofibroblasts Through Activation of Prostaglandin E2 Production

    Directory of Open Access Journals (Sweden)

    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.

  16. Prostaglandin E2 formation by rat gastroduodenal tissue following intragastric acid perfusion.

    Science.gov (United States)

    Kapicioglu, S; McNamara, D B; Vacarella, M Y; Kadowitz, P J; Hoda, S; Ertan, A

    1990-04-01

    Rat gastroduodenal mucosa forms prostaglandin (PG) E2. However, little is known about regional differences in PGE2 formation or the effect of gastric hydrochloric acid (HC1) perfusion on regional PGE2 formation. In this study, the rats were divided into 3 groups. Group 1 received intravenous (i.v.), 1 Ml/h, and intragastric (i.g.), 8 ml/h, perfusions of saline simultaneously for 3 h. Group 2 received saline i.v. and 0.15 N HC1 i.g., 8 ml/h. Group 3 was injected with a bolus of asprin (ASA), 60 mg/kg, followed by ASA, 40 mg/kg/h i.v., and 0.15 N HC1 i.g.. The gastric aspirates were analyzed for volume and pH. Segments of gastroduodenal tissue from the fundus, corpus, antrum, and duodenum were minced and then incubated in 1 ml of 5 mM Tris buffer, pH 8.4, for 30 sec with mixing; the incubate was assayed for PGE2 by radioimmunoassay. Intragastric HC1 decreased the pH of aspirate without producing gastric mucosal lesions. However, when combined with i.v. ASA, ulcer formation was present in all animals (p less than 0.05). PGE2 was formed by isolated tissue from four different gastroduodenal regions. The duodenum formed significantly greater amounts than the fundus, antrum, or corpus, which were similar. Intragastric HC1 produced a trend toward increased PGE2 formation (pmol PGE2/mg tissue) in the fundus, 143 +/- 36 to 237 +/- 57; corpus, 87 +/- 13 to 200 +/- 57; antrum, 157 +/- 28 to 224 +/- 65; and duodenum, 235 +/- 56 to 338 +/- 51. However, statistical significance was not reached.

  17. (-)-Epigallocatechin gallate synergistically potentiates prostaglandin E2-stimulated osteoprotegerin synthesis in osteoblasts.

    Science.gov (United States)

    Kuroyanagi, Gen; Tokuda, Haruhiko; Yamamoto, Naohiro; Kainuma, Shingo; Fujita, Kazuhiko; Ohguchi, Reou; Kawabata, Tetsu; Sakai, Go; Matsushima-Nishiwaki, Rie; Harada, Atsushi; Kozawa, Osamu; Otsuka, Takanobu

    2017-01-01

    (-)-Epigallocatechin gallate (EGCG), the most abundant flavonoid in green tea, and chlorogenic acid, the main polyphenol found in coffee, attract significant attention owing to health benefits. We have previously demonstrated that prostaglandin E 2 (PGE 2 ) stimulates osteoprotegerin synthesis through the activation of p38 mitogen-activated protein (MAP) kinase and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the effects of EGCG or chlorogenic acid on the PGE 2 -stimulated osteoprotegerin synthesis in MC3T3-E1 cells. EGCG significantly amplified the PGE 2 -induced release. EGCG markedly enhanced the expression levels of osteoprotegerin mRNA induced by PGE 2 . On the contrary, chlorogenic acid had no effect on the PGE 2 -stimulated release of osteoprotegerin. EGCG significantly strengthened the PGE 2 -induced phosphorylation of p38 MAP kinase and SAPK/JNK, whereas chlorogenic acid failed to affect them. BIRB0796 and SP600125, a p38 MAP kinase inhibitor and a SAPK/JNK inhibitor, respectively, markedly reduced the amplification by EGCG of the PGE 2 -stimulated osteoprotegerin release. These results strongly suggest that EGCG synergistically enhances the PGE 2 -stimulated osteoprotegerin synthesis via potentiation of p38 MAP kinase and SAPK/JNK in osteoblasts. Our present findings could present a new significant aspect in the favorable effect of EGCG on the prevention of osteoporotic bone loss and fracture especially in elderly people since osteoprotegerin secreted from osteoblasts is well-recognized to act as a suppressor of osteoclastic bone resorption. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. [Effects of exogenous prostaglandin E2 on collagen content of Achilles tendon of rabbits in vivo].

    Science.gov (United States)

    Li, Hui; Tang, Kanglai; Deng, Yinshuan; Xie, Meiming; Chang, Dehai; Tao, Xu; Xu, Jianzhong

    2012-03-01

    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 tendinopathy by observing the changes of collagen content and proportion after the Achilles tendon of rabbits is repeatedly exposed to PGE2. Twenty-four Japanese rabbits (aged 3-4 months, weighing 2.0-2.5 kg, and male or female) were equally randomized into 2 groups according to injection dose of PGE2: low dose group (50 ng) and high dose group (500 ng). Corresponding PGE2 (0.2 mL) was injected into the middle segment of the Achilles tendon of hindlimb, the same dose saline into the same site of the other side as controls once a week for 4 weeks or 8 weeks. The Achilles tendons were harvested at 4 and 8 weeks after injection. HE staining was used to observe the cell structure and matrix, and picric acid-sirius red staining to observe the distribution and types of collagen fibers, and transmission electron microscopy was used to measure the density of the unit area and diameter of collagen fibers. HE staining showed that collagen structural damage was observed in low dose and high dose groups. Picric acid-sirius red staining showed that the content of type I collagen significantly decreased while the content of type III collagen significantly increased in experimental side of 2 groups at 4 and 8 weeks after injection when compared with control sides (P Achilles tendon of rabbit to PGE2 can cause the decrease of type I collagen, the increase of type III collagen, the reverse ratio of type I to type III, reduced unit density of collagen fibers, and thinner collagen fibers diameter, which is related with tendinopathy.

  19. Prostaglandin E2 functions as a luteotrophic factor in the dog.

    Science.gov (United States)

    Kowalewski, Mariusz P; Fox, Barbara; Gram, Aykut; Boos, Alois; Reichler, Iris

    2013-03-01

    The luteal phase in dogs is governed by many poorly understood regulatory mechanisms. Functioning of the corpus luteum (CL) is unaffected by hysterectomy. Recently, the role of prostaglandins in regulating canine CL function was addressed suggesting a luteotrophic effect of prostaglandin E2 (PGE2) during the early luteal phase. However, compelling functional evidence was lacking. The potential of PGE2 to stimulate steroidogenesis was tested in canine primary luteal cells isolated from developing CL of non-pregnant dogs. In addition, the luteal expression of prostaglandin transporter (PGT) and steroidogenic acute regulatory protein (STAR) was demonstrated and characterized in CL from non-pregnant bitches during the course of dioestrus as well as from pregnant animals during the pre-implantation, post-implantation and mid-gestation periods of pregnancy and during luteolysis; the luteal expression of PGE2 receptors (EP2 and EP4) has been investigated at the protein level throughout pregnancy. Our findings show that PGE2 is an activator of STAR expression in canine luteal cells from early luteal phase, significantly up-regulating STAR promoter activity and protein expression resulting in increased steroidogenesis. The 3βHSD (HSD3B2) and P450scc (CYP11A1) expression remained unaffected by PGE2 treatment. The expression of PGT was confirmed in CL during both pregnancy and dioestrus and generally localized to the luteal cells. After initial up-regulation during the earlier stages of the CL phase, its expression declined towards the luteal regression. Together with the demonstration of EP2 and EP4 throughout pregnancy, and the decline in EP2 at prepartum, our findings further support our hypothesis that intra-luteal PGE2 may play an important role in regulating progesterone secretion in the canine CL.

  20. 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.

  1. Prostaglandin E2 and thromboxane B2 release from human monocytes treated with bacterial lipopolysaccharide

    International Nuclear Information System (INIS)

    Nichols, F.C.; Garrison, S.W.; Davis, H.W.

    1988-01-01

    We investigated the capacity of counterflow-isolated human monocytes to independently synthesize thromboxane B2 (TxB2) and prostaglandin E2 (PGE2) when stimulated with bacterial lipopolysaccharide (LPS). Independent metabolism was confirmed by establishing different specific activities (dpm/ng) of TxB2 and PGE2 released from LPS-treated cells. For metabolites released during the initial 2-hr treatment period, the specific activity of PGE2 was approximately threefold higher than that of TxB2 regardless of labeling with [3H]arachidonic acid (AA) or [14C]AA. Cells that were pulse-labeled for 2 hr with [3H]AA demonstrated a decreasing PGE2 specific activity over 24 hr, whereas the TxB2 specific activity remained unchanged. In contrast, cells continuously exposed to [14C]AA demonstrated an increasing TxB2 specific activity that approached the level of PGE2 by 24 hr. These results suggest the presence of at least 2 cyclooxygenase metabolic compartments in counterflow-isolated monocytes. Although freshly isolated monocytes have been reported to contain variable numbers of adherent platelets, additional experiments demonstrated that counterflow-isolated platelets are not capable of releasing elevated levels of TxB2 or PGE2 when treated with LPS. It is proposed from these findings that at least two subsets of monocytes exist in peripheral blood that can be distinguished on the basis of independent conversion of AA to TxB2 and PGE2

  2. Prostaglandin E2 levels in gingival crevicular fluid during tooth- and bone-borne expansion.

    Science.gov (United States)

    Sari, Emel; Kadioglu, Onur; Ucar, Cihan; Altug, H Ayberk

    2010-06-01

    The purpose of this study was to compare Prostaglandin E(2) (PGE(2)) levels in gingival crevicular fluid (GCF) of young adults with maxillary constriction during tooth- and bone-borne expansion. Thirty patients, 15 females and 15 males, with a mean age of 17.3 +/- 2.8 years were divided into three groups. Group I consisted of 10 patients, five females and five males, treated by transpalatal distraction (TPD) as a bone-borne device, group II 10 patients, five females and five males, with a Hyrax appliance as a tooth-borne device, and a control group of 10 patients, five females and five males, without any expansion appliances. GCF samples were collected with filter paper strips at six observation periods in order to evaluate the effect of heavy orthopaedic forces in both groups. In group II, the samples were additionally collected at two pre-treatment time points in order to evaluate the effect of the forces generated by the separators. An automated enzyme immunoassay was used to measure PGE(2) in the GCF. The differences within the groups were evaluated with a pairwise t-test and the differences between the groups were determined by the Mann-Whitney U-test. The mean PGE(2) level was significantly elevated on day 4 after placement of the separators in group II (P < 0.05). The PGE(2) values in group II were significantly different to those in group I and the controls at all observation periods. Lower PGE(2) levels were observed in group I compared with group II and the controls. Expansion using the TPD method could potentially enhance the prognosis of the teeth by inducing more skeletal dental changes when compared with the Hyrax appliance.

  3. Effects of prostaglandin E2 on alveolar bone resorption during orthodontic tooth movement.

    Science.gov (United States)

    Chao, C F; Shih, C; Wang, T M; Lo, T H

    1988-01-01

    Twenty Sprague-Dawley rats weighing 280-300 g were divided into two groups of ten animals each. They were treated by daily submucosal injections of 50 micrograms prostaglandin E2 (PGE2) per kilogram body weight into the region below the apex of the left first maxillary molar (experimental), or vehicle into the region below the apex of the right first molar (control), for a period of 5 days. The animals of the first group were sacrificed immediately following the treatment period, while those of the second group were sacrificed 5 days after the treatment period. Twenty-two hours prior to sacrifice, a piece of latex orthodontic elastic was secured to the adjacent area between the first and second maxillary molars of both sides of each rat by using two mosquito hemostats. The periodontal ligament (PDL) mesial to the mesiobuccal root of the first maxillary molar was assayed for changes in PDL cell factors. The results showed that immediately following the 5-day treatment period the left PDL had a significant decrease in the total number of fibroblasts and a significant increase in the total number of both osteoclasts and nuclei per osteoclast, while no significant changes in the osteoblasts when compared with those of the right control PDL. The left PDL of animals which were sacrificed 5 days after the treatment period revealed a significant decrease in the number of total fibroblasts and only a slight decrease in both numbers of total osteoclasts and total nuclei per osteoclast, but again no significant changes in osteoblasts when compared with those of the right control PDL.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Effects of various analgesics on the level of prostaglandin E2 during orthodontic tooth movement.

    Science.gov (United States)

    Tunçer, Zeynep; Polat-Ozsoy, Omur; Demirbilek, Muge; Bostanoglu, Ebru

    2014-06-01

    The aim of this double-blind, randomized, placebo-controlled clinical study was to evaluate the analgesic effects of preoperative/postoperative ibuprofen and acetaminophen use after bonding and to find a relation between the pain level and the amount of prostaglandin released. Forty-eight patients were included and randomly divided to three equal groups that received either ibuprofen, acetaminophen or placebo for pain relief. The pain levels were measured before bonding, after bonding, at first, second, third, and seventh days on a 100 mm visual analogue scale (VAS) and gingival crevicular fluid (GCF) samples were collected at the same time intervals to measure the amount of prostaglandin E2 (PGE2) released. PGE2 levels were determined with ELISA test. The results were evaluated with Wilcoxon and Kruskal–Wallis tests with Bonferroni correction. Acetaminophen and placebo groups showed similar pain levels during the first 2 days, whereas ibuprofen group showed lower pain levels during the first day after bonding. PGE2 levels did not show statistically significant difference in time within the analgesic groups. No significant relation between the pain perceived and PGE2 released was found. The biggest limitation of this study is the subjective nature of pain and its method of evaluation. The perception of pain by patients taking ibuprofen and acetaminophen at pre/post appliance placement was not different from patients taking placebo. No time-related differences in PGE2 level were found between the groups and no significant correlation was found between the perception of pain and PGE2 levels.

  5. The effects of exogenous prostaglandin E2 on root resorption in rats.

    Science.gov (United States)

    Boekenoogen, D I; Sinha, P K; Nanda, R S; Ghosh, J; Currier, G F; Howes, R I

    1996-03-01

    This study evaluated the amount and depth of root resorption associated with varying concentrations and frequencies of injectable, exogenous prostaglandin E2 (PGE2) in conjunction with orthodontic tooth movement in rats. The sample consisted of 155 maxillary right and left first molars from 88, 8-week old, male Sprague-Dawley rats. The animals were divided into three control groups and two experimental groups. The control animals were divided into one nonappliance and two appliance groups. The experimental animals were divided into 2- and 4-week experimental time periods that were further subdivided based on single and weekly injection intervals of PGE2 and four different injectable concentration levels, i.e., 0.1, 1.0, 5.0, and 10.0 micrograms. A fixed orthodontic appliance was ligated between the maxillary incisors and maxillary first molars with closed-coil nickel-titanium springs. The appliance had an initial activating force of 60 gm. Serial histologic sections of the mesial root of the maxillary first molar were made, and a quantitative histomorphometric analysis of root resorption on the mesial and distal surfaces was performed. This study demonstrated increased root surface resorption when using exogenous PGE2 injections to enhance orthodontic tooth movement over a 2-week period with increasing root resorption on the mesial surface as compared with the distal surface in PGE2 treated teeth. No differences in root resorption were found with either multiple injections or increasing concentration in the 4-week experimental group. Local injection of PGE2 appeared to have no effect on the number or depth of resorption lacunae in either the 2- or 4-week groups.

  6. The involvement of prostaglandin E2in interleukin-1β evoked anorexia is strain dependent.

    Science.gov (United States)

    Nilsson, Anna; Elander, Louise; Hallbeck, Martin; Örtegren Kugelberg, Unn; Engblom, David; Blomqvist, Anders

    2017-02-01

    From experiments in mice in which the prostaglandin E 2 (PGE 2 ) synthesizing enzyme mPGES-1 was genetically deleted, as well as from experiments in which PGE 2 was injected directly into the brain, PGE 2 has been implicated as a mediator of inflammatory induced anorexia. Here we aimed at examining which PGE 2 receptor (EP 1-4 ) that was critical for the anorexic response to peripherally injected interleukin-1β (IL-1β). However, deletion of neither EP receptor in mice, either globally (for EP 1 , EP 2 , and EP 3 ) or selectively in the nervous system (EP 4 ), had any effect on the IL-1β induced anorexia. Because these mice were all on a C57BL/6 background, whereas previous observations demonstrating a role for induced PGE 2 in IL-1β evoked anorexia had been carried out on mice on a DBA/1 background, we examined the anorexic response to IL-1β in mice with deletion of mPGES-1 on a C57BL/6 background and a DBA/1 background, respectively. We confirmed previous findings that mPGES-1 knock-out mice on a DBA/1 background displayed attenuated anorexia to IL-1β; however, mice on a C57BL/6 background showed the same profound anorexia as wild type mice when carrying deletion of mPGES-1, while displaying almost normal food intake after pretreatment with a cyclooxygenase-2 inhibitor. We conclude that the involvement of induced PGE 2 in IL-1β evoked anorexia is strain dependent and we suggest that different routes that probably involve distinct prostanoids exist by which inflammatory stimuli may evoke an anorexic response and that these routes may be of different importance in different strains of mice. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Prostaglandin E2 metabolism in rat brain: Role of the blood-brain interfaces

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    Strazielle Nathalie

    2008-03-01

    Full Text Available Abstract Background Prostaglandin E2 (PGE2 is involved in the regulation of synaptic activity and plasticity, and in brain maturation. It is also an important mediator of the central response to inflammatory challenges. The aim of this study was to evaluate the ability of the tissues forming the blood-brain interfaces to act as signal termination sites for PGE2 by metabolic inactivation. Methods The specific activity of 15-hydroxyprostaglandin dehydrogenase was measured in homogenates of microvessels, choroid plexuses and cerebral cortex isolated from postnatal and adult rat brain, and compared to the activity measured in peripheral organs which are established signal termination sites for prostaglandins. PGE2 metabolites produced ex vivo by choroid plexuses were identified and quantified by HPLC coupled to radiochemical detection. Results The data confirmed the absence of metabolic activity in brain parenchyma, and showed that no detectable activity was associated with brain microvessels forming the blood-brain barrier. By contrast, 15-hydroxyprostaglandin dehydrogenase activity was measured in both fourth and lateral ventricle choroid plexuses from 2-day-old rats, albeit at a lower level than in lung or kidney. The activity was barely detectable in adult choroidal tissue. Metabolic profiles indicated that isolated choroid plexus has the ability to metabolize PGE2, mainly into 13,14-dihydro-15-keto-PGE2. In short-term incubations, this metabolite distributed in the tissue rather than in the external medium, suggesting its release in the choroidal stroma. Conclusion The rat choroidal tissue has a significant ability to metabolize PGE2 during early postnatal life. This metabolic activity may participate in signal termination of centrally released PGE2 in the brain, or function as an enzymatic barrier acting to maintain PGE2 homeostasis in CSF during the critical early postnatal period of brain development.

  8. Autocrine prostaglandin E2 signaling promotes tumor cell survival and proliferation in childhood neuroblastoma.

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    Agnes Rasmuson

    Full Text Available BACKGROUND: Prostaglandin E(2 (PGE(2 is an important mediator in tumor-promoting inflammation. High expression of cyclooxygenase-2 (COX-2 has been detected in the embryonic childhood tumor neuroblastoma, and treatment with COX inhibitors significantly reduces tumor growth. Here, we have investigated the significance of a high COX-2 expression in neuroblastoma by analysis of PGE(2 production, the expression pattern and localization of PGE(2 receptors and intracellular signal transduction pathways activated by PGE(2. PRINCIPAL FINDINGS: A high expression of the PGE(2 receptors, EP1, EP2, EP3 and EP4 in primary neuroblastomas, independent of biological and clinical characteristics, was detected using immunohistochemistry. In addition, mRNA and protein corresponding to each of the receptors were detected in neuroblastoma cell lines. Immunofluorescent staining revealed localization of the receptors to the cellular membrane, in the cytoplasm, and in the nuclear compartment. Neuroblastoma cells produced PGE(2 and stimulation of serum-starved neuroblastoma cells with PGE(2 increased the intracellular concentration of calcium and cyclic AMP with subsequent phosphorylation of Akt. Addition of 16,16-dimethyl PGE(2 (dmPGE(2 increased cell viability in a time, dose- and cell line-dependent manner. Treatment of neuroblastoma cells with a COX-2 inhibitor resulted in a diminished cell growth and viability that was reversed by the addition of dmPGE(2. Similarly, PGE(2 receptor antagonists caused a decrease in neuroblastoma cell viability in a dose-dependent manner. CONCLUSIONS: These findings demonstrate that PGE(2 acts as an autocrine and/or paracrine survival factor for neuroblastoma cells. Hence, specific targeting of PGE(2 signaling provides a novel strategy for the treatment of childhood neuroblastoma through the inhibition of important mediators of tumor-promoting inflammation.

  9. Configuration and Assessment of the GISS ModelE2 Contributions to the CMIP5 Archive

    Science.gov (United States)

    Schmidt, Gavin A.; Kelley, Max; Nazarenko, Larissa; Ruedy, Reto; Russell, Gary L.; Aleinov, Igor; Bauer, Mike; Bauer, Susanne E.; Bhat, Maharaj K.; Bleck, Rainer; hide

    2014-01-01

    We present a description of the ModelE2 version of the Goddard Institute for Space Studies (GISS) General Circulation Model (GCM) and the configurations used in the simulations performed for the Coupled Model Intercomparison Project Phase 5 (CMIP5). We use six variations related to the treatment of the atmospheric composition, the calculation of aerosol indirect effects, and ocean model component. Specifically, we test the difference between atmospheric models that have noninteractive composition, where radiatively important aerosols and ozone are prescribed from precomputed decadal averages, and interactive versions where atmospheric chemistry and aerosols are calculated given decadally varying emissions. The impact of the first aerosol indirect effect on clouds is either specified using a simple tuning, or parameterized using a cloud microphysics scheme. We also use two dynamic ocean components: the Russell and HYbrid Coordinate Ocean Model (HYCOM) which differ significantly in their basic formulations and grid. Results are presented for the climatological means over the satellite era (1980-2004) taken from transient simulations starting from the preindustrial (1850) driven by estimates of appropriate forcings over the 20th Century. Differences in base climate and variability related to the choice of ocean model are large, indicating an important structural uncertainty. The impact of interactive atmospheric composition on the climatology is relatively small except in regions such as the lower stratosphere, where ozone plays an important role, and the tropics, where aerosol changes affect the hydrological cycle and cloud cover. While key improvements over previous versions of the model are evident, these are not uniform across all metrics.

  10. Perspective of microsomal prostaglandin E2 synthase-1 as drug target in inflammation-related disorders.

    Science.gov (United States)

    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. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. An evaluation of prostaglandin E2 vaginal gel use in practice.

    Science.gov (United States)

    Taylor, S J; Peat, J K; Armour, C L

    1999-08-01

    The purpose of this study was to investigate the effectiveness of prostaglandin E2 vaginal gel as used in practice, rather than its efficacy as assessed in randomised, controlled, clinical trials. This product is used to ripen the cervix prior to induction of labour, sometimes making unnecessary the use of the standard treatment for induction, artificial rupture of the membranes (ARM) plus oxytocin. In this study, effectiveness of the gel was assessed in terms of changes in mode of delivery, and in particular the risk of Caesarean section. An historical control was used and the risk of Caesarean section for women induced in the 1990/91 (before the introduction of the gel) was compared with that for women induced in 1992/93 (after the introduction of the gel). Maternal characteristics which may have been different in the two groups and factors which might influence the risk of Caesarean section were controlled for statistically using logistic regression, thus reducing any bias towards one group. After adjusting for the factors which had a significant effect on the process of labour from induction to birth, it was found that the risk of Caesarean section was not significantly lower in the 1992/93-time period, when the gel was in regular use, from that in the 2 years prior to its introduction (Odds ratio 1.09, CI95% 0.88, 1.36). Following the introduction of PGE2 gel, no difference in effectiveness, as measured in terms of mode of delivery, was detected in this study of practice, which included patients with more complex obstetric problems.

  12. Effects of prostaglandin E2 on synaptic transmission in the rat spinal trigeminal subnucleus caudalis.

    Science.gov (United States)

    Mizutani, Yuka; Ohi, Yoshiaki; Kimura, Satoko; Miyazawa, Ken; Goto, Shigemi; Haji, Akira

    2015-11-02

    The spinal trigeminal subnucleus caudalis (Vc) receives preferentially nociceptive afferent signals from the orofacial area. Nociceptive stimuli to the orofacial area induce cyclooxygenase both peripherally and centrally, which can synthesize a major prostanoid prostaglandin E2 (PGE2) that implicates in diverse physiological functions. To clarify the roles of centrally-synthesized PGE2 in nociception, effects of exogenous PGE2 on synaptic transmission in the Vc neurons were investigated in the rat brainstem slice. Spontaneously occurring excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) were recorded, respectively, under pharmacological blockade of inhibitory and excitatory transmission by whole-cell patch-clamp mode. Perfusion of PGE2 (1-5 μM) increased the frequency of sIPSCs in a concentration-dependent manner but had no significant effect on the amplitude. Similarly to the effects on sIPSCs, PGE2 increased the sEPSC frequency without any effect on the amplitude. These facilitatory effects of PGE2 on spontaneous synaptic transmissions were blocked by an EP1 antagonist SC19220 but not by an EP4 antagonist AH23848. Electrical stimulation of the trigeminal tract evoked short latency EPSCs (eEPSCs) in the Vc neurons. PGE2 (5 μM) was ineffective on the eEPSCs. The present study demonstrated that PGE2 facilitated spontaneous synaptic transmissions in the Vc neurons through activating the presynaptic EP1 receptors but had no effect on the trigeminal tract-mediated excitatory transmission. These results suggest that centrally-synthesized PGE2 modifies the synaptic transmission in the Vc region, thereby contributing to the processing of nociceptive signals originated from the orofacial area. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. E2a/Pbx1 oncogene inhibits terminal differentiation but not myeloid potential of pro-T cells.

    Science.gov (United States)

    Bourette, R P; Grasset, M-F; Mouchiroud, G

    2007-01-11

    E2a/Pbx1 is a fusion oncoprotein resulting from the t(1;19) translocation found in human pre-B acute lymphocytic leukemia and in a small number of acute T-lymphoid and myeloid leukemias. It was previously suggested that E2a/Pbx1 could cooperate with normal or oncogenic signaling pathways to immortalize myeloid and lymphoid progenitor cells. To address this question, we introduced the receptor of the macrophage-colony-stimulating factor (M-CSF-R) in pro-T cells immortalized by a conditional, estradiol-dependent, E2a/Pbx1-protein, and continuously proliferating in response to stem cell factor and interleukin-7. We asked whether M-CSF-R would be functional in an early T progenitor cell and influence the fate of E2a/Pbx1-immortalized cells. E2a-Pbx1 immortalized pro-T cells could proliferate and shifted from lymphoid to myeloid lineage after signaling through exogenously expressed M-CSF-R, irrespective of the presence of estradiol. However, terminal macrophage differentiation of the cells was obtained only when estradiol was withdrawn from cultures. This demonstrated that M-CSF-R is functional for proliferation and differentiation signaling in a T-lymphoid progenitor cell, which, in addition, unveiled myeloid potential of pro-T progenitors. Moreover, the block of differentiation induced by the E2a/Pbx1 oncogene could be modulated by hematopoietic cytokines such as M-CSF, suggesting plasticity of leukemic progenitor cells. Finally, additional experiments suggested that PU.1 and eight twenty-one transcriptional regulators might be implicated in the mechanisms of oncogenesis by E2a/Pbx1.

  14. Dynamical behaviors of Rb-E2F pathway including negative feedback loops involving miR449.

    Science.gov (United States)

    Yan, Fang; Liu, Haihong; Hao, Junjun; Liu, Zengrong

    2012-01-01

    MiRNAs, which are a family of small non-coding RNAs, regulate a broad array of physiological and developmental processes. However, their regulatory roles have remained largely mysterious. E2F is a positive regulator of cell cycle progression and also a potent inducer of apoptosis. Positive feedback loops in the regulation of Rb-E2F pathway are predicted and shown experimentally. Recently, it has been discovered that E2F induce a cluster of miRNAs called miR449. In turn, E2F is inhibited by miR449 through regulating different transcripts, thus forming negative feedback loops in the interaction network. Here, based on the integration of experimental evidence and quantitative data, we studied Rb-E2F pathway coupling the positive feedback loops and negative feedback loops mediated by miR449. Therefore, a mathematical model is constructed based in part on the model proposed in Yao-Lee et al. (2008) and nonlinear dynamical behaviors including the stability and bifurcations of the model are discussed. A comparison is given to reveal the implication of the fundamental differences of Rb-E2F pathway between regulation and deregulation of miR449. Coherent with the experiments it predicts that miR449 plays a critical role in regulating the cell cycle progression and provides a twofold safety mechanism to avoid excessive E2F-induced proliferation by cell cycle arrest and apoptosis. Moreover, numerical simulation and bifurcation analysis shows that the mechanisms of the negative regulation of miR449 to three different transcripts are quite distinctive which needs to be verified experimentally. This study may help us to analyze the whole cell cycle process mediated by other miRNAs more easily. A better knowledge of the dynamical behaviors of miRNAs mediated networks is also of interest for bio-engineering and artificial control.

  15. Dynamical behaviors of Rb-E2F pathway including negative feedback loops involving miR449.

    Directory of Open Access Journals (Sweden)

    Fang Yan

    Full Text Available MiRNAs, which are a family of small non-coding RNAs, regulate a broad array of physiological and developmental processes. However, their regulatory roles have remained largely mysterious. E2F is a positive regulator of cell cycle progression and also a potent inducer of apoptosis. Positive feedback loops in the regulation of Rb-E2F pathway are predicted and shown experimentally. Recently, it has been discovered that E2F induce a cluster of miRNAs called miR449. In turn, E2F is inhibited by miR449 through regulating different transcripts, thus forming negative feedback loops in the interaction network. Here, based on the integration of experimental evidence and quantitative data, we studied Rb-E2F pathway coupling the positive feedback loops and negative feedback loops mediated by miR449. Therefore, a mathematical model is constructed based in part on the model proposed in Yao-Lee et al. (2008 and nonlinear dynamical behaviors including the stability and bifurcations of the model are discussed. A comparison is given to reveal the implication of the fundamental differences of Rb-E2F pathway between regulation and deregulation of miR449. Coherent with the experiments it predicts that miR449 plays a critical role in regulating the cell cycle progression and provides a twofold safety mechanism to avoid excessive E2F-induced proliferation by cell cycle arrest and apoptosis. Moreover, numerical simulation and bifurcation analysis shows that the mechanisms of the negative regulation of miR449 to three different transcripts are quite distinctive which needs to be verified experimentally. This study may help us to analyze the whole cell cycle process mediated by other miRNAs more easily. A better knowledge of the dynamical behaviors of miRNAs mediated networks is also of interest for bio-engineering and artificial control.

  16. Regulation of a senescence checkpoint response by the E2F1 transcription factor and p14ARF tumor suppressor

    Energy Technology Data Exchange (ETDEWEB)

    Dimri, Goberdhan P.; Itahana, Koji; Acosta, Meileen; Campisi, Judith

    1999-11-05

    Normal cells do not divide indefinitely due to a process known as replicative senescence. Human cells arrest growth with a senescent phenotype when they acquire one or more critically short telomere as a consequence of cell division. Recent evidence suggests that certain types of DNA damage, chromatin remodeling, or oncogenic forms of Rasor Raf can also elicit a senescence response. We show here that E2F1, a multifunctional transcription factor that binds the retinoblastoma (pRb) tumor suppressor and can either promote or suppress tumorigenesis, induces a senescent phenotype when overexpressed in normal human fibroblasts. Normal human cells stably arrested proliferation and expressed several markers of replicative senescence in response to E2F1. This activity of E2F1 was independent of its pRb binding activity, but dependent on its ability to stimulate gene expression. The E2F1 target gene critical for the senescence response appeared to be the p14ARF tumor suppressor. Replicatively senescent human fibroblasts overexpressed p14ARF, and ectopic expression of p14ARF in presenescent cells induced a phenotype similar to that induced by E2F1. Consistent with a critical role for p14ARF, cells with compromised p53 function were immune to senescence induction by E2F1, as were cells deficient in p14ARF. Our findings support the idea that the senescence response is a critical tumor suppressive mechanism, provide an explanation for the apparently paradoxical roles of E2F1 in oncogenesis, and identify p14ARF as a potentially important mediator of the senescent phenotype.

  17. E2F-Rb complexes assemble and inhibit cdc25A transcription in cervical carcinoma cells following repression of human papillomavirus oncogene expression

    DEFF Research Database (Denmark)

    Wu, L; Goodwin, E C; Naeger, L K

    2000-01-01

    in the absence of E2 expression. Expression of the E2 protein also led to posttranscriptional increase in the level of E2F4, p105(Rb), and p130 and induced the formation of nuclear E2F4-p130 and E2F4-p105(Rb) complexes. This resulted in marked rearrangement of the protein complexes that formed at the distal E2F...... site in the cdc25A promoter, including the replacement of free E2F complexes with E2F4-p105(Rb) complexes. These experiments indicated that repression of E2F-responsive promoters following HPV E6/E7 repression was mediated by activation of the Rb tumor suppressor pathway and the assembly of repressing...

  18. Electric Monopole Transition Strengths in the Stable Nickel Isotopes

    Science.gov (United States)

    Evitts, Lee John

    A series of measurements of stable nickel isotopes were performed at the Australian National University in Canberra. Excited states in 58,60,62Ni were populated via inelastic scattering of proton beams delivered by the 14UD Pelletron accelerator. Multiple setups were used in order to determine the structure of low-lying states. The CAESAR array of Compton-suppressed HPGe detectors was used to measure the (E2/M1) mixing ratio of transitions from angular distributions of gamma rays. The Super-e spectrometer was used to measure conversion coefficients for a number of J to J transitions. The data obtained from both devices was combined with previously measured parent lifetimes and branching ratios to determine E0 transition strengths between J-pi transitions. The E0 transition strength for the second 0+ to first 0+ transitions in 60,62Ni have been measured for the first time through internal conversion electron detection. The experimental value of 132(+59,-70) for 62Ni agrees within 2 sigma of the previous result obtained from internal pair formation. However it is likely that the previous experimental results used an outdated theoretical model for internal pair formation emission. This work also represents the first measurements of E0 transition strengths between 2+ states in Ni isotopes. There is generally large E0 strength between the 2+ states, particularly in the second 2+ to first 2+ transition, however there is also a large uncertainty in the measurements owing to the difficulties involved in measuring conversion coefficients. In 62Ni, the E0 transition strength of 172(+62,-77) for the second 2+ to first 2+ transition gives further weight to the argument against the spherical vibrator model, as an E0 transition is forbidden if there is a change of only one phonon. The large measurement also indicates the presence of shape coexistence, complementing the recent experimental work carried out in the neutron-rich Ni isotopes.

  19. COUNTRIES IN TRANSITION

    International Development Research Centre (IDRC) Digital Library (Canada)

    Cathy Egan

    transition during the past three decades — in transition from dictatorship to democratic ... research under the harshest conditions of danger and privation. This is research that can prepare a stronger ... any government, IDRC would be freer than most government agencies to work in territories that did not constitute a state.

  20. Generalizing smooth transition autoregressions

    DEFF Research Database (Denmark)

    Chini, Emilio Zanetti

    We introduce a variant of the smooth transition autoregression - the GSTAR model - capable to parametrize the asymmetry in the tails of the transition equation by using a particular generalization of the logistic function. A General-to-Specific modelling strategy is discussed in detail...

  1. Transitive probabilistic CLIR models.

    NARCIS (Netherlands)

    Kraaij, W.; de Jong, Franciska M.G.

    2004-01-01

    Transitive translation could be a useful technique to enlarge the number of supported language pairs for a cross-language information retrieval (CLIR) system in a cost-effective manner. The paper describes several setups for transitive translation based on probabilistic translation models. The

  2. Transitivity of Preferences

    Science.gov (United States)

    Regenwetter, Michel; Dana, Jason; Davis-Stober, Clintin P.

    2011-01-01

    Transitivity of preferences is a fundamental principle shared by most major contemporary rational, prescriptive, and descriptive models of decision making. To have transitive preferences, a person, group, or society that prefers choice option "x" to "y" and "y" to "z" must prefer "x" to…

  3. Origins of evolutionary transitions

    Indian Academy of Sciences (India)

    2014-03-15

    Mar 15, 2014 ... was to define a major transition by identifying a pattern that is common across an otherwise diverse set of ... been many major evolutionary events that this definition of a transition excludes. The evolution of ...... fragmentation periodic, or brings it under endogenous con- trol. So the mechanisms are far from ...

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

    Directory of Open Access Journals (Sweden)

    Konstantin A Tsetsarkin

    2009-08-01

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

  5. Structural basis of CBP/p300 recruitment in leukemia induction by E2A-PBX1.

    Science.gov (United States)

    Denis, Christopher M; Chitayat, Seth; Plevin, Michael J; Wang, Feng; Thompson, Patrick; Liu, Shuang; Spencer, Holly L; Ikura, Mitsuhiko; LeBrun, David P; Smith, Steven P

    2012-11-08

    E-proteins are critical transcription factors in B-cell lymphopoiesis. E2A, 1 of 3 E-protein-encoding genes, is implicated in the induction of acute lymphoblastic leukemia through its involvement in the chromosomal translocation 1;19 and consequent expression of the E2A-PBX1 oncoprotein. An interaction involving a region within the N-terminal transcriptional activation domain of E2A-PBX1, termed the PCET motif, which has previously been implicated in E-protein silencing, and the KIX domain of the transcriptional coactivator CBP/p300, critical for leukemogenesis. However, the structural details of this interaction remain unknown. Here we report the structure of a 1:1 complex between PCET motif peptide and the KIX domain. Residues throughout the helical PCET motif that contact the KIX domain are important for both binding KIX and bone marrow immortalization by E2A-PBX1. These results provide molecular insights into E-protein-driven differentiation of B-cells and the mechanism of E-protein silencing, and reveal the PCET/KIX interaction as a therapeutic target for E2A-PBX1-induced leukemia.

  6. Synthesis and Antimycobacterial and Photosynthesis-Inhibiting Evaluation of 2-[(E-2-Substituted-ethenyl]-1,3-benzoxazoles

    Directory of Open Access Journals (Sweden)

    Ales Imramovsky

    2014-01-01

    Full Text Available A series of twelve 2-[(E-2-substituted-ethenyl]-1,3-benzoxazoles was designed. All the synthesized compounds were tested against three mycobacterial strains. The compounds were also evaluated for their ability to inhibit photosynthetic electron transport (PET in spinach (Spinacia oleracea L. chloroplasts. 2-[(E-2-(4-Methoxyphenylethenyl]-1,3-benzoxazole, 2-[(E-2-(2,3-dihydro-1-benzofuran-5-ylethenyl]-1,3-benzoxazole and 2-{(E-2-[4-(methylsulfanylphenyl]ethenyl}-1,3-benzoxazole showed the highest activity against M. tuberculosis, M. kansasii, and M. avium, and they demonstrated significantly higher activity against M. avium and M. kansasii than isoniazid. The PET-inhibiting activity of the most active ortho-substituted compound 2-[(E-2-(2-methoxyphenylethenyl]-1,3-benzoxazole was IC50 = 76.3 μmol/L, while the PET-inhibiting activity of para-substituted compounds was significantly lower. The site of inhibitory action of tested compounds is situated on the donor side of photosystem II. The structure-activity relationships are discussed.

  7. E2~Ub conjugates regulate the kinase activity of Shigella effector OspG during pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Pruneda, Jonathan N. [Department of Biochemistry, University of Washington, Seattle WA USA; Smith, F. Donelson [Howard Hughes Medical Institute, Department of Pharmacology, University of Washington, Seattle WA USA; Daurie, Angela [Department of Microbiology and Immunology, Dalhousie University, Halifax NS Canada; Swaney, Danielle L. [Department of Genome Sciences, University of Washington, Seattle WA USA; Villén, Judit [Department of Genome Sciences, University of Washington, Seattle WA USA; Scott, John D. [Howard Hughes Medical Institute, Department of Pharmacology, University of Washington, Seattle WA USA; Stadnyk, Andrew W. [Department of Pediatrics, Dalhousie University, Halifax NS Canada; Le Trong, Isolde [Department of Biological Structure, University of Washington, Seattle WA USA; Stenkamp, Ronald E. [Department of Biochemistry, University of Washington, Seattle WA USA; Department of Biological Structure, University of Washington, Seattle WA USA; Klevit, Rachel E. [Department of Biochemistry, University of Washington, Seattle WA USA; Rohde, John R. [Department of Microbiology and Immunology, Dalhousie University, Halifax NS Canada; Brzovic, Peter S. [Department of Biochemistry, University of Washington, Seattle WA USA

    2014-01-20

    Pathogenic bacteria introduce effector proteins directly into the cytosol of eukaryotic cells to promote invasion and colonization. OspG, a Shigella spp. effector kinase, plays a role in this process by helping to suppress the host inflammatory response. OspG has been reported to bind host E2 ubiquitin-conjugating enzymes activated with ubiquitin (E2~Ub), a key enzyme complex in ubiquitin transfer pathways. A cocrystal structure of the OspG/UbcH5c~Ub complex reveals that complex formation has important ramifications for the activity of both OspG and the UbcH5c~Ub conjugate. OspG is a minimal kinase domain containing only essential elements required for catalysis. UbcH5c~Ub binding stabilizes an active conformation of the kinase, greatly enhancing OspG kinase activity. In contrast, interaction with OspG stabilizes an extended, less reactive form of UbcH5c~Ub. Recognizing conserved E2 features, OspG can interact with at least ten distinct human E2s~Ub. Mouse oral infection studies indicate that E2~Ub conjugates act as novel regulators of OspG effector kinase function in eukaryotic host cells.

  8. [Construction and evaluation of hepatitis C virus (HCV) DNA vaccine containing E2-gAD fusion gene].

    Science.gov (United States)

    Wen, Bo; Deng, Yao; Tan, Wen-Jie; Ying, Xiao; Gao, Ji-Ming; Ruan, Li

    2010-02-01

    To rational design HCV DNA vaccine candidates and evaluate their specific We design to construct two DNA vaccine candidates, one consists of immunity to HCV in mice. We design to construct two DNA vaccine candidates, one consists of E2 (the envelope glycoprotein 2 of HCV) gene only, the second consists of E2-gAD (Globular Domain of Human Adiponectin) fusion gene via overlapping PCR. Confirm the expression of the DNA vaccines by Western blotting, and then vaccinated by injection of DNA vaccines with gene electrotransfer (GET) in BALB/c mice. The immune response was measured by IFN-gamma ELISPOT. The DNA vaccine candidate consists of E2-gAD could effectively express in vitro , and it could induced a higher anti-HCV T cell response in mice than the one consists of E2 only. The HCV DNA vaccine consists of E2-gAD fusion can increase the immunity of the E, to some extend, and the research paved a way to develop and optimize the novel HCV DNA vaccine.

  9. Involvement of the transcriptional factor E2F1 in the regulation of the rRNA promoter

    International Nuclear Information System (INIS)

    Ayrault, Olivier; Andrique, Laetitia; Seite, Paule

    2006-01-01

    p16 INK4a -pRB-E2F and ARF-MDM2-p53 are two major tumor suppressor networks involved in cell proliferation control. The nucleolar ARF protein binds to MDM2 to activate the growth suppressive functions of p53, but can also exert its tumor suppressor activity independently of p53, through mechanisms involving other regulators: in that manner, p14 ARF has been shown to inhibit the transcriptional activity of E2F1 in vitro, suggesting that the two pathways intersect with one another. More recently, ARF has been shown to inhibit ribosomal RNA processing, and to specifically interact with the rRNA promoter, suggesting a role in the regulation of both maturation and transcription processes. We show here that E2F1 can bind the rRNA promoter and modulate its activity through the interaction with two E2F1-binding sequences we have identified. The regulation of ribosome biogenesis appears as a major p53-independent process, which involves both ARF and E2F1 to control cell proliferation

  10. Comprehensive analysis of the codon usage patterns in the envelope glycoprotein E2 gene of the classical swine fever virus.

    Directory of Open Access Journals (Sweden)

    Ye Chen

    Full Text Available The classical swine fever virus (CSFV, circulating worldwide, is a highly contagious virus. Since the emergence of CSFV, it has caused great economic loss in swine industry. The envelope glycoprotein E2 gene of the CSFV is an immunoprotective antigen that induces the immune system to produce neutralizing antibodies. Therefore, it is essential to study the codon usage of the E2 gene of the CSFV. In this study, 140 coding sequences of the E2 gene were analyzed. The value of effective number of codons (ENC showed low codon usage bias in the E2 gene. Our study showed that codon usage could be described mainly by mutation pressure ENC plot analysis combined with principal component analysis (PCA and translational selection-correlation analysis between the general average hydropathicity (Gravy and aromaticity (Aroma, and nucleotides at the third position of codons (A3s, T3s, G3s, C3s and GC3s. Furthermore, the neutrality analysis, which explained the relationship between GC12s and GC3s, revealed that natural selection had a key role compared with mutational bias during the evolution of the E2 gene. These results lay a foundation for further research on the molecular evolution of CSFV.

  11. Lost in Transit

    DEFF Research Database (Denmark)

    Lange, Ida Sofie Gøtzsche; Laursen, Lea Louise Holst; Lassen, Claus

    Thinking of Transit Places, the first sites that comes to mind will probably be airports, train stations and motorways. Such places are overall mono-functional with the embedded rationales of people's desires to move (themselves or goods) from one place to another. Often different service functions...... and commerce are added to such places facilitating the accomplishment of comfortable and easy transit. Apart from those being in transit, people do not visit these places and apart from those working at such transit places, people do not stay for longer periods. Certainly people do not live or spend the whole...... of their daily lives here. This is on the contrary what many people do in cities and towns - places where people live, work and stay, and that they purposefully visit in their spare times. The article addresses what happens, when an inhabited place obtain the properties normally connected with transit...

  12. Contemporary Transitional Justice

    DEFF Research Database (Denmark)

    Gissel, Line Engbo

    2017-01-01

    This article studies the contemporary expression of transitional justice, a field of practice through which global governance is exercised. It argues that transitional justice is being normalised, given the normative and empirical de-legitimisation of its premise of exceptionalism. The article...... theorises exceptionalism and normalcy in transitional justice and identifies three macro-level causes of normalisation: the legalisation, internationalisation, and professionalization of the field. This argument is illustrated by a study of Uganda’s trajectory of transitional justice since 1986. Across five...... phases of transitional justice, processes of legalisation, internationalisation, and professionalization have contributed to the gradual dismantling of the country’s exceptional justice. The case demonstrates, further, that normalization is a contested and incomplete process....

  13. An inhibitory switch derepressed by pbx, hox, and Meis/Prep1 partners regulates DNA-binding by pbx1 and E2a-pbx1 and is dispensable for myeloid immortalization by E2a-pbx1.

    Science.gov (United States)

    Calvo, K R; Knoepfler, P; McGrath, S; Kamps, M P

    1999-12-23

    The Pbx/Exd family of homeodomain (HD) proteins contribute to the transcriptional and developmental roles of other Hox and Meis/Prep1/Hth HD proteins through heterodimer formation. E2a-Pbx1 is an oncogenic derrivative of Pbx1 produced by the t(1;19) translocation in pediatric pre-B cell acute lymphoblastic leukemia. E2a-Pbx1 heterodimerizes with Hox but not with Meis/Prep1 proteins, produces acute myeloid leukemia in mice, and blocks differentiation of cultured murine myeloid progenitors. Here, we characterize negative and positive regulatory sequences that flank the Pbx1 HD and determine their importance for myeloid immortalization by E2a-Pbx1. A 25 residue predicted alpha helix preceding the Pbx1 HD bound the HD and prevented both its binding to DNA and its ability to heterodimerize with Hox proteins. Addition of 39 residues N-terminal to this inhibitory helix exposed a Pbx dimerization interface that orchestrated cooperative DNA-binding of E2a-Pbx1 and all Pbx proteins as homodimers and heterdimers. Sequences inhibiting DNA-binding and mediating Pbx dimerization coincided with those reported to have nuclear export function. An additional 103 residues N-terminal to the Pbx dimerization interface restored heterodimerization with Hox and Meis1/Prep1 proteins. This negative switch domain - comprised of the inhibitory helix and N-terminal regions required for its partner-mediated derepression - was dispensable for myeloid immortalization by E2a-Pbx1. While stabilizing the heterodimer, the 310 helix C-terminal to the Pbx1 HD was also dispensable for the ability of E2a-Pbx1 to heterodimerize with Hox proteins and immortalize myeloblasts. Retention of myeloid immortalization by E2a-Pbx1 proteins lacking all Pbx1 sequences N- or C-terminal to the HD indicates that Hox proteins, or a yet undefined factor that binds the Pbx1 HD and derepresses DNA-binding by the HD, cooperate with E2a-Pbx1 in myeloid immortalization.

  14. Novel contraceptive targets to inhibit ovulation: the prostaglandin E2 pathway

    Science.gov (United States)

    Duffy, Diane M.

    2015-01-01

    BACKGROUND Prostaglandin E2 (PGE2) is an essential intrafollicular regulator of ovulation. In contrast with the one-gene, one-protein concept for synthesis of peptide signaling molecules, production and metabolism of bioactive PGE2 requires controlled expression of many proteins, correct subcellular localization of enzymes, coordinated PGE2 synthesis and metabolism, and prostaglandin transport in and out of cells to facilitate PGE2 action and degradation. Elevated intrafollicular PGE2 is required for successful ovulation, so disruption of PGE2 synthesis, metabolism or transport may yield effective contraceptive strategies. METHODS This review summarizes case reports and studies on ovulation inhibition in women and macaques treated with cyclooxygenase inhibitors published from 1987 to 2014. These findings are discussed in the context of studies describing levels of mRNA, protein, and activity of prostaglandin synthesis and metabolic enzymes as well as prostaglandin transporters in ovarian cells. RESULTS The ovulatory surge of LH regulates the expression of each component of the PGE2 synthesis-metabolism-transport pathway within the ovulatory follicle. Data from primary ovarian cells and cancer cell lines suggest that enzymes and transporters can cooperate to optimize bioactive PGE2 levels. Elevated intrafollicular PGE2 mediates key ovulatory events including cumulus expansion, follicle rupture and oocyte release. Inhibitors of the prostaglandin-endoperoxide synthase 2 (PTGS2) enzyme (also known as cyclooxygenase-2 or COX2) reduce ovulation rates in women. Studies in macaques show that PTGS2 inhibitors can reduce the rates of cumulus expansion, oocyte release, follicle rupture, oocyte nuclear maturation and fertilization. A PTGS2 inhibitor reduced pregnancy rates in breeding macaques when administered to simulate emergency contraception. However, PTGS2 inhibition did not prevent pregnancy in monkeys when administered to simulate monthly contraceptive use. CONCLUSION

  15. Novel contraceptive targets to inhibit ovulation: the prostaglandin E2 pathway.

    Science.gov (United States)

    Duffy, Diane M

    2015-01-01

    Prostaglandin E2 (PGE2) is an essential intrafollicular regulator of ovulation. In contrast with the one-gene, one-protein concept for synthesis of peptide signaling molecules, production and metabolism of bioactive PGE2 requires controlled expression of many proteins, correct subcellular localization of enzymes, coordinated PGE2 synthesis and metabolism, and prostaglandin transport in and out of cells to facilitate PGE2 action and degradation. Elevated intrafollicular PGE2 is required for successful ovulation, so disruption of PGE2 synthesis, metabolism or transport may yield effective contraceptive strategies. This review summarizes case reports and studies on ovulation inhibition in women and macaques treated with cyclooxygenase inhibitors published from 1987 to 2014. These findings are discussed in the context of studies describing levels of mRNA, protein, and activity of prostaglandin synthesis and metabolic enzymes as well as prostaglandin transporters in ovarian cells. The ovulatory surge of LH regulates the expression of each component of the PGE2 synthesis-metabolism-transport pathway within the ovulatory follicle. Data from primary ovarian cells and cancer cell lines suggest that enzymes and transporters can cooperate to optimize bioactive PGE2 levels. Elevated intrafollicular PGE2 mediates key ovulatory events including cumulus expansion, follicle rupture and oocyte release. Inhibitors of the prostaglandin-endoperoxide synthase 2 (PTGS2) enzyme (also known as cyclooxygenase-2 or COX2) reduce ovulation rates in women. Studies in macaques show that PTGS2 inhibitors can reduce the rates of cumulus expansion, oocyte release, follicle rupture, oocyte nuclear maturation and fertilization. A PTGS2 inhibitor reduced pregnancy rates in breeding macaques when administered to simulate emergency contraception. However, PTGS2 inhibition did not prevent pregnancy in monkeys when administered to simulate monthly contraceptive use. PTGS2 inhibitors alone may be suitable

  16. Prostaglandin E2 protects murine lungs from bleomycin-induced pulmonary fibrosis and lung dysfunction

    Science.gov (United States)

    Dackor, Ryan T.; Cheng, Jennifer; Voltz, James W.; Card, Jeffrey W.; Ferguson, Catherine D.; Garrett, Ryan C.; Bradbury, J. Alyce; DeGraff, Laura M.; Lih, Fred B.; Tomer, Kenneth B.; Flake, Gordon P.; Travlos, Gregory S.; Ramsey, Randle W.; Edin, Matthew L.; Morgan, Daniel L.

    2011-01-01

    Prostaglandin E2 (PGE2) is a lipid mediator that is produced via the metabolism of arachidonic acid by cyclooxygenase enzymes. In the lung, PGE2 acts as an anti-inflammatory factor and plays an important role in tissue repair processes. Although several studies have examined the role of PGE2 in the pathogenesis of pulmonary fibrosis in rodents, results have generally been conflicting, and few studies have examined the therapeutic effects of PGE2 on the accompanying lung dysfunction. In this study, an established model of pulmonary fibrosis was used in which 10–12-wk-old male C57BL/6 mice were administered a single dose (1.0 mg/kg) of bleomycin via oropharyngeal aspiration. To test the role of prostaglandins in this model, mice were dosed, via surgically implanted minipumps, with either vehicle, PGE2 (1.32 μg/h), or the prostacyclin analog iloprost (0.33 μg/h) beginning 7 days before or 14 days after bleomycin administration. Endpoints assessed at 7 days after bleomycin administration included proinflammatory cytokine levels and measurement of cellular infiltration into the lung. Endpoints assessed at 21 days after bleomycin administration included lung function assessment via invasive (FlexiVent) analysis, cellular infiltration, lung collagen content, and semiquantitative histological analysis of the degree of lung fibrosis (Ashcroft method). Seven days after bleomycin administration, lymphocyte numbers and chemokine C-C motif ligand 2 expression were significantly lower in PGE2- and iloprost-treated animals compared with vehicle-treated controls (P bleomycin challenge, PGE2 also protected against the decline in lung static compliance, lung fibrosis, and collagen production that is associated with 3 wk of bleomycin exposure. However, PGE2 had no therapeutic effect on these parameters when administered 14 days after bleomycin challenge. In summary, PGE2 prevented the decline in lung static compliance and protected against lung fibrosis when it was administered

  17. Effect of prostaglandin E2 injection on the structural properties of the rat patellar tendon

    Directory of Open Access Journals (Sweden)

    Ferry Scott T

    2012-01-01

    Full Text Available Abstract Background Increased tendon production of the inflammatory mediator prostaglandin E2 (PGE2 has been suggested to be a potential etiologic agent in the development of tendinopathy. Repeated injection of PGE2 into tendon has been proposed as a potential animal model for studying treatments for tendinopathy. In contrast, nonsteroidal anti-inflammatory drugs (NSAIDs which inhibit PGE2 production and are commonly prescribed in treating tendinopathy have been shown to impair the healing of tendon after acute injury in animal models. The contradictory literature suggests the need to better define the functional effects of PGE2 on tendon. Our objective was to characterize the effects of PGE2 injection on the biomechanical and biochemical properties of tendon and the activity of the animals. Our hypothesis was that weekly PGE2 injection to the rat patellar tendon would lead to inferior biomechanical properties. Methods Forty rats were divided equally into four groups. Three groups were followed for 4 weeks with the following peritendinous injection procedures: No injection (control, 4 weekly injections of saline (saline, 4 weekly injections of 800 ng PGE2 (PGE2-4 wks. The fourth group received 4 weekly injections of 800 ng PGE2 initially and was followed for a total of 8 weeks. All animals were injected bilaterally. The main outcome measurements included: the structural and material properties of the patellar tendon under tensile loading to failure, tendon collagen content, and weekly animal activity scores. Results The ultimate load of PGE2-4 wks tendons at 4 weeks was significantly greater than control or saline group tendons. The stiffness and elastic modulus of the PGE2 injected tendons at 8 weeks was significantly greater than the control or saline tendons. No differences in animal activity, collagen content, or mean fibril diameter were observed between groups. Conclusions Four weekly peritendinous injections of PGE2 to the rat patellar

  18. Role of the prostaglandin E2 EP1 receptor in traumatic brain injury.

    Directory of Open Access Journals (Sweden)

    Alexander V Glushakov

    Full Text Available Brain injuries promote upregulation of so-called proinflammatory prostaglandins, notably prostaglandin E2 (PGE2, leading to overactivation of a class of its cognate G-protein-coupled receptors, including EP1, which is considered a promising target for treatment of ischemic stroke. However, the role of the EP1 receptor is complex and depends on the type of brain injury. This study is focused on the investigation of the role of the EP1 receptor in a controlled cortical impact (CCI model, a preclinical model of traumatic brain injury (TBI. The therapeutic effects of post-treatments with a widely studied EP1 receptor antagonist, SC-51089, were examined in wildtype and EP1 receptor knockout C57BL/6 mice. Neurological deficit scores (NDS were assessed 24 and 48 h following CCI or sham surgery, and brain immunohistochemical pathology was assessed 48 h after surgery. In wildtype mice, CCI resulted in an obvious cortical lesion and localized hippocampal edema with an associated significant increase in NDS compared to sham-operated animals. Post-treatments with the selective EP1 receptor antagonist SC-51089 or genetic knockout of EP1 receptor had no significant effects on cortical lesions and hippocampal swelling or on the NDS 24 and 48 h after CCI. Immunohistochemistry studies revealed CCI-induced gliosis and microglial activation in selected ipsilateral brain regions that were not affected by SC-51089 or in the EP1 receptor-deleted mice. This study provides further clarification on the respective contribution of the EP1 receptor in TBI and suggests that, under this experimental paradigm, the EP1 receptor would have limited effects in modulating acute neurological and anatomical pathologies following contusive brain trauma. Findings from this protocol, in combination with previous studies demonstrating differential roles of EP1 receptor in ischemic, neurotoxic, and hemorrhagic conditions, provide scientific background and further clarification of

  19. Impaired neonatal macrophage phagocytosis is not explained by overproduction of prostaglandin E2

    Directory of Open Access Journals (Sweden)

    Ballinger Megan N

    2011-12-01

    Full Text Available Abstract Background Neonates and young infants manifest increased susceptibility to bacterial, viral and fungal lung infections. Previous work has identified a role for eicosanoids in mediating host defense functions of macrophages. This study examines the relationship between alveolar macrophage (AM host defense and production of lipid mediators during the neonatal period compared to adult AMs. Methods AMs were harvested from young (day 7 and day 14 and adult (~10 week rats. The functionality of these cells was assessed by examining their ability to phagocytose opsonized targets, produce cytokines, eicosanoids and intracellular cAMP measured by enzyme immunoassays, and gene expression of proteins, enzymes and receptors essential for eicosanoid generation and phagocytosis measured by real time RT-PCR. Results AMs from young animals (day 7 and 14 were defective in their ability to phagocytose opsonized targets and produce tumor necrosis factor (TNF- α. In addition, young AMs produce more prostaglandin (PG E2, a suppressor of host defense, and less leukotriene (LT B4, a promoter of host defense. Young AMs express higher levels of enzymes responsible for the production of PGE2 and LTB4; however, there was no change in the expression of E prostanoid (EP receptors or LT receptors. Despite the similar EP profiles, young AMs are more responsive to PGE2 as evidenced by their increased production of the important second messenger, cyclic AMP. In addition, young AMs express higher levels of PDE3B and lower levels of PDE4C compared to adult AMs. However, even though the young AMs produced a skewed eicosanoid profile, neither the inhibition of PGE2 by aspirin nor the addition of exogenous LTB4 rescued the defective opsonized phagocytosis. Examination of a receptor responsible for mediating opsonized phagocytosis showed a significant decrease in the gene expression levels of the Fcgamma receptor in young (day 7 AMs compared to adult AMs. Conclusion These

  20. On the Performance of In-Band Full-Duplex Cooperative Communications

    KAUST Repository

    Khafagy, Mohammad Galal

    2016-06-01

    In-band full-duplex, by which radios may simultaneously transmit and receive over the same channel, has been always considered practically-unfeasible due to the prohibitively strong self-interference. Indeed, a freshly-generated transmit signal power is typically ten orders of magnitude higher than that of a naturally-attenuated received signal. While unable to manage such an overwhelming interference, wireless communications resorted to half-duplex operation, transmitting and receiving over orthogonal channel resources. Recent research has demonstrated the practical feasibility of full-duplexing via successive sophisticated stages of signal suppression/cancellation, bringing this long-held assumption down and reviving the promising full-duplex potentials. Full-duplex relaying (FDR), where intermediate nodes may now support source-destination communication via simultaneous listening/forwarding, represents one of two full-duplex settings currently recommended for deployment in future fifth-generation (5G) systems. Theoretically, it has been widely accepted that FDR potentially doubles the channel capacity when compared to its half-duplex counterpart. Although FDR doubles the multiplexing gain, the effective signal-to-noise ratio (SNR) can be significantly degraded due to the residual self-interference (RSI) if not properly handled. In this work, efficient protocols are devised for different FDR settings. Selective cooperation is proposed for the canonical three-terminal FDR channel with RSI, which exploits the cooperative diversity offered by the independently fading source/relay message replicas arriving at the destination. Closed-form expressions are derived for the end-to-end SNR cumulative distribution function (CDF) under Rayleigh and Nakagami-m fading. Further, the offered diversity gain is presented as a function of the RSI scaling trend with the relay power. We show that the existing diversity problem in simple FDR protocols can be considerably fixed via

  1. E2GPR - Edit your geometry, Execute GprMax2D and Plot the Results!

    Science.gov (United States)

    Pirrone, Daniele; Pajewski, Lara

    2015-04-01

    can be employed to import synthetic data created by GprMax using the binary-format option into MATLAB, in order to be processed and/or visualized. Further MATLAB procedures for the visualization of GprMax synthetic data have been developed within the COST Action TU1208 [2] and are available for free public download on www.GPRadar.eu. The current version of GprMax3D is compiled with OpenMP, supporting multi-platform shared memory multiprocessing which allows GprMax3D to take advantage of multiple cores/CPUs. GprMax2D, instead, exploits a single core when executed. E2GPR is a new software tool, available free of charge for both academic and commercial use, conceived to: 1) assist in the creation, modification and analysis of GprMax2D models, through a Computer-Aided Design (CAD) system; 2) allow parallel and/or distributed computing with GprMax2D, on a network of computers; 3) automatically plot A-scans and B-scans generated by GprMax2D. The CAD and plotter parts of the tool are implemented in Java and can run on any Java Virtual Machine (JVM) regardless of computer architecture. The part of the tool devoted to supporting parallel and/or distributed computing, instead, requires the set up of a Web-Service (on a server emulator or server); in fact, it is currently configured only for Windows Server and Internet Information Services (IIS). In this work, E2GPR is presented and examples are provided which demonstrate its use. The tool can be currently obtained by contacting the authors. It will soon be possible to download it from www.GPRadar.eu. Acknowledgement This work is a contribution to the COST Action TU1208 'Civil Engineering Applications of Ground Penetrating Radar.' The authors thank COST for funding the Action TU1208. References [1] A. Giannopoulos, 'Modelling ground penetrating radar by GprMax,' Construction and Building Materials, vol. 19, pp. 755-762, 2005. [2] L. Pajewski, A. Benedetto, X. Dérobert, A. Giannopoulos, A. Loizos, G. Manacorda, M. Marciniak, C

  2. DES15E2mlf: a spectroscopically confirmed superluminous supernova that exploded 3.5 Gyr after the big bang

    Science.gov (United States)

    Pan, Y.-C.; Foley, R. J.; Smith, M.; Galbany, L.; D'Andrea, C. B.; González-Gaitán, S.; Jarvis, M. J.; Kessler, R.; Kovacs, E.; Lidman, C. Nichol, R. C.; Papadopoulos, A.; Sako, M.; Sullivan, M.; Abbott, T. M. C.; Abdalla, F. B.; Annis, J.; Bechtol, K.; Benoit-Lévy, A.; Brooks, D.; Buckley-Geer, E.; Burke, D. L.; Carnero Rosell, A.; Carrasco Kind, M.; Carretero, J.; Castander, F. J.; Cunha, C. E.; da Costa, L. N.; Desai, S.; Diehl, H. T.; Doel, P.; Eifler, T. F.; Finley, D. A.; Flaugher, B.; Frieman, J.; García-Bellido, J.; Goldstein, D. A.; Gruen, D.; Gruendl, R. A.; Gschwend, J.; Gutierrez, G.; James, D. J.; Kim, A. G.; Krause, E.; Kuehn, K.; Kuropatkin, N.; Lahav, O.; Lima, M.; Maia, M. A. G.; March, M.; Marshall, J. L.; Martini, P.; Miquel, R.; Nugent, P.; Plazas, A. A.; Romer, A. K.; Sanchez, E.; Scarpine, V.; Schubnell, M.; Sevilla-Noarbe, I.; Smith, R. C.; Sobreira, F.; Suchyta, E.; Swanson, M. E. C.; Thomas, R. C.; Walker, A. R.; DES Collaboration

    2017-10-01

    We present the Dark Energy Survey (DES) discovery of DES15E2mlf, the most distant superluminous supernova (SLSN) spectroscopically confirmed to date. The light curves and Gemini spectroscopy of DES15E2mlf indicate that it is a Type I superluminous supernova (SLSN-I) at z = 1.861 (a lookback time of ˜10 Gyr) and peaking at MAB = -22.3 ± 0.1 mag. Given the high redshift, our data probe the rest-frame ultraviolet (1400-3500 Å) properties of the SN, finding velocity of the C III feature changes by ˜5600 km s- 1 over 14 d around maximum light. We find the host galaxy of DES15E2mlf has a stellar mass of 3.5^{+3.6}_{-2.4} × 109 M⊙, which is more massive than the typical SLSN-I host galaxy.

  3. Systems Biology-Based Identification of Crosstalk between E2F Transcription Factors and the Fanconi Anemia Pathway

    Directory of Open Access Journals (Sweden)

    Moe Tategu

    2007-01-01

    Full Text Available Fanconi anemia (FA is an autosomal recessive disorder characterized by congenital abnormalities, bone marrow failure, chromosome fragility, and cancer susceptibility. At least eleven members of the FA gene family have been identified using complementation experiments. Ubiquitin-proteasome has been shown to be a key regulator of FA proteins and their involvement in the repair of DNA damage. Here, we identifi ed a novel functional link between the FA/BRCA pathway and E2F-mediated cell cycle regulome. In silico mining of a transcriptome database and promoter analyses revealed that a significant number of FA gene members were regulated by E2F transcription factors, known to be pivotal regulators of cell cycle progression – as previously described for BRCA1. Our findings suggest that E2Fs partly determine cell fate through the FA/BRCA pathway.

  4. Investigation on the average serum E2 level and menopausal age in healthy women in Wuhan area

    International Nuclear Information System (INIS)

    Chen Huilin; Lan Jian; Zhang Yangyang; Li Fei; Zhang Yuanji

    2008-01-01

    Objective: To investigate the average serum E 2 level and menopausal age of healthy women in Wuhan area and assess the appropriateness of hormone replacement therapy in these women. Methods: Serum E 2 levels were measured with RIA in 2020 healthy women (26-75 yr old) in Wuhan area. Results: (1) Serum E 2 levels reached peak in 31-35yr group, significantly dropped in 46-50yr group and reached menopausal level in 51-55 yr group. (2) The average menopausal age in Wuhan area was rather early-48.08yr. Conclusion: The average menopausal age in Wuhan area was 2.3yr earlier than the nationwide 1989 screening result, which should be a concern for the maternity health workers. (authors)

  5. The efficacy of CP7_E2alf: an animal study involving piglets from C–strain vaccinated sows

    DEFF Research Database (Denmark)

    Rangelova, Desislava Yordanova; Nielsen, Jens; Strandbygaard, Bertel

    previously vaccinated with C-strain interferes with the efficacy of CP7_E2alf vaccination. To study the interaction with maternal antibodies, the efficacy of CP7_E2alf in piglets from C-strain vaccinated sows was examined. At 5 or at 8 weeks of age, piglets were vaccinated with CP7_E2alf. The vaccinated....... Interestingly, the antibodies in the mock-vaccinated control piglets partly neutralized the challenge virus. In earlier studies CSFV Koslov has resulted in 100% mortality in naïve piglets, in this study mortality was reduced to 30% in the piglets infected at 7 weeks of age and to 50% in the piglets infected...... at 10 weeks of age. In the present study optimal time point for vaccination of piglets with passive immunity was found to be 5 weeks of age....

  6. Absolute Transition Probabilities from the 453.1 keV Level in {sup 183}W

    Energy Technology Data Exchange (ETDEWEB)

    Malmskog, S.G.

    1966-10-15

    The half life of the 453.1 keV level in {sup 183}W has been measured by the delayed coincidence method to 18.4 {+-} 0.5 nsec. This determines twelve absolute M1 and E2 transition probabilities, out of which nine are K-forbidden. All transition probabilities are compared with the single particle estimate. The three K-allowed E2, {delta}K = 2 transition rates to the 1/2{sup -} (510) rotational band are furthermore compared with the Nilsson model. An attempt to give a quantitative explanation of the observed transition rates has been made by including the effects from admixtures into the single particle wave functions.

  7. Absolute Transition Probabilities from the 453.1 keV Level in 183W

    International Nuclear Information System (INIS)

    Malmskog, S.G.

    1966-10-01

    The half life of the 453.1 keV level in 183 W has been measured by the delayed coincidence method to 18.4 ± 0.5 nsec. This determines twelve absolute M1 and E2 transition probabilities, out of which nine are K-forbidden. All transition probabilities are compared with the single particle estimate. The three K-allowed E2, ΔK = 2 transition rates to the 1/2 - (510) rotational band are furthermore compared with the Nilsson model. An attempt to give a quantitative explanation of the observed transition rates has been made by including the effects from admixtures into the single particle wave functions

  8. Coordination of IVI and transit signal priority on transit evacuations.

    Science.gov (United States)

    2011-02-01

    During an emergency evacuation, execution time is always critical to the evacuees who are : transit dependent. Transit Signal Priority (TSP) can speed up the transit services by prioritizing : the approaching bus at a signalized intersection. With th...

  9. E2A-PBX1 Remodels Oncogenic Signaling Networks in B-cell Precursor Acute Lymphoid Leukemia.

    Science.gov (United States)

    Duque-Afonso, Jesús; Lin, Chiou-Hong; Han, Kyuho; Wei, Michael C; Feng, Jue; Kurzer, Jason H; Schneidawind, Corina; Wong, Stephen Hon-Kit; Bassik, Michael C; Cleary, Michael L

    2016-12-01

    There is limited understanding of how signaling pathways are altered by oncogenic fusion transcription factors that drive leukemogenesis. To address this, we interrogated activated signaling pathways in a comparative analysis of mouse and human leukemias expressing the fusion protein E2A-PBX1, which is present in 5%-7% of pediatric and 50% of pre-B-cell receptor (preBCR + ) acute lymphocytic leukemia (ALL). In this study, we describe remodeling of signaling networks by E2A-PBX1 in pre-B-ALL, which results in hyperactivation of the key oncogenic effector enzyme PLCγ2. Depletion of PLCγ2 reduced proliferation of mouse and human ALLs, including E2A-PBX1 leukemias, and increased disease-free survival after secondary transplantation. Mechanistically, E2A-PBX1 bound promoter regulatory regions and activated the transcription of its key target genes ZAP70, SYK, and LCK, which encode kinases upstream of PLCγ2. Depletion of the respective upstream kinases decreased cell proliferation and phosphorylated levels of PLCγ2 (pPLCγ2). Pairwise silencing of ZAP70, SYK, or LCK showed additive effects on cell growth inhibition, providing a rationale for combination therapy with inhibitors of these kinases. Accordingly, inhibitors such as the SRC family kinase (SFK) inhibitor dasatinib reduced pPLCγ2 and inhibited proliferation of human and mouse preBCR + /E2A-PBX1 + leukemias in vitro and in vivo Furthermore, combining small-molecule inhibition of SYK, LCK, and SFK showed synergistic interactions and preclinical efficacy in the same setting. Our results show how the oncogenic fusion protein E2A-PBX1 perturbs signaling pathways upstream of PLCγ2 and renders leukemias amenable to targeted therapeutic inhibition. Cancer Res; 76(23); 6937-49. ©2016 AACR. ©2016 American Association for Cancer Research.

  10. Gene order for rubella virus structural proteins is NH/sub 2/-C-E2-E1-COOH

    Energy Technology Data Exchange (ETDEWEB)

    Oker-Blom, C.

    1984-08-01

    The order of translation in vivo of the genes coding for rubella virus structural proteins was studied in infected B-Vero cells. The proteins were sequentially pulse-chase labeled with (/sup 35/S)methionine after synchronization of translation initiation with hypertonic salt treatment. A sequential labeling procedure (window-labeling) to specifically label defined segments of the structural proteins was also used. The labeled proteins were identified by sodium dodecyl sulfate-gel electrophoresis after immunoprecipitation with specific antisera directed against the two virion glycoproteins (E1 and E2a/E2b) and the nucleocapsid (C) protein. The order of translation was found to be NH/sub 2/-C-E2-E1-COOH. We have previously shown that the structural proteins are synthesized in vitro from a cytoplasmic 24S subgenomic mRNA as a 110,000-dalton (p110) precursor. Here, it is shown that p110 is precipitated with anti-C, anti-E2, and anti-E1 sera, indicating that p110 is the precursor of all three structural proteins. Two major in vitro translation products (M/sub r/s, 66,000 and 62,000) that could represent preterminated polypeptide chains or proteolytic cleavage products were precipitated with anti-C and anti-Es sera, but not with anti-E1 serum, indicating, in conformity with the in vivo results, that the genes for the C and E2 proteins are adjacent to each other. Using these specific antisera, we have also confirmed the identity of the unglycosylated forms of E1 (M/sub r/, 53,000) and E2 (M/sub r/ 30,000) immunoprecipitated from tunicamycin-treated infected cells. 18 references, 6 figures.

  11. Gene order for rubella virus structural proteins is NH2-C-E2-E1-COOH

    International Nuclear Information System (INIS)

    Oker-Blom, C.

    1984-01-01

    The order of translation in vivo of the genes coding for rubella virus structural proteins was studied in infected B-Vero cells. The proteins were sequentially pulse-chase labeled with [ 35 S]methionine after synchronization of translation initiation with hypertonic salt treatment. A sequential labeling procedure (window-labeling) to specifically label defined segments of the structural proteins was also used. The labeled proteins were identified by sodium dodecyl sulfate-gel electrophoresis after immunoprecipitation with specific antisera directed against the two virion glycoproteins (E1 and E2a/E2b) and the nucleocapsid (C) protein. The order of translation was found to be NH 2 -C-E2-E1-COOH. We have previously shown that the structural proteins are synthesized in vitro from a cytoplasmic 24S subgenomic mRNA as a 110,000-dalton (p110) precursor. Here, it is shown that p110 is precipitated with anti-C, anti-E2, and anti-E1 sera, indicating that p110 is the precursor of all three structural proteins. Two major in vitro translation products (M/sub r/s, 66,000 and 62,000) that could represent preterminated polypeptide chains or proteolytic cleavage products were precipitated with anti-C and anti-Es sera, but not with anti-E1 serum, indicating, in conformity with the in vivo results, that the genes for the C and E2 proteins are adjacent to each other. Using these specific antisera, we have also confirmed the identity of the unglycosylated forms of E1 (M/sub r/, 53,000) and E2 (M/sub r/ 30,000) immunoprecipitated from tunicamycin-treated infected cells. 18 references, 6 figures

  12. Intracellular Distribution and Involvement of GPR30 in the Actions of E2 on C2C12 Cells.

    Science.gov (United States)

    Ronda, Ana C; Boland, Ricardo L

    2016-03-01

    G-protein-coupled receptor 30 (GPR30) is an estrogen receptor that initiates several rapid, non-genomic signaling events triggered by E2. GPR30 has recently been identified in C2C12 cells; however, little is known about the intracelular distribution and its role in C2C12 myoblasts and myotubes. By western blotting and immunohistochemistry, we evidenced expression of GPR30. While in C2C12 myoblasts, the receptor was present in nucleus, mitochondria, and endoplasmic reticulum, in C2C12 myotubes, it was additionally found in cytoplasm. Using trypan blue uptake assay to determine cellular death and fluorescent microscopy to evaluate picnotic nuclei and mitochondrial distribution, we demonstated that treatment of C2C12 myoblasts with G1 (GPR30 agonist) did not protect the cells against apoptosis induced by H2O2 as E2. However, when G15 (GPR30 antagonist) was used, E2 could not prevent the damage caused by the oxidative stress. Further, some of the molecular mechanisms involved were investigated by wertern blot assays. Thus, E2 was able to induce AKT phosphorylation in apoptotic conditions and ERK phosphorylation in proliferating C2C12 cells but not when the cultures were incubated with G15. Additionally, using G15 antagonist we have found that GPR30 participates in the myogenin expression and creatine kinase activity stimulated by E2 in the first steps of C2C12 differentiation. Althogether these findings provide evidences showing that GPR30 is expressed in diverse intracellular compartments in undifferentiated and differentiated C2C12 cells and mediates E2 actions. © 2015 Wiley Periodicals, Inc.

  13. Induction of immune responses in mice and pigs by oral administration of classical swine fever virus E2 protein expressed in rice calli.

    Science.gov (United States)

    Jung, Myunghwan; Shin, Yun Ji; Kim, Ju; Cha, Seung-Bin; Lee, Won-Jung; Shin, Min-Kyoung; Shin, Seung Won; Yang, Moon-Sik; Jang, Yong-Suk; Kwon, Tae-Ho; Yoo, Han Sang

    2014-12-01

    Classical swine fever (CSF), caused by the CSF virus (CSFV), is a highly contagious disease in pigs. In Korea, vaccination using a live-attenuated strain (LOM strain) has been used to control the disease. However, parenteral vaccination using a live-attenuated strain still faces a number of problems related to storage, cost, injection stress, and differentiation of CSFV infected and vaccinated pigs. Therefore, two kinds of new candidates for oral vaccination have been developed based on the translation of the E2 gene of the SW03 strain, which was isolated from an outbreak of CSF in 2002 in Korea, in transgenic rice calli (TRCs) from Oriza sativa L. cv. Dongjin to express a recombinant E2 protein (rE2-TRCs). The expression of the recombinant E2 protein (rE2) in rE2-TRCs was confirmed using Northern blot, SDS-PAGE, and Western blot analysis. Immune responses to the rE2-TRC in mice and pigs were investigated after oral administration. The administration of rE2-TRCs increased E2-specific antibodies titers and antibody-secreting cells when compared to animals receiving the vector alone (p Pigs receiving rE2-TRCs also showed an increase in IL-8, CCL2, and the CD8+ subpopulation in response to stimulation with prE2. These results suggest that oral administration of rE2-TRCs can induce E2-specific immune responses.

  14. HCV-E2 inhibits hepatocellular carcinoma metastasis by stimulating mast cells to secrete exosomal shuttle microRNAs

    OpenAIRE

    Xiong, Li; Zhen, Shuqing; Yu, Qionghua; Gong, Zuojiong

    2017-01-01

    Exosomal miRNAs are emerging as mediators of the interaction between mast cells (MCs) and tumor cells. The exosomal miRNAs can be internalized by liver cancer cells to inhibit cell metastasis. We explored the interaction between MCs and hepatocellular carcinoma (HCC) cells. We used hepatitis C virus E2 envelope glycoprotein (HCV-E2) to stimulate MCs and harvest MCs-derived exosomes to detect the miRNAs and changes of exosomal miRNAs before and after stimulation. Through miRNA microarray analy...

  15. Cosmological phase transitions

    International Nuclear Information System (INIS)

    Kolb, E.W.

    1987-01-01

    If the universe stated from conditions of high temperature and density, there should have been a series of phase transitions associated with spontaneous symmetry breaking. The cosmological phase transitions could have observable consequences in the present Universe. Some of the consequences including the formation of topological defects and cosmological inflation are reviewed here. One of the most important tools in building particle physics models is the use of spontaneous symmetry breaking (SSB). The proposal that there are underlying symmetries of nature that are not manifest in the vacuum is a crucial link in the unification of forces. Of particular interest for cosmology is the expectation that are the high temperatures of the big bang symmetries broken today will be restored, and that there are phase transitions to the broken state. The possibility that topological defects will be produced in the transition is the subject of this section. The possibility that the Universe will undergo inflation in a phase transition will be the subject of the next section. Before discussing the creation of topological defects in the phase transition, some general aspects of high-temperature restoration of symmetry and the development of the phase transition will be reviewed. 29 references, 1 figure, 1 table

  16. Milestoning with transition memory

    Science.gov (United States)

    Hawk, Alexander T.; Makarov, Dmitrii E.

    2011-12-01

    Milestoning is a method used to calculate the kinetics and thermodynamics of molecular processes occurring on time scales that are not accessible to brute force molecular dynamics (MD). In milestoning, the conformation space of the system is sectioned by hypersurfaces (milestones), an ensemble of trajectories is initialized on each milestone, and MD simulations are performed to calculate transitions between milestones. The transition probabilities and transition time distributions are then used to model the dynamics of the system with a Markov renewal process, wherein a long trajectory of the system is approximated as a succession of independent transitions between milestones. This approximation is justified if the transition probabilities and transition times are statistically independent. In practice, this amounts to a requirement that milestones are spaced such that trajectories lose position and velocity memory between subsequent transitions. Unfortunately, limiting the number of milestones limits both the resolution at which a system's properties can be analyzed, and the computational speedup achieved by the method. We propose a generalized milestoning procedure, milestoning with transition memory (MTM), which accounts for memory of previous transitions made by the system. When a reaction coordinate is used to define the milestones, the MTM procedure can be carried out at no significant additional expense as compared to conventional milestoning. To test MTM, we have applied its version that allows for the memory of the previous step to the toy model of a polymer chain undergoing Langevin dynamics in solution. We have computed the mean first passage time for the chain to attain a cyclic conformation and found that the number of milestones that can be used, without incurring significant errors in the first passage time is at least 8 times that permitted by conventional milestoning. We further demonstrate that, unlike conventional milestoning, MTM permits

  17. 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

    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......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...... during virus growth. E4-ORF4 has previously been shown to bind to and activate the cellular protein phosphatase 2A. The inhibitory effect of E4-ORF4 was relieved by okadaic acid, which inhibits protein phosphatase 2A activity, suggesting that E4-ORF4 represses E2 transcription by inducing transcription...

  18. A prostaglandin E2 receptor antagonist prevents pregnancies during a preclinical contraceptive trial with female macaques.

    Science.gov (United States)

    Peluffo, M C; Stanley, J; Braeuer, N; Rotgeri, A; Fritzemeier, K-H; Fuhrmann, U; Buchmann, B; Adevai, T; Murphy, M J; Zelinski, M B; Lindenthal, B; Hennebold, J D; Stouffer, R L

    2014-07-01

    Can administration of a prostaglandin (PG) E2 receptor 2 (PTGER2) antagonist prevent pregnancy in adult female monkeys by blocking periovulatory events in the follicle without altering menstrual cyclicity or general health? This is the first study to demonstrate that a PTGER2 antagonist can serve as an effective non-hormonal contraceptive in primates. The requirement for PGE2 in ovulation and the release of an oocyte surrounded by expanded cumulus cells (cumulus-oocyte expansion; C-OE) was established through the generation of PTGS2 and PTGER2 null-mutant mice. A critical role for PGE2 in primate ovulation is supported by evidence that intrafollicular injection of indomethacin in rhesus monkeys suppressed follicle rupture, whereas co-injection of PGE2 with indomethacin resulted in ovulation. First, controlled ovulation protocols were performed in adult, female rhesus monkeys to analyze the mRNA levels for genes encoding PGE2 synthesis and signaling components in the naturally selected pre-ovulatory follicle at different times after the ovulatory hCG stimulus (0, 12, 24, 36 h pre-ovulation; 36 h post-ovulation, n = 3-4/time point). Second, controlled ovarian stimulation cycles were utilized to obtain multiple cumulus-oocyte complexes (COCs) from rhesus monkeys to evaluate the role of PGE2 in C-OE in vitro (n = 3-4 animals/treatment; ≥3 COCs/animal/treatment). Third, adult cycling female cynomolgus macaques were randomly assigned (n = 10/group) to vehicle (control) or PTGER2 antagonist (BAY06) groups to perform a contraceptive trial. After the first treatment cycle, a male of proven fertility was introduced into each group and they remained housed together for the duration of the 5-month contraceptive trial that was followed by a post-treatment reversibility trial. Quantitative real-time PCR, COC culture and expansion, immunofluorescence/confocal microscopy, enzyme immunoassay, contraceptive trial, ultrasonography, complete blood counts, serum biochemistry tests

  19. Transition nozzle combustion system

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Won-Wook; McMahan, Kevin Weston; Maldonado, Jaime Javier

    2016-11-29

    The present application provides a combustion system for use with a cooling flow. The combustion system may include a head end, an aft end, a transition nozzle extending from the head end to the aft end, and an impingement sleeve surrounding the transition nozzle. The impingement sleeve may define a first cavity in communication with the head end for a first portion of the cooling flow and a second cavity in communication with the aft end for a second portion of the cooling flow. The transition nozzle may include a number of cooling holes thereon in communication with the second portion of the cooling flow.

  20. Variational Transition State Theory

    Energy Technology Data Exchange (ETDEWEB)

    Truhlar, Donald G. [Univ. of Minnesota, Minneapolis, MN (United States)

    2016-09-29

    This is the final report on a project involving the development and applications of variational transition state theory. This project involved the development of variational transition state theory for gas-phase reactions, including optimized multidimensional tunneling contributions and the application of this theory to gas-phase reactions with a special emphasis on developing reaction rate theory in directions that are important for applications to combustion. The development of variational transition state theory with optimized multidimensional tunneling as a useful computational tool for combustion kinetics involved eight objectives.