Size Effects on Deformation and Fracture of Scandium Deuteride Films.

Energy Technology Data Exchange (ETDEWEB)

Teresi, C. S. [Univ. of Minnesota, Minneapolis, MN (United States); Hintsala, E. [Univ. of Minnesota, Minneapolis, MN (United States); Hysitron, Inc., Eden Prairie, MN (United States); Adams, David P. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Yang, Nancy Y. C. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Kammler, Daniel [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Moody, N. R. [Univ. of Minnesota, Minneapolis, MN (United States); Gerberich, W. W. [Univ. of Minnesota, Minneapolis, MN (United States)

2017-07-01

Metal hydride films have been observed to crack during production and use, prompting mechanical property studies of scandium deuteride films. The following focuses on elastic modulus, fracture, and size effects observed in the system for future film mechanical behavior modeling efforts. Scandium deuteride films were produced through the deuterium charging of electron beam evaporated scandium films using X-ray diffraction, scanning Auger microscopy, and electron backscatter diffraction to monitor changes in the films before and after charging. Scanning electron microscopy, nanoindentation, and focused ion beam machined micropillar compression tests were used for mechanical characterization of the scandium deuteride films. The micropillars showed a size effect for flow stress, indicating that film thickness is a relevant tuning parameter for film performance, and that fracture was controlled by the presence of grain boundaries. Elastic modulus was determined by both micropillar compression and nanoindentation to be approximately 150 GPa, Fracture studies of bulk film channel cracking as well as compression induced cracks in some of the pillars yielded a fracture toughness around 1.0 MPa-m1/2. Preliminary Weibull distributions of fracture in the micropillars are provided. Despite this relatively low value of fracture toughness, scandium deuteride micropillars can undergo a large degree of plasticity in small volumes and can harden to some degree, demonstrating the ductile and brittle nature of this material

Complexonometric photometric titration of scandium in the presence of xylenol orange

International Nuclear Information System (INIS)

Kornev, V.I.

1977-01-01

Possibility has been studied of using xylenol orange (XO) for chelatometric determination of scandium by means of various chelates with the aid of photometric techniques. It has been established that the chelates applicable for the purpose are ethylenediamineteraacetic acid (EDTA), diethylenediaminetetraacetic acid (DEDTA), diethylenetriaminepentaacetic acid (DETPA), upon introducing of which into a solution containing a complex of scandium with XO (maximum light adsorption at 550 nm) the optical density gradually diminishes. Weakening of the light absorption is, evidently, associated with the destruction of the scandium complex with XO and formation of a colourless chelate acetate with one of the chelates. Chelatometric determination of scandium, using EDTA, DEDTA and DEPTA solutions with XO should be carried out in an acidic medium at pH=2.5-3.0. In this range of pH values interferences caused by the appearance of the Sc-XO complex in the solution are insignificant

Analysis of separation quality of scandium-46 and titanium using silica gel column

International Nuclear Information System (INIS)

Muhamad Basit Febrian; Yanuar Setiadi; Duyeh Setiawan; Titin Sri Mulyati; Nana Suherman

2015-01-01

In this study, quality test of scandium and titanium mixture separation system using a silica gel column has been conducted. This system will be used in the separation of medical radioisotopes of 47 Sc from TiO 2 enriched targets. 20 mg of TiO 2 and 5 mg of Sc 2 O 3 dissolved using 0.5 mL of 50% HF solvent with gentle heating at 60°C - 80°C for 1 hour then 4.5 mL H 2 O was added. Sc and Ti mixture is separated by passing it through a column of silica gel. In the determination of scandium released from silica gel, Sc-46 radiotracer was used. Only 51.60 ± 4.5% of 5 mg of scandium could be retained in the silica gel column. From 51.60% of absorbed scandium in the column, 98.29 ± 3.4% were eluted with 5 mL of H 2 O eluent. During elution of scandium from silica gel column, 2.81 grams of 20 mg of titanium came apart as breakthrough. In determination of recovery of titanium from silica gel, 51.76 ± 5.5% of the 20 mg Ti can be recovered from silica gel column using 5M HCl eluent, whereas remaining Ti were eluted using 40 ml of HCl 5M. Based on those result, it can be concluded that there are still titanium portion in scandium after the separation using a silica gel column. Further purification step using fresh silica gel column, can separate escaped titanium from scandium. (author)

Lifetime measurements and oscillator strengths in singly ionized scandium and the solar abundance of scandium

Science.gov (United States)

Pehlivan Rhodin, A.; Belmonte, M. T.; Engström, L.; Lundberg, H.; Nilsson, H.; Hartman, H.; Pickering, J. C.; Clear, C.; Quinet, P.; Fivet, V.; Palmeri, P.

2017-12-01

The lifetimes of 17 even-parity levels (3d5s, 3d4d, 3d6s and 4p2) in the region 57 743-77 837 cm-1 of singly ionized scandium (Sc II) were measured by two-step time-resolved laser induced fluorescence spectroscopy. Oscillator strengths of 57 lines from these highly excited upper levels were derived using a hollow cathode discharge lamp and a Fourier transform spectrometer. In addition, Hartree-Fock calculations where both the main relativistic and core-polarization effects were taken into account were carried out for both low- and high-excitation levels. There is a good agreement for most of the lines between our calculated branching fractions and the measurements of Lawler & Dakin in the region 9000-45 000 cm-1 for low excitation levels and with our measurements for high excitation levels in the region 23 500-63 100 cm-1. This, in turn, allowed us to combine the calculated branching fractions with the available experimental lifetimes to determine semi-empirical oscillator strengths for a set of 380 E1 transitions in Sc II. These oscillator strengths include the weak lines that were used previously to derive the solar abundance of scandium. The solar abundance of scandium is now estimated to logε⊙ = 3.04 ± 0.13 using these semi-empirical oscillator strengths to shift the values determined by Scott et al. The new estimated abundance value is in agreement with the meteoritic value (logεmet = 3.05 ± 0.02) of Lodders, Palme & Gail.

Scandium effect on mechanical properties of Al-6.5 % Mg alloy

International Nuclear Information System (INIS)

Drits, M.E.; Toropova, L.S.; Bykov, Yu.G.

1982-01-01

Quantitative evaluation of influence of small scandium additions (up to 0.5 wt%) on properties of Al-6.5% Mg binary alloy are carried out depending on test temperature in the range of -196 to 310 deg C. Alloys were tested on ''Instron'' machine at 1.3x10 - 3 s - 1 strain rate. Scandium additions are shown to increase plasticity at -196 deg C. Yield strength also increases with introduction of 0.2% Sc if deformation temperature does not exceed 250 deg C. The growth of ultimate strength is less significant. Elevated strength properties of alloys with scandium additions can be explained by a fine-grained structure

Scandium fluorides

International Nuclear Information System (INIS)

Melnikov, P.; Nalin, M.; Messaddeq, Y.

1997-01-01

A new modification of scandium fluoride has been synthesised. The compound is deficient in fluorine, with the composition ScF 2.76 . It belongs to the tetragonal system, lattice parameters being a=3.792 and c=6.740 A and may be obtained at low temperatures by the decomposition of the precursor NH 4 ScF 4 . The reaction is topotactic, tetragonal parameters of the precursor are a=4.021 and c=6.744 A. Structural relationships with various fluorides and ammonium aminofluorides are discussed. This synthesis route with IR-assisted decomposition should be considered as a soft-chemistry approach. (orig.)

The characteristics of aluminum-scandium alloys processed by ECAP

International Nuclear Information System (INIS)

Venkateswarlu, K.; Rajinikanth, V.; Ray, Ajoy Kumar; Xu Cheng; Langdon, Terence G.

2010-01-01

Aluminum-scandium alloys were prepared having different scandium additions of 0.2, 1.0 and 2.0 wt.% and these alloys were processed by equal-channel angular pressing (ECAP) at 473 K. The results show the grain refinement of the aluminum matrix and the morphology of the Al 3 Sc precipitates depends strongly on the scandium concentration. The tensile properties were evaluated after ECAP by pulling to failure at initial strain rates from 1.0 x 10 -3 to 1.0 x 10 -1 s -1 . The Al-1% Sc alloy exhibited the highest tensile strength of ∼250 MPa at a strain rate of 1.0 x 10 -1 s -1 . This alloy also exhibited a superior grain refinement of ∼0.4 μm after ECAP where this is attributed to a smaller initial grain size and an optimum volume fraction of dispersed Al 3 Sc precipitates having both micrometer and nanometer sizes.

A new model for prediction of dispersoid precipitation in aluminium alloys containing zirconium and scandium

International Nuclear Information System (INIS)

Robson, J.D.

2004-01-01

A model has been developed to predict precipitation of ternary Al 3 (Sc, Zr) dispersoids in aluminium alloys containing zirconium and scandium. The model is based on the classical numerical method of Kampmann and Wagner, extended to predict precipitation of a ternary phase. The model has been applied to the precipitation of dispersoids in scandium containing AA7050. The dispersoid precipitation kinetics and number density are predicted to be sensitive to the scandium concentration, whilst the dispersoid radius is not. The dispersoids are predicted to enrich in zirconium during precipitation. Coarsening has been investigated in detail and it has been predicted that a steady-state size distribution is only reached once coarsening is well advanced. The addition of scandium is predicted to eliminate the dispersoid free zones observed in scandium free 7050, greatly increasing recrystallization resistance

Scandium Terminal Imido Chemistry.

Science.gov (United States)

Lu, Erli; Chu, Jiaxiang; Chen, Yaofeng

2018-02-20

Research into transition metal complexes bearing multiply bonded main-group ligands has developed into a thriving and fruitful field over the past half century. These complexes, featuring terminal M═E/M≡E (M = transition metal; E = main-group element) multiple bonds, exhibit unique structural properties as well as rich reactivity, which render them attractive targets for inorganic/organometallic chemists as well as indispensable tools for organic/catalytic chemists. This fact has been highlighted by their widespread applications in organic synthesis, for example, as olefin metathesis catalysts. In the ongoing renaissance of transition metal-ligand multiple-bonding chemistry, there have been reports of M═E/M≡E interactions for the majority of the metallic elements of the periodic table, even some actinide metals. In stark contrast, the largest subgroup of the periodic table, rare-earth metals (Ln = Sc, Y, and lanthanides), have been excluded from this upsurge. Indeed, the synthesis of terminal Ln═E/Ln≡E multiple-bonding species lagged behind that of the transition metal and actinide congeners for decades. Although these species had been pursued since the discovery of a rare-earth metal bridging imide in 1991, such a terminal (nonpincer/bridging hapticities) Ln═E/Ln≡E bond species was not obtained until 2010. The scarcity is mainly attributed to the energy mismatch between the frontier orbitals of the metal and the ligand atoms. This renders the putative terminal Ln═E/Ln≡E bonds extremely reactive, thus resulting in the formation of aggregates and/or reaction with the ligand/environment, quenching the multiple-bond character. In 2010, the stalemate was broken by the isolation and structural characterization of the first rare-earth metal terminal imide-a scandium terminal imide-by our group. The double-bond character of the Sc═N bond was unequivocally confirmed by single-crystal X-ray diffraction. Theoretical investigations revealed the presence

Effects of iron on intermetallic compound formation in scandium modified Al–Si–Mg Alloys

Energy Technology Data Exchange (ETDEWEB)

Patakham, Ussadawut [National Metal and Materials Technology Center, National Science and Technology Development Agency, 114 Thailand Science Park, Klong Nueng, Klong Luang, Pathumthani 12120 (Thailand); Limmaneevichitr, Chaowalit, E-mail: chaowalit.lim@mail.kmutt.ac.th [Production Engineering Department, Faculty of Engineering, King Mongkut’s University of Technology Thonburi, 126 Pracha-Utid Rd., Bangmod, Tungkhru, Bangkok 10140 (Thailand)

2014-12-15

Highlights: • Iron reduces the modification effects of scandium in Al–Si–Mg alloys. • Morphologies of Sc-rich intermetallic phases vary with Fe and Sc contents and the cooling rates. • Sc neutralizes effects of Fe by changing Fe-rich intermetallic phases from platelets to more cubic. - Abstract: In general, iron has a strong tendency to dissolve in molten aluminum. Iron has very low solid solubility in aluminum–silicon casting alloys, so it will form intermetallic compounds that cause detrimental effects on mechanical properties. In this work, the effects of iron on intermetallic compound formations in scandium modified Al–Si–Mg alloys were studied. There were two levels of iron addition (0.2 and 0.4 wt.%) and two levels of scandium addition (0.2 and 0.4 wt.%). We found that the effects of scandium modification decreased with increasing iron addition. The morphologies of the complex intermetallic compounds were characterized by scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS) and electron backscatter diffraction (EBSD) techniques. It was found that scandium changes the morphology of Fe-rich intermetallic compounds from β-phase (plate-like) to α-phase, which reduces the harmful effects of β-phase.

Thermomechanical treatment of welded joints of aluminum-lithium alloys modified by scandium

Science.gov (United States)

Malikov, A. G.

2017-12-01

At present, the aeronautical equipment manufacture involves up-to-date high-strength aluminum alloys of decreased density resulting from the lithium admixture. Various technologies of fusible welding of these alloys are being developed. The paper presents experimental investigations of the optimization of the laser welding of aluminum alloys with the scandium-modified welded joint after thermomechanical treatment. The effect of scandium on the micro- and macrostructure is studied along with strength characteristics of the welded joint. It is found that thermomechanical treatment allows us to obtain the strength of the welded joint 0.89 for the Al-Mg-Li system and 0.99 for the Al-Cu-Li system with the welded joint modified by scandium in comparison with the base alloy after treatment.

Study of competitive complexing in scandium(3)-xylenol-orange-hydroxyethyliminodiacetic acid system

International Nuclear Information System (INIS)

Kornev, V.I.; Mukanov, I.P.; Artem'eva, O.A.

1976-01-01

The competitive complexing in the system scandium(3)-xylene orange (XO)-hydroxyethyliminodiacetic acid (H 3 L) has been studied. Ligands act as competitive particles. It has been established preliminarily that introduction of H 3 L into the solution containing a mixture of Sc and Xo changes considerably the absorption spectra of the coloured complex. Weakening of light absorption indicates that the coloured complex with XO is destructed and colourless hydroxyethyliminodiacetate of scandium is formed. The formation of scandium hydroxyethyliminoacetate has been studied spectrophotometrically by equilibrium between the complexes. The dependence of optical density on pH, when the concentrations of reagents are constant, as well as on concetration of H 3 L has been studied. The composition of the complex (1:1) formed at pH 3.2 has been established graphically and the constant of the complex ScHL + instability has been calculated (PKsub(H)=10.69+-0.45). It has been shown that H 3 L, when interacting with scandium, behaves as dibasic ligand. It is most probable that during complex formation the hydrogen ion of the hydroxygroup is not replaced, although the participation of hydroxygroup in coordination is possible due to a donor-acceptor bond

Formation of scandium carbides and scandium oxycarbide from the elements at high-(P, T) conditions

International Nuclear Information System (INIS)

Juarez-Arellano, Erick A.; Winkler, Bjoern; Bayarjargal, Lkhamsuren; Friedrich, Alexandra; Milman, Victor; Kammler, Daniel R.; Clark, Simon M.; Yan Jinyuan; Koch-Mueller, Monika; Schroeder, Florian; Avalos-Borja, Miguel

2010-01-01

Synchrotron diffraction experiments with in situ laser heated diamond anvil cells and multi-anvil press synthesis experiments have been performed in order to investigate the reaction of scandium and carbon from the elements at high-(P,T) conditions. It is shown that the reaction is very sensitive to the presence of oxygen. In an oxygen-rich environment the most stable phase is ScO x C y , where for these experiments x=0.39 and y=0.50-0.56. If only a small oxygen contamination is present, we have observed the formation of Sc 3 C 4 , Sc 4 C 3 and a new orthorhombic ScC x phase. All the phases formed at high pressures and temperatures are quenchable. Experimentally determined elastic properties of the scandium carbides are compared to values obtained by density functional theory based calculations. - Graphical Abstract Legend (TOC Figure): Table of Contents Figure Selected images recorded with a MAR345 image plate detector show the reaction of α-Sc and graphite at high-(P,T) conditions. Left: mixture of α-Sc and graphite. Right: recovered sample after laser heated the diamond anvil cell.

Knight shift in scandium and its alloys with hafnium and titanium

International Nuclear Information System (INIS)

Chachkhiani, Z.B.; Chechernikov, V.I.; Martynova, L.F.; Nidel'ko, V.I.; Chachkhiani, L.G.; Georgadze, G.S.

1981-01-01

Results of the investigation of NMR on 45 Sc nuclei and magnetic susceptibility of scandium and its solid solutions with titanium and hafnium are presented. It is shown that the existing hybridization of S and d zones in pure scandium and its alloys with titanium and hafnium affects the Knight shift reducing the value of the contact contribution. The temperature behaviour of the Knight shift from the temperature dependence and spin susceptibility of collectivized d electrons [ru

Biamperometric analysis of nonaqueous scandium solutions containing lanthanides, lead and thorium

International Nuclear Information System (INIS)

Gevorgyan, A.M.; Talipov, Sh.T.; Kostylev, V.S.; Khadeev, V.A.; Nadol'skij, M.Ya.

1978-01-01

Investigated was a possibility of direct scandium titration in the presence of large rare earth quantities, and also a possibility of complexonometric scandium and rare earth sum determination at their joint presence in non-aqueous acetic acid solution. The titration was carried out at electrode voltage of 0.95V, background electrolyte concentration of lithium perchlorate being 0.2M. Non-aqueous magnesium complexonate was used as titrating reagent. Th and Pb complexonates are shown to be less stable as compared to Sc complexonate, and consequently, Th and Pb ions must not interfere with biamperometric titration of Sc ion. A method applied to analysis of binary mixture, containing scandium, and a method for model alloy and thortveitite mineral was developed. Well reproducible and precise enough results are obtained in all the cases. Ions of Bi, Cu, Cd, Zn, In, Ga and Ti interfere with determination

In situ observation of the reaction of scandium and carbon by neutron diffraction

Energy Technology Data Exchange (ETDEWEB)

Juarez-Arellano, Erick A., E-mail: eajuarez@unpa.edu.m [Institut fuer Geowissenschaften, Universitaet Frankfurt, Altenhoeferallee 1, 60438 Frankfurt a.M. (Germany); Universidad del Papaloapan, Circuito Central 200, Parque Industrial, Tuxtepec 68301 (Mexico); Winkler, Bjorn [Institut fuer Geowissenschaften, Universitaet Frankfurt, Altenhoeferallee 1, 60438 Frankfurt a.M. (Germany); Vogel, Sven C. [Los Alamos National Laboratory, Lujan Center. Mail Stop H805, Los Alamos, NM 87545 (United States); Senyshyn, Anatoliy [Forschungsneutronenquelle Heinz Maier-Leibnitz (FRM II), Technische Universitaet Muenchen, Lichtenbergstr. 1, D-85747 Garching (Germany); Materialwissenschaft, TU Darmstadt, Petersensstr. 23, D-64287 Darmstadt (Germany); Kammler, Daniel R. [Sandia National Laboratories, Albuquerque, NM 87185 (United States); Avalos-Borja, Miguel [CNyN, UNAM, A. Postal 2681, Ensenada, B.C. (Mexico)

2011-01-05

Research highlights: {yields} Exist two ScC cubic phases with B1-structure type differing in site occupancy of C. {yields} A new orthorhombic scandium carbide phase is formed at 1473(50) K. {yields} The recrystallization of alpha-Sc occurs between 1000 and 1223 K. - Abstract: The formation of scandium carbides by reaction of the elements has been investigated by in situ neutron diffraction up to 1823 K. On heating, the recrystallization of {alpha}-Sc occurs between 1000 and 1223 K. The formation of Sc{sub 2}C and ScC (NaCl-B1 type structure) phases has been detected at 1323 and 1373 K, respectively. The formation of a new orthorhombic scandium carbide phase was observed at 1473(50) K. Once the scandium carbides are formed they are stable upon heating or cooling. No other phases were detected in the present study, in which the system was always carbon saturated. The thermal expansion coefficients of all phases have been determined, they are constant throughout the temperature interval studied.

The enthalpy of solid scandium in the temperature range 406 - 1812 K

International Nuclear Information System (INIS)

Lyapunov, K.M.; Baginskij, A.V.; Stankus, S.V.

2001-01-01

Enthalpy of pure scandium was measured on massive calorimeter in the range from 406 to 1812 K by mixing method. The enthalpy of face centered close cubic lattice - body centered cubic lattice transformation is equal to ΔH t 4068 J/mol. Obtained value within the limits of error is compatible with the results given earlier (4009 J/mol). The dependence of the middle specific heat of scandium C p (T) on the temperature was shown in correlation with the results of other works. The results of the conducted experiments reinforce the conclusion made earlier about an absence (or a little) in the decomposition of an anharmonic component of the oscillation specific heat of scandium C p a (T) members proportional to the first or the second degrees of temperature [ru

Effect of scandium additions on microstructure and mechanical properties of Al-Zn-Mg alloy welds

International Nuclear Information System (INIS)

Dev, Selvi; Stuart, A. Archibald; Kumaar, R.C. Ravi Dev; Murty, B.S.; Rao, K. Prasad

2007-01-01

The microstructure and mechanical properties of fusion zones of medium strength Al-Zn-Mg alloy (RDE-40) welds obtained by using different fillers containing various amount of scandium was investigated. It was observed that addition of scandium led to very significant grain refinement in the fusion zone especially for scandium levels greater than the eutectic composition (0.55 wt%). The grain refinement led to the reduction in solidification cracking and improved the tensile properties of fusion zone compared to the ones obtained by the commercial AA5556 filler

Scandium/carbon filters for soft x rays

NARCIS (Netherlands)

Artioukov, IA; Kasyanov, YS; Kopylets, IA; Pershin, YP; Romanova, SA

2003-01-01

This Note deals with thin-film soft x-ray filters for operation at the wavelengths near carbon K edge (similar to4.5 nm). The filters were fabricated by magnetron sputtering deposition of thin layers of scandium (total thickness 0.1-0.2 mum) onto films of polypropylene (thickness 1.5 mum) and

Complexing of scandium with eriochromecyanine R and cetyltrimethylammonium

International Nuclear Information System (INIS)

Tikhonov, V.N.; Samarkina, T.V.

1978-01-01

Complexing of scandium with eriochromecyanine R (ECC) in the presence of cetyltrimethylammonium (CTA) is studied. At optimum value of pH 6.2 a three-component complex of blue colour is forming with the Sc:ECC:CTA = 1:3:5 relation of compounds. Lambdasub(max) for the complex varies from 585 to 615 nm, molarabsorption coefficient is equal to (1.48+-0.02)x10 5 . A method of photometric determination of Sc with ECC and CTA is suggested. Even considerable quantities of Mg, Ca, Sr, Zn, Cd, La, Mn, Ni do not affect the Sc determination, whereas Cu, Be, Al, Ga, Fe(3) and Pd(2) affect it to a great degree even in relation of 1:1. Camouflaging substances such as fluorides, citrates, tartrates and EDTA prevent from scandium complexing, that is why they should not be used to increase the determination selectivity

Pressure-induced structural change from hexagonal to fcc metal lattice in scandium trihydride

International Nuclear Information System (INIS)

Ohmura, A.; Machida, A.; Watanuki, T.; Aoki, K.; Nakano, S.; Takemura, K.

2007-01-01

We synthesized scandium hydrides by hydrogenation of a scandium foil with hydrogen fluid under high pressure at ambient temperature. Scandium dihydride (ScH 2 ) and trihydride (ScH 3 ) were prepared near 4 and 5 GPa, respectively. The hydrogenation process and pressure-induced structural changes in ScH 3 were investigated by synchrotron radiation X-ray diffraction measurements up to 54.7 GPa. A structural transition from hexagonal to the fcc lattice began at 30 GPa and was completed at 46 GPa via an intermediate state similar to those reported for other hexagonal trihydrides. The intermediate state was not interpreted in terms of a coexisting state for the low-pressure hexagonal and the high-pressure fcc structures. The onset transition pressure of ScH 3 supported the previously proposed relation that the hexagonal-fcc transition pressure is inversely proportional to the ionic radius of the trihydride

Scandium: its occurrence, chemistry, physics, metallurgy, biology, and technology

International Nuclear Information System (INIS)

Horovitz, C.T.

1975-01-01

This book describes the following aspects of scandium: discovery and history, occurrence in nature, geochemistry and mineralogy, chemical, physical and technological properties, fabrication and metallurgy, its biological significance and toxicology, and its uses. (Extensive references for each chapter)

Thermoelectric material comprising scandium doped zinc cadmium oxide

DEFF Research Database (Denmark)

2016-01-01

There is presented a composition of scandium doped Zinc Cadmium Oxide with the general formula ZnzCdxScyO which the inventors have prepared, and for which material the inventors have made the insight that it is particularly advantageous as an n-type oxide material, such as particularly advantageous...

Effect of scandium on the phase composition and mechanical properties of ABM alloys

Science.gov (United States)

Molchanova, L. V.

2010-09-01

The effect of scandium on the composition and mechanical properties of ABM-1 alloys (Al-30% Be-5% Mg) is studied. The scandium content is varied from 0.1 to 0.5 wt %. It is established that, in the studied part of the Al-Be-Mg-Sc system, an aluminum solid solution (Al) and the ScBe13 compound are in equilibrium with a beryllium solid solution (Be). Magnesium dissolves in both the aluminum component and the ScBe13 compound. The strengthening effect related to the decomposition of the solid solution and the precipitation of Al3Sc cannot be extended to the strengthening of ABM-type alloys. Additions of 0.1-0.15 wt % Sc only weakly improve the mechanical properties of the alloys due to the refinement of beryllium-component grains. At high scandium contents, the strength increases insignificantly due to primary precipitation of ScBe13 and the plasticity decreases simultaneously.

Influence of scandium on the pitting behaviour of Al-Zn-Mg-Cu alloys

Energy Technology Data Exchange (ETDEWEB)

Wloka, J. [Department of Materials Sciences, University of Erlangen-Nuremberg, Martensstrasse 7, D-91058 Erlangen (Germany); Virtanen, S. [Department of Materials Sciences, University of Erlangen-Nuremberg, Martensstrasse 7, D-91058 Erlangen (Germany)], E-mail: virtanen@ww.uni-erlangen.de

2007-11-15

In this paper the influence of small scandium additions (<0.26 wt.%) on the corrosion properties of the high-strength Al-Zn-Mg-Cu alloy AA7010 is investigated. The addition of scandium (in combination with the grain refiner Zr) leads to the formation of Al{sub 3}Sc{sub x}Zr{sub 1-x} phases. These coarse particles disturb the grain structure near the particle/matrix interface, which facilitates the initiation of localized corrosion in potentio-dynamic scans. Microelectrochemical investigations revealed a slightly cathodic character of these particles and a passive range beyond the breakdown potential of the matrix. Mass loss measurements show that the addition of scandium increases the mass loss during the initial period. The corrosion morphology was investigated with optical and scanning electron microscopy. The composition of the phases was determined with energy-dispersive X-ray analysis. Micro-capillary measurements were performed to investigate the electrochemical properties of single phases surrounded by matrix.

Complexometric determination of scandium and aluminium

International Nuclear Information System (INIS)

Tikhonov, V.N.

1980-01-01

Described is the complexometric determination of scandium and aluminium by the method of reverse titration of EDTA excess by indium salt solution in the presence of the xylenol orange indicator. For the method selectivity increase fluorides are used as a camouflage substance at low pH values (2.5-3.0). The excess fluoride-ions preventing titration are bound by boric acid. Y, Tb, Ti, Zr, Cu, Zn, V, Mo, Co, Cr prevent the determination of Sc and Al

Use of scandium ionic associates with salicylic- or 2-phenylquinoline-4-carboxylic acid and rhodamine C

Energy Technology Data Exchange (ETDEWEB)

Kononenko, L.I.; Bel' tyukova, S V; Drobyazko, V N; Poluehktov, N S [AN Ukrainskoj SSR, Kiev. Inst. Obshchej i Neorganicheskoj Khimii; AN Ukrainskoj SSR, Odessa. Inst. Obshchej i Neorganicheskoj Khimii)

1975-09-01

With salicylic or 2-phenylquinoline-4-carboxylic acid and rhodamine C scandium forms ion associations whose benzene solutions are capable of luminescence. Optimum conditions for the formation of complexes and the composition of the complex with the ratio of Sc:acid:rhodamine C = 1:2:1 are established. A possibility of luminescence determination of scandium in the presence of rare earths is shown.

Hardening mechanisms of spray formed Al-Zn-Mg-Cu alloys with scandium and other elemental additions

International Nuclear Information System (INIS)

Sharma, M.M.; Amateau, M.F.; Eden, T.J.

2006-01-01

The hardening mechanisms in spray formed Al-Zn-Mg-Cu alloys with additions of chromium, zinc and scandium were studied. The microstructure of the spray formed alloys was analyzed by transmission electron microscopy. A range of tensile strengths were achieved, and varied based on elemental additions, and second phase particle strengthening. To explain the significantly higher strength in one alloy with scandium, theoretical results due to the yield stress of Al-Zn-Mg-Cu alloys as a function of volume fraction and precipitate particle size, were compared to experimental data. Both the possibilities of coherency and order strengthening are examined. The significant additional hardening achieved in the alloy with scandium is attributed to small ordered particles of Al 3 Sc, which precipitated during aging

Incommensurate composite crystal structure of scandium-II

International Nuclear Information System (INIS)

Fujihisa, Hiroshi; Gotoh, Yoshito; Yamawaki, Hiroshi; Sakashita, Mami; Takeya, Satoshi; Honda, Kazumasa; Akahama, Yuichi; Kawamura, Haruki

2005-01-01

The long-unknown crystal structure of the high pressure phase scandium-II was solved by powder x-ray diffraction and was found to have tetragonal host channels along the c axis and guest chains that are incommensurate with the host, as well as the high pressure phases of Ba, Sr, Bi, and Sb. The pressure dependences of the lattice constants, the incommensurability, the atomic distances, and the atomic volume were investigated

Solvent extraction of tricomponent complexes of zirconium and scandium with salicylic acid and collidine

International Nuclear Information System (INIS)

Kochetkova, S.K.; Fadeeva, V.I.; Kalistratova, V.P.

1976-01-01

Extraction of tricomponent compounds of zirconium and scandium with salicylic acid (Sal) and collidine (Col) has been studied. Addition of Col widens considerably the pH range of maximum extraction of zirconium salicylate and makes it possible to extract quantitatively both zirconium and scandium in the following pH range: scandium at pH 3.8-5.2; zirconium at pH 2-4. Optimum concentrations of salicylic acid and collidine are 0.05 mol/l and 0.375 mol/l, respectively. The composition of the complexes being extracted has been studied by the shift equilibrium method. Chloroform extracts complexes having the ratio Zr:Sal:Col=1:2:1(pH=3); Sc:Sal:Col=1:3:1(pH=4), and 1:2:1(pH=5). The composition of the complexes being formed is assumed to be [Zr(OH) 3 (HSal) 2 ] - [ColH + ] (pH=3); Sc(HSal) 3 xCol (pH=4.0); Sc(OH)(HSal) 2 xCol (pH=5.0). Extraction of collidine-salicylate complexes of Hf, Th, La, and Y under the conditions of optimum extraction of zirconium and scandium has been investigated when concentration of Zr and Sc in the solution is 3.0.10μ- 5 -1.37.10 -4 mol/l, respectively. It has been shown that hafnium is extracted quantitatively (95-100%) at pH 2.3-4.6; thorium at pH 3.0-6.4; 60% of yttrium is extracted at pH 4.0-4.8; 25% of lanthanum is extracted at pH 3.3-4.9. At pH 2.0 it is possible to separate Zr from Sc,Y, and La; at pH 1.4-1.5 from small amounts of Hf and Tn. Separation of zirconium, from small amounts of hafnium, 10-fold amounts of thorium, 100-fold amounts of scandium and lanthanum is also possible

Solvent extraction of tricomponent complexes of zirconium and scandium with salicylic acid and collidine

Energy Technology Data Exchange (ETDEWEB)

Kochetkova, S K; Fadeeva, V I; Kalistratova, V P [Moskovskij Gosudarstvennyj Univ. (USSR)

1976-01-01

Extraction of tricomponent compounds of zirconium and scandium with salicylic acid (Sal) and collidine (Col) has been studied. Addition of Col widens considerably the pH range of maximum extraction of zirconium salicylate and makes it possible to extract quantitatively both zirconium and scandium in the following pH range: scandium at pH 3.8-5.2; zirconium at pH 2-4. Optimum concentrations of salicylic acid and collidine are 0.05 mol/l and 0.375 mol/l, respectively. The composition of the complexes being extracted has been studied by the shift equilibrium method. Chloroform extracts complexes having the ratio Zr:Sal:Col=1:2:1(pH=3); Sc:Sal:Col=1:3:1(pH=4), and 1:2:1(pH=5). The composition of the complexes being formed is assumed to be (Zr(OH)/sub 3/(HSal)/sub 2/)/sup -/(ColH/sup +/) (pH=3); Sc(HSal)/sub 3/xCol (pH=4.0); Sc(OH)(HSal)/sub 2/xCol (pH=5.0). Extraction of collidine-salicylate complexes of Hf, Th, La, and Y under the conditions of optimum extraction of zirconium and scandium has been investigated when concentration of Zr and Sc in the solution is 3.0.10..mu..-/sup 5/-1.37.10/sup -4/ mol/l, respectively. It has been shown that hafnium is extracted quantitatively (95-100%) at pH 2.3-4.6; thorium at pH 3.0-6.4; 60% of yttrium is extracted at pH 4.0-4.8; 25% of lanthanum is extracted at pH 3.3-4.9. At pH 2.0 it is possible to separate Zr from Sc,Y, and La; at pH 1.4-1.5 from small amounts of Hf and Tn. Separation of zirconium, from small amounts of hafnium, 10-fold amounts of thorium, 100-fold amounts of scandium and lanthanum is also possible.

Pilot-scale recovery of rare earths and scandium from phosphogypsum and uranium leachates

Directory of Open Access Journals (Sweden)

Mashkovtsev Maxim

2016-01-01

Full Text Available Ural Federal University (UrFU and VTT have performed joint research on development of industrial technologies for the extraction of REM and Scandium compounds from phosphogypsum and Uranium ISL leachate solutions. Leaching-absorption experiments at UrFU have been supported with multicomponent solution modelling by VTT. The simulations have been performed with VTT’s ChemSheet/Balas program and can be used for speciation calculations in the lixiviant solution. The experimental work combines solvent extraction with advanced ion exchange methodology in a pilot facility capable of treating 5 m3 solution per hour. Currently, the plant produces cerium carbonate, lanthanum oxide, neodymium oxide and concentrate of heavy rare earth metals. A batch of 45 t solids has been processed with the gain of 100 kg’s of REM concentrate. A mini-pilot plant with productivity above 50 liters per hour has been applied to recover scandium oxide and REE concentrates from the uranium ISL solution. As the preliminary product contains radioactivity (mainly strontium, an additional decontamination and cleaning of both concentrates by extraction has rendered a necessity. Finally a purified 99% concentrate of scandium oxide as well as 99% rare earth concentrate are received.

Extraction of scandium salicylate by tetraethyldiamidoheptyl phosphate

Energy Technology Data Exchange (ETDEWEB)

Kamenev, V F; Fadeeva, V I; Zyk, N V [Moskovskij Gosudarstvennyj Univ. (USSR). Kafedra Analiticheskoj Khimii

1976-11-01

Scandium salicylate is extracted with chloroform in a narrow pH range 3-4 and at the maximum concentration of salicylic acid (H/sub 2/A) in an organic phase, the distribution coefficient reaches 0.1. In the presence of tetraethyldiamideheptylphosphate (DAHP) the zone of maximum extraction grows and the distribution coefficient increases. The ratio of the components in the complex extracted is Sc:H/sub 2/A:DAHPh=1:3:2. The extraction constant is Ksub(ex)=(2.00+-0.02).

Ternary scandium and transition metals germanides

International Nuclear Information System (INIS)

Kotur, B.Ya.

1992-01-01

Brief review of data on phase diagram of ternary Sc-Me-Ge systems (Me-d - , f-transition element) is given. Isothermal sections at 870 and 1070 K of 17 ternary systems are plotted. Compositions and their structural characteristics are presented. Variability of crystal structure is typical for ternary scandium germanides: 70 compounds with the studied structure belong to 23 structural types. Ternary germanides isostructural to types of Sm 4 Ge 4 , ZrCrSi 2 , ZrNiAl, ScCeSi, TiNiSi U 4 Re 7 Si 6 145 compounds from 70 under investigation are mostly formed in studied systems

3He release characteristics of metal tritides and scandium--tritium solid solutions

International Nuclear Information System (INIS)

Perkins, W.G.; Kass, W.J.; Beavis, L.C.

1975-01-01

Tritides of such metals as scandium, titanium, and erbium are useful materials for determining the effects of helium accumulation in metallic solids, for example, CTR first wall materials. Such effects include lattice strain and gross deformation, as reported elsewhere, which are related to 3 He retention and ultimate release. Long term gas release studies have indicated that, during the early life of a metal ditritide, a large fraction of the 3 He is retained in the solid. At more advanced ages (2 to 4 years, depending on the parent metal), the 3 He release rate becomes comparable to the generation rate. Statistical analysis of the data indicates that the acceleration in 3 He release rate depends on accumulated 3 He concentration rather than strictly on age. 3 He outgassing results are presented for thin films of ScT 2 , TiT 2 , and ErT 2 , and the critical 3 He concentrations are discussed in terms of a percolation model. Phase transformations which occur on tritide formation cast some doubt on the validity of extrapolating results obtained for metal tritides to predictions regarding the accumulation of helium in metals. Scandium is unique among the early transition and rare-earth metals in that the metal exhibits a very high room temperature tritium solubility (T/Sc = 0.4) with no phase transformation. Indeed, even the lattice parameters of the hcp scandium lattice are only minimally changed by tritium solution, and we have succeeded in obtaining single crystal ScT 0 . 3 samples in two crystallographic orientations. Using a very sensitive technique, we have measured 3 He emission from both these samples, as well as from fine-grained thin film scandium-tritium solid solution samples (ScT 0 . 3 - 0 . 4 ). The fine-grained film samples release 3 He at 2 to 3 percent of the generation rate, while the emission rate from the single-crystal samples is approximately 0.05 percent of the generation rate, indicating a strong grain size effect

Scandium interaction with diantipyrylmethane homologues and 2-(n-sulphophenylazo)-1,8-dihydroxynaphthalene-3,6 sodium disulphonate

Energy Technology Data Exchange (ETDEWEB)

Ganago, L I; Alinovskaya, L A [AN Belorusskoj SSR, Minsk. Inst. Fiziki Tverdogo Tela i Poluprovodnikov

1979-01-01

The reactions of scandium with homologs of diantipyrilmethane (DAM)-propyldiantipyrilmethane (PDAM) and phenyldiantipyrilmethane (PhDAM) - are studied. The relationship of components in the complexes formed is found, and chemism of their formation is established. The complexes Sc-SPADNE (sodium salt 2-(n-sulphophenylazo)-1,8-dioxynaphthalene-3,6-disulphonic acid) are shown to form within a wide pH range. The maximum yield of complexes is observed at 6.0-7.5 pH. By the ion-exchange method the anion character of heteroligand scandium complexes is established. The complex Sc-SPADNE-PDAM is faster as compared with the complexes Sc-SPADNE-DAM and Sc-SPADNE-PhDAM. The decrease in amine excess and increase in the sensitivity of heteroligand formation of the complexes of scandium with SPADNE and PDAM make them better suited for analysis. The technique is developed for the determination of Sc/sub 2/O/sub 3/ in perovskites using the complete differential spectrophotometry method.

Determination of scandium with salicylaldehyde and 2-aminobenzenearsonic acid

International Nuclear Information System (INIS)

Farias, P.A.M.; Hainberger, L.; Andrade, H.A.S.

1984-01-01

A new method for the spectrophotometric determination of scandium by means of a coloured complex formed with salicylaldehyde and 2-aminobenzenearsonic acid is described. Lambert-Beer's law is followed in the range of 0.2 - 2.0 μg/ml of the final solution. The maximum amounts of 39 ions that may be present without interfering in the method are listed. (Author) [pt

Thermodynamic and kinetic study of scandium(III) complexes of DTPA and DOTA: a step toward scandium radiopharmaceuticals.

Science.gov (United States)

Pniok, Miroslav; Kubíček, Vojtěch; Havlíčková, Jana; Kotek, Jan; Sabatie-Gogová, Andrea; Plutnar, Jan; Huclier-Markai, Sandrine; Hermann, Petr

2014-06-23

Diethylenetriamine-N,N,N',N'',N''-pentaacetic acid (DTPA) and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) scandium(III) complexes were investigated in the solution and solid state. Three (45)Sc NMR spectroscopic references suitable for aqueous solutions were suggested: 0.1 M Sc(ClO4)3 in 1 M aq. HClO4 (δSc =0.0 ppm), 0.1 M ScCl3 in 1 M aq. HCl (δSc =1.75 ppm) and 0.01 M [Sc(ox)4](5-) (ox(2-) = oxalato) in 1 M aq. K2C2O4 (δSc =8.31 ppm). In solution, [Sc(dtpa)](2-) complex (δSc = 83 ppm, Δν = 770 Hz) has a rather symmetric ligand field unlike highly unsymmetrical donor atom arrangement in [Sc(dota)](-) anion (δSc = 100 ppm, Δν = 4300 Hz). The solid-state structure of K8[Sc2(ox)7]⋅13 H2O contains two [Sc(ox)3](3-) units bridged by twice "side-on" coordinated oxalate anion with Sc(3+) ion in a dodecahedral O8 arrangement. Structures of [Sc(dtpa)](2-) and [Sc(dota)](-) in [(Hguanidine)]2[Sc(dtpa)]⋅3 H2O and K[Sc(dota)][H6 dota]Cl2⋅4 H2O, respectively, are analogous to those of trivalent lanthanide complexes with the same ligands. The [Sc(dota)](-) unit exhibits twisted square-antiprismatic arrangement without an axial ligand (TSA' isomer) and [Sc(dota)](-) and (H6 dota)(2+) units are bridged by a K(+) cation. A surprisingly high value of the last DOTA dissociation constant (pKa =12.9) was determined by potentiometry and confirmed by using NMR spectroscopy. Stability constants of scandium(III) complexes (log KScL 27.43 and 30.79 for DTPA and DOTA, respectively) were determined from potentiometric and (45)Sc NMR spectroscopic data. Both complexes are fully formed even below pH 2. Complexation of DOTA with the Sc(3+) ion is much faster than with trivalent lanthanides. Proton-assisted decomplexation of the [Sc(dota)](-) complex (τ1/2 =45 h; 1 M aq. HCl, 25 °C) is much slower than that for [Ln(dota)](-) complexes. Therefore, DOTA and its derivatives seem to be very suitable ligands for scandium

Potential for photocatalytic degradation of the potassic diclofenac using scandium and silver modified titanium dioxide thin films

International Nuclear Information System (INIS)

Ciola, R.A.; Oliveira, C.T.; Lopes, S.A.; Cavalheiro, A.A.

2011-01-01

The potential for photocatalytic degradation of the potassic diclofenac drug was investigated using titanium dioxide thin films modified with two modifier types, scandium and silver, both prepared by Sol-Gel method. It was demonstrated by UVVis spectroscopy analysis of the solutions containing the drug, under UV-A light irradiation that the degradation efficiency of the titanium dioxide photocatalyst is dependent of the semiconductor nature and that the scandium accelerates the first step of the degradation when compared to the silver. This result seems to be related to the redox potential of the electron-hole pair, once the scandium modifying sample generates a p type semiconductor that reduces the band gap. The extra holes attract more strongly the chorine ion present in diclofenac and leading to the releasing more easily. However, after the first byproducts degradation the following steps are not facilitated, making the silver modifying more advantageous. (author)

The influence of the diluent nature on scandium extraction by the phenol-formaldehyde resol oligomer yarrezin B

International Nuclear Information System (INIS)

Semenov, S.A.; Valkina, E.M.; Reznik, A.M.

1996-01-01

The paper studies the effect of diluent nature on scandium extraction by Yarrezin B phenol-formaldehyde resol oligomer using n-octan, toluene, chloroform, n-octanol and kerosene as an example. Correlation coefficients of dependences of scandium distribution factor on some parameters of diluents are calculated. Possibility to use some parameters of diluents to predict their effect on extraction indices is determined. Hildebrandt solubility parameter of extracting agent and parameters of extracting agent-diluent interaction according to Flory-Haggins are calculated. 13 refs., 2 figs., 4 tabs

The effects of aluminum or scandium on the toughness, density and ...

African Journals Online (AJOL)

The effects of the substitution of aluminum or scandium on the density, toughness as well as the stability of the phases formed by such an addition on platinum, iridium, rhodium and palladium metals were evaluated with the density functional quantum mechanical calculation methods. All the metals had four atoms per ...

Influence of scandium on the microstructure and strength properties of the welded joint at the laser welding of aluminum-lithium alloys

Science.gov (United States)

Malikov, A. G.; Golyshev, A. A.; Ivanova, M. Yu.

2017-10-01

Today, aeronautical equipment manufacture involves up-to-date high-strength aluminum alloys of decreased density resulting from lithium admixture. Various technologies of fusible welding of these alloys are being developed. Serious demands are imposed to the welded joints of aluminum alloys in respect to their strength characteristics. The paper presents experimental investigations of the optimization of the laser welding of aluminum alloys with the scandium-modified welded joint. The effect of scandium on the micro-and macro-structure has been studied as well as the strength characteristics of the welded joint. It has been found that scandium under in the laser welding process increases the welded joint elasticity for the system Al-Mg-Li, aluminum alloy 1420 by 20 %, and almost doubles the same for the system Al-Cu-Li, aluminum alloy 1441.

Tetragonal ternary borides: superconductivity, ferromagnetism and the role of scandium

International Nuclear Information System (INIS)

Matthias, B.T.; Patel, C.K.N.; Barz, H.; Corenzwit, E.; Vandenberg, J.M.

1978-01-01

The authors report and discuss two discoveries made while studying the condensation phenomena of ternary rhodium borides, MRh 4 B 4 . M is generally a trivalent transition metal, usually a rare earth element RE. An exception is scandium which by itself does not form an isomorphous boride, but in combination with many other elements will do just that. A suprising correlation between ferromagnetic and superconducting transition temperatures has been found. (Auth.)

Kinetics and mechanism of hydrolysis of scandium sulfate

International Nuclear Information System (INIS)

Koshchej, E.V.; Stryapkov, A.V.; Podosenov, D.E.; Makarov, G.V.; Razdobreev, D.A.

1998-01-01

The Sc 2 (SO 4 ) 3 -H 2 SO 4 -H 2 O system is studied through the methods of pH-potentiometry, conductometry and turbidimetry at 298 and 318 K and ion force 0.01, 0.1 and 1.0. The hydrolysis mechanism including the processes in the system homogenous and heterogeneous constituents. The hydrolysis rates of scandium salts and their dependences on OH-ions concentration, solution ions force and temperature are found; the constants of the processes rate with participation of OH - and SO 4 2- ions and constants of the solid phase formation rate are calculated [ru

Interaction of scandium sesquioxide with carbon

International Nuclear Information System (INIS)

Vodop'yanov, A.G.; Zakharov, R.G.

1986-01-01

In the range of 2350-2470 degrees K at a PCO = 0.0 MPa, interaction in Sc 2 O 3 with carbon mixtures initially occurs by CO chemisorption at the scandium oxide surface and disproportionation into CO 2 and C, with subsequent replacement of oxygen in the oxide anion sublattice by carbon to form ScC. The carbide melt, creating a contact between the reagents, then transforms the process to a diffusion-based one. At 1820-2220 K in vacuum, reduction of the studied mixtures occurs by dissociative vaporization of the oxide, with precipitation of ScC at the carbon surface and generation of CO. The appearance of CO in the vapors of mixture leads to formation of an oxycarbide phase and to the partial occurrence of oxide dissociation

Vibrational spectra of double oxides of calcium and scandium

International Nuclear Information System (INIS)

Porotnikov, N.V.; Kondratov, O.I.; Petrov, K.I.; Olikov, I.I.

1981-01-01

The vibrational spectra of calcium and scandium double oxides 40 CaSc 2 O 4 and 44 CaSc 2 O 4 in the range of 30-1000 cm -1 are studied. In the approximation of the polymer chains of the method of valent-force field the calculation of the theoretical vibrational spectrum of isotope-substituted compounds is made, the attribution of the experimental spectra is suggested, the frequency branches of the vibrations of periodic chains are built, the force field of crystals is evaluated [ru

Diagrammatic Representation of Electronic Correlations in Photoionization Process: Application to Scandium

International Nuclear Information System (INIS)

Liu Mengmeng; Ma Xiaoguang

2011-01-01

The conversion rules under which an algebraic expression can be obtained from a corresponding photoionization Goldstone diagram have been given systematically in the present work. The electronic correlations in the photoionization processes then could be studied diagrammatically. The application to atomic scandium shows that the present theoretical scheme can give reasonable photoionization cross sections, which agree well with the experimental results. (atomic and molecular physics)

Structural differences of half-sandwich complexes of scandium and yttrium containing bulky substituents

Czech Academy of Sciences Publication Activity Database

Fridrichová, Adéla; Růžička, A.; Lamač, Martin; Horáček, Michal

2017-01-01

Roč. 76, FEB 2017 (2017), s. 62-66 ISSN 1387-7003 R&D Projects: GA ČR(CZ) GAP207/12/2368 Institutional support: RVO:61388955 Keywords : scandium * yttrium * half-sandwich Subject RIV: CF - Physical ; Theoretical Chemistry OBOR OECD: Physical chemistry Impact factor: 1.640, year: 2016

Study on the coextraction of scandium-yttrium-lumogallion complex

International Nuclear Information System (INIS)

Okada, T.; Shimoishi, Y.; Miyata, H.; Toei, K.

1977-01-01

The coextraction of scandium-yttrium-lumogallion [LMG;4-chloro-6-(2,4-dihydroxyphenylazo)-1-hydroxybenzene-2-sulfonic acid] into diethyl ether has been studied. The acid dissociation constants of LMG, pKsub(a2) and pKsub(a3), were estimated to be 6.24 and 8.05 respectively. The composition of the complex extracted was determined by using the radioisotopes 46 Sc and 90 Y and by spectrophotometry of LMG and the ratio of the components was Sc:Y:LMG = 1:1:3. The coextraction scheme was discussed briefly. (author)

Study of strength properties of semi-finished products from economically alloyed high-strength aluminium-scandium alloys for application in automobile transport and shipbuilding

Science.gov (United States)

Baranov, Vladimir; Sidelnikov, Sergey; Zenkin, Evgeny; Frolov, Viktor; Voroshilov, Denis; Yakivyuk, Olga; Konstantinov, Igor; Sokolov, Ruslan; Belokonova, Irina

2018-04-01

The results of a study on the strength of rolled products from aluminium alloys doped with scandium under various processing conditions of hot and cold rolling are presented. The regularities of metal flow and the level of strength of deformed semi-finished products from aluminum-scandium alloys are established, depending on the total degree of deformation and the various modes of single reduction during rolling. It is shown that when using one heating of a cast billet to obtain high-quality semi-finished products, the temperature during the rolling process should not be lower than 350-370°, and the total degree of deformation does not exceed 50-60%. It was found that the semi-finished products from alloys with a content of scandium in the range 0.11-0.12% in the deformed state had elevated values of ultimate tensile strength and yield strength of the metal, which allows them to be recommended for industrial production of sheet metal products.

Multiscale Study of Hydrogen Adsorption on Six Designed Covalent Organic Frameworks Based on Porphyrazine, Cyclobutane and Scandium

International Nuclear Information System (INIS)

Li Le-Le; Gao Teng-Fei; Zhang Ruan-Yu; Zhang Hong

2014-01-01

The first-principles method of hydrogen adsorption is used to investigate the interaction of H_2 with the scandium-porphyrazine (Sc-Pz) and porphyrazine (Pz) clusters. The result shows that the interaction of H_2 with Sc-Pz is stronger than with Pz. Then grand canonical Monte Carlo simulations are used to investigate hydrogen adsorption in six designed covalent organic frameworks (COFs), which are designed based on porphyrazine, cyclobutane and scandium. When the pressure is from 0.1 to 100 bar and the temperature is 298 K and 77 K, the hydrogen adsorption capacities of the six COFs are calculated. We further study the importance of Sc and fillers to improve the H_2 uptake in the modified COFs by analyzing the isosteric heat of hydrogen adsorption. (condensed matter: electronic structure, electrical, magnetic, and optical properties)

Scandium sorption by immobilized microdispersed forms of phosporus-containing ion exchangers

International Nuclear Information System (INIS)

Sokolova, Yu.V.; Kurdyumov, G.M.; Smirnov, A.V.; Mezhirov, M.S.

1991-01-01

The possibility to improve considerably kinetics of scandium sorption by phosphate ion exchangers, immobilized into polyacrylonitrile (PAN) fibers, as compared with granular samples of ion exchangers, was shown. The influence of dispersion degree of immobilized ionite particles on sorption rate was studied. It is ascertained that the ionite grinding to the particle size ≤ 52 μm is sufficient for the rate increase by 1-1.5 orders. A lower swelling of the immobilized ion exchanger is its additional advantage as compared with granular form

The crystal structure of scandium dyhydrate triglycolate

International Nuclear Information System (INIS)

Dukareva, L.M.; Antishkina, A.S.; Porai-Koshits, M.A.; Ostrikova, V.N.; Arkhangel'skij, I.V.; Amanov, A.Z.

1978-01-01

The structure of colorless crystals of scandium glycolate dehydrate Sc(CH 2 OHCOO) 3 x2H 2 O, synthesized at the chemical department of MSU has been investigated. Parameters of the monoclinic lattice are determined according to roentgenograms of swing and Kforograms and are specified using the DRON-1 diffractor: a=14.624-+0.005 A; b=13.052-+0.003 A; c=5.730+-0.003 A; γ=96.26 deg+-0.01 deg; rhosub(exper.)=1.09 g/cm 3 ; Z=4; Sp.=P 2/b. Experimental photographic data are obtained using the KFOR chamber. Scannings of the layer lines h anti Ko-h anti K4, containing 742 independent reflexes are taken. Deciphering of the structure is carried out by means of analysis of the Paterson functions distribution and conventional and differential electron densities. Description of the system is presented

Order-disorder phenomenon in lead scandium tantalate

International Nuclear Information System (INIS)

Wang, H.C.; Schulze, W.A.

1990-01-01

Lead scandium tatalate (PST) is a ferroelectric relaxor with the perovskite structure of A(B'B double-prime)O 3 . By suitable heat treatment, the B-site cations can be brought from a structurally disordered state into various degree of ordering. The degree of ordering is strongly affected by the amount of vacancies present in the materials. To suppress PbO loss during the sintering or annealing process, a PbO-rich atmosphere is supplied by materials having high PbO vapor pressure, such as PbZrO 3 . For PST ceramics with nearly zero weight loss, very long annealing times and higher annealing temperatures are required for ordering. The higher PbO-loss materials are found to be easily ordered. The introduction of a reducing atmosphere during annealing enhances the ordering process. The ordering process is characterized quantitatively by X-ray diffraction and qualitatively by Raman spectroscopy

Synthesis, structures, and electroluminescent properties of scandium N,O-chelated complexes toward near-white organic light-emitting diodes.

Science.gov (United States)

Katkova, Marina A; Balashova, Tatyana V; Ilichev, Vasilii A; Konev, Alexey N; Isachenkov, Nikolai A; Fukin, Georgy K; Ketkov, Sergey Yu; Bochkarev, Mikhail N

2010-06-07

Three members of a new class of electroluminescent, neutral, and monomeric scandium N,O-chelate complexes, namely, Sc(III)-tris-2-(2-benzoimidazol-2-yl)phenolate (1), Sc(III)-tris-2-(2-benzoxyazol-2-yl)phenolate (2), and Sc(III)-tris-2-(2-benzothiazol-2-yl)phenolate (3), have been prepared and X-ray characterized. DFT calculations have been performed. In contrast to the most frequently applied dual or multiple dopants in multilayer white OLED devices, all our simpler devices with the configuration of indium tin oxide/N,N'-bis(3-methylphenyl)-N,N'-diphenylbenzidine/neat scandium complex/Yb exhibit close to near-white emission with a blue hue (CIE(x,y) = 0.2147, 0.2379) in the case of 1, a cyan hue (0.2702, 0.3524) in the case of 2, and a yellowish hue (0.3468; 0.4284) in the case of 3.

Sc2[Se2O5]3: The First Rare-Earth Metal Oxoselenate(IV with Exclusively [Se2O5]2− Anions

Directory of Open Access Journals (Sweden)

Stefan Greiner

2018-04-01

Full Text Available The scandium oxodiselenate(IV Sc2[Se2O5]3 was synthesized via solid-state reactions between scandium sesquioxide (Sc2O3 and selenium dioxide (SeO2 with thallium(I chloride (TlCl as fluxing agent in molar ratios of 1:4:2. Evacuated fused silica ampoules were used as reactions vessels for annealing the mixtures for five days at 800 °C. The new scandium compound crystallizes in the triclinic space group P 1 ¯ with the lattice parameters a = 663.71(5 pm, b = 1024.32(7 pm, c = 1057.49(8 pm, α = 81.034(2°, β = 87.468(2°, γ = 89.237(2° and Z = 2. There are two distinct Sc3+ positions, which show six-fold coordination by oxygen atoms as [ScO6]9− octahedra (d(Sc–O = 205–212 pm. Three different [Se2O5]2− anions provide these oxygen atoms with their terminal ligands (Ot. Each of the six selenium(IV central atoms exhibit a stereochemically active lone pair of electrons, so that all [Se2O5]2− anions consist of two ψ1-tetrahedral [SeO3]2− subunits (d(Se–Ot = 164–167 pm, d(Se–Ob = 176–185 pm, ∢(O–Se–O = 93–104° sharing one bridging oxygen atom (Ob with ∢(Se–Ob–Se = 121–128°. The vibrational modes of the complex anionic [Se2O5]2− entities were characterized via single-crystal Raman spectroscopy.

Laboratory studies into the use of the scandium-46-EDTA complex as a tracer for groundwater flow

International Nuclear Information System (INIS)

Cheng, H.; Nixon, S.C.

1988-01-01

Gamma ray emitting metal radionuclides, when complexed with an appropriate complexing agent, provide a wide choice of water tracers particularly for groundwater studies where a radionuclide of appropriate half-life suited to the particular study can be selected. Scandium-46 has easily detectable gamma emission and a suitable half-life (84 days) for medium term studies. It has been widely and successfully used as a tracer in studies of sediment movement but has not yet been introduced as a groundwater tracer. In our experiments the chemical aspects of the preparation of Sc-46-EDTA were studied in some detail and its behaviour in various mineralogical environments was evaluated with reference to the standard tracer, tritiated water. The experimental results have shown that the scandium cation can be easily complexed with EDTA to form soluble SC-EDTA. The complex is very stable in a wide range of pH; the adsorptive properties of Sc-EDTA in the batch studies and the retardation and recovery in the column tests in comparison with tritiated water are quite satisfactory. In general Sc-46-EDTA is a promising tracer for groundwater studies. In the report the appropriate conditions, procedures and some rational and efficient methods for testing the purity of Sc-46-EDTA in the preparation of the tracer solution of Sc-46-EDTA are described. In addition, it has been found that the formation of the metal hydroxide colloids is the major reason for the great loss in groundwater aquifers of most trivalent metal nuclide tracers in the cationic form including scandium-46. (author). 29 refs, 11 figs, 12 tabs

Determination of aluminium, scandium and rare earth elements by emission flame spectrometry

International Nuclear Information System (INIS)

Otruba, V.; Sommer, L.

1989-01-01

Emission spectrometry in nitrous oxide-acetylene flames in combination with a highly resolving double monochromator and sensitive detecting system enables simple, sensitive and selective determinations of aluminium, scandium and all rare earth elements with exception of cerium in complicated matrices. Calibration plots are linear for a large concentration interval (≤ 100 μgxml -1 ), detection limits are in ngxml -1 level and RSD does not exceed 3% on the optimal concentration level of the particular element. The determination of Al, Sc, Eu and Yb showed particular advantages as to methods using ICP-spectrometry. (orig.)

Process Design Aspects for Scandium-Selective Leaching of Bauxite Residue with Sulfuric Acid

OpenAIRE

Konstantinos Hatzilyberis; Theopisti Lymperopoulou; Lamprini-Areti Tsakanika; Klaus-Michael Ochsenkühn; Paraskevas Georgiou; Nikolaos Defteraios; Fotios Tsopelas; Maria Ochsenkühn-Petropoulou

2018-01-01

Aiming at the industrial scale development of a Scandium (Sc)-selective leaching process of Bauxite Residue (BR), a set of process design aspects has been investigated. The interpretation of experimental data for Sc leaching yield, with sulfuric acid as the leaching solvent, has shown significant impact from acid feed concentration, mixing time, liquid to solids ratio (L/S), and number of cycles of leachate re-usage onto fresh BR. The thin film diffusion model, as the fundamental theory for l...

Magnetic susceptibility of scandium-hydrogen and lutetium-hydrogen solid-solution alloys from 2 to 3000K

International Nuclear Information System (INIS)

Stierman, R.J.

1982-12-01

Results for pure Sc show that the maximum and minimum in the susceptibility discovered earlier are enhanced as the impurity level of iron in scandium decreases. The Stoner enhancement factor, calculated from low-temperature heat capacity data, susceptibility data, and band-structure calculations show Sc to be a strongly enhanced paramagnet. Below 2 0 K, the magnetic anisotropy between the hard and easy directions of scandium decreases linearly with decreasing temperature, tending toward zero at 0 K. The large increase in the susceptibility of Sc at lower temperatures indicates magnetic ordering. Pure Lu and Lu-H alloys showed an anisotropy in susceptibility vs orientation; thus the samples were not random polycrystalline samples. Pure Lu shows the shallow maximum and minimum, but the increase in susceptibility at low temperatures is larger than previously observed. The susceptibility-composition dependence of the Lu-H alloys also did not match other data. The susceptibility-composition dependence does not match the composition dependence of the electronic specific heat constant below 150 K, showing the electronic specific heat is being affected by terms other than phonon-electron and pure electron-electron interactions

Hydrogen storage in thin film magnesium-scandium alloys

International Nuclear Information System (INIS)

Niessen, R.A. H.; Notten, P.H. L.

2005-01-01

Thorough electrochemical materials research has been performed on thin films of novel magnesium-scandium hydrogen storage alloys. It was found that palladium-capped thin films of Mg x Sc (1-x) with different compositions (ranging from x=0.50 -0.90) show an increase in hydrogen storage capacity of more than 5-20% as compared to their bulk equivalents using even higher discharge rates. The maximum reversible hydrogen storage capacity at the optimal composition (Mg 80 Sc 20 ) amounts to 1795-bar mAh/g corresponding to a hydrogen content of 2.05 H/M or 6.7-bar wt.%, which is close to five times that of the commonly used hydride-forming materials in commercial NiMH batteries. Galvanostatic intermittent titration technique (GITT) measurements show that the equilibrium pressure during discharge is lower than that of bulk powders by one order of magnitude (10 -7 -bar mbar versus 10 -6 -bar mbar, respectively)

Application of scandium oxide in an electron emission material

International Nuclear Information System (INIS)

Suqiu, Y.; Zhizheng, Z.; Yongde, W.

1985-01-01

Modern microwave devices impose a number of harsh requirements on the cathodes. For instance, they require cathodes having low working temperature, high emissive current density, slow evaporation rate of the emissive-active material, long lifetime, quick heating and so on. The commercial B-cathode is no longer able to meet these requirements completely. A scandate cathode may be a promising one for use in these devices. Adding rare-earth elements in the electron emission material has been reported in many papers. Based on a B-cathode we add a little amount of scandium oxide (about 3%) into emission material to manufacture a scandate cathode. The emission property of such a cathode has been improved greatly. If the composition is controlled correctly, the emission level of such a cathode may be five times more as high as the B-cathode

Development of methods for the selective separation of scandium, zirconium and tin for radiopharmaceutical applications; Entwicklung von Methoden zur selektiven Trennung von Scandium, Zirkonium und Zinn fuer radiopharmazeutische Anwendungen

Energy Technology Data Exchange (ETDEWEB)

Dirks-Fandrei, Carina

2014-07-01

The subject of the present work is the development of fast and highly selective methods for the separation and purification of scandium, zirconium and tin radionuclides from potential target materials for use in nuclear medicine. A number of selected resins (TrisKem International) were first characterized with respect to their extraction behaviour towards a large number of cations. Characterization studies were performed in batch experiments by determination of weight distribution ratios D{sub w} and further the influence of interferences on the uptake of these elements was evaluated. Weight distribution ratios were determined in different acids and acid concentrations with main focus on scandium, tin or zirconium. The interference of macro amounts of Calcium and Ti on the Sc extraction was evaluated as well as the interference of macro amounts of Y on the Zr extraction. Best suited uptake conditions were found for Scandium on DGA were determined to be 2.5 M HNO{sub 3} for Ti-Targets and 0.1 M HNO{sub 3} for Calcium-Targets. Otherwise it is also possible to extract Sc with TRU Resin. High uptakes were obtained at 2.5 M HNO{sub 3} for simulated Ti- and Calcium-targets. Separation methods were developed using elution studies; employed conditions were chosen according to parameters evaluated in the batch-experiment. The developed methods allowed separating Sc very rapidly in high purity very rapidly from Ti- or Calcium-targets. For Zr a separation method based on UTEVA Resin has been developed. Following results of batch experiments simulated Y-target solution were loaded onto a UTEVA resin column from 6 M HNO{sub 3}; the elution of Zr could be performed in 0.01 M oxalic acid. Decontamination factors in the order of 10{sup 4}-10{sup 5} could be obtained applying the developed method; the method thus allowed separating Zr in a high purity. Initial testing of a method for the separation of Sn from Cd targets based on the use of TBP Resin showed that the TBP resin seems

Smelting of Scandium by Microwave Irradiation

Directory of Open Access Journals (Sweden)

Satoshi Fujii

2017-09-01

Full Text Available Scandium is being explored as an alloying element for aluminum alloys, which are gaining importance as high-performance lightweight structural alloys in the transportation industry. A few years ago, Sc was also found to be suitable for use in electrical devices. High-Sc-content ScAlN thin films have attracted significant attention because of their strong piezoelectricity. The piezoelectric response of ScAlN suggests that ScAlN thin films formed on a hard substrate would be suitable surface acoustic wave wideband filters for next-generation wireless communication systems. However, it is often difficult to use ScAlN thin films in MEMS devices—including acoustic ones—because of the extremely high price of metallic Sc, given the difficulty associated with smelting it. Here, we propose a novel process for smelting Sc metal by microwave irradiation. Sc metal was able to be obtained successfully from ScF3 through a microwave-irradiation-based carbon reduction reaction. The reaction temperature for this reduction process was approximately 880°C, which is half of that for the conventional smelting process involving reduction with Ca. Thus, the proposed microwave irradiation process has significant potential for use in the smelting of Sc metal.

Effect of composition on the superplasticity of aluminium scandium alloys

International Nuclear Information System (INIS)

Bradley, E.L. III; Morris, J.W. Jr.

1992-01-01

Several aluminum alloys have been shown to exhibit superplasticty in the as-rolled condition. Previous work has shown that aluminum-scandium alloys also exhibit this behavior, but only with the addition of ternary alloying elements such as lithium and magnesium. These additions raised the strain-rate sensitivity of these alloys to 0.4-0.5 for selected strain rates at temperatures above 400 degrees C. A systematic study was undertaken of five Al-Sc alloys with varying lithium and magnesium concentrations in order to fully characterize the high temperature deformation mechanism. Specimens were deformed at a constant strain rate to predetermined true strains for textural and microstructural characterization. In this paper work is presented that will elucidate the effect of these different ternary additives on the superplastic deformation mechanism in these alloys

Aluminum-Scandium: A Material for Semiconductor Packaging

Science.gov (United States)

Geissler, Ute; Thomas, Sven; Schneider-Ramelow, Martin; Mukhopadhyay, Biswajit; Lang, Klaus-Dieter

2016-10-01

A well-known aluminum-scandium (Al-Sc) alloy, already used in lightweight sports equipment, is about to be established for use in electronic packaging. One application for Al-Sc alloy is manufacture of bonding wires. The special feature of the alloy is its ability to harden by precipitation. The new bonding wires with electrical conductivity similar to pure Al wires can be processed on common wire bonders for aluminum wedge/wedge (w/w) bonding. The wires exhibit very fine-grained microstructure. Small Al3Sc particles are the main reason for its high strength and prevent recrystallization and grain growth at higher temperatures (>150°C). After the wire-bonding process, the interface is well closed. Reliability investigations by active power cycling demonstrated considerably improved lifetime compared with pure Al heavy wires. Furthermore, the Al-Sc alloy was sputter-deposited onto silicon wafer to test it as chip metallization in copper (Cu) ball/wedge bonding technology. After deposition, the layers exhibited fine-grained columnar structure and small coherent Al3Sc particles with dimensions of a few nanometers. These particles inhibit softening processes such as Al splashing in fine wire bonding processes and increase the thickness of remnant Al under the copper balls to 85% of the initial thickness.

Scandium-doped zinc cadmium oxide as a new stable n-type oxide thermoelectric material

DEFF Research Database (Denmark)

Han, Li; Christensen, Dennis Valbjørn; Bhowmik, Arghya

2016-01-01

Scandium-doped zinc cadmium oxide (Sc-doped ZnCdO) is proposed as a new n-type oxide thermoelectric material. The material is sintered in air to maintain the oxygen stoichiometry and avoid instability issues. The successful alloying of CdO with ZnO at a molar ratio of 1 : 9 significantly reduced...... is a good candidate for improving the overall conversion efficiencies in oxide thermoelectric modules. Meanwhile, Sc-doped ZnCdO is robust in air at high temperatures, whereas other n-type materials, such as Al-doped ZnO, will experience rapid degradation of their electrical conductivity and ZT....

Effects of scandium and zirconium combination alloying on as-cast microstructure and mechanical properties of Al-4Cu-1.5Mg alloy

Directory of Open Access Journals (Sweden)

Xiang Qingchun

2011-02-01

Full Text Available The influences of minor scandium and zirconium combination alloying on the as-cast microstructure and mechanical properties of Al-4Cu-1.5Mg alloy have been experimentally investigated. The experimental results show that when the minor elements of scandium and zirconium are simultaneously added into the Al-4Cu-1.5Mg alloy, the as-cast microstructure of the alloy is effectively modified and the grains of the alloy are greatly refined. The coarse dendrites in the microstructure of the alloy without Sc and Zr additions are refined to the uniform and fine equiaxed grains. As the additions of Sc and Zr are 0.4% and 0.2%, respectively, the tensile strength, yield strength and elongation of the alloy are relatively better, which are 275.0 MPa, 176.0 MPa and 8.0% respectively. The tensile strength is increased by 55.3%, and the elongation is nearly raised three times, compared with those of the alloy without Sc and Zr additions.

Bottom sediment transport study at Haiphong port using radioactive scandium as tracer

International Nuclear Information System (INIS)

Pham Ngoc Chuong; Phan Son Hai; Pham Duy Hien

1993-01-01

A radioisotope tracer experiment was performed for investigating the bedload movement at the site near the access channel to Haiphong port, North Vietnam. The scandium glass and a number of mechanical devices were manufactured locally for the experiment. Simple and safe procedures were adopted for the production, transportation and injection of radioactive tracer materials. Five tracking experiments were carried out covering the period of 84 days in winter 1992-1993. The experimental results provide a firm basis for elaborating appropriate measures against the siltation problem at Haiphong port, especially for the design of a new access channel with a better orientation with respect to the directions of the water flow and bedload transport, as proposed recently by the Port Authority. (Author). 2 refs, 4 figs

Complexometric determination of aluminium and scandium using fluorides as masking agent at low pH value

International Nuclear Information System (INIS)

Tikhonov, V.N.

1978-01-01

A complexometric method is suggested to determine Al and Sc by back titration of Bi(NO 3 ) 3 solution with xylenol orange indicator at low pH values. To increase selectivity fluoride additions were used which were masked by boron acid at the end titration point. EDTA was used as a complexing agent. Metals which create at low pH values stable complexes with EDTA undestroyed by fluoride, do not interfere with Al and Sc determination. Scandium is shown to be determined more selectively than aluminium

Insights into the mantle geochemistry of scandium from a meta-analysis of garnet data

Science.gov (United States)

Chassé, Mathieu; Griffin, William L.; Alard, Olivier; O'Reilly, Suzanne Y.; Calas, Georges

2018-06-01

The meta-analysis of about 13,000 analyses of scandium content in garnet grains shows that, below the spinel-garnet transition, this phase carries about three-quarters of the Sc budget of the mantle, indicating its control on Sc mobility. The Sc content of garnets in mafic rocks is low, due to a dilution effect resulting from their high modal content in garnet. Garnets from ultramafic rocks exhibit a wider range of Sc concentrations. We assess the relative influence of thermobarometry, crystal chemistry and fluid-related events on the distribution of Sc in garnet from such rocks to improve the tracking of geochemical processes in the mantle. Pressure and temperature of equilibration in the mantle are second-order factors influencing the Sc content of garnet, while crystal chemistry, in particular Cr/Cr+Al and Ca/Ca+Mg, is the main parameter controlling the compatibility of Sc. Scandium is incorporated in both X and Y sites of Cr-Ca-rich garnets, resulting in a behaviour intermediate between rare-earth elements, incorporated in the X site, and trivalent transition elements, occupying the Y site. This affinity for both sites results in a mild compatibility of Sc in the garnet stability field of the mantle; hence Sc concentration in garnet increases with melt extraction and can be reduced by silicate-melt metasomatism. In contrast, metasomatism by volatile-rich fluids increases the Sc concentration in garnet. The control of garnet on the compatibility of Sc in deep lithospheric rocks demonstrates the potential of using Sc to track the conditions of formation of magmas and their residual rocks, as well as the origin and nature of metasomatic fluids.

Potential for photocatalytic degradation of the potassic diclofenac using scandium and silver modified titanium dioxide thin films; Potencial de degradacao fotocatalitica do diclofenaco potassico utilizando filmes finos de dioxido de titanio modificado com escandio e prata

Energy Technology Data Exchange (ETDEWEB)

Ciola, R.A.; Oliveira, C.T.; Lopes, S.A.; Cavalheiro, A.A., E-mail: rafaelciola@hotmail.com [Universidade Estadual de Mato Grosso do Sul (UFMS), Navirai, MS (Brazil). Centro de Pesquisas Tecnologicas em Recursos Naturais

2011-07-01

The potential for photocatalytic degradation of the potassic diclofenac drug was investigated using titanium dioxide thin films modified with two modifier types, scandium and silver, both prepared by Sol-Gel method. It was demonstrated by UVVis spectroscopy analysis of the solutions containing the drug, under UV-A light irradiation that the degradation efficiency of the titanium dioxide photocatalyst is dependent of the semiconductor nature and that the scandium accelerates the first step of the degradation when compared to the silver. This result seems to be related to the redox potential of the electron-hole pair, once the scandium modifying sample generates a p type semiconductor that reduces the band gap. The extra holes attract more strongly the chorine ion present in diclofenac and leading to the releasing more easily. However, after the first byproducts degradation the following steps are not facilitated, making the silver modifying more advantageous. (author)

Dielectric matrix, dynamical matrix and phonon dispersion in hcp transition metal scandium

International Nuclear Information System (INIS)

Singh, Joginder; Singh, Natthi; Prakash, S.

1976-01-01

Complete dielectric matrix is evaluated for hcp transition metal scandium using the non-interacting s- and d-band model. The local field corrections which are consequence of the non-diagonal part of the dielectric matrix are calculated explicitly. The free electron approximation is used for the s-electrons and the simple tight-binding approximation is used for the d-electrons. The theory developed by Singh and others is used to invert the dielectric matrix and the explicit expressions for the dynamical matrix are obtained. The phonon dispersion relations are investigated by using the renormalized Animalu transition metal model potential (TMMP) for bare ion potential. The contribution due to non-central forces which arise due to local fields is found to be 20%. The results are found in resonably good agreement with the experimental values. (author)

Influence of scandium on the microstructure and mechanical properties of A319 alloy

International Nuclear Information System (INIS)

Emadi, Daryoush; Rao, A.K. Prasada; Mahfoud, Musbah

2010-01-01

Recycling of aluminum scrap alloys by melting is gaining its importance in foundry sector. During recycling, some of the alloying elements present in scrap alloys eventually become trace/tramp impurities in the recycled alloy. These elements could potentially affect the alloy's microstructure and hence its mechanical properties. In the present work, an attempt has been made to investigate the effect of one of such trace elements on the microstructure and mechanical properties of A319 alloy. The element chosen for the present investigation is scandium (Sc). This paper discusses the effects of the additions of trace amount of Sc on the microstructure and mechanical properties of A319 alloy in as-cast, T6 and T7 heat treated conditions.

Double tungstates of metals of scandium and ammonium subgroups

Energy Technology Data Exchange (ETDEWEB)

Maksin, V I [AN Ukrainskoj SSR, Kiev. Inst. Kolloidnoj Khimii i Khimii Vody

1980-06-01

The methods of pH-potentiometry, conductometry, determination of residual concentrations of liquid phases and precipitations, selected by chemical analysis have been used for investigation R(NO/sub 3/)/sub 3/-(NH/sub 4/)/sub 2/WO/sub 2/-H/sub 2/O systems, (where R=Sc, Y, La). The formation of double tungstates NH/sub 4/R(WO/sub 4/)/sub 2/xnH/sub 2/O is established. The NH/sub 4/Sc(WO/sub 4/)/sub 2/x4.5H/sub 2/O, NH/sub 4/Yx(WO/sub 4/)/sub 2/x3H/sub 2/O, NH/sub 4/La(WO/sub 4/)/sub 2/x1.5H/sub 2/O compounds are synthesized in individual form. Precipitation conditions (pH, concentration ratio) and composition of the solid phase are determined. The behaviour of synthesized slats at thermolysis up to 880 deg C is studied. Physicochemical properties (color, solubility of the simple and double tungstates of scandium, yttrium and lanthanum with ammonium) is studied. IR spectra and X-ray diffraction analysis give idea about double salts structural transformations.

Interaction of scandium and titanium atoms with a carbon surface containing five- and seven-membered rings

International Nuclear Information System (INIS)

Krasnov, P. O.; Eliseeva, N. S.; Kuzubov, A. A.

2012-01-01

The use of carbon nanotubes coated by atoms of transition metals to store molecular hydrogen is associated with the problem of the aggregation of these atoms, which leads to the formation of metal clusters. The quantum-chemical simulation of cluster models of the carbon surface of a graphene type with scandium and titanium atoms has been performed. It has been shown that the presence of five- and seven-membered rings, in addition to six-membered rings, in these structures makes it possible to strongly suppress the processes of the migration of metal atoms over the surface, preventing their clustering.

Partitioning of Iron and Scandium in Soils Having Water Drainage Limitations

International Nuclear Information System (INIS)

Aide, M.; Braden, I.; Mueller, W.

2010-01-01

Soil chemistry of Fe includes weathering reactions, adsorption, hydrolysis, complexation, and oxidation-reduction reactions. Soil chemistry for scandium (Sc) is similar, but Sc does not include oxidation-reduction reactions. To determine if geochemical analysis may be used to identify Sc partitioning with respect to Fe among the particle size fractions, two Alfisol and two Ultisol soils were assessed using an aqua-regia digestion to estimate Sc and Fe concentrations for whole soil and particle size separates. Aqua-regia digestion data showed Sc depletion relative to Fe in sand separate. Sand separate is largely composed on quartz sand and Fe-Mn-bearing nodules, which are redoximorphic features produced by alternating oxic and suboxic/anoxic conditions associated with seasonally fluctuating water tables. Relative partitioning of Fe and Sc in these soils warrants further study to assess if selective extractions could quantify the extent of modern or ancestral oxidation-reduction processes responsible in some soil features involved in soil genesis.

Thermodynamic study of sublimation, melting and vaporization of scandium(III) dipivaloylmethanate derivatives

International Nuclear Information System (INIS)

Zherikova, Kseniya V.; Zelenina, Ludmila N.; Chusova, Tamara P.; Gelfond, Nikolay V.; Morozova, Natalia B.

2016-01-01

Highlights: • Thermal properties of two volatile fluorinated Sc(III) beta-diketonates were studied. • Saturated and unsaturated vapor pressures were measured. • DSC analysis was carried out. • Sublimation, evaporation and melting enthalpies and entropies were derived. • Effect of fluorine introduction on volatility and thermal stability was established. - Abstract: The present work deals with the investigation of thermal properties of two volatile scandium(III) beta-diketonates with 2,2,6,6-tetramethyl-4-fluoro-3,5-heptanedione and 1,1,1-trifluoro-5,5-dimethyl-2,4-hexanedione which have been synthesized and purified. Using the static method with glass membrane gauge-manometer the temperature dependencies of saturated and unsaturated vapor pressure were measured for the first time. The temperatures and enthalpies of melting were measured for these compounds by differential scanning calorimetry. The standard thermodynamic characteristics of enthalpy and entropy for sublimation, vaporization and melting processes were derived.

Modification mechanism of eutectic silicon in Al–6Si–0.3Mg alloy with scandium

Energy Technology Data Exchange (ETDEWEB)

Patakham, Ussadawut [Manufacturing and Systems Engineering Program, Department of Production Engineering, Faculty of Engineering, King Mongkut’s University of Technology Thonburi, 126 Pracha-Utid Rd., Bangmod, Tungkhru, Bangkok 10140 (Thailand); Kajornchaiyakul, Julathep [National Metal and Material Technology Center, National Science and Technology Development Agency, 114 Thailand Science Park, Klong Nueng, Klong Luang, Pathumthani 12120 (Thailand); Limmaneevichitr, Chaowalit, E-mail: chaowalit.lim@kmutt.ac.th [Manufacturing and Systems Engineering Program, Department of Production Engineering, Faculty of Engineering, King Mongkut’s University of Technology Thonburi, 126 Pracha-Utid Rd., Bangmod, Tungkhru, Bangkok 10140 (Thailand)

2013-10-25

Highlights: •Morphologies and growth of Sc and Sr-modified eutectic silicon resemble those of dendrites. •Crystal orientation of eutectic aluminum depends on growth characteristics of eutectic silicon. •We report strong evidence of the occurrence of an impurity-induced twinning mechanism. -- Abstract: The modification mechanism of eutectic silicon in Al–6Si–0.3Mg alloy with scandium was studied. The crystallographic orientation relationships between primary dendrites and the eutectic phase of unmodified and modified Al–6Si–0.3 Mg alloys were determined using electron backscatter diffraction (EBSD). The orientation of aluminum modified with scandium in the eutectic phase was different from that of the neighboring primary dendrites. This result implies that eutectic aluminum grows epitaxially from the surrounding primary aluminum dendrites in the unmodified alloy and that eutectic aluminum grows competitively from the surrounding primary aluminum dendrites in the modified alloy. The pole figure maps of eutectic Si in the [1 0 0], [1 1 0] and [1 1 1] axes of the unmodified and Sc-modified alloys were different, suggesting that the eutectic Al and Si crystals in modified alloy growth are more isotropic and cover a larger set of directions. The lattice fringes of Si of the alloys with and without Sc modification were different in the TEM results. The lattice fringes of Si in modified alloy were found to be multiple twins. However, this was not observed in the unmodified alloy. The growth characteristic of eutectic Si crystal in modified alloy suggests the occurrence of multiple twinning reactions and the formation of a high density of twins. This modification mechanism by Sc is explained by the results of scanning electron microscopy (SEM), electron backscatter diffraction (EBSD) and transmission electron microscopy (TEM) analysis, which provide strong evidence of the occurrence of the impurity-induced twinning (IIT) mechanism.

Determination of rare-earth elements, yttrium and scandium in manganese nodules by inductively-coupled argon-plastma emission spectrometry

Science.gov (United States)

Fries, T.; Lamothe, P.J.; Pesek, J.J.

1984-01-01

A sequential-scanning, inductively-coupled argon plasma emission spectrometer is used for the determination of the rare-earth elements, plus yttrium and scandium, in manganese nodules. Wavelength selection is optimized to minimize spectral interferences from manganese nodule components. Samples are decomposed with mixed acids in a sealed polycarbonate vessel, and elements are quantified without further treatment. Results for U.S. Geological Survey manganese nodule standards A-1 and P-1 had average relative standard deviations of 6.8% and 8.1%, respectively, and results were in good agreement with those obtained by other methods. ?? 1984.

Determination of scandium in acid mine drainage by ICP-OES with flow injection on-line preconcentration using oxidized multiwalled carbon nanotubes.

Science.gov (United States)

Jerez, Javier; Isaguirre, Andrea C; Bazán, Cristian; Martinez, Luis D; Cerutti, Soledad

2014-06-01

An on-line scandium preconcentration and determination system implemented with inductively coupled plasma optical emission spectrometry associated with flow injection was studied. Trace amounts of scandium were preconcentrated by sorption on a minicolumn packed with oxidized multiwalled carbon nanotubes, at pH 1.5. The retained analyte was removed from the minicolumn with 30% (v/v) nitric acid. A total enrichment factor of 225-fold was obtained within a preconcentration time of 300 s (for a 25 mL sample volume). The overall time required for preconcentration and elution of 25 mL of sample was about 6 min; the throughput was about 10 samples per hour. The value of the detection limit was 4 ng L(-1) and the precision for 10 replicate determinations at 100 ng L(-1) Sc level was 5% relative standard deviation, calculated from the peak heights obtained. The calibration graph using the preconcentration system was linear with a correlation coefficient of 0.9996 at levels near the detection limits up to at least 10 mg L(-1). After optimization, the method was successfully applied to the determination of Sc in an acid drainage from an abandoned mine located in the province of San Luis, Argentina. Copyright © 2014 Elsevier B.V. All rights reserved.

Scandium complexes with the tetraphenylethylene and anthracene dianions.

Science.gov (United States)

Ellis, John E; Minyaev, Mikhail E; Nifant'ev, Ilya E; Churakov, Andrei V

2018-06-01

The structural study of Sc complexes containing dianions of anthracene and tetraphenylethylene should shed some light on the nature of rare-earth metal-carbon bonding. The crystal structures of (18-crown-6)bis(tetrahydrofuran-κO)sodium bis(η 6 -1,1,2,2-tetraphenylethenediyl)scandium(III) tetrahydrofuran disolvate, [Na(C 4 H 8 O) 2 (C 12 H 24 O 6 )][Sc(C 26 H 20 ) 2 ]·2C 4 H 8 O or [Na(18-crown-6)(THF) 2 ][Sc(η 6 -C 2 Ph 4 ) 2 ]·2(THF), (1b), (η 5 -1,3-diphenylcyclopentadienyl)(tetrahydrofuran-κO)(η 6 -1,1,2,2-tetraphenylethenediyl)scandium(III) toluene hemisolvate, [Sc(C 17 H 13 )(C 26 H 20 )(C 4 H 8 O)]·0.5C 7 H 8 or [(η 5 -1,3-Ph 2 C 5 H 3 )Sc(η 6 -C 2 Ph 4 )(THF)]·0.5(toluene), (5b), poly[[(μ 2 -η 3 :η 3 -anthracenediyl)bis(η 6 -anthracenediyl)bis(η 5 -1,3-diphenylcyclopentadienyl)tetrakis(tetrahydrofuran)dipotassiumdiscandium(III)] tetrahydrofuran monosolvate], {[K 2 Sc 2 (C 14 H 10 ) 3 (C 17 H 13 ) 2 (C 4 H 8 O) 4 ]·C 4 H 8 O} n or [K(THF) 2 ] 2 [(1,3-Ph 2 C 5 H 3 ) 2 Sc 2 (C 14 H 10 ) 3 ]·THF, (6), and 1,4-diphenylcyclopenta-1,3-diene, C 17 H 14 , (3a), have been established. The [Sc(η 6 -C 2 Ph 4 ) 2 ] - complex anion in (1b) contains the tetraphenylethylene dianion in a symmetrical bis-η 3 -allyl coordination mode. The complex homoleptic [Sc(η 6 -C 2 Ph 4 ) 2 ] - anion retains its structure in THF solution, displaying hindered rotation of the coordinated phenyl rings. The 1D 1 H and 13 C{ 1 H}, and 2D COSY 1 H- 1 H and 13 C- 1 H NMR data are presented for M[Sc(Ph 4 C 2 ) 2 ]·xTHF [M = Na and x = 4 for (1a); M = K and x = 3.5 for (2a)] in THF-d 8 media. Complex (5b) exhibits an unsymmetrical bis-η 3 -allyl coordination mode of the dianion, but this changes to a η 4 coordination mode for (1,3-Ph 2 C 5 H 3 )Sc(Ph 4 C 2 )(THF) 2 , (5a), in THF-d 8 solution. A 45 Sc NMR study of (2a) and UV-Vis studies of (1a), (2a) and (5a) indicate a significant covalent contribution to the Sc-Ph 4 C 2 bond character. The unique Sc ate complex, (6

Why does the lumen maintenance of sodium-scandium metal halide lamps improve by VHF operation?

International Nuclear Information System (INIS)

Van Erk, W; Luijks, G M J F; Hitchcock, W

2011-01-01

Lifetime experiments show that sodium-scandium metal halide lamps perform better on very high frequency (VHF) drivers than on low frequency (LF) constant wattage autotransformer (CWA) ballasts. The question why, will be addressed with focus on arc tube aspects. It is argued that at high frequency operation sodium loss is less, and that the absence of thermal fluctuations in the electrode tip causes less damage and cracking to this part of the electrode. Sudden lm W -1 drops, observed with CWA-operated lamps, most probably occur when the arc attaches on such a corroded and cracked surface. Thorium is effective as an emitter both in the CWA and the VHF operation mode, despite the absence of cataphoretic transport to the cathode in the VHF case.

Why does the lumen maintenance of sodium-scandium metal halide lamps improve by VHF operation?

Energy Technology Data Exchange (ETDEWEB)

Van Erk, W [Philips Lighting, Sondervick 47, 5505 NB Veldhoven (Netherlands); Luijks, G M J F [Advanced Development Lighting, Philips Lighting, PO Box 80020, 5600 JM Eindhoven (Netherlands); Hitchcock, W, E-mail: Gerard.luijks@philips.com [Philips Lighting Company, 7265 Route 54, Bath, NY 14810 (United States)

2011-06-08

Lifetime experiments show that sodium-scandium metal halide lamps perform better on very high frequency (VHF) drivers than on low frequency (LF) constant wattage autotransformer (CWA) ballasts. The question why, will be addressed with focus on arc tube aspects. It is argued that at high frequency operation sodium loss is less, and that the absence of thermal fluctuations in the electrode tip causes less damage and cracking to this part of the electrode. Sudden lm W{sup -1} drops, observed with CWA-operated lamps, most probably occur when the arc attaches on such a corroded and cracked surface. Thorium is effective as an emitter both in the CWA and the VHF operation mode, despite the absence of cataphoretic transport to the cathode in the VHF case.

The spectrum of four times ionized scandium, Sc V

International Nuclear Information System (INIS)

Smitt, R.; Ekberg, J.O.

1985-01-01

The spectrum of four times ionized scandium emitted from a sliding spark discharge has been observed using a 3 m normal incidence spectrograph and a 5 m grazing incidence spectrograph. About 450 lines in the wavelength region 160 A to 220 A have been identified as combinations between 46 odd levels belonging to the 3s 2 3p 5 , 3s 2 3p 4 4p and 3s3p 5 3d configurations and 72 even levels of the 3s3p 6 , 3s 2 3p 4 3d, 4d, 4s and 5s configurations. Of the previous identifications we have confirmed 18 levels. The level structure of the observed configurations has been theoretically interpreted by including configuration interaction effects. The inclusion of 3s 2 3p 3 3d 2 in the calculations of the odd parity configurations is found to be important. Almost all levels of 3s3p 5 3d show a considerable mixing with levels of 3s 2 3p 3 3d 2 , in some cases by as much as 50%. The energy parameters determined from least-squares fits to the observed level values are compared with Hartree-Fock calculations. The ionization energy is estimated to be 739 500 +- 1000 cm -1 . (91.65 +- 0,12 eV). (orig.)

Self-Assembled Nanocomposite Organic Polymers with Aluminum and Scandium as Heterogeneous Water-Compatible Lewis Acid Catalysts.

Science.gov (United States)

Miyamura, Hiroyuki; Sonoyama, Arisa; Hayrapetyan, Davit; Kobayashi, Shū

2015-09-01

While water-compatible Lewis acids have great potential as accessible and environmentally benign catalysts for various organic transformations, efficient immobilization of such Lewis acids while keeping high activity and without leaching of metals even under aqueous conditions is a challenging task. Self-assembled nanocomposite catalysts of organic polymers, carbon black, aluminum reductants, and scandium salts as heterogeneous water-compatible Lewis acid catalysts are described. These catalysts could be successfully applied to various C-C bond-forming reactions without leaching of metals. Scanning transmission electron microscopy analyses revealed that the nanocomposite structure of Al and Sc was fabricated in these heterogeneous catalysts. It is noted that Al species, which are usually decomposed rapidly in the presence of water, are stabilized under aqueous conditions. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Structural characteristics and physical properties of diortho(pyro)silicate crystals of lanthanides yttrium and scandium grown by the Czochralski technique

Energy Technology Data Exchange (ETDEWEB)

Anan' eva, G.V.; Karapetyan, V.E.; Korovkin, A.M.; Merkulyaeva, T.I.; Peschanskaya, I.A.; Savinova, I.P.; Feofilov, P.P. (Gosudarstvennyj Opticheskij Inst., Leningrad (USSR))

1982-03-01

Optically uniform monocrystals of diortho (pyro) silicates of lanthanides, yttrium, and scandium were grown by the Czochralski technique. Four structural types of Ln/sub 2/(Si/sub 2/O/sub 7/) crystals were determined by the roentgenographic method. The presence of structural subgroups was also supported by the method of spectroscopic probes. Structural parameters were determined and data on certain physical properties (fusion temperature, density, refractive indices, transparency) of investigated crystals were presented. The generation of induced emission at lambda=1.057 ..mu..m was obtained in La/sub 2/(Si/sub 2/O/sub 7/)-Nd/sup 3 +/ crystal.

Phenomenological theory of the dielectric response of lead magnesium niobate and lead scandium tantalate

International Nuclear Information System (INIS)

Qian, H.; Bursill, L.A.

1997-01-01

The influence of the random field effects originating from charges chemical defects and non-domain textures of the formation and dynamics of polar clusters is analyzed. The spatial distribution of the local fields is not totally random but contains some correlations in direction and strength. Polar clusters are classified to be dynamic or frozen according to their dynamic characteristics in the random fields. The relaxation formula of a dipolar moment in an anisotropic double-well potential is deduced. Two percolation models are introduced, one to account for frustration effects associated with multiple orientations of polar clusters, which results in a broad diffuse dielectric response and the second to account for the case whereby there may be a phase transition to a ferroelectric state. The dielectric permittivity and dissipation factor of the typical relaxors lead magnesium niobate and lead scandium tantalate are predicted as a function of both temperature and frequency, which results are in good agreement with the experimental measurements. 30 refs., 9 figs

Microstructure and age-hardening effects of aluminium alloys with additions of scandium and zirconium

Energy Technology Data Exchange (ETDEWEB)

Galun, R.; Mordike, B.L. [Inst. fuer Werkstoffkunde und Werkstofftechnik, Technische Univ. Clausthal, Clausthal-Zellerfeld (Germany); Maiwald, T.; Smola, B. [Zentrum fuer Funktionswerkstoffe GmbH, Clausthal-Zellerfeld (Germany); Mergen, R.; Manner, M.; Uitz, W. [Miba Gleitlager GmbH, Laakirchen (Australia)

2004-12-01

The aim of the work presented in this report was to produce age-hardenable aluminium alloys containing scandium and zirconium by a casting process with similar cooling conditions like an industrial casting process. Microstructure, precipitation structure and age-hardening response of different alloys with up to 0.4 wt.% Sc and Zr were investigated. Age-hardening experiments from the as-cast condition without solution annealing showed a significant increase of hardness of about 100% for Sc-rich alloys and of 50% for Zr-rich alloys compared to the as-cast condition. TEM investigations revealed the formation of precipitates of ternary Al{sub 3}(Sc{sub x}Zr{sub 1-x}) phases with a cubic cP4 crystal structure. In addition to the strengthening effect, a high thermal stability especially of the precipitates in Zr-rich alloys up to 400 C let these alloys look very promising for high-temperature applications. (orig.)

Adsorption of hydrogen in Scandium/Titanium decorated nitrogen doped carbon nanotube

Energy Technology Data Exchange (ETDEWEB)

Mananghaya, Michael, E-mail: mikemananghaya@gmail.com [De La Salle University, 2401 Taft Ave, 0922, Manila (Philippines); DLSU STC Laguna Boulevard, LTI Spine Road Barangays Biñan and Malamig, Biñan City, Laguna (Philippines); DOST-ASTHRDP, PCIEERD, Gen. Santos Ave., Bicutan, Taguig City 1631 (Philippines); Belo, Lawrence Phoa; Beltran, Arnel [De La Salle University, 2401 Taft Ave, 0922, Manila (Philippines); DLSU STC Laguna Boulevard, LTI Spine Road Barangays Biñan and Malamig, Biñan City, Laguna (Philippines)

2016-09-01

Nitrogen doped Carbon Nanotube with divacancy (4ND-CN{sub x}NT) that is decorated with Scandium and Titanium as potential hydrogen storage medium using the pseudo potential density functional method was investigated. Highly localized states near the Fermi level, which are derived from the nitrogen defects, contribute to strong Sc and Ti bindings, which prevent metal aggregation and improve the material stability. A detailed Comparison of the Hydrogen adsorption capability with promising system-weight efficiency of Sc over Ti was elucidated when functionalized with 4ND-CN{sub x}NT. Finally, the (Sc/4ND){sub 10}-CN{sub x}CNT composite material has a thermodynamically favorable adsorption and consecutive adsorption energy for ideal reversible adsorption and desorption of hydrogen at room temperature such that it can hold at least 5.8 wt% hydrogen molecules at the LDA and GGA level. - Highlights: • Carbon Nanotube with divacancy (4ND-CN{sub x}NT) decorated with Sc and Ti. • Nitrogen defects, contribute to strong Sc and Ti bindings. • H{sub 2} and (Sc/4ND){sub 10}-CN{sub x}CNT has a favorable adsorption. • 5.8 wt% adsorption at the LDA and GGA level.

Bonding in scandium monosulfide a NaCl crystal type

International Nuclear Information System (INIS)

Merrick, J.A.

1980-08-01

The transition temperature of an order-disorder transition in Sc 0 81 S (R anti 3m to Fm3m) occurs at 700 0 C. A group of ordered sublattices on the NaCl-type lattice (Fm3m) was generated and a Madelung energy and configurational entropy were calculated for each sublattice assuming the ions to be Sc 2 48+ and S 2- . Mean field and pair interaction approximations were used to model long-range and short-range orderings, respectively. The electrostatic model fails to predict the observed short-range and long-range orderings. The high temperature vaporization of ScP was investigated by mass spectrometry and target collection Knudsen effusion at 1767 to 2209K. The composition ScP 1 00 vaporizes congruently to the gaseous species Sc, P, and P 2 . A temperature independent third law enthalpy of atomization (ΔH 0 /sub atom,298/ = 252.2 +- 2.8 kcal mole -1 ) has a value approx. 12 kcal larger than that reported for ScS. Nonrelativistic, nonself-consistent LAPW band structure calculations are reported for ScS. XPS and UPS measurements are reported for Sc 2 S 3 and several compositions Sc/sub 1-x/S (0.0 less than or equal to x less than or equal to 0.2). The Sc and S 2p binding energies (XPS) obtained for the defect scandium monosulfides are very close to those found in the pure elements, suggesting covalent bonding. The Sc 2p energy region has an interesting satellite structure

Random-field Potts model for the polar domains of lead magnesium niobate and lead scandium tantalate

Energy Technology Data Exchange (ETDEWEB)

Qian, H.; Bursill, L.A

1997-06-01

A random filed Potts model is used to establish the spatial relationship between the nanoscale distribution of charges chemical defects and nanoscale polar domains for the perovskite-based relaxor materials lead magnesium niobate (PMN) and lead scandium tantalate (PST). The random fields are not set stochastically but are determined initially by the distribution of B-site cations (Mg, Nb) or (Sc, Ta) generated by Monte Carlo NNNI-model simulations for the chemical defects. An appropriate random field Potts model is derived and algorithms developed for a 2D lattice. It is shown that the local fields are strongly correlated with the chemical domain walls and that polar domains as a function of decreasing temperature is simulated for the two cases of PMN and PST. The dynamics of the polar clusters is also discussed. 33 refs., 9 figs.

Two anionically derivatized scandium oxoselenates(IV): ScF[SeO3] and Sc2O2[SeO3

Science.gov (United States)

Greiner, Stefan; Chou, Sheng-Chun; Schleid, Thomas

2017-02-01

Scandium fluoride oxoselenate(IV) ScF[SeO3] and scandium oxide oxoselenate(IV) Sc2O2[SeO3] could be synthesized through solid-state reactions. ScF[SeO3] was obtained phase-pure, by reacting mixtures of Sc2O3, ScF3 and SeO2 (molar ratio: 1:1:3) together with CsBr as fluxing agent in corundum crucibles embedded into evacuated glassy silica ampoules after firing at 700 °C for seven days. Sc2O2[SeO3] first emerged as by-product during the attempts to synthesize ScCl[SeO3] following aforementioned synthesis route and could later be reproduced from appropriate Sc2O3/SeO3 mixtures. ScF[SeO3] crystallizes monoclinically in space group P21/m with a=406.43(2), b =661.09(4), c=632.35(4) pm, β=93.298(3)° and Z=2. Sc2O2[SeO3] also crystallizes in the monoclinic system, but in space group P21/n with a=786.02(6), b=527.98(4), c=1086.11(8) pm, β=108.672(3)° for Z=4. The crystal structures of both compounds are strongly influenced by the stereochemically active lone pairs of the ψ1-tetrahedral [SeO3]2- anions. They also show partial structures, where the derivatizing F- or O2- anions play an important role. For ScF[SeO3] chains of the composition 2+∞ 1[FS c 2 / 2 ] form from connected [FSc2]5+ dumbbells, while [OSc3]7+ pyramids and [OSc4]10+ tetrahedra units are condensed to layers according to 2+ ∞ 2[O2Sc2 ] in Sc2O2[SeO3].

Solvent extraction of anionic chelate complexes of lanthanum(III), europium(III), lutetium(III), scandium(III), and indium(III) with 2-thenoyltrifluoroacetone as ion-pairs with tetrabutylammonium ions

International Nuclear Information System (INIS)

Noro, Junji; Sekine, Tatsuya.

1992-01-01

The solvent extraction of lanthanum(III), europium(III), lutetium(III), scandium(III), and indium(III) in 0.1 mol dm -3 sodium nitrate solutions with 2-thenoyltrifluoroacetone (Htta) in the absence and presence of tetrabutylammonium ions (tba + ) into carbon tetrachloride was measured. The extraction of lanthanum(III), europium(III), and lutetium(III) was greatly enhanced by the addition of tba + ; this could be explained in terms of the extraction of a ternary complex, M(tta) 4 - tba + . However, the extractions of scandium(III) and indium(III) were nearly the same when tba + was added. The data were treated on the basis of the formation equilibrium of the ternary complex from the neutral chelate, M(tta) 3 , with the extracted ion-pairs of the reagents, tta - tba + , in the organic phase. It was concluded that the degree of association of M(tta) 3 with the ion-pair, tta - tba + , is greater in the order La(tta) 3 ≅ Eu(tta) 3 > Lu(tta) 3 , or that the stability of the ternary complex in the organic phase is higher in the order La(tta) 4 - tba + ≅ Eu(tta) 4 - tba + > Lu(tta) 4 - tba + . This is similar to those of adduct metal chelates of Htta with tributylphosphate (TBP) in synergistic extraction systems. (author)

Scandium doping brings speed improvement in Sb2Te alloy for phase change random access memory application.

Science.gov (United States)

Chen, Xin; Zheng, Yonghui; Zhu, Min; Ren, Kun; Wang, Yong; Li, Tao; Liu, Guangyu; Guo, Tianqi; Wu, Lei; Liu, Xianqiang; Cheng, Yan; Song, Zhitang

2018-05-01

Phase change random access memory (PCRAM) has gained much attention as a candidate for nonvolatile memory application. To develop PCRAM materials with better properties, especially to draw closer to dynamic random access memory (DRAM), the key challenge is to research new high-speed phase change materials. Here, Scandium (Sc) has been found it is helpful to get high-speed and good stability after doping in Sb 2 Te alloy. Sc 0.1 Sb 2 Te based PCRAM cell can achieve reversible switching by applying even 6 ns voltage pulse experimentally. And, Sc doping not only promotes amorphous stability but also improves the endurance ability comparing with pure Sb 2 Te alloy. Moreover, according to DFT calculations, strong Sc-Te bonds lead to the rigidity of Sc centered octahedrons, which may act as crystallization precursors in recrystallization process to boost the set speed.

A novel boron-rich quaternary scandium borocarbosilicide Sc3.67-xB41.4-y-zC0.67+zSi0.33-w

International Nuclear Information System (INIS)

Tanaka, Takaho; Yamamoto, Akiji; Sato, Akira

2004-01-01

A novel quaternary scandium borocarbosilicide Sc 3.67-x B 41.4-y-z C 0.67+z Si 0.33-w was found. Single crystallites were obtained as an intergrowth phase in the float-zoned single crystal of Sc 0.83-x B 10.0-y C 0.17+y Si 0.083-z that has a face-centered cubic crystal structure. Single crystal structure analysis revealed that the compound has a hexagonal structure with lattice constants a = b = 1.43055(8) nm and c = 2.37477(13) nm and space group P6-barm2 (No. 187). The crystal composition calculated from the structure analysis for the crystal with x = 0.52, y = 1.42, z = 1.17, and w = 0.02 was ScB 12.3 C 0.58 Si 0.10 and that agreed rather well with the composition of ScB 11.5 C 0.61 Si 0.04 measured by EPMA. In the crystal structure that is a new structure type of boron-rich borides, there are 79 structurally independent atomic sites, 69 boron and/or carbon sites, two silicon sites and eight scandium sites. Boron and carbon form seven structurally independent B 12 icosahedra, one B 9 polyhedron, one B 10 polyhedron, one irregularly shaped B 16 polyhedron in which only 10.7 boron atoms are available because of partial occupancies and 10 bridging sites. All polyhedron units and bridging site atoms interconnect each other forming a three-dimensional boron framework structure. Sc atoms reside in the open spaces in the boron framework structure

Effect of Aqueous Media on the Recovery of Scandium by Selective Precipitation

Directory of Open Access Journals (Sweden)

Bengi Yagmurlu

2018-05-01

Full Text Available This research presents a novel precipitation method for scandium (Sc concentrate refining from bauxite residue leachates and the effect of aqueous media on this triple-stage successive precipitation process. The precipitation pattern and the precipitation behavior of the constituent elements was investigated using different precipitation agents in three major mineral acid media, namely, H2SO4, HNO3, and HCl in a comparative manner. Experimental investigations showed behavioral similarities between HNO3 and HCl media, while H2SO4 media was different from them because of the nature of the formed complexes. NH4OH was found to be the best precipitation agent in every leaching media to remove Fe(III with low Sc co-precipitation. To limit Sc loss from the system, Fe(III removal was divided into two steps, leading to more than 90% of Fe(III removal at the end of the process. Phosphate concentrates were produced in the final step of the precipitation process with dibasic phosphates which have a strong affinity towards Sc. Concentrates containing more than 50% of ScPO4 were produced in each case from the solutions after Fe(III removal, as described. A flow diagram of the selective precipitation process is proposed for these three mineral acid media with their characteristic parameters.

Tumor protein 53-induced nuclear protein 1 (TP53INP1 enhances p53 function and represses tumorigenesis

Directory of Open Access Journals (Sweden)

Jeyran eShahbazi

2013-05-01

Full Text Available Tumor protein 53-induced nuclear protein 1 (TP53INP1 is a stress-induced p53 target gene whose expression is modulated by transcription factors such as p53, p73 and E2F1. TP53INP1 gene encodes two isoforms of TP53INP1 proteins, TP53INP1α and TP53INP1β, both of which appear to be key elements in p53 function. When associated with homeodomain-interacting protein kinase-2 (HIPK2, TP53INP1 phosphorylates p53 protein at Serine 46, enhances p53 protein stability and its transcriptional activity, leading to transcriptional activation of p53 target genes such as p21, PIG-3 and MDM2, cell growth arrest and apoptosis upon DNA damage stress. The anti-proliferative and pro-apoptotic activities of TP53INP1 indicate that TP53INP1 has an important role in cellular homeostasis and DNA damage response. Deficiency in TP53INP1 expression results in increased tumorigenesis; while TP53INP1 expression is repressed during early stages of cancer by factors such as miR-155. This review aims to summarize the roles of TP53INP1 in blocking tumor progression through p53-dependant and p53-independent pathways, as well as the elements which repress TP53INP1 expression, hence highlighting its potential as a therapeutic target in cancer treatment.

Restoration of mp53 to wtp53 by chemical chaperones restores p53-dependent apoptosis after radiotherapy

International Nuclear Information System (INIS)

Ohnishi, T.; Asakawa, I.; Tamamoto, T.; Takahashi, A.; Ohnishi, K.

2003-01-01

The mutations of many kinds of cancer related genes have been investigated for the predictive assay against cancer therapy by the application of molecular biology. A tumor suppressor gene product of wtp53 plays important roles in cancer suppression through the induction of cell growth arrest, DNA repair or apoptosis. The p53 exerts its function by induction of downstream genes and/or interaction to various proteins. Mutations in the p53 gene (mp53) cause conformational alterations in the p53 protein, the majority of which can no longer induce expression of the downstream genes. The genetic status of p53 gene has been focused as the most important candidate among them for cancer therapy. The gene therapy of p53 has been already applied. We reported that the transfection of mp53 gene increased the radio-, thermo- and chemo-resistance, and depressed apoptosis introduced with them through bax-induction and proteolysis of PARP and caspase-3. From these results, we propose that the gene therapy of wtp53 to p53-deleted cancer cells may be very useful for cancer therapy by the combination with radiotherapy. Even in the case of mp53 cancer cells, we succeeded the restoration of mp53 to wtp53 by glycerol or C-terminal peptide of p53 as chemical chaperones. These experimental progresses might support effective cancer therapy against individual patients bearing with different p53 gene status by the use of the most suitable treatment to them in the near future

OTUD5 regulates p53 stability by deubiquitinating p53.

Directory of Open Access Journals (Sweden)

Judong Luo

Full Text Available The p53 tumour suppressor protein is a transcription factor that prevents oncogenic progression by activating the expression of apoptosis and cell-cycle arrest genes in stressed cells. The stability of p53 is tightly regulated by ubiquitin-dependent degradation, driven mainly by its negative regulators ubiquitin ligase MDM2.In this study, we have identified OTUD5 as a DUB that interacts with and deubiquitinates p53. OTUD5 forms a direct complex with p53 and controls level of ubiquitination. The function of OTUD5 is required to allow the rapid activation of p53-dependent transcription and a p53-dependent apoptosis in response to DNA damage stress.As a novel deubiquitinating enzyme for p53, OTUD5 is required for the stabilization and the activation of a p53 response.

Modification of radiation sensitivity by salts of the metals beryllium and indium and the rare earths cerium, lanthanum and scandium

International Nuclear Information System (INIS)

Floersheim, G.L.

1995-01-01

The LD 50 of 46 salts of metals and rare earths (lanthanoids) was determined in mice. Half the LD 50 of the compounds was then combined with lethal radiation (10.5 Gy) and the modification of survival time was scored. Only the metals beryllium and indium and the rare earths cerium, lanthanum and scandium displayed activity in our assay. There were then tested at a wider range of lower doses and reduced survival time in a dose-dependent fashion. This appears to be compatible with enhancement of radiation sensitivity. The interaction of these metals and rare earths with radiation adds a new facet to their toxicological spectrum and, by enhancing radiation effects, may influence estimates of risk. On the other hand, radiosensitizing properties of the metals may be useful for further development of compounds to be used as adjuncts in specific situations of cancer radiotherapy. 31 refs., 1 fig., 1 tab

Binary and ternary chelates of scandium (III), Yttrium (III) and lanthanum (III) with ethyleneglycol-bis(. beta. -aminoethylether)-tetraacetic acid as primary and substituted salicylic acids as secondary ligands

Energy Technology Data Exchange (ETDEWEB)

Pandey, A K; Chandra, M; Agarwala, B V; Dey, A K [Allahabad Univ. (India). Chemical Labs.

1980-01-01

Formation constants of binary and ternary complexes of the systems of the type: M-L and M-egta-L (M = scandium(III), yttrium(III) and lanthanum(III), egta = ethylene glycol-bis(..beta..-aminoethylether)-tetra acetic acid, L = o-cresotic acid (o-ca), m-cresotic acid (m-ca), 5-chlorosalicyclic acid(csa), and 3,5-dibromosalicylic acid (dbsa)) have been determined pH-metrically at 25deg and ..mu.. = 0.1M (KNO/sub 3/) in 50% (v/v) aqueous-ethanol medium. The order of stabilities of ternary complexes has been compared with those of corresponding binary complexes, and results discussed on the basis of coulombic interactions.

Inability of p53-reactivating compounds Nutlin-3 and RITA to overcome p53 resistance in tumor cells deficient in p53Ser46 phosphorylation.

Science.gov (United States)

Ma, Teng; Yamada, Shumpei; Ichwan, Solachuddin J A; Iseki, Sachiko; Ohtani, Kiyoshi; Otsu, Megumi; Ikeda, Masa-Aki

2012-01-20

The p53 tumor suppressor protein plays key roles in protecting cells from tumorigenesis. Phosphorylation of p53 at Ser46 (p53Ser46) is considered to be a crucial modification regulating p53-mediated apoptosis. Because the activity of p53 is impaired in most human cancers, restoration of wild-type p53 (wt-p53) function by its gene transfer or by p53-reactivating small molecules has been extensively investigated. The p53-reactivating compounds Nutlin-3 and RITA activate p53 in the absence of genotoxic stress by antagonizing the action of its negative regulator Mdm2. Although controversial, Nutlin-3 was shown to induce p53-mediated apoptosis in a manner independent of p53 phosphorylation. Recently, RITA was shown to induce apoptosis by promoting p53Ser46 phosphorylation. Here we examined whether Nutlin-3 or RITA can overcome resistance to p53-mediated apoptosis in p53-resistant tumor cell lines lacking the ability to phosphorylate p53Ser46. We show that Nutlin-3 did not rescue the apoptotic defect of a Ser46 phosphorylation-defective p53 mutant in p53-sensitive tumor cells, and that RITA neither restored p53Ser46 phosphorylation nor induced apoptosis in p53Ser46 phosphorylation-deficient cells retaining wt-p53. Furthermore, treatment with Nutlin-3 or RITA together with adenoviral p53 gene transfer also failed to induce apoptosis in p53Ser46 phosphorylation-deficient cells either expressing or lacking wt-p53. These results indicate that neither Nutlin-3 nor RITA in able to induce p53-mediated apoptosis in the absence of p53Ser46 phosphorylation. Thus, the dysregulation of this phosphorylation in tumor cells may be a critical factor that limits the efficacy of these p53-based cancer therapies. Copyright © 2011 Elsevier Inc. All rights reserved.

Impact of layer and substrate properties on the surface acoustic wave velocity in scandium doped aluminum nitride based SAW devices on sapphire

Energy Technology Data Exchange (ETDEWEB)

Gillinger, M., E-mail: manuel.gillinger@tuwien.ac.at; Knobloch, T.; Schneider, M.; Schmid, U. [Institute of Sensor and Actuator Systems, TU Wien, 1040 Vienna (Austria); Shaposhnikov, K.; Kaltenbacher, M. [Institute of Mechanics and Mechatronics, TU Wien, 1040 Vienna (Austria)

2016-06-06

This paper investigates the performance of surface acoustic wave (SAW) devices consisting of reactively sputter deposited scandium doped aluminum nitride (Sc{sub x}Al{sub 1-x}N) thin films as piezoelectric layers on sapphire substrates for wireless sensor or for RF-MEMS applications. To investigate the influence of piezoelectric film thickness on the device properties, samples with thickness ranging from 500 nm up to 3000 nm are fabricated. S{sub 21} measurements and simulations demonstrate that the phase velocity is predominantly influenced by the mass density of the electrode material rather than by the thickness of the piezoelectric film. Additionally, the wave propagation direction is varied by rotating the interdigital transducer structures with respect to the crystal orientation of the substrate. The phase velocity is about 2.5% higher for a-direction compared to m-direction of the sapphire substrate, which is in excellent agreement with the difference in the anisotropic Young's modulus of the substrate corresponding to these directions.

Binding of rare earths to serum proteins and DNA

International Nuclear Information System (INIS)

Rosoff, B.; Spencer, H.

1979-01-01

In order to investigate further the physiological behavior of rare earths and rare earth chelates, studies of the binding of 46 Sc, 91 Y, and 140 La to serum proteins and to nucleic acids were performed using the methods of equilibrium dialysis and ultrafiltration. The binding of lanthanum and yttrium as the chlorides to α-globulin increased as the free rare earth concentration increased. When scandium and lanthanum were chelated in nitrilotriacetate (NTA) the binding to α-globulin was considerably less and there was no binding to albumin. The binding of 46 Sc chelated to ethylenediamine di(O-hydroxyphenylacetate) (EDDHA) was five times greater than of 46 Sc chloride. When the free scandium concentration was increased, the moles bound per mole of protein increased proportionally and the binding was reversible. Scandium was 100% filterable from a mixture of human serum and from the scandium chelates with high stability constants scandium diethylenetriaminepentaacetate (ScDTPA), scandium ethylenediaminetetraacetate (ScEDTA) and scandium cyclohexane trans-1,2-diaminetetraacetate (ScCDTA) respectively. In contrast, only 2% of the scandium was filterable when scandium nitrilotriacetate, a scandium chelate of low stability constant, was used. (Auth.)

RITA (Reactivating p53 and Inducing Tumor Apoptosis) is efficient against TP53abnormal myeloma cells independently of the p53 pathway.

Science.gov (United States)

Surget, Sylvanie; Descamps, Géraldine; Brosseau, Carole; Normant, Vincent; Maïga, Sophie; Gomez-Bougie, Patricia; Gouy-Colin, Nadège; Godon, Catherine; Béné, Marie C; Moreau, Philippe; Le Gouill, Steven; Amiot, Martine; Pellat-Deceunynck, Catherine

2014-06-14

The aim of this study was to evaluate the efficacy of the p53-reactivating drugs RITA and nutlin3a in killing myeloma cells. A large cohort of myeloma cell lines (n = 32) and primary cells (n = 21) was used for this study. This cohort contained cell lines with various TP53 statuses and primary cells with various incidences of deletion of chromosome 17. Apoptosis was evaluated using flow cytometry with Apo2.7 staining of the cell lines or via the loss of the myeloma-specific marker CD138 in primary cells. Apoptosis was further confirmed by the appearance of a subG1 peak and the activation of caspases 3 and 9. Activation of the p53 pathway was monitored using immunoblotting via the expression of the p53 target genes p21, Noxa, Bax and DR5. The involvement of p53 was further studied in 4 different p53-silenced cell lines. Both drugs induced the apoptosis of myeloma cells. The apoptosis that was induced by RITA was not related to the TP53 status of the cell lines or the del17p status of the primary samples (p = 0.52 and p = 0.80, respectively), and RITA did not commonly increase the expression level of p53 or p53 targets (Noxa, p21, Bax or DR5) in sensitive cells. Moreover, silencing of p53 in two TP53(mutated) cell lines failed to inhibit apoptosis that was induced by RITA, which confirmed that RITA-induced apoptosis in myeloma cells was p53 independent. In contrast, apoptosis induced by nutlin3a was directly linked to the TP53 status of the cell lines and primary samples (p RITA, in contrast to nutlin3a, effectively induced apoptosis in a subset of MM cells independently of p53. The findings and could be of interest for patients with a 17p deletion, who are resistant to current therapies.

CH-53K Heavy Lift Replacement Helicopter (CH-53K)

Science.gov (United States)

2015-12-01

Selected Acquisition Report (SAR) RCS: DD-A&T(Q&A)823-390 CH-53K Heavy Lift Replacement Helicopter (CH-53K) As of FY 2017 President’s Budget...December 2015 SAR March 4, 2016 10:04:18 UNCLASSIFIED 4 Col Henry Vanderborght PMA-261 Heavy Lift Helicopters Program Executive Office - Air, Anti...757-5780 Fax: 301-757-5109 DSN Phone: 757-5780 DSN Fax: 757-5109 Date Assigned: May 29, 2014 Program Information Program Name CH-53K Heavy Lift

Expression signature based on TP53 target genes doesn't predict response to TP53-MDM2 inhibitor in wild type TP53 tumors

OpenAIRE

Sonkin, Dmitriy

2015-01-01

eLife digest Damaged cells in the human body can develop into tumors if left unchecked. TP53 (also called p53) is a protein that normally helps to repair or eliminate these damaged cells and prevent tumors from forming. About half of all cancerous tumors have mutations that prevent TP53 from working. In tumors with normal TP53 (called TP53 wild type tumors), another protein that acts to keep TP53 in check is often overly active. This overactive protein (called MDM2) prevents TP53 from suppres...

Comparative microstructure and electrical property studies of lead scandium tantalate thin films as prepared by LDCVD, sol-gel and sputtering techniques

International Nuclear Information System (INIS)

Huang, Z; Donohue, P P; Zhang, Q; Williams, D J; Anthony, C J; Whatmore, R W; Todd, M A

2003-01-01

Lead scandium tantalate (PST) thin films for uncooled infrared (IR) detector applications have been deposited by liquid delivery chemical vapour deposition (LDCVD), sputtering and sol-gel techniques. The sol-gel and sputtered films were deposited at low temperature into a non-ferroelectric phase with the required perovskite structure being formed using a high temperature rapid thermal anneal (RTA). In contrast to this, the LDCVD films were deposited at high temperature directly into the perovskite phase but were found to still require a high temperature RTA step to optimize their merit for IR detection. Detailed structural and electrical characterization of the PST films deposited by these different methods have revealed that there is no simple relationship between microstructure and electrical properties. The sol-gel and LDCVD techniques produce thin films with excellent microstructures, as determined by x-ray diffraction analysis and transmission electron microscopy, but inferior electrical properties and relatively low merit figures. By contrast, the sputtered and then rapid thermal annealed films have inferior microstructures, characterized by extensive voiding, but excellent electrical properties and high merit figures

INGN 201: Ad-p53, Ad5CMV-p53, Adenoviral p53, INGN 101, p53 gene therapy--Introgen, RPR/INGN 201.

Science.gov (United States)

2003-01-01

Introgen's adenoviral p53 gene therapy [INGN 201, ADVEXIN] is in clinical development for the treatment of various cancers. The p53 tumour suppressor gene is deleted or mutated in many tumour cells and is one of the most frequently mutated genes in human tumours. INGN 201 has been shown to kill cancer cells directly. In August 2002, Introgen announced plans to file an application for INGN 201 with the European Agency for the Evaluation of Medicinal Products (EMEA) for the treatment of head and neck cancer; the European filing will be submitted simultaneously with the previously scheduled (planned for 2004) submission of a Biologics License Application (BLA) for ADVEXIN to the US FDA. On 20 February 2003, INGN 201 received orphan drug designation from the US FDA for head and neck cancer. INGN 201 is available for licensing although Introgen favours retaining partial or full rights to the therapy in the US. Introgen Therapeutics and its collaborative partner for the p53 programme, Aventis Gencell, have been developing p53 gene therapy products. The agreement was originally signed by Rhône-Poulenc Rorer's Gencell division, which became Aventis Gencell after Rhône-Poulenc Rorer merged with Hoechst Marion Roussel to form Aventis Pharma. According to the original agreement, Introgen was responsible for phase I and preclinical development in North America, while Aventis Gencell was responsible for clinical trials conducted in Europe and for clinical trials in North America beyond phase I. In April 2001, Aventis Gencell and Introgen restructured their existing collaboration agreement for p53 gene therapy products. Aventis Gencell indicated that p53 research had suffered from internal competition for resources and was pulling back from its development agreement with Introgen for p53 gene therapy products. Introgen will assume responsibility for worldwide development of all p53 programmes and will obtain exclusive worldwide commercial rights to p53-based gene therapy

Inhibition of p53 acetylation by INHAT subunit SET/TAF-Iβ represses p53 activity.

Science.gov (United States)

Kim, Ji-Young; Lee, Kyu-Sun; Seol, Jin-Ee; Yu, Kweon; Chakravarti, Debabrata; Seo, Sang-Beom

2012-01-01

The tumor suppressor p53 responds to a wide variety of cellular stress signals. Among potential regulatory pathways, post-translational modifications such as acetylation by CBP/p300 and PCAF have been suggested for modulation of p53 activity. However, exactly how p53 acetylation is modulated remains poorly understood. Here, we found that SET/TAF-Iβ inhibited p300- and PCAF-mediated p53 acetylation in an INHAT (inhibitor of histone acetyltransferase) domain-dependent manner. SET/TAF-Iβ interacted with p53 and repressed transcription of p53 target genes. Consequently, SET/TAF-Iβ blocked both p53-mediated cell cycle arrest and apoptosis in response to cellular stress. Using different apoptosis analyses, including FACS, TUNEL and BrdU incorporation assays, we also found that SET/TAF-Iβ induced cellular proliferation via inhibition of p53 acetylation. Furthermore, we observed that apoptotic Drosophila eye phenotype induced by either dp53 overexpression or UV irradiation was rescued by expression of dSet. Inhibition of dp53 acetylation by dSet was observed in both cases. Our findings provide new insights into the regulation of stress-induced p53 activation by HAT-inhibiting histone chaperone SET/TAF-Iβ.

Investigation of concentration-dependence of thermodynamic properties of lanthanum, yttrium, scandium and terbium in eutectic LiCl-KCl molten salt

Energy Technology Data Exchange (ETDEWEB)

Wang, Yafei; Zhou, Wentao; Zhang, Jinsuo, E-mail: zhang.3558@osu.edu

2016-09-15

Thermodynamic properties of rare earth metals in LiCl-KCl molten salt electrolyte are crucial to the development of electrochemical separation for the treatment of used nuclear fuels. In the present study, activity coefficient, apparent potential, and diffusion coefficient of lanthanum, yttrium, scandium, and terbium in the molten salt (58 at% LiCl and 42 at% KCl) were calculated by the method of molecular dynamics simulation up to a concentration around 3 at% at temperatures of 723 K and 773 K. It was found that the activity coefficient and the apparent potential increase with the species concentration while diffusion coefficient shows a trend of increase followed by decrease. The calculated results were validated by available measurement data of dilution cases. This research extends the range of data to a wide component and would provide further insight to the pyroprocessing design and safeguards. - Highlights: • Investigation of activity coefficient, apparent potential and diffusion coefficient at different concentrations. • MD simulation was studied for the calculation of thermodynamic properties of rare earth elements in molten salt. • The present study is a pioneering work focusing on the concentration dependence of thermodynamic properties.

Nuclear inclusion bodies of mutant and wild-type p53 in cancer: a hallmark of p53 inactivation and proteostasis remodelling by p53 aggregation.

Science.gov (United States)

De Smet, Frederik; Saiz Rubio, Mirian; Hompes, Daphne; Naus, Evelyne; De Baets, Greet; Langenberg, Tobias; Hipp, Mark S; Houben, Bert; Claes, Filip; Charbonneau, Sarah; Delgado Blanco, Javier; Plaisance, Stephane; Ramkissoon, Shakti; Ramkissoon, Lori; Simons, Colinda; van den Brandt, Piet; Weijenberg, Matty; Van England, Manon; Lambrechts, Sandrina; Amant, Frederic; D'Hoore, André; Ligon, Keith L; Sagaert, Xavier; Schymkowitz, Joost; Rousseau, Frederic

2017-05-01

Although p53 protein aggregates have been observed in cancer cell lines and tumour tissue, their impact in cancer remains largely unknown. Here, we extensively screened for p53 aggregation phenotypes in tumour biopsies, and identified nuclear inclusion bodies (nIBs) of transcriptionally inactive mutant or wild-type p53 as the most frequent aggregation-like phenotype across six different cancer types. p53-positive nIBs co-stained with nuclear aggregation markers, and shared molecular hallmarks of nIBs commonly found in neurodegenerative disorders. In cell culture, tumour-associated stress was a strong inducer of p53 aggregation and nIB formation. This was most prominent for mutant p53, but could also be observed in wild-type p53 cell lines, for which nIB formation correlated with the loss of p53's transcriptional activity. Importantly, protein aggregation also fuelled the dysregulation of the proteostasis network in the tumour cell by inducing a hyperactivated, oncogenic heat-shock response, to which tumours are commonly addicted, and by overloading the proteasomal degradation system, an observation that was most pronounced for structurally destabilized mutant p53. Patients showing tumours with p53-positive nIBs suffered from a poor clinical outcome, similar to those with loss of p53 expression, and tumour biopsies showed a differential proteostatic expression profile associated with p53-positive nIBs. p53-positive nIBs therefore highlight a malignant state of the tumour that results from the interplay between (1) the functional inactivation of p53 through mutation and/or aggregation, and (2) microenvironmental stress, a combination that catalyses proteostatic dysregulation. This study highlights several unexpected clinical, biological and therapeutically unexplored parallels between cancer and neurodegeneration. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2016 Pathological Society of Great

Knockout and transgenic mice of Trp53: what have we learned about p53 in breast cancer?

International Nuclear Information System (INIS)

Blackburn, Anneke C; Jerry, D Joseph

2002-01-01

The human p53 tumor suppressor gene TP53 is mutated at a high frequency in sporadic breast cancer, and Li-Fraumeni syndrome patients who carry germline mutations in one TP53 allele have a high incidence of breast cancer. In the 10 years since the first knockout of the mouse p53 tumor suppressor gene (designated Trp53) was published, much has been learned about the contribution of p53 to biology and tumor suppression in the breast through the use of p53 transgenic and knockout mice. The original mice deficient in p53 showed no mammary gland phenotype. However, studies using BALB/c-Trp53-deficient mice have demonstrated a delayed involution phenotype and a mammary tumor phenotype. Together with other studies of mutant p53 transgenes and p53 bitransgenics, a greater understanding has been gained of the role of p53 in involution, of the regulation of p53 activity by hormones, of the effect of mouse strain and modifier genes on tumor phenotype, and of the cooperation between p53 and other oncogenic pathways, chemical carcinogens and hormonal stimulation in mammary tumorigenesis. Both p53 transgenic and knockout mice are important in vivo tools for understanding breast cancer, and are yet to be exploited for developing therapeutic strategies in breast cancer

p53 Acetylation: Regulation and Consequences

International Nuclear Information System (INIS)

Reed, Sara M.; Quelle, Dawn E.

2014-01-01

Post-translational modifications of p53 are critical in modulating its tumor suppressive functions. Ubiquitylation, for example, plays a major role in dictating p53 stability, subcellular localization and transcriptional vs. non-transcriptional activities. Less is known about p53 acetylation. It has been shown to govern p53 transcriptional activity, selection of growth inhibitory vs. apoptotic gene targets, and biological outcomes in response to diverse cellular insults. Yet recent in vivo evidence from mouse models questions the importance of p53 acetylation (at least at certain sites) as well as canonical p53 functions (cell cycle arrest, senescence and apoptosis) to tumor suppression. This review discusses the cumulative findings regarding p53 acetylation, with a focus on the acetyltransferases that modify p53 and the mechanisms regulating their activity. We also evaluate what is known regarding the influence of other post-translational modifications of p53 on its acetylation, and conclude with the current outlook on how p53 acetylation affects tumor suppression. Due to redundancies in p53 control and growing understanding that individual modifications largely fine-tune p53 activity rather than switch it on or off, many questions still remain about the physiological importance of p53 acetylation to its role in preventing cancer

p53 Acetylation: Regulation and Consequences

Energy Technology Data Exchange (ETDEWEB)

Reed, Sara M. [Department of Pharmacology, The University of Iowa Carver College of Medicine, Iowa City, IA 52242 (United States); Medical Scientist Training Program, The University of Iowa Carver College of Medicine, Iowa City, IA 52242 (United States); Quelle, Dawn E., E-mail: dawn-quelle@uiowa.edu [Department of Pharmacology, The University of Iowa Carver College of Medicine, Iowa City, IA 52242 (United States); Medical Scientist Training Program, The University of Iowa Carver College of Medicine, Iowa City, IA 52242 (United States); Department of Pathology, The University of Iowa Carver College of Medicine, Iowa City, IA 52242 (United States)

2014-12-23

Post-translational modifications of p53 are critical in modulating its tumor suppressive functions. Ubiquitylation, for example, plays a major role in dictating p53 stability, subcellular localization and transcriptional vs. non-transcriptional activities. Less is known about p53 acetylation. It has been shown to govern p53 transcriptional activity, selection of growth inhibitory vs. apoptotic gene targets, and biological outcomes in response to diverse cellular insults. Yet recent in vivo evidence from mouse models questions the importance of p53 acetylation (at least at certain sites) as well as canonical p53 functions (cell cycle arrest, senescence and apoptosis) to tumor suppression. This review discusses the cumulative findings regarding p53 acetylation, with a focus on the acetyltransferases that modify p53 and the mechanisms regulating their activity. We also evaluate what is known regarding the influence of other post-translational modifications of p53 on its acetylation, and conclude with the current outlook on how p53 acetylation affects tumor suppression. Due to redundancies in p53 control and growing understanding that individual modifications largely fine-tune p53 activity rather than switch it on or off, many questions still remain about the physiological importance of p53 acetylation to its role in preventing cancer.

Glycerol restores the p53 function in human lingual cancer cells bearing mutant p53

International Nuclear Information System (INIS)

Ota, Ichiro; Yane, Katsunari; Yuki, Kazue; Kanata, Hirokazu; Hosoi, Hiroshi; Miyahara, Hiroshi

2001-01-01

Mutations in p53, tumor suppressor gene, have recently been shown to have an impact on the clinical course of several human tumors, including head and neck cancers. The genetic status of the p53 gene has been focused on as the most important candidate among various cancer-related genes for prognosis-predictive assays of cancer therapy. We examined the restoration of radiation- or cisplatin (CDDP)-induced p53-dependent apoptosis in human lingual cancer cells. The results suggest that glycerol is effective in inducing a conformational change of p53 and restoring normal function of mutant p53, leading to enhanced radiosensitivity or chemosensitivity through the induction of apoptosis. We have also represented the same results in vivo as in vitro. Thus, this novel tool for enhancement of radiosensitivity or chemosensitivity in cancer cells bearing m p53 may be applicable for p53-targeted cancer therapy. (author)

Urodele p53 tolerates amino acid changes found in p53 variants linked to human cancer

Directory of Open Access Journals (Sweden)

Villiard Éric

2007-09-01

Full Text Available Abstract Background Urodele amphibians like the axolotl are unique among vertebrates in their ability to regenerate and their resistance to develop cancers. It is unknown whether these traits are linked at the molecular level. Results Blocking p53 signaling in axolotls using the p53 inhibitor, pifithrin-α, inhibited limb regeneration and the expression of p53 target genes such as Mdm2 and Gadd45, suggesting a link between tumor suppression and regeneration. To understand this relationship we cloned the p53 gene from axolotl. When comparing its sequence with p53 from other organisms, and more specifically human we observed multiple amino acids changes found in human tumors. Phylogenetic analysis of p53 protein sequences from various species is in general agreement with standard vertebrate phylogeny; however, both mice-like rodents and teleost fishes are fast evolving. This leads to long branch attraction resulting in an artefactual basal emergence of these groups in the phylogenetic tree. It is tempting to assume a correlation between certain life style traits (e.g. lifespan and the evolutionary rate of the corresponding p53 sequences. Functional assays of the axolotl p53 in human or axolotl cells using p53 promoter reporters demonstrated a temperature sensitivity (ts, which was further confirmed by performing colony assays at 37°C. In addition, axolotl p53 was capable of efficient transactivation at the Hmd2 promoter but has moderate activity at the p21 promoter. Endogenous axolotl p53 was activated following UV irradiation (100 j/m2 or treatment with an alkylating agent as measured using serine 15 phosphorylation and the expression of the endogenous p53 target Gadd45. Conclusion Urodele p53 may play a role in regeneration and has evolved to contain multiple amino acid changes predicted to render the human protein defective in tumor suppression. Some of these mutations were probably selected to maintain p53 activity at low temperature. However

p53 Aggregates penetrate cells and induce the co-aggregation of intracellular p53.

Directory of Open Access Journals (Sweden)

Karolyn J Forget

Full Text Available Prion diseases are unique pathologies in which the infectious particles are prions, a protein aggregate. The prion protein has many particular features, such as spontaneous aggregation, conformation transmission to other native PrP proteins and transmission from an individual to another. Protein aggregation is now frequently associated to many human diseases, for example Alzheimer's disease, Parkinson's disease or type 2 diabetes. A few proteins associated to these conformational diseases are part of a new category of proteins, called prionoids: proteins that share some, but not all, of the characteristics associated with prions. The p53 protein, a transcription factor that plays a major role in cancer, has recently been suggested to be a possible prionoid. The protein has been shown to accumulate in multiple cancer cell types, and its aggregation has also been reproduced in vitro by many independent groups. These observations suggest a role for p53 aggregates in cancer development. This study aims to test the «prion-like» features of p53. Our results show in vitro aggregation of the full length and N-terminally truncated protein (p53C, and penetration of these aggregates into cells. According to our findings, the aggregates enter cells using macropinocytosis, a non-specific pathway of entry. Lastly, we also show that once internalized by the cell, p53C aggregates can co-aggregate with endogenous p53 protein. Together, these findings suggest prion-like characteristics for p53 protein, based on the fact that p53 can spontaneously aggregate, these aggregates can penetrate cells and co-aggregate with cellular p53.

The p53-dependent radioadaptive response

Science.gov (United States)

Ohnishi, Takeo

We already reported that conditioning exposures at low doses, or at low dose-rates, lowered radiation-induced p53-dependent apoptosis in cultured cells in vitro and in the spleens of mice in vivo. In this study, the aim was to characterize the p53-dependent radioadaptive response at the molecular level. We used wild-type (wt) p53 and mutated (m) p53 containing cells derived from the human lung cancer H1299 cell line, which is p53-null. Cellular radiation sensitivities were determined with a colony-forming assay. The accumulation of p53, Hdm2, and iNOS was analyzed with Western blotting. The quantification of chromosomal aberrations was estimated by scoring dicentrics per cell. In wtp53 cells, it was demonstrated that the lack of p53 accumulation was coupled with the activation of Hdm2 after low dose irradiation (0.02 Gy). Although NO radicals were only minimally induced in wtp53 cells irradiated with a challenging irradiation (6 Gy) alone, NO radicals were seen to increase about 2-4 fold after challenging irradiation following a priming irradiation (0.02 Gy). Under similar irradiation conditions with a priming and challenging irradiation in wtp53 cells, induction of radioresistance and a depression of chromosomal aberrations were observed only in the absence of Pifithrin-α (a p53 inhibitor), RITA or Nutlin-3 (p53-Hdm2 interaction inhibitors), aminoguanidine (an iNOS inhibitor) and c-PTIO (an NO radical scavenger). On the other hand, in p53 dysfunctional cells, a radioadaptive response was not observed in the presence or absence of those inhibitors. Moreover, radioresistance developed when wtp53 cells were treated with ISDN (an NO generating agent) alone. These findings suggest that NO radicals are an initiator of the radioadaptive response acting through the activation of Hdm2 and the depression of p53 accumulations.

Thermal, spectroscopic and laser properties of Nd3+ in gadolinium scandium gallium garnet crystal produced by optical floating zone method

Science.gov (United States)

Tian, Li; Wang, Shuxian; Wu, Kui; Wang, Baolin; Yu, Haohai; Zhang, Huaijin; Cai, Huaqiang; Huang, Hui

2013-12-01

A neodymium-doped gadolinium scandium gallium garnet (Nd:GSGG) single crystal with dimensions of Φ 5 × 20 mm2 has been grown by means of optical floating zone (OFZ). X-ray powder diffraction (XRPD) result shows that the as-grown Nd:GSGG crystal possesses a cubic structure with space group Ia3d and a cell parameter of a = 1.2561 nm. Effective elemental segregation coefficients of the Nd:GSGG as-grown crystal were calculated by using X-ray fluorescence (XRF). The thermal properties of the Nd:GSGG crystal were systematically studied by measuring the specific heat, thermal expansion and thermal diffusion coefficient, and the thermal conductivity of this crystal was calculated. The absorption and luminescence spectra of Nd:GSGG were measured at room temperature (RT). By using the Judd-Ofelt (J-O) theory, the theoretical radiative lifetime was calculated and compared with the experimental result. Continuous wave (CW) laser performance was achieved with the Nd:GSGG at the wavelength of 1062 nm when it was pumped by a laser diode (LD). A maximum output power of 0.792 W at 1062 nm was obtained with a slope efficiency of 11.89% under a pump power of 7.36 W, and an optical-optical conversion efficiency of 11.72%.

14 CFR 460.53 - Security.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Security. 460.53 Section 460.53 Aeronautics and Space COMMERCIAL SPACE TRANSPORTATION, FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF....53 Security. An operator must implement security requirements to prevent any space flight participant...

40 CFR 73.53 - Notification.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Notification. 73.53 Section 73.53 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) SULFUR DIOXIDE ALLOWANCE SYSTEM Allowance Transfers § 73.53 Notification. (a) Notification of recordation. The...

AHP 2A: China's na53 mʑi 53 Tibetans: Life, Language and Folklore

Directory of Open Access Journals (Sweden)

Libu Lakhi (Li Jianfu 李建富, Dawa Tenzin ཟླ་བ་བསྟན་འཛིན།

2009-06-01

Full Text Available This remarkable book is the product of a fruitful collaboration among a native speaker of na53 mʑi53 kha11 tho11, Tibetan and Chinese consultants, and a dedicated group of Westerners resident in China. It affords the reader an intimate glimpse into traditional na53 mʑi53 life, now well on its way to disappearing along with hundreds of similar minority cultures in the world.

AHP 2B: China's na53 mʑi 53 Tibetans: Life, Language and Folklore

Directory of Open Access Journals (Sweden)

Libu Lakhi (Li Jianfu 李建富, Dawa Tenzin ཟླ་བ་བསྟན་འཛིན།

2009-06-01

Full Text Available This remarkable book is the product of a fruitful collaboration among a native speaker of na53 mʑi53 kha11 tho11, Tibetan and Chinese consultants, and a dedicated group of Westerners resident in China. It affords the reader an intimate glimpse into traditional na53 mʑi53 life, now well on its way to disappearing along with hundreds of similar minority cultures in the world.

7 CFR 1900.53 - Applicability.

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2010-01-01

... 7 Agriculture 12 2010-01-01 2010-01-01 false Applicability. 1900.53 Section 1900.53 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS-COOPERATIVE... GENERAL Adverse Decisions and Administrative Appeals § 1900.53 Applicability. (a) Appeals of adverse...

7 CFR 53.3 - Authority.

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2010-01-01

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15 CFR 400.53 - Information.

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2010-01-01

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27 CFR 53.1 - Introduction.

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2010-04-01

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45 CFR 86.53 - Recruitment.

Science.gov (United States)

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Recruitment. 86.53 Section 86.53 Public Welfare... in Employment in Education Programs or Activities Prohibited § 86.53 Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment...

Scandium complexes: physico-chemical study and evaluation of stability in vitro and in vivo for nuclear medicine application

International Nuclear Information System (INIS)

Kerdjoudj, Rabha

2014-01-01

Among the different isotopes of Scandium that can be used in nuclear medicine may be mentioned the 47 Sc and 44 Sc. The first decays by emitting an electron associated with a 159 keV gamma can thus be used either for radiotherapy or TEMP imaging. The 44 Sc (3.97 h) decays in 94.27% in case by emitting a positron, with a γ photon energy equal to 1.157 MeV. This isotope is then an ideal candidate for applications in PET imaging. Currently, the Cyclotron of high energy and high intensity ARRONAX produce 44 Sc and co-produces the isomeric state the 44m Sc (2.44 d). The 44m Sc has properties (E(γ) = 270 keV, 98.8%), which allows to consider its use as a potential in vivo generator. Previous work had demonstrated that the DOTA ligand is most suitable and stable for Sc. This thesis aims; make in evidence the feasibility of the in vivo 44m / 44 Sc generator. Initially a procedure was optimized and validated for the production of 44m / 44 Sc with a high specific activity and chemical purity. Radiolabeling of DOTA conjugated peptides was then developed and optimized. Theoretical and experimental studies have been performed in order to demonstrate the feasibility of 44m / 44 Sc as a potential in vivo generator. Finally, in vitro stability studies on radiolabeled 44m / 44 Sc complexes were performed, followed by biodistribution studies and PET imaging. (author)

Aluminum-Scandium Alloys: Material Characterization, Friction Stir Welding, and Compatibility With Hydrogen Peroxide (MSFC Center Director's Discretionary Fund Final Report, Proj. No. 04-14)

Science.gov (United States)

Lee, J. A.; Chen, P. S.

2004-01-01

This Technical Memorandum describes the development of several high-strength aluminum (Al) alloys that are compatible with hydrogen peroxide (H2O2) propellant for NASA Hypersonic-X (Hyper-X) vehicles fuel tanks and structures. The yield strengths for some of these Al-magnesium-based alloys are more than 3 times stronger than the conventional 5254-H112 Al alloy, while maintaining excellent H2O2 compatibility similar to class 1 5254 alloy. The alloy development strategy is to add scandium, zirconium, and other transitional metals with unique electrochemical properties, which will not act as catalysts, to decompose the highly concentrated 90 percent H2O2. Test coupons are machined from sheet metals for H2O2 long-term exposure testing and mechanical properties testing. In addition, the ability to weld the new alloys using friction stir welding has also been explored. The new high-strength alloys could represent an enabling material technology for Hyper-X vehicles, where flight weight reduction is a critical requirement.

14 CFR 171.53 - Reports.

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2010-01-01

... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Reports. 171.53 Section 171.53 Aeronautics... FACILITIES NON-FEDERAL NAVIGATION FACILITIES Instrument Landing System (ILS) Facilities § 171.53 Reports. The owner of each facility to which this subpart applies shall make the following reports, at the times...

32 CFR 643.53 - Consideration.

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2010-07-01

... 32 National Defense 4 2010-07-01 2010-07-01 true Consideration. 643.53 Section 643.53 National... Leases § 643.53 Consideration. (a) Unless otherwise authorized by this regulation or directed by the SA, the consideration for a lease of real estate will be the appraised fair market rental value. However...

42 CFR 21.53 - Examination.

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2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Examination. 21.53 Section 21.53 Public Health... Appointment § 21.53 Examination. The examination of candidates for original appointment as officers to any... education and their training and experience. In the discretion of the Surgeon General the examination of any...

PAF53 is essential in mammalian cells: CRISPR/Cas9 fails to eliminate PAF53 expression.

Science.gov (United States)

Rothblum, Lawrence I; Rothblum, Katrina; Chang, Eugenie

2017-05-15

When mammalian cells are nutrient and/or growth factor deprived, exposed to inhibitors of protein synthesis, stressed by heat shock or grown to confluence, rDNA transcription is essentially shut off. Various mechanisms are available to accomplish this downshift in ribosome biogenesis. Muramatsu's laboratory (Hanada et al., 1996) first demonstrated that mammalian PAF53 was essential for specific rDNA transcription and that PAF53 levels were regulated in response to growth factors. While S. cerevisae A49, the homologue of vertebrate PAF53, is not essential for viability (Liljelund et al., 1992), deletion of yA49 results in colonies that grow at 6% of the wild type rate at 25°C. Experiments described by Wang et al. (2015) identified PAF53 as a gene "essential for optimal proliferation". However, they did not discriminate genes essential for viability. Hence, in order to resolve this question, we designed a series of experiments to determine if PAF53 was essential for cell survival. We set out to delete the gene product from mammalian cells using CRISPR/CAS9 technology. Human 293 cells were transfected with lentiCRISPR v2 carrying genes for various sgRNA that targeted PAF53. In some experiments, the cells were cotransfected in parallel with plasmids encoding FLAG-tagged mouse PAF53. After treating the transfected cells with puromycin (to select for the lentiCRISPR backbone), cells were cloned and analyzed by western blots for PAF53 expression. Genomic DNA was amplified across the "CRISPRd" exon, cloned and sequenced to identify mutated PAF53 genes. We obtained cell lines in which the endogenous PAF53 gene was "knocked out" only when we rescued with FLAG-PAF53. DNA sequencing demonstrated that in the absence of ectopic PAF53 expression, cells demonstrated unique means of surviving; including recombination or the utilization of alternative reading frames. We never observed a clone in which one PAF53 gene is expressed, unless there was also ectopic expression In the

32 CFR 935.53 - Contempt.

Science.gov (United States)

2010-07-01

... 32 National Defense 6 2010-07-01 2010-07-01 false Contempt. 935.53 Section 935.53 National Defense... CODE Penalties § 935.53 Contempt. A Judge may, in any civil or criminal case or proceeding, punish any person for disobedience of any order of the Court, or for any contempt committed in the presence of the...

28 CFR 32.53 - Review.

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Review. 32.53 Section 32.53 Judicial... BENEFIT CLAIMS Director Appeals and Reviews § 32.53 Review. (a) Upon the filing of the approval (under subpart E of this part) of a claim, the Director shall review the same. (b) The Director may review— (1...

Serum sample levels of bromine, iron, scandium and zinc in preschool children of Atayal and Bunun aborigines living in central Taiwan

International Nuclear Information System (INIS)

Chien-Yi Chen; Ding-Bang Lin; Yuan-Yaw Wei

2006-01-01

This study determined bromine, iron, scandium and zinc serum levels in Taiwanese aboriginal preschool children living in remote mountainous areas to increase the understanding of the social, cultural, nutrient and ethnic background of the Taiwanese children. Seventy-three serum samples were taken from two ethnic groups of preschool children, Atayal aborigines (AAPC) and Bunun aborigines (BAPC). Sera of these children were freeze dried. Trace elements in sera were identified by instrumental neutron activation analysis (INAA). The accuracy and precision of INAA was evaluated using certified reference materials: Tomato Leaves (NIST-SRM 1570a) and Lichen (IAEA-336). Statistical analysis identified several different patterns for ethnic groups, gender and age via the two-tailed Student's t-test. Analytical results showed that the ranges of Br, Fe, Sc and Zn in sera were somewhat wide. The Zn serum levels (p < 0.05) and Br serum levels (p < 0.01) in the AAPC were significantly lower than those in the BAPC. However, there were no significant differences in Fe or Sc serum levels between the two groups. Analytical results were compared to published data for different counties. This study is the first investigating trace elements in Taiwanese aborigines and can be used to establish a much-needed serum element database. (author)

S100A4 interacts with p53 in the nucleus and promotes p53 degradation.

Science.gov (United States)

Orre, L M; Panizza, E; Kaminskyy, V O; Vernet, E; Gräslund, T; Zhivotovsky, B; Lehtiö, J

2013-12-05

S100A4 is a small calcium-binding protein that is commonly overexpressed in a range of different tumor types, and it is widely accepted that S100A4 has an important role in the process of cancer metastasis. In vitro binding assays has shown that S100A4 interacts with the tumor suppressor protein p53, indicating that S100A4 may have additional roles in tumor development. In the present study, we show that endogenous S100A4 and p53 interact in complex samples, and that the interaction increases after inhibition of MDM2-dependent p53 degradation using Nutlin-3A. Further, using proximity ligation assay, we show that the interaction takes place in the cell nucleus. S100A4 knockdown experiments in two p53 wild-type cell lines, A549 and HeLa, resulted in stabilization of p53 protein, indicating that S100A4 is promoting p53 degradation. Finally, we demonstrate that S100A4 knockdown leads to p53-dependent cell cycle arrest and increased cisplatin-induced apoptosis. Thus, our data add a new layer to the oncogenic properties of S100A4 through its inhibition of p53-dependent processes.

40 CFR 53.43 - Test procedures.

Science.gov (United States)

2010-07-01

... sampling zone (see § 53.42(d)). To meet the maximum blockage limit of § 53.42(a) or for convenience, part... PM10 § 53.43 Test procedures. (a) Sampling effectiveness—(1) Technical definition. The ratio (expressed... evenly spaced isokinetic samplers in the sampling zone (see § 53.42(d)) of the wind tunnel. Collect...

Regulation of autophagy by cytoplasmic p53.

Science.gov (United States)

Tasdemir, Ezgi; Maiuri, M Chiara; Galluzzi, Lorenzo; Vitale, Ilio; Djavaheri-Mergny, Mojgan; D'Amelio, Marcello; Criollo, Alfredo; Morselli, Eugenia; Zhu, Changlian; Harper, Francis; Nannmark, Ulf; Samara, Chrysanthi; Pinton, Paolo; Vicencio, José Miguel; Carnuccio, Rosa; Moll, Ute M; Madeo, Frank; Paterlini-Brechot, Patrizia; Rizzuto, Rosario; Szabadkai, Gyorgy; Pierron, Gérard; Blomgren, Klas; Tavernarakis, Nektarios; Codogno, Patrice; Cecconi, Francesco; Kroemer, Guido

2008-06-01

Multiple cellular stressors, including activation of the tumour suppressor p53, can stimulate autophagy. Here we show that deletion, depletion or inhibition of p53 can induce autophagy in human, mouse and nematode cells subjected to knockout, knockdown or pharmacological inhibition of p53. Enhanced autophagy improved the survival of p53-deficient cancer cells under conditions of hypoxia and nutrient depletion, allowing them to maintain high ATP levels. Inhibition of p53 led to autophagy in enucleated cells, and cytoplasmic, not nuclear, p53 was able to repress the enhanced autophagy of p53(-/-) cells. Many different inducers of autophagy (for example, starvation, rapamycin and toxins affecting the endoplasmic reticulum) stimulated proteasome-mediated degradation of p53 through a pathway relying on the E3 ubiquitin ligase HDM2. Inhibition of p53 degradation prevented the activation of autophagy in several cell lines, in response to several distinct stimuli. These results provide evidence of a key signalling pathway that links autophagy to the cancer-associated dysregulation of p53.

SV40 large T-p53 complex: evidence for the presence of two immunologically distinct forms of p53

International Nuclear Information System (INIS)

Milner, J.; Gamble, J.

1985-01-01

The transforming protein of SV40 is the large T antigen. Large T binds a cellular protein, p53, which is potentially oncogenic by virtue of its functional involvement in the control of cell proliferation. This raises the possibility that p53 may mediate, in part, the transforming function of SV40 large T. Two immunologically distinct forms of p53 have been identified in normal cells: the forms are cell-cycle dependent, one being restricted to nondividing cells (p53-Go) and the second to dividing cells (p53-G divided by). The authors have now dissociated and probed the multimeric complex of SV40 large T-p53 for the presence of immunologically distinct forms of p53. Here they present evidence for the presence of p53-Go and p53-G divided by complexed with SV40 large T

The removal of bisphenol A from aqueous solutions by MIL-53(Al) and mesostructured MIL-53(Al).

Science.gov (United States)

Zhou, Meimei; Wu, Yi-Nan; Qiao, Junlian; Zhang, Jing; McDonald, Amanda; Li, Guangtao; Li, Fengting

2013-09-01

In this work, metal-organic framework MIL-53(Al){Al(OH)[O2C-C6H4-CO2]} and MIL-53(Al)-F127{Al(OH)[O2C-C6H4-CO2]} were synthesized and used as sorbents to remove bisphenol A (BPA) from aqueous system. The sorption kinetics data of BPA were found to be in agreement with the pseudo-second-order model. The equilibrium sorption amounts of BPA on MIL-53(Al) and MIL-53(Al)-F127 reached 329.2±16.5 and 472.7±23.6 mg g(-1), respectively, far more than that of commercial activated carbons (ranging from 129.6 to 263.1 mg g(-1)). Both MIL-53(Al) and MIL-53(Al)-F127 could remove BPA fast from aqueous solutions, and the required contact time to reach equilibrium was approximately 90 min for MIL-53(Al) and 30 min for MIL-53(Al)-F127, respectively. The optimum pH levels for the removal of BPA using MIL-53 (Al) and MIL-53(Al)-F127 were 4 and 6 separately. The optimum temperature for the sorption behavior of BPA on the two sorbents was 20 °C. The results performed show that the resulting products, as one kind of MOFs, can be regarded as a new class of sorbents for water treatment and could find great applications in the fields of environmental water pollution control and resources reuse. Copyright © 2013 Elsevier Inc. All rights reserved.

p53 Over-expression and p53 mutations in colon carcinomas: Relation to dietary risk factors

NARCIS (Netherlands)

Voskuil, D.W.; Kampman, E.; Kraats, A.A. van; Balder, H.F.; Muijen, G.N.P. van; Goldbohm, R.A.; Veer, P. van 't

1999-01-01

Epidemiological studies have suggested that dietary factors may differently affect p53-dependent and p53-independent pathways to colon cancer. Results of such studies may depend on the method used to assess p53 status. This case-control study of 185 colon-cancer cases and 259 controls examines this

The effect of scandium addition on microstructure and mechanical properties of Al–Si–Mg alloy: A multi-refinement modifier

Energy Technology Data Exchange (ETDEWEB)

Xu, Cong, E-mail: xucong55555@gmail.com [Key Laboratory of Aerospace Advanced Materials and Performance of Ministry of Education, School of Material Science and Engineering, Beihang University, Beijing 100191 (China); Xiao, Wenlong, E-mail: wlxiao@buaa.edu.cn [Key Laboratory of Aerospace Advanced Materials and Performance of Ministry of Education, School of Material Science and Engineering, Beihang University, Beijing 100191 (China); Hanada, Shuji [Institute for Materials Research, Tohoku University, Sendai 980-8577 (Japan); Yamagata, Hiroshi [Center for Advanced Die Engineering and Technology, Gifu University, 1-1 Yanagido, Gifu City, Gifu 501-1193 (Japan); Ma, Chaoli [Key Laboratory of Aerospace Advanced Materials and Performance of Ministry of Education, School of Material Science and Engineering, Beihang University, Beijing 100191 (China)

2015-12-15

Effect of scandium (Sc) additions on the microstructure, mechanical properties and fracture behavior of Al–Si–Mg casting alloy (F357) were systematically investigated. It was found that Sc addition caused a multi-refining efficiency on the microstructure of as-cast F357 alloy, including refinement of grains and secondary dendrite arm spacing (SDAS), modification of eutectic Si and harmless disposal of β-Al{sub 5}FeSi phase. Subsequent T6 heat treatment had further induced the complete spheroidization of eutectic Si and precipitation of fine secondary Al{sub 3}Sc dispersoids in the Sc modified alloys. Thus the mechanical properties, especially the ductility, were significantly enhanced by the addition of Sc combined with the heat treatment. The highest ultimate tensile strength, yield strength and elongation were achieved in 0.8 wt.% Sc modified F357 alloy combined with T6 heat treatment. Furthermore, fractographic examinations indicated that the ductile fracture mechanism served as a dominate role in the modified alloys due to the formation of fine, deep and uniformly distributed dimples. - Highlights: • Detailed characterization of the multi-refining microstructure of Sc modified F357 alloy was performed. • The multi-refinement was proposed to refine grain and SDAS, modify eutectic Si and β-phase. • Sc modifier combined with T6 treatment is effective in improving tensile properties. • Modification of eutectic Si in F357 alloy with Sc is consistent with the IIT mechanism.

48 CFR 53.209 - Contractor qualifications.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Contractor qualifications. 53.209 Section 53.209 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS FORMS Prescription of Forms 53.209 Contractor qualifications. ...

48 CFR 53.242 - Contract administration.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Contract administration. 53.242 Section 53.242 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS FORMS Prescription of Forms 53.242 Contract administration. ...

Human neuroblastoma cells with acquired resistance to the p53 activator RITA retain functional p53 and sensitivity to other p53 activating agents.

Science.gov (United States)

Michaelis, M; Rothweiler, F; Agha, B; Barth, S; Voges, Y; Löschmann, N; von Deimling, A; Breitling, R; Doerr, H Wilhelm; Rödel, F; Speidel, D; Cinatl, J

2012-04-05

Adaptation of wild-type p53 expressing UKF-NB-3 cancer cells to the murine double minute 2 inhibitor nutlin-3 causes de novo p53 mutations at high frequency (13/20) and multi-drug resistance. Here, we show that the same cells respond very differently when adapted to RITA, a drug that, like nutlin-3, also disrupts the p53/Mdm2 interaction. All of the 11 UKF-NB-3 sub-lines adapted to RITA that we established retained functional wild-type p53 although RITA induced a substantial p53 response. Moreover, all RITA-adapted cell lines remained sensitive to nutlin-3, whereas only five out of 10 nutlin-3-adapted cell lines retained their sensitivity to RITA. In addition, repeated adaptation of the RITA-adapted sub-line UKF-NB-3(r)RITA(10 μM) to nutlin-3 resulted in p53 mutations. The RITA-adapted UKF-NB-3 sub-lines displayed no or less pronounced resistance to vincristine, cisplatin, and irradiation than nutlin-3-adapted UKF-NB-3 sub-lines. Furthermore, adaptation to RITA was associated with fewer changes at the expression level of antiapoptotic factors than observed with adaptation to nutlin-3. Transcriptomic analyses indicated the RITA-adapted sub-lines to be more similar at the gene expression level to the parental UKF-NB-3 cells than nutlin-3-adapted UKF-NB-3 sub-lines, which correlates with the observed chemotherapy and irradiation sensitivity phenotypes. In conclusion, RITA-adapted cells retain functional p53, remain sensitive to nutlin-3, and display a less pronounced resistance phenotype than nutlin-3-adapted cells.

7 CFR 1794.53 - Environmental report.

Science.gov (United States)

2010-01-01

... 7 Agriculture 12 2010-01-01 2010-01-01 false Environmental report. 1794.53 Section 1794.53... AGRICULTURE (CONTINUED) ENVIRONMENTAL POLICIES AND PROCEDURES Procedure for Environmental Assessments With Scoping § 1794.53 Environmental report. (a) After scoping procedures have been completed, RUS shall...

29 CFR 1926.53 - Ionizing radiation.

Science.gov (United States)

2010-07-01

... 29 Labor 8 2010-07-01 2010-07-01 false Ionizing radiation. 1926.53 Section 1926.53 Labor... § 1926.53 Ionizing radiation. (a) In construction and related activities involving the use of sources of ionizing radiation, the pertinent provisions of the Nuclear Regulatory Commission's Standards for...

14 CFR 23.53 - Takeoff performance.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Takeoff performance. 23.53 Section 23.53... STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Flight Performance § 23.53 Takeoff performance. (a) For normal, utility, and acrobatic category airplanes, the takeoff distance must be...

Screening of medicinal plant phytochemicals as natural antagonists of p53-MDM2 interaction to reactivate p53 functioning.

Science.gov (United States)

Riaz, Muhammad; Ashfaq, Usman A; Qasim, Muhammad; Yasmeen, Erum; Ul Qamar, Muhammad T; Anwar, Farooq

2017-10-01

In most types of cancer, overexpression of murine double minute 2 (MDM2) often leads to inactivation of p53. The crystal structure of MDM2, with a 109-residue amino-terminal domain, reveals that MDM2 has a core hydrophobic region to which p53 binds as an amphipathic α helix. The interface depends on the steric complementarity between MDM2 and the hydrophobic region of p53. Especially, on p53's triad, amino acids Phe19, Trp23 and Leu26 bind to the MDM2 core. Results from studies suggest that the structural motif of both p53 and MDM2 can be attributed to similarities in the amphipathic α helix. Thus, in the current investigation it is hypothesized that the similarity in the structural motif might be the cause of p53 inactivation by MDM2. Hence, molecular docking and phytochemical screening approaches are appraised to inhibit the hydrophobic cleft of MDM2 and to stop p53-MDM2 interaction, resulting in reactivation of p53 activity. For this purpose, a library of 2295 phytochemicals were screened against p53-MDM2 to find potential candidates. Of these, four phytochemicals including epigallocatechin gallate, alvaradoin M, alvaradoin E and nordihydroguaiaretic acid were found to be potential inhibitors of p53-MDM2 interaction. The screened phytochemicals, derived from natural extracts, may have negligible side effects and can be explored as potent antagonists of p53-MDM2 interactions, resulting in reactivation of the normal transcription of p53.

4 CFR 5.3 - Merit pay.

Science.gov (United States)

2010-01-01

... 4 Accounts 1 2010-01-01 2010-01-01 false Merit pay. 5.3 Section 5.3 Accounts GOVERNMENT ACCOUNTABILITY OFFICE PERSONNEL SYSTEM COMPENSATION § 5.3 Merit pay. The Comptroller General may promulgate regulations establishing a merit pay system for such employees of the Government Accountability Office as the...

19 CFR 134.53 - Examination packages.

Science.gov (United States)

2010-04-01

... 19 Customs Duties 1 2010-04-01 2010-04-01 false Examination packages. 134.53 Section 134.53... TREASURY COUNTRY OF ORIGIN MARKING Articles Found Not Legally Marked § 134.53 Examination packages. (a) Site of marking—(1) Customs custody. Articles (or containers) in examination packages may be marked by...

7 CFR 3430.53 - Program income.

Science.gov (United States)

2010-01-01

... 7 Agriculture 15 2010-01-01 2010-01-01 false Program income. 3430.53 Section 3430.53 Agriculture...-GENERAL AWARD ADMINISTRATIVE PROVISIONS Post-Award and Closeout § 3430.53 Program income. (a) General... for program income related to projects financed in whole or in part with Federal funds. (b) Addition...

36 CFR 5.3 - Business operations.

Science.gov (United States)

2010-07-01

... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Business operations. 5.3 Section 5.3 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR COMMERCIAL AND PRIVATE OPERATIONS § 5.3 Business operations. Engaging in or soliciting any business in park...

47 CFR 53.209 - Biennial audit.

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2010-10-01

... 47 Telecommunication 3 2010-10-01 2010-10-01 false Biennial audit. 53.209 Section 53.209... PROVISIONS CONCERNING BELL OPERATING COMPANIES Separate Affiliate; Safeguards § 53.209 Biennial audit. (a) A... obtain and pay for a Federal/State joint audit every two years conducted by an independent auditor to...

7 CFR 550.53 - Financial reporting.

Science.gov (United States)

2010-01-01

... 7 Agriculture 6 2010-01-01 2010-01-01 false Financial reporting. 550.53 Section 550.53 Agriculture... Reports and Records § 550.53 Financial reporting. Financial Status Report. (a) Each REE Agency shall.... A financial status report shall consist of the following information: (1) The name and address of...

Targeting the p53 Pathway in Ewing Sarcoma

Science.gov (United States)

Neilsen, Paul M.; Pishas, Kathleen I.; Callen, David F.; Thomas, David M.

2011-01-01

The p53 tumour suppressor plays a pivotal role in the prevention of oncogenic transformation. Cancers frequently evade the potent antitumour surveillance mechanisms of p53 through mutation of the TP53 gene, with approximately 50% of all human malignancies expressing dysfunctional, mutated p53 proteins. Interestingly, genetic lesions in the TP53 gene are only observed in 10% of Ewing Sarcomas, with the majority of these sarcomas expressing a functional wild-type p53. In addition, the p53 downstream signaling pathways and DNA-damage cell cycle checkpoints remain functionally intact in these sarcomas. This paper summarizes recent insights into the functional capabilities and regulation of p53 in Ewing Sarcoma, with a particular focus on the cross-talk between p53 and the EWS-FLI1 gene rearrangement frequently associated with this disease. The development of several activators of p53 is discussed, with recent evidence demonstrating the potential of small molecule p53 activators as a promising systemic therapeutic approach for the treatment of Ewing Sarcomas with wild-type p53. PMID:21197471

The novel fusion proteins, GnRH-p53 and GnRHIII-p53, expression and their anti-tumor effect.

Directory of Open Access Journals (Sweden)

Peiyuan Jia

Full Text Available p53, one of the most well studied tumor suppressor factor, is responsible to a variety of damage owing to the induction of apoptosis and cell cycle arrest in the tumor cells. More than 50% of human tumors contain mutation or deletion of p53. Gonadotrophin-releasing hormone (GnRH, as the ligand of Gonadotrophin-releasing hormone receptor (GnRH-R, was used to deliver p53 into tumor cells. The p53 fusion proteins GnRH-p53 and GnRH iii-p53 were expressed and their targeted anti-tumor effects were determined. GnRH mediates its fusion proteins transformation into cancer cells. The intracellular delivery of p53 fusion proteins exerted the inhibition of the growth of H1299 cells in vitro and the reduction of tumor volume in vivo. Their anti-tumor effect was functioned by the apoptosis and cell cycle arrest induced by p53. Hence, the fusion protein could be a novel protein drug for anti-tumor therapy.

Enhancement of radiosensitivity of recombinant Ad-p53 gene on human lung adenocarcinoma cell with different p53 status

International Nuclear Information System (INIS)

Pang Dequan; Wang Peiguo; Wang Ping; Zhang Weiming

2008-01-01

Objective: To investigate the enhancement of radiosensitivity of recombinant Ad-p53 gene on human lung adenocarcinoma cell lines(A549 and GLC-82) with different p53 status in vitro. Methods: Two human lung adenocarcinoma cell lines of A549 and GLC-82 were examined on their difference in p53 status with immunohistochemistry stain and PCR-SSCP technique. Expand Ad-wtp53 was transfected into tumor cells. Clonogenic assays were performed to evaluate the inhibition effect on cell growth and the degree of sensitization to irradiation. Apoptosis and cell cycle changes were determined using the flow cytometry assay. Results: The A549 cell line presented positive P53 expression while GLC-82 negative. GLC-82 bore mutant p53 on the exon 7. The wtp53 gene could be efficiently expressed in the two cell lines and greatly inhibit the cell growth. Its efficiency didn't depend on the intrinsic p53 genetic status. After irradiation, its function of inducing G 1 arrest and apoptosis on GLC-82 cell line was much stronger than the A549 cell line. In both the A549 and GLC-82 cell lines, the combination of Ad-p53 plus radiation resulted in more apoptosis than the others. There was no significant difference between two groups. Conclusions: Ad-p53 can depress the tumor growth and enhance the radiosensitivity of human lung adenocarcinoma cells. And this effect is independent of endogenous p53 status. (authors)

25 CFR 700.53 - Dwelling, replacement.

Science.gov (United States)

2010-04-01

... 25 Indians 2 2010-04-01 2010-04-01 false Dwelling, replacement. 700.53 Section 700.53 Indians THE... Policies and Instructions Definitions § 700.53 Dwelling, replacement. The term replacement dwelling means a dwelling selected by the head of a household as a replacement dwelling that meets the criteria of this...

7 CFR 15a.53 - Recruitment.

Science.gov (United States)

2010-01-01

... 7 Agriculture 1 2010-01-01 2010-01-01 false Recruitment. 15a.53 Section 15a.53 Agriculture Office... Activities Prohibited § 15a.53 Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment and hiring of employees. Where a recipient has...

42 CFR 71.53 - Nonhuman primates.

Science.gov (United States)

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Nonhuman primates. 71.53 Section 71.53 Public... FOREIGN QUARANTINE Importations § 71.53 Nonhuman primates. (a) Definitions. As used in this section the... nonhuman primates from a foreign country within a period of 31 days, beginning with the importation date...

P53 family members modulate the expression of PRODH, but not PRODH2, via intronic p53 response elements.

Directory of Open Access Journals (Sweden)

Ivan Raimondi

Full Text Available The tumor suppressor p53 was previously shown to markedly up-regulate the expression of the PRODH gene, encoding the proline dehydrogenase (PRODH enzyme, which catalyzes the first step in proline degradation. Also PRODH2, which degrades 4-hydroxy-L-proline, a product of protein (e.g. collagen catabolism, was recently described as a p53 target. Here, we confirmed p53-dependent induction of endogenous PRODH in response to genotoxic damage in cell lines of different histological origin. We established that over-expression of TAp73β or TAp63β is sufficient to induce PRODH expression in p53-null cells and that PRODH expression parallels the modulation of endogenous p73 by genotoxic drugs in several cell lines. The p53, p63, and p73-dependent transcriptional activation was linked to specific intronic response elements (REs, among those predicted by bioinformatics tools and experimentally validated by a yeast-based transactivation assay. p53 occupancy measurements were validated in HCT116 and MCF7 human cell lines. Conversely, PRODH2 was not responsive to p63 nor p73 and, at best, could be considered a weak p53 target. In fact, minimal levels of PRODH2 transcript induction by genotoxic stress was observed exclusively in one of four p53 wild-type cell lines tested. Consistently, all predicted p53 REs in PRODH2 were poor matches to the p53 RE consensus and showed very weak responsiveness, only to p53, in the functional assay. Taken together, our results highlight that PRODH, but not PRODH2, expression is under the control of p53 family members, specifically p53 and p73. This supports a deeper link between proteins of the p53-family and metabolic pathways, as PRODH modulates the balance of proline and glutamate levels and those of their derivative alpha-keto-glutarate (α-KG under normal and pathological (tumor conditions.

DRAGO (KIAA0247), a new DNA damage-responsive, p53-inducible gene that cooperates with p53 as oncosuppressor. [Corrected].

Science.gov (United States)

Polato, Federica; Rusconi, Paolo; Zangrossi, Stefano; Morelli, Federica; Boeri, Mattia; Musi, Alberto; Marchini, Sergio; Castiglioni, Vittoria; Scanziani, Eugenio; Torri, Valter; Broggini, Massimo

2014-04-01

p53 influences genomic stability, apoptosis, autophagy, response to stress, and DNA damage. New p53-target genes could elucidate mechanisms through which p53 controls cell integrity and response to damage. DRAGO (drug-activated gene overexpressed, KIAA0247) was characterized by bioinformatics methods as well as by real-time polymerase chain reaction, chromatin immunoprecipitation and luciferase assays, time-lapse microscopy, and cell viability assays. Transgenic mice (94 p53(-/-) and 107 p53(+/-) mice on a C57BL/6J background) were used to assess DRAGO activity in vivo. Survival analyses were performed using Kaplan-Meier curves and the Mantel-Haenszel test. All statistical tests were two-sided. We identified DRAGO as a new p53-responsive gene induced upon treatment with DNA-damaging agents. DRAGO is highly conserved, and its ectopic overexpression resulted in growth suppression and cell death. DRAGO(-/-) mice are viable without macroscopic alterations. However, in p53(-/-) or p53(+/-) mice, the deletion of both DRAGO alleles statistically significantly accelerated tumor development and shortened lifespan compared with p53(-/-) or p53(+/-) mice bearing wild-type DRAGO alleles (p53(-/-), DRAGO(-/-) mice: hazard ratio [HR] = 3.25, 95% confidence interval [CI] = 1.7 to 6.1, P < .001; p53(+/-), DRAGO(-/-) mice: HR = 2.35, 95% CI = 1.3 to 4.0, P < .001; both groups compared with DRAGO(+/+) counterparts). DRAGO mRNA levels were statistically significantly reduced in advanced-stage, compared with early-stage, ovarian tumors, but no mutations were found in several human tumors. We show that DRAGO expression is regulated both at transcriptional-through p53 (and p73) and methylation-dependent control-and post-transcriptional levels by miRNAs. DRAGO represents a new p53-dependent gene highly regulated in human cells and whose expression cooperates with p53 in tumor suppressor functions.

Interplay between PTB and miR-1285 at the p53 3'UTR modulates the levels of p53 and its isoform Δ40p53α.

Science.gov (United States)

Katoch, Aanchal; George, Biju; Iyyappan, Amrutha; Khan, Debjit; Das, Saumitra

2017-09-29

p53 and its translational isoform Δ40p53 are involved in many important cellular functions like cell cycle, cell proliferation, differentiation and metabolism. Expression of both the isoforms can be regulated at different steps. In this study, we explored the role of 3'UTR in regulating the expression of these two translational isoforms. We report that the trans acting factor, Polypyrimidine Tract Binding protein (PTB), also interacts specifically with 3'UTR of p53 mRNA and positively regulates expression of p53 isoforms. Our results suggest that there is interplay between miRNAs and PTB at the 3'UTR under normal and stress conditions like DNA damage. Interestingly, PTB showed some overlapping binding regions in the p53 3'UTR with miR-1285. In fact, knockdown of miR-1285 as well as expression of p53 3'UTR with mutated miR-1285 binding sites resulted in enhanced association of PTB with the 3'UTR, which provides mechanistic insights of this interplay. Taken together, the results provide a plausible molecular basis of how the interplay between miRNAs and the PTB protein at the 3'UTR can play pivotal role in fine tuning the expression of the two p53 isoforms. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

48 CFR 53.205-1 - Paid advertisements.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Paid advertisements. 53.205-1 Section 53.205-1 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS FORMS Prescription of Forms 53.205-1 Paid advertisements. SF 1449, prescribed in 53.212, shall be used to place orders for paid...

p53 mutations promote proteasomal activity.

Science.gov (United States)

Oren, Moshe; Kotler, Eran

2016-07-27

p53 mutations occur very frequently in human cancer. Besides abrogating the tumour suppressive functions of wild-type p53, many of those mutations also acquire oncogenic gain-of-function activities. Augmentation of proteasome activity is now reported as a common gain-of-function mechanism shared by different p53 mutants, which promotes cancer resistance to proteasome inhibitors.

On new ternary equiatomic scandium transition metal aluminum compounds ScTAl with T = Cr, Ru, Ag, Re, Pt, and Au

Energy Technology Data Exchange (ETDEWEB)

Radzieowski, Mathis; Janka, Oliver [Muenster Univ. (Germany). Inst. fuer Anorganische und Analytische Chemie; Benndorf, Christopher [Muenster Univ. (Germany). Inst. fuer Anorganische und Analytische Chemie; Muenster Univ. (Germany). Inst. fuer Physikalische Chemie; Haverkamp, Sandra [Muenster Univ. (Germany). Inst. fuer Physikalische Chemie; Eckert, Hellmut [Muenster Univ. (Germany). Inst. fuer Physikalische Chemie; University of Sao Paulo, Sao Carlos, SP (Brazil). Inst. of Physics

2016-08-01

The new equiatomic scandium transition metal aluminides ScTAl for T = Cr, Ru, Ag, Re, Pt, and Au were obtained by arc-melting of the elements followed by subsequent annealing for crystal growth. The samples were studied by powder and single crystal X-ray diffraction. The structures of three compounds were refined from single crystal X-ray diffractometer data: ScCrAl, MgZn{sub 2} type, P6{sub 3}/mmc, a = 525.77(3), c = 858.68(5) pm, R{sub 1} = 0.0188, wR{sub 2} = 0.0485, 204 F{sup 2} values, 13 variables, ScPtAl, TiNiSi type, Pnma, a = 642.83(4), b = 428.96(2), c = 754.54(5) pm, R{sub 1} = 0.0326, wR{sub 2} = 0.0458, 448 F{sup 2} values, 20 variables and ScAuAl, HfRhSn type, P anti 62c, a = 722.88(4), c = 724.15(4) pm, R{sub 1} = 0.0316, wR{sub 2} = 0.0653, 512 F{sup 2} values, 18 variables. Phase pure samples of all compounds were furthermore investigated by magnetic susceptibility measurements, and Pauli-paramagnetism but no superconductivity was observed down to 2.1 K for all of them. The local structural features and disordering phenomena have been characterized by {sup 27}Al and {sup 45}Sc magic angle spinning (MAS) and static NMR spectroscopic investigations.

40 CFR 407.53 - [Reserved

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 28 2010-07-01 2010-07-01 true [Reserved] 407.53 Section 407.53 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS CANNED AND PRESERVED FRUITS AND VEGETABLES PROCESSING POINT SOURCE CATEGORY Dehydrated Potato Products...

The expanding universe of p53 targets.

Science.gov (United States)

Menendez, Daniel; Inga, Alberto; Resnick, Michael A

2009-10-01

The p53 tumour suppressor is modified through mutation or changes in expression in most cancers, leading to the altered regulation of hundreds of genes that are directly influenced by this sequence-specific transcription factor. Central to the p53 master regulatory network are the target response element (RE) sequences. The extent of p53 transactivation and transcriptional repression is influenced by many factors, including p53 levels, cofactors and the specific RE sequences, all of which contribute to the role that p53 has in the aetiology of cancer. This Review describes the identification and functionality of REs and highlights the inclusion of non-canonical REs that expand the universe of genes and regulation mechanisms in the p53 tumour suppressor network.

p53-dependent and p53-independent anticancer activity of a new indole derivative in human osteosarcoma cells

Energy Technology Data Exchange (ETDEWEB)

Cappadone, C., E-mail: concettina.cappadone@unibo.it [Department of Pharmacy and Biotechnology, University of Bologna, Bologna (Italy); Stefanelli, C. [Department for Life Quality Studies, University of Bologna, Rimini Campus, Rimini (Italy); Malucelli, E. [Department of Pharmacy and Biotechnology, University of Bologna, Bologna (Italy); Zini, M. [Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna (Italy); Onofrillo, C. [Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna (Italy); Locatelli, A.; Rambaldi, M.; Sargenti, A. [Department of Pharmacy and Biotechnology, University of Bologna, Bologna (Italy); Merolle, L. [ELETTRA–Sincrotrone Trieste S.C.p.A., Trieste (Italy); Farruggia, G. [Department of Pharmacy and Biotechnology, University of Bologna, Bologna (Italy); National Institute of Biostructures and Biosystems, Roma (Italy); Graziadio, A. [Department of Pharmacy and Biotechnology, University of Bologna, Bologna (Italy); Montanaro, L. [Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna (Italy); Iotti, S. [Department of Pharmacy and Biotechnology, University of Bologna, Bologna (Italy); National Institute of Biostructures and Biosystems, Roma (Italy)

2015-11-13

Osteosarcoma (OS) is the most common primary malignant tumor of bone, occurring most frequently in children and adolescents. The mechanism of formation and development of OS have been studied for a long time. Tumor suppressor pathway governed by p53 gene are known to be involved in the pathogenesis of osteosarcoma. Moreover, loss of wild-type p53 activity is thought to be a major predictor of failure to respond to chemotherapy in various human cancers. In previous studies, we described the activity of a new indole derivative, NSC743420, belonging to the tubulin inhibitors family, capable to induce apoptosis and arrest of the cell cycle in the G2/M phase of various cancer cell lines. However, this molecule has never been tested on OS cell line. Here we address the activity of NSC743420 by examine whether differences in the p53 status could influence its effects on cell proliferation and death of OS cells. In particular, we compared the effect of the tested molecule on p53-wild type and p53-silenced U2OS cells, and on SaOS2 cell line, which is null for p53. Our results demonstrated that NSC743420 reduces OS cell proliferation by p53-dependent and p53-independent mechanisms. In particular, the molecule induces proliferative arrest that culminate to apoptosis in SaOS2 p53-null cells, while it brings a cytostatic and differentiating effect in U2OS cells, characterized by the cell cycle arrest in G0/G1 phase and increased alkaline phosphatase activity. - Highlights: • The indole derivative NSC743420 induces antitumor effects on osteosarcoma cells. • p53 status could drive the activity of antitumor agents on osteosarcoma cells. • NSC743420 induces cytostatic and differentiating effects on U2OS cells. • NSC743420 causes apoptosis on p53-null SaOS2 cells.

p53-dependent and p53-independent anticancer activity of a new indole derivative in human osteosarcoma cells

International Nuclear Information System (INIS)

Cappadone, C.; Stefanelli, C.; Malucelli, E.; Zini, M.; Onofrillo, C.; Locatelli, A.; Rambaldi, M.; Sargenti, A.; Merolle, L.; Farruggia, G.; Graziadio, A.; Montanaro, L.; Iotti, S.

2015-01-01

Osteosarcoma (OS) is the most common primary malignant tumor of bone, occurring most frequently in children and adolescents. The mechanism of formation and development of OS have been studied for a long time. Tumor suppressor pathway governed by p53 gene are known to be involved in the pathogenesis of osteosarcoma. Moreover, loss of wild-type p53 activity is thought to be a major predictor of failure to respond to chemotherapy in various human cancers. In previous studies, we described the activity of a new indole derivative, NSC743420, belonging to the tubulin inhibitors family, capable to induce apoptosis and arrest of the cell cycle in the G2/M phase of various cancer cell lines. However, this molecule has never been tested on OS cell line. Here we address the activity of NSC743420 by examine whether differences in the p53 status could influence its effects on cell proliferation and death of OS cells. In particular, we compared the effect of the tested molecule on p53-wild type and p53-silenced U2OS cells, and on SaOS2 cell line, which is null for p53. Our results demonstrated that NSC743420 reduces OS cell proliferation by p53-dependent and p53-independent mechanisms. In particular, the molecule induces proliferative arrest that culminate to apoptosis in SaOS2 p53-null cells, while it brings a cytostatic and differentiating effect in U2OS cells, characterized by the cell cycle arrest in G0/G1 phase and increased alkaline phosphatase activity. - Highlights: • The indole derivative NSC743420 induces antitumor effects on osteosarcoma cells. • p53 status could drive the activity of antitumor agents on osteosarcoma cells. • NSC743420 induces cytostatic and differentiating effects on U2OS cells. • NSC743420 causes apoptosis on p53-null SaOS2 cells.

44 CFR 5.3 - Definitions.

Science.gov (United States)

2010-10-01

... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Definitions. 5.3 Section 5.3 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY... means all books, papers, maps, photographs, or other documentary materials, regardless of physical form...

9 CFR 53.1 - Definitions.

Science.gov (United States)

2010-01-01

...). Animals. Livestock, poultry, and all other members of the animal kingdom, including birds whether... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Definitions. 53.1 Section 53.1 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE COOPERATIVE...

Interplay between PTB and miR-1285 at the p53 3′UTR modulates the levels of p53 and its isoform Δ40p53α

Science.gov (United States)

Katoch, Aanchal; George, Biju; Iyyappan, Amrutha; Khan, Debjit

2017-01-01

Abstract p53 and its translational isoform Δ40p53 are involved in many important cellular functions like cell cycle, cell proliferation, differentiation and metabolism. Expression of both the isoforms can be regulated at different steps. In this study, we explored the role of 3′UTR in regulating the expression of these two translational isoforms. We report that the trans acting factor, Polypyrimidine Tract Binding protein (PTB), also interacts specifically with 3′UTR of p53 mRNA and positively regulates expression of p53 isoforms. Our results suggest that there is interplay between miRNAs and PTB at the 3′UTR under normal and stress conditions like DNA damage. Interestingly, PTB showed some overlapping binding regions in the p53 3′UTR with miR-1285. In fact, knockdown of miR-1285 as well as expression of p53 3′UTR with mutated miR-1285 binding sites resulted in enhanced association of PTB with the 3′UTR, which provides mechanistic insights of this interplay. Taken together, the results provide a plausible molecular basis of how the interplay between miRNAs and the PTB protein at the 3′UTR can play pivotal role in fine tuning the expression of the two p53 isoforms. PMID:28973454

RITA can induce cell death in p53-defective cells independently of p53 function via activation of JNK/SAPK and p38.

Science.gov (United States)

Weilbacher, A; Gutekunst, M; Oren, M; Aulitzky, W E; van der Kuip, H

2014-07-10

Significant advances have been made in the development of small molecules blocking the p53/MDM2 interaction. The Mdm2 inhibitor Nutlin-3 is restricted to tumors carrying wtp53. In contrast, RITA, a compound that binds p53, has recently been shown also to restore transcriptional functions of mtp53. As more than 50% of solid tumors carry p53 mutations, RITA promises to be a more effective therapeutic strategy than Nutlin-3. We investigated effects of RITA on apoptosis, cell cycle and induction of 45 p53 target genes in a panel of 14 cell lines from different tumor entities with different p53 status as well as primary lymphocytes and fibroblasts. Nine cell strains expressed wtp53, four harbored mtp53, and three were characterized by the loss of p53 protein. A significant induction of cell death upon RITA was observed in 7 of 16 cell lines. The nonmalignant cells in our panel were substantially less sensitive. We found that in contrast to Nultin-3, RITA is capable to induce cell death not only in tumor cells harboring wtp53 and mtp53 but also in p53-null cells. Importantly, whereas p53 has a central role for RITA-mediated effects in wtp53 cells, neither p53 nor p63 or p73 were essential for the RITA response in mtp53 or p53-null cells in our panel demonstrating that besides the known p53-dependent action of RITA in wtp53 cells, RITA can induce cell death also independently of p53 in cells harboring defective p53. We identified an important role of both p38 and JNK/SAPK for sensitivity to RITA in these cells leading to a typical caspase- and BAX/BAK-dependent mitochondrial apoptosis. In conclusion, our data demonstrate that RITA can induce apoptosis through p38 and JNK/SAPK not only in tumor cells harboring wtp53 and mtp53 but also in p53-null cells, making RITA an interesting tumor-selective drug.

34 CFR 106.53 - Recruitment.

Science.gov (United States)

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false Recruitment. 106.53 Section 106.53 Education... Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment and hiring of employees. Where a recipient has been found to be presently...

RELAP5-3D User Problems

Energy Technology Data Exchange (ETDEWEB)

Riemke, Richard Allan

2002-09-01

The Reactor Excursion and Leak Analysis Program with 3D capability1 (RELAP5-3D) is a reactor system analysis code that has been developed at the Idaho National Engineering and Environmental Laboratory (INEEL) for the U. S. Department of Energy (DOE). The 3D capability in RELAP5-3D includes 3D hydrodynamics2 and 3D neutron kinetics3,4. Assessment, verification, and validation of the 3D capability in RELAP5-3D is discussed in the literature5,6,7,8,9,10. Additional assessment, verification, and validation of the 3D capability of RELAP5-3D will be presented in other papers in this users seminar. As with any software, user problems occur. User problems usually fall into the categories of input processing failure, code execution failure, restart/renodalization failure, unphysical result, and installation. This presentation will discuss some of the more generic user problems that have been reported on RELAP5-3D as well as their resolution.

RELAP5-3D User Problems

International Nuclear Information System (INIS)

Riemke, Richard Allan

2001-01-01

The Reactor Excursion and Leak Analysis Program with 3D capability (RELAP5-3D) is a reactor system analysis code that has been developed at the Idaho National Engineering and Environmental Laboratory (INEEL) for the U. S. Department of Energy (DOE). The 3D capability in RELAP5-3D includes 3D hydrodynamics and 3D neutron kinetics. Assessment, verification, and validation of the 3D capability in RELAP5-3D is discussed in the literature. Additional assessment, verification, and validation of the 3D capability of RELAP5-3D will be presented in other papers in this users seminar. As with any software, user problems occur. User problems usually fall into the categories of input processing failure, code execution failure, restart/renodalization failure, unphysical result, and installation. This presentation will discuss some of the more generic user problems that have been reported on RELAP5-3D as well as their resolution

48 CFR 53.215 - Contracting by negotiation.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Contracting by negotiation. 53.215 Section 53.215 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS FORMS Prescription of Forms 53.215 Contracting by negotiation...

Human neuroblastoma cells with acquired resistance to the p53 activator RITA retain functional p53 and sensitivity to other p53 activating agents

NARCIS (Netherlands)

Michaelis, M.; Rothweiler, F.; Agha, B.; Barth, S.; Voges, Y.; Loeschmann, N.; von Deimling, A.; Breitling, R.; Doerr, H. Wilhelm; Roedel, F.; Speidel, D.; Cinatl, J.; Cinatl Jr., J.; Stephanou, A.

Adaptation of wild-type p53 expressing UKF-NB-3 cancer cells to the murine double minute 2 inhibitor nutlin-3 causes de novo p53 mutations at high frequency (13/20) and multi-drug resistance. Here, we show that the same cells respond very differently when adapted to RITA, a drug that, like nutlin-3,

The RD53A Integrated Circuit

CERN Document Server

Garcia-Sciveres, Maurice

2017-01-01

Implementation details for the RD53A pixel readout integrated circuit designed by the RD53 Collaboration. This is a companion to the specifications document and will eventually become a reference for chip users. RD53A is not intended to be a final production IC for use in an experiment, and contains design variations for testing purposes, making the pixel matrix non-uniform. The chip size is 20.0 mm by 11.8 mm.

Specific TP53 Mutants Overrepresented in Ovarian Cancer Impact CNV, TP53 Activity, Responses to Nutlin-3a, and Cell Survival

Directory of Open Access Journals (Sweden)

Lisa K. Mullany

2015-10-01

Full Text Available Evolutionary Action analyses of The Cancer Gene Atlas data sets show that many specific p53 missense and gain-of-function mutations are selectively overrepresented and functional in high-grade serous ovarian cancer (HGSC. As homozygous alleles, p53 mutants are differentially associated with specific loss of heterozygosity (R273; chromosome 17; copy number variation (R175H; chromosome 9; and up-stream, cancer-related regulatory pathways. The expression of immune-related cytokines was selectively related to p53 status, showing for the first time that specific p53 mutants impact, and are related to, the immune subtype of ovarian cancer. Although the majority (31% of HGSCs exhibit loss of heterozygosity, a significant number (24% maintain a wild-type (WT allele and represent another HGSC subtype that is not well defined. Using human and mouse cell lines, we show that specific p53 mutants differentially alter endogenous WT p53 activity; target gene expression; and responses to nutlin-3a, a small molecular that activates WT p53 leading to apoptosis, providing “proof of principle” that ovarian cancer cells expressing WT and mutant alleles represent a distinct ovarian cancer subtype. We also show that siRNA knock down of endogenous p53 in cells expressing homozygous mutant alleles causes apoptosis, whereas cells expressing WT p53 (or are heterozygous for WT and mutant p53 alleles are highly resistant. Therefore, despite different gene regulatory pathways associated with specific p53 mutants, silencing mutant p53 might be a suitable, powerful, global strategy for blocking ovarian cancer growth in those tumors that rely on mutant p53 functions for survival. Knowing p53 mutational status in HGSC should permit new strategies tailored to control this disease.

Expression of Egr1 and p53 in human carotid plaques and apoptosis induced by 7-oxysterol or p53.

Science.gov (United States)

Miah, Sayem; Zadeh, Shahram Nour Mohammad; Yuan, Xi-Ming; Li, Wei

2013-07-01

Egr-1 and p53 are involved in pathology of both atherosclerosis and cancer. However, it is unknown whether p53 and Egr1 are interactively involved in apoptosis in atherosclerosis. We found that in human carotid plaques, the expression of p53 was inversely correlated with Egr1. In U937 cells, 7β-hydroxycholesterol and 7-ketocholesterol induced production of reactive oxygen species (ROS), transient up-regulation of Egr1 followed by late induction of p53 and apoptosis. Cells with nuclear fragmentation induced by 7-oxysterol or p53 showed increased levels of p53, but decreased levels of Egr1. In conclusion, ROS induced by 7-oxysterols may function as an early initiator of Egr1 expression. The late induced p53 by 7-oxysterols contributes to apoptotic cell death and is linked to the reduction of Egr1 levels, which resembles the differential expression of p53 and Egr1 in human atheroma progression. Copyright © 2012 Elsevier GmbH. All rights reserved.

Chemical Variations on the p53 Reactivation Theme

Directory of Open Access Journals (Sweden)

Carlos J. A. Ribeiro

2016-05-01

Full Text Available Among the tumor suppressor genes, p53 is one of the most studied. It is widely regarded as the “guardian of the genome”, playing a major role in carcinogenesis. In fact, direct inactivation of the TP53 gene occurs in more than 50% of malignancies, and in tumors that retain wild-type p53 status, its function is usually inactivated by overexpression of negative regulators (e.g., MDM2 and MDMX. Hence, restoring p53 function in cancer cells represents a valuable anticancer approach. In this review, we will present an updated overview of the most relevant small molecules developed to restore p53 function in cancer cells through inhibition of the p53-MDMs interaction, or direct targeting of wild-type p53 or mutated p53. In addition, optimization approaches used for the development of small molecules that have entered clinical trials will be presented.

TRIM65 negatively regulates p53 through ubiquitination

Energy Technology Data Exchange (ETDEWEB)

Li, Yang [Department of Respiration, The First Hospital of Jilin University, Changchun 130021 (China); Ma, Chengyuan [Department of Neurosurgery, The First Hospital of Jilin University, Changchun 130021 (China); Zhou, Tong [Department of Endocrinology, The First Hospital of Jilin University, Changchun 130021 (China); Liu, Ying [Department of Respiration, The First Hospital of Jilin University, Changchun 130021 (China); Sun, Luyao [Department of Infectious Diseases, The First Hospital of Jilin University, Changchun 130021 (China); Yu, Zhenxiang, E-mail: zhenxiangyu2015@gmail.com [Department of Respiration, The First Hospital of Jilin University, Changchun 130021 (China)

2016-04-22

Tripartite-motif protein family member 65 (TRIM65) is an important protein involved in white matter lesion. However, the role of TRIM65 in human cancer remains less understood. Through the Cancer Genome Atlas (TCGA) gene alteration database, we found that TRIM65 is upregulated in a significant portion of non-small cell lung carcinoma (NSCLC) patients. Our cell growth assay revealed that TRIM65 overexpression promotes cell proliferation, while knockdown of TRIM65 displays opposite effect. Mechanistically, TRIM65 binds to p53, one of the most critical tumor suppressors, and serves as an E3 ligase toward p53. Consequently, TRIM65 inactivates p53 through facilitating p53 poly-ubiquitination and proteasome-mediated degradation. Notably, chemotherapeutic reagent cisplatin induction of p53 is markedly attenuated in response to ectopic expression of TRIM65. Cell growth inhibition by TRIM65 knockdown is more significant in p53 positive H460 than p53 negative H1299 cells, and knockdown of p53 in H460 cells also shows compromised cell growth inhibition by TRIM65 knockdown, indicating that p53 is required, at least in part, for TRIM65 function. Our findings demonstrate TRIM65 as a potential oncogenic protein, highly likely through p53 inactivation, and provide insight into development of novel approaches targeting TRIM65 for NSCLC treatment, and also overcoming chemotherapy resistance. - Highlights: • TRIM65 expression is elevated in NSCLC. • TRIM65 inactivates p53 through mediating p53 ubiquitination and degradation. • TRIM65 attenuates the response of NSCLC cells to cisplatin.

Disruption of focal adhesion kinase and p53 interaction with small molecule compound R2 reactivated p53 and blocked tumor growth

International Nuclear Information System (INIS)

Golubovskaya, Vita M; Ho, Baotran; Zheng, Min; Magis, Andrew; Ostrov, David; Morrison, Carl; Cance, William G

2013-01-01

Focal Adhesion Kinase (FAK) is a 125 kDa non-receptor kinase that plays a major role in cancer cell survival and metastasis. We performed computer modeling of the p53 peptide containing the site of interaction with FAK, predicted the peptide structure and docked it into the three-dimensional structure of the N-terminal domain of FAK involved in the complex with p53. We screened small molecule compounds that targeted the site of the FAK-p53 interaction and identified compounds (called Roslins, or R compounds) docked in silico to this site. By different assays in isogenic HCT116p53 + / + and HCT116 p53 - / - cells we identified a small molecule compound called Roslin 2 (R2) that bound FAK, disrupted the binding of FAK and p53 and decreased cancer cell viability and clonogenicity in a p53-dependent manner. In addition, dual-luciferase assays demonstrated that the R2 compound increased p53 transcriptional activity that was inhibited by FAK using p21, Mdm-2, and Bax-promoter targets. R2 also caused increased expression of p53 targets: p21, Mdm-2 and Bax proteins. Furthermore, R2 significantly decreased tumor growth, disrupted the complex of FAK and p53, and up-regulated p21 in HCT116 p53 + / + but not in HCT116 p53 - / - xenografts in vivo. In addition, R2 sensitized HCT116p53 + / + cells to doxorubicin and 5-fluorouracil. Thus, disruption of the FAK and p53 interaction with a novel small molecule reactivated p53 in cancer cells in vitro and in vivo and can be effectively used for development of FAK-p53 targeted cancer therapy approaches

RD53A Integrated Circuit Specifications

CERN Document Server

Garcia-Sciveres, Mauricio

2015-01-01

Specifications for the RD53 collaboration’s first engineering wafer run of an integrated circuit (IC) for hybrid pixel detector readout, called RD53A. RD53A is intended to demonstrate in a large format IC the suitability of the technology (including radiation tolerance), the stable low threshold operation, and the high hit and trigger rate capabilities, required for HL-LHC upgrades of ATLAS and CMS. The wafer scale production will permit the experiments to prototype bump bonding assembly with realistic sensors in this new technology and to measure the performance of hybrid assemblies. RD53A is not intended to be a final production IC for use in an experiment, and will contain design variations for testing purposes, making the pixel matrix non-uniform.

53BP1 and USP28 mediate p53-dependent cell cycle arrest in response to centrosome loss and prolonged mitosis.

Science.gov (United States)

Fong, Chii Shyang; Mazo, Gregory; Das, Tuhin; Goodman, Joshua; Kim, Minhee; O'Rourke, Brian P; Izquierdo, Denisse; Tsou, Meng-Fu Bryan

2016-07-02

Mitosis occurs efficiently, but when it is disturbed or delayed, p53-dependent cell death or senescence is often triggered after mitotic exit. To characterize this process, we conducted CRISPR-mediated loss-of-function screens using a cell-based assay in which mitosis is consistently disturbed by centrosome loss. We identified 53BP1 and USP28 as essential components acting upstream of p53, evoking p21-dependent cell cycle arrest in response not only to centrosome loss, but also to other distinct defects causing prolonged mitosis. Intriguingly, 53BP1 mediates p53 activation independently of its DNA repair activity, but requiring its interacting protein USP28 that can directly deubiquitinate p53 in vitro and ectopically stabilize p53 in vivo. Moreover, 53BP1 can transduce prolonged mitosis to cell cycle arrest independently of the spindle assembly checkpoint (SAC), suggesting that while SAC protects mitotic accuracy by slowing down mitosis, 53BP1 and USP28 function in parallel to select against disturbed or delayed mitosis, promoting mitotic efficiency.

7 CFR 53.15 - Accessibility to livestock.

Science.gov (United States)

2010-01-01

... 7 Agriculture 3 2010-01-01 2010-01-01 false Accessibility to livestock. 53.15 Section 53.15... AGRICULTURAL MARKETING ACT OF 1946 AND THE EGG PRODUCTS INSPECTION ACT (CONTINUED) LIVESTOCK (GRADING, CERTIFICATION, AND STANDARDS) Regulations Service § 53.15 Accessibility to livestock. (a) The applicant shall...

7 CFR 1219.53 - Budget and expenses.

Science.gov (United States)

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Budget and expenses. 1219.53 Section 1219.53..., AND INFORMATION Hass Avocado Promotion, Research, and Information Order Budgets, Expenses, and Assessments § 1219.53 Budget and expenses. (a) The Board is authorized to incur such expenses, including...

48 CFR 53.301-1447 - Solicitation/Contract.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Solicitation/Contract. 53.301-1447 Section 53.301-1447 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS FORMS Illustrations of Forms 53.301-1447 Solicitation/Contract. ER22AP08.001...

10 CFR 39.53 - Energy compensation source.

Science.gov (United States)

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Energy compensation source. 39.53 Section 39.53 Energy NUCLEAR REGULATORY COMMISSION LICENSES AND RADIATION SAFETY REQUIREMENTS FOR WELL LOGGING Equipment § 39.53 Energy compensation source. The licensee may use an energy compensation source (ECS) which is...

25 CFR 273.53 - Applicable procurement regulations.

Science.gov (United States)

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false Applicable procurement regulations. 273.53 Section 273.53 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR INDIAN SELF-DETERMINATION AND EDUCATION ASSISTANCE ACT PROGRAM EDUCATION CONTRACTS UNDER JOHNSON-O'MALLEY ACT General Contract Requirements § 273.53...

7 CFR 1786.53 - Discounted present value.

Science.gov (United States)

2010-01-01

... 7 Agriculture 12 2010-01-01 2010-01-01 false Discounted present value. 1786.53 Section 1786.53... Special Discounted Prepayments on RUS Direct/Insured Loans § 1786.53 Discounted present value. The Discounted Present Value shall be calculated five business days before prepayment is made by summing the...

7 CFR 53.1 - Meaning of words.

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2010-01-01

... 7 Agriculture 3 2010-01-01 2010-01-01 false Meaning of words. 53.1 Section 53.1 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards..., CERTIFICATION, AND STANDARDS) Regulations Definitions § 53.1 Meaning of words. Words used in this subpart in the...

7 CFR 761.53 - Interest bearing accounts.

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2010-01-01

... 7 Agriculture 7 2010-01-01 2010-01-01 false Interest bearing accounts. 761.53 Section 761.53... AGRICULTURE SPECIAL PROGRAMS GENERAL PROGRAM ADMINISTRATION Supervised Bank Accounts § 761.53 Interest bearing accounts. (a) A supervised bank account, if possible, will be established as an interest bearing deposit...

RD53A Integrated Circuit Specifications

OpenAIRE

Garcia-Sciveres, Mauricio

2015-01-01

Specifications for the RD53 collaboration’s first engineering wafer run of an integrated circuit (IC) for hybrid pixel detector readout, called RD53A. RD53A is intended to demonstrate in a large format IC the suitability of the technology (including radiation tolerance), the stable low threshold operation, and the high hit and trigger rate capabilities, required for HL-LHC upgrades of ATLAS and CMS. The wafer scale production will permit the experiments to prototype bump bonding assembly with...

48 CFR 53.301-26 - Award/Contract.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Award/Contract. 53.301-26 Section 53.301-26 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS FORMS Illustrations of Forms 53.301-26 Award/Contract. ER22AP08.000 [73 FR 21785, Apr...

A surrogate p53 reporter in Drosophila reveals the interaction of eIF4E and p53

International Nuclear Information System (INIS)

Corujo, G.; Campagno, R.; Rivera Pomar, R.; Ferrero, P.; Lu, W.J.

2011-01-01

eIF4E promotes translation upon binding the mRNA 5'cap and it is required for cell proliferation. p53 is a proapoptotic protein which is activated in response to DNA damage. There is evidence that suggests that eIF4E and p53 are connected in a mechanism that regulates their function. We propose a model for that such a mechanism to explain the equilibrium between apoptosis and cell proliferation. Our data shows a correlation between the overexpression of eIF4E and the suppression of apoptosis triggered by the overexpression of p53 in Drosophila imaginal discs. We also studied a reporter transgene which expresses GFP in response to p53 activation by gamma radiation. We could confirm that this p53 surrogate works in imaginal discs as well as in embryos. This provided us a tool to quantify the effect on the GFP signal by overexpression of eIF4E to confirm how these two proteins could interact in vivo. Our results suggest that p53 and eIF4E are indeed in an equilibrium that decides if a cell shall proliferate or die. (authors)

42 CFR 431.53 - Assurance of transportation.

Science.gov (United States)

2010-10-01

... 42 Public Health 4 2010-10-01 2010-10-01 false Assurance of transportation. 431.53 Section 431.53... Requirements § 431.53 Assurance of transportation. A State plan must— (a) Specify that the Medicaid agency will ensure necessary transportation for recipients to and from providers; and (b) Describe the methods that...

48 CFR 53.301-25 - Performance Bond.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Performance Bond. 53.301-25 Section 53.301-25 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS FORMS Illustrations of Forms 53.301-25 Performance Bond. ER18DE98.007 ER18DE98.008 [63...

Exploring a minimal two-component p53 model

International Nuclear Information System (INIS)

Sun, Tingzhe; Zhu, Feng; Shen, Pingping; Yuan, Ruoshi; Xu, Wei

2010-01-01

The tumor suppressor p53 coordinates many attributes of cellular processes via interlocked feedback loops. To understand the biological implications of feedback loops in a p53 system, a two-component model which encompasses essential feedback loops was constructed and further explored. Diverse bifurcation properties, such as bistability and oscillation, emerge by manipulating the feedback strength. The p53-mediated MDM2 induction dictates the bifurcation patterns. We first identified irradiation dichotomy in p53 models and further proposed that bistability and oscillation can behave in a coordinated manner. Further sensitivity analysis revealed that p53 basal production and MDM2-mediated p53 degradation, which are central to cellular control, are most sensitive processes. Also, we identified that the much more significant variations in amplitude of p53 pulses observed in experiments can be derived from overall amplitude parameter sensitivity. The combined approach with bifurcation analysis, stochastic simulation and sampling-based sensitivity analysis not only gives crucial insights into the dynamics of the p53 system, but also creates a fertile ground for understanding the regulatory patterns of other biological networks

Identification and characterization of Burkholderia multivorans CCA53.

Science.gov (United States)

Akita, Hironaga; Kimura, Zen-Ichiro; Yusoff, Mohd Zulkhairi Mohd; Nakashima, Nobutaka; Hoshino, Tamotsu

2017-07-06

A lignin-degrading bacterium, Burkholderia sp. CCA53, was previously isolated from leaf soil. The purpose of this study was to determine phenotypic and biochemical features of Burkholderia sp. CCA53. Multilocus sequence typing (MLST) analysis based on fragments of the atpD, gltD, gyrB, lepA, recA and trpB gene sequences was performed to identify Burkholderia sp. CCA53. The MLST analysis revealed that Burkholderia sp. CCA53 was tightly clustered with B. multivorans ATCC BAA-247 T . The quinone and cellular fatty acid profiles, carbon source utilization, growth temperature and pH were consistent with the characteristics of B. multivorans species. Burkholderia sp. CCA53 was therefore identified as B. multivorans CCA53.

The Transcriptional Landscape of p53 Signalling Pathway

Directory of Open Access Journals (Sweden)

Chizu Tanikawa

2017-06-01

Full Text Available Although recent cancer genomics studies have identified a large number of genes that were mutated in human cancers, p53 remains as the most frequently mutated gene. To further elucidate the p53-signalling network, we performed transcriptome analysis on 24 tissues in p53+/+ or p53−/− mice after whole-body X-ray irradiation. Here we found transactivation of a total of 3551 genes in one or more of the 24 tissues only in p53+/+ mice, while 2576 genes were downregulated. p53 mRNA expression level in each tissue was significantly associated with the number of genes upregulated by irradiation. Annotation using TCGA (The Cancer Genome Atlas database revealed that p53 negatively regulated mRNA expression of several cancer therapeutic targets or pathways such as BTK, SYK, and CTLA4 in breast cancer tissues. In addition, stomach exhibited the induction of Krt6, Krt16, and Krt17 as well as loricrin, an epidermal differentiation marker, after the X-ray irradiation only in p53+/+ mice, implying a mechanism to protect damaged tissues by rapid induction of differentiation. Our comprehensive transcriptome analysis elucidated tissue specific roles of p53 and its signalling networks in DNA-damage response that will enhance our understanding of cancer biology.

42 CFR 489.53 - Termination by CMS.

Science.gov (United States)

2010-10-01

... 42 Public Health 5 2010-10-01 2010-10-01 false Termination by CMS. 489.53 Section 489.53 Public... Reinstatement After Termination § 489.53 Termination by CMS. (a) Basis for termination of agreement with any provider. CMS may terminate the agreement with any provider if CMS finds that any of the following failings...

p53 specific (auto)immunity in mice

NARCIS (Netherlands)

Lauwen, Marjolein Monique

2008-01-01

Self-tolerance to p53 is a major potential limitation for the activation of the endogenous T-cell repertoire. So far, p53 specific CD8+ and CD4+ T-cell immunity has been described in cancer patients and healthy individuals. However, the restrictions of tolerance on the recruitment of p53 specific T

p53 and the pathogenesis of skin cancer

International Nuclear Information System (INIS)

Benjamin, Cara L.; Ananthaswamy, Honnavara N.

2007-01-01

The p53 tumor suppressor gene and gene product are among the most diverse and complex molecules involved in cellular functions. Genetic alterations within the p53 gene have been shown to have a direct correlation with cancer development and have been shown to occur in nearly 50% of all cancers. p53 mutations are particularly common in skin cancers and UV irradiation has been shown to be a primary cause of specific 'signature' mutations that can result in oncogenic transformation. There are certain 'hot-spots' in the p53 gene where mutations are commonly found that result in a mutated dipyrimidine site. This review discusses the role of p53 from normal function and its dysfunction in pre-cancerous lesions and non-melanoma skin cancers. Additionally, special situations are explored, such as Li-Fraumeni syndrome in which there is an inherited p53 mutation, and the consequences of immune suppression on p53 mutations and the resulting increase in non-melanoma skin cancer in these patients

Biologic effect of exogenous wild p53 combined with irradiation on human melanoma cell lines with different p53 status

International Nuclear Information System (INIS)

Min Fengling; Zhang Hong; Li Wenjian; Liu Bing; Zhou Qingming; Duan Xin; Gao Qingxiang

2007-01-01

Objective: To investigate the effect of low dose irradiation on gene transfer efficiency and the effect of adenoviral-mediated exogenous P53 overexpression on apoptosis and radiosensitivity of radioresistant human melanoma cell lines A375(wild type p53)and WM983a(mutant type p53). Methods: Control vector, a replication deficient recombinant adenoviral vector containing a CMV promoter and green fluorescent protein (AdCMV-GFP), was used to transfect A375 cells and WM983a cells preirradiated with or without 1 Gy X-ray. The transduction efficiency of GFP gene was determined with fluorescence microscope directly. These two types of cells irradiated by 1 Gy X-ray were transfected with a replication deficient recombinant adenoviral vector carrying human wild p53 (AdCMV-p53), and mRNA level was detected by RT-PCR. The cell cycle delay and the expression of exogenous P53 were detected using flow cytometry (FCM) at different times after transfection. Tunel technique was used to detect cell apoptosis. The radiosensivity of A375 and WM983a cells after p53 transduction was analyzed by colony formation. Results: It is found that 1 Gy irradiation increased the gene transfection efficiency of A375 and WM983a cells. The expression of exogenous P53 was found to range from 60% to 80% among transfected cells during the first three days after transduction and then declined continuously down to the control level on day 10. G 1 cell cycle arrest was also observed after p53 gene transduction. WM983a cells transfected with p53 showed higher sensitivity to X-ray-induced cell killing than A375 cells. Conclusions: It is indicated that low dose of ionizing radiation can improve gene transfection efficiency of A375 and WM983a cells mediated by adenovirus vector. Althrough the overexpresion of exogenous p53 may not inhibit cell growth and induce apoptosis of melanoma cell line A375 and WM983a irt vitro, the two cell lines are much more sensitive to cell death induced by irradiation. It is

Tumor hypoxia, p53, and prognosis in cervical cancers

International Nuclear Information System (INIS)

Haensgen, Gabriele; Krause, Ulf; Becker, Axel; Stadler, Peter; Lautenschlaeger, Christine; Wohlrab, Wolfgang; Rath, Friedrich W.; Molls, Michael; Dunst, Juergen

2001-01-01

Background: The p53 protein is involved in the regulation of initiation of apoptosis. In vitro, p53-deficient cells do not respond to hypoxia with apoptosis as do p53-normal cells, and this may lead to a relative growth advantage of cells without a functioning p53 under hypoxia. On the basis of this hypothesis, a selection of cells with a functionally inactive p53 may occur in hypoxic tumors. The development of uterine cervical carcinomas is closely associated with infections of human papilloma viruses, which may cause a degradation of the tumor suppressor gene p53, resulting in a restriction of apoptosis. Thus, cervical cancers have often a functionally inactive p53. The purpose of our clinical study was therefore to investigate the association between p53, hypoxia, and prognosis in cervical cancers in which the oxygenation status can be determined by clinical methods. Material and Methods: Seventy patients with locally advanced squamous cell cervical cancer Stages IIB (n=14), IIIB (n=49), and IVA (n=7) were investigated in the period from 1996 through 1999. All were treated with definitive radiotherapy with curative intent by a combination of external radiotherapy plus high-dose-rate afterloading. Before therapy, tumor oxygenation was measured with a needle probe polarographically using the Eppendorf histograph. Hypoxic tumors were defined as those with pO 2 measurements below 5 mm Hg (HF5). Pretreatment biopsies were taken and analyzed immunohistologically for p53 protein expression with the DO-7 antibody. The DNA index was measured by flow cytometry. The statistical data analysis was done with SPSS 9.0 for Windows. Results: The 3-year overall survival was 55% for the whole group of patients. Clinical prognostic factors in a multivariate analysis were pretreatment hemoglobin level (3-year survival 62% for patients with a pretreatment hemoglobin ≥11 g/dl vs. 27% for hemoglobin <11 g/dl, p=0.006) and FIGO stage (Stage IIB: 65%; Stage IIIB: 60%; Stage IVA: 29%, p

21 CFR 640.53 - Testing the blood.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Testing the blood. 640.53 Section 640.53 Food and... ADDITIONAL STANDARDS FOR HUMAN BLOOD AND BLOOD PRODUCTS Cryoprecipitate § 640.53 Testing the blood. (a) Blood... prescribed in § 610.40 of this chapter and § 640.5 (a), (b), and (c). (b) The tests shall be performed on a...

Regulation of p53 tetramerization and nuclear export by ARC.

Science.gov (United States)

Foo, Roger S-Y; Nam, Young-Jae; Ostreicher, Marc Jason; Metzl, Mark D; Whelan, Russell S; Peng, Chang-Fu; Ashton, Anthony W; Fu, Weimin; Mani, Kartik; Chin, Suet-Feung; Provenzano, Elena; Ellis, Ian; Figg, Nichola; Pinder, Sarah; Bennett, Martin R; Caldas, Carlos; Kitsis, Richard N

2007-12-26

Inactivation of the transcription factor p53 is central to carcinogenesis. Yet only approximately one-half of cancers have p53 loss-of-function mutations. Here, we demonstrate a mechanism for p53 inactivation by apoptosis repressor with caspase recruitment domain (ARC), a protein induced in multiple cancer cells. The direct binding in the nucleus of ARC to the p53 tetramerization domain inhibits p53 tetramerization. This exposes a nuclear export signal in p53, triggering Crm1-dependent relocation of p53 to the cytoplasm. Knockdown of endogenous ARC in breast cancer cells results in spontaneous tetramerization of endogenous p53, accumulation of p53 in the nucleus, and activation of endogenous p53 target genes. In primary human breast cancers with nuclear ARC, p53 is almost always WT. Conversely, nearly all breast cancers with mutant p53 lack nuclear ARC. We conclude that nuclear ARC is induced in cancer cells and negatively regulates p53.

Expression of p53 in oligodendrogliomas

NARCIS (Netherlands)

J.M. Kros (Johan); J.J.C.J. Godschalk (J. J C J); K.K. Krishnadath (Kausilia); C.G. van Eden (C.)

1993-01-01

textabstractThe expression of the nuclear protein p53 in oligodendrogliomas was investigated by immunohistochemistry, using a monoclonal anti-p53 antibody (DO-7) on formalin-fixed, paraffin-embedded material in 84 histologically verified cases, and compared with the histopathological grade and

Expression of p53 in oligodendrogliomas

NARCIS (Netherlands)

Kros, J. M.; Godschalk, J. J.; Krishnadath, K. K.; van Eden, C. G.

1993-01-01

The expression of the nuclear protein p53 in oligodendrogliomas was investigated by immunohistochemistry, using a monoclonal anti-p53 antibody (DO-7) on formalin-fixed, paraffin-embedded material in 84 histologically verified cases, and compared with the histopathological grade and survival.

Battle Against Cancer: An Everlasting Saga of p53

Directory of Open Access Journals (Sweden)

Qian Hao

2014-12-01

Full Text Available Cancer is one of the most life-threatening diseases characterized by uncontrolled growth and spread of malignant cells. The tumor suppressor p53 is the master regulator of tumor cell growth and proliferation. In response to various stress signals, p53 can be activated and transcriptionally induces a myriad of target genes, including both protein-encoding and non-coding genes, controlling cell cycle progression, DNA repair, senescence, apoptosis, autophagy and metabolism of tumor cells. However, around 50% of human cancers harbor mutant p53 and, in the majority of the remaining cancers, p53 is inactivated through multiple mechanisms. Herein, we review the recent progress in understanding the molecular basis of p53 signaling, particularly the newly identified ribosomal stress—p53 pathway, and the development of chemotherapeutics via activating wild-type p53 or restoring mutant p53 functions in cancer. A full understanding of p53 regulation will aid the development of effective cancer treatments.

Gain-of-function mutant p53 but not p53 deletion promotes head and neck cancer progression in response to oncogenic K-ras

Science.gov (United States)

Acin, Sergio; Li, Zhongyou; Mejia, Olga; Roop, Dennis R; El-Naggar, Adel K; Caulin, Carlos

2015-01-01

Mutations in p53 occur in over 50% of the human head and neck squamous cell carcinomas (SCCHN). The majority of these mutations result in the expression of mutant forms of p53, rather than deletions in the p53 gene. Some p53 mutants are associated with poor prognosis in SCCHN patients. However, the molecular mechanisms that determine the poor outcome of cancers carrying p53 mutations are unknown. Here, we generated a mouse model for SCCHN and found that activation of the endogenous p53 gain-of-function mutation p53R172H, but not deletion of p53, cooperates with oncogenic K-ras during SCCHN initiation, accelerates oral tumour growth, and promotes progression to carcinoma. Mechanistically, expression profiling of the tumours that developed in these mice and studies using cell lines derived from these tumours determined that mutant p53 induces the expression of genes involved in mitosis, including cyclin B1 and cyclin A, and accelerates entry in mitosis. Additionally, we discovered that this oncogenic function of mutant p53 was dependent on K-ras because the expression of cyclin B1 and cyclin A decreased, and entry in mitosis was delayed, after suppressing K-ras expression in oral tumour cells that express p53R172H. The presence of double-strand breaks in the tumours suggests that oncogene-dependent DNA damage resulting from K-ras activation promotes the oncogenic function of mutant p53. Accordingly, DNA damage induced by doxorubicin also induced increased expression of cyclin B1 and cyclin A in cells that express p53R172H. These findings represent strong in vivo evidence for an oncogenic function of endogenous p53 gain-of-function mutations in SCCHN and provide a mechanistic explanation for the genetic interaction between oncogenic K-ras and mutant p53. PMID:21952947

28 CFR 91.53 - Other guidance.

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Other guidance. 91.53 Section 91.53 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) GRANTS FOR CORRECTIONAL FACILITIES Environmental... Justice has also published NEPA procedures that incorporate the CEQ regulations at 28 CFR part 61...

Are Trp53 rescue of Brca1 embryonic lethality and Trp53/Brca1 breast cancer association related?

International Nuclear Information System (INIS)

McAllister, Kimberly A; Wiseman, Roger W

2002-01-01

Brca1 is involved in multiple biological pathways including DNA damage repair, transcriptional regulation, and cell-cycle progression. A complex pattern of interactions of Brca1 with Trp53 has also emerged. Xu and coworkers found that haploid loss of Trp53 significantly reduces the embryonic lethality observed in mice with a homozygous in-frame deletion of Brca1 exon 11. They report that widespread apoptosis correlates with the embryonic lethality resulting from this homozygous Δ11 Brca1 mutation. A mechanism responsible for Brca1-associated carcinogenesis is proposed. These experiments extend our knowledge of a complex Brca1/Trp53 relationship. However, the precise mechanisms through which Brca1 interacts with Trp53 to suppress mammary tumor formation have yet to be elucidated

Aggregation-primed molten globule conformers of the p53 core domain provide potential tools for studying p53C aggregation in cancer.

Science.gov (United States)

Pedrote, Murilo M; de Oliveira, Guilherme A P; Felix, Adriani L; Mota, Michelle F; Marques, Mayra de A; Soares, Iaci N; Iqbal, Anwar; Norberto, Douglas R; Gomes, Andre M O; Gratton, Enrico; Cino, Elio A; Silva, Jerson L

2018-05-31

The functionality of the tumor suppressor p53 is altered in more than 50% of human cancers, and many individuals with cancer exhibit amyloid-like buildups of aggregated p53. An understanding of what triggers the pathogenic amyloid conversion of p53 is required for the further development of cancer therapies. Here, perturbation of the p53 core domain (p53C) with sub-denaturing concentrations of guanidine hydrochloride and high hydrostatic pressure revealed native-like molten globule (MG) states, a subset of which were highly prone to amyloidogenic aggregation. We found that MG conformers of p53C, likely representing population-weighted averages of multiple states, have different volumetric properties, as determined by pressure perturbation and size-exclusion chromatography. We also found that they bind the fluorescent dye 4,4'-dianilino-1,1'-binaphthyl-5,5'-disulfonic acid (bis-ANS) and have a native-like tertiary structure that occludes the single Trp residue in p53. Fluorescence experiments revealed conformational changes of the single Trp and Tyr residues before p53 unfolding and the presence of MG conformers, some of which were highly prone to aggregation. P53C exhibited marginal unfolding cooperativity, which could be modulated from unfolding to aggregation pathways with chemical or physical forces. We conclude that trapping amyloid precursor states in solution is a promising approach for understanding p53 aggregation in cancer. Our findings support the use of single-Trp fluorescence as a probe for evaluating p53 stability, effects of mutations, and the efficacy of therapeutics designed to stabilize p53. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

Comparative evaluation of surface topography of tooth prepared using erbium, chromium: Yttrium, scandium, gallium, garnet laser and bur and its clinical implications.

Science.gov (United States)

Verma, Mahesh; Kumari, Pooja; Gupta, Rekha; Gill, Shubhra; Gupta, Ankur

2015-01-01

Erbium, chromium: Yttrium, scandium, gallium, garnet (Er, Cr: YSGG) laser has been successfully used in the ablation of dental hard and soft tissues. It has been reported that this system is also useful for preparing tooth surfaces and etching, but no consensus exist in the literature regarding the advantage of lasers over conventional tooth preparation technique. Labial surfaces of 25 extracted human maxillary central incisors were divided into two halves. Right half was prepared with diamond bur and left half with Er, Cr; YSGG laser and a reduction of 0.3-0.5 mm was carried out. Topography of prepared surfaces of five teeth were examined under scanning electron microscope (SEM). The remaining samples were divided into 4 groups of 10 specimens each based on the surface treatment received: One group was acid etched and other was nonetched. Composite resin cylinders were bonded on prepared surfaces and shear bond strength was assessed using a universal testing machine. The SEM observation revealed that the laser prepared surfaces were clean, highly irregular and devoid of a smear layer. Bur prepared surfaces were relatively smooth but covered with smear layer. Highest bond strength was shown by laser prepared acid etched group, followed by bur prepared the acid etched group. The bur prepared nonacid etched group showed least bond strength. Er, Cr: YSGG laser can be used for preparing tooth and bond strength value achieved by laser preparation alone without surface treatment procedure lies in the range of clinical acceptability.

p53 in differentiation of thyroid cancer

International Nuclear Information System (INIS)

Seyama, Toshio; Ito, Takashi; Akiyama, Mitoshi; Hayashi, Yuzo; Dohi, Kiyohiko.

1993-01-01

P53 is a tumor suppressor gene with such a recessive nature and is inactivated in many carcinomas. DNA was extracted from 10 primary papillary adenocarcinomas and eight undifferentiated carcinomas of the thyroid, using three 5 μm sliced paraffin segments, and then amplified by PCR. The products were analyzed for mutations in the p53 gene exons 5 to 8 by the direct sequencing method and for allelic deletion by the RFLP method. In five human thyroid carcinomas, DNA was extracted from each tissue and analyzed. Mutations in the p53 gene exons 5 to 8 and p53 gene deletions were not detected in the 10 papillary adenocarcinomas, mutations were detected in seven of eight cases and allelic deletions was detected in three of the five cases examined. In each of the five cases which had both differentiated and undifferentiated tissues in the same tumor, p53 gene mutations were not detected in the differentiated tissues while mutations and gene deletions were detected in the undifferentiated sections. The p53 gene was analyzed using paraffin-embedded tissues by the combined use of the direct sequencing and PCR methods and by the RFLP method. It was found that the progression of human thyroid carcinoma is closely related to the p53 genetic changes. Furthermore, the analysis of differentiated and undifferentiated tissues in the same tumor showed that human undifferentiated thyroid carcinomas develop from differentiated carcinomas. (J.P.N.)

40 CFR 61.53 - Stack sampling.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Stack sampling. 61.53 Section 61.53 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) NATIONAL... sampling. (a) Mercury ore processing facility. (1) Unless a waiver of emission testing is obtained under...

48 CFR 53.236-1 - Construction.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Construction. 53.236-1... AND FORMS FORMS Prescription of Forms 53.236-1 Construction. The following forms are prescribed, as stated below, for use in contracting for construction, alteration, or repair, or dismantling, demolition...

System-based strategies for p53 recovery.

Science.gov (United States)

Azam, Muhammad Rizwan; Fazal, Sahar; Ullah, Mukhtar; Bhatti, Aamer I

2018-06-01

The authors have proposed a systems theory-based novel drug design approach for the p53 pathway. The pathway is taken as a dynamic system represented by ordinary differential equations-based mathematical model. Using control engineering practices, the system analysis and subsequent controller design is performed for the re-activation of wild-type p53. p53 revival is discussed for both modes of operation, i.e. the sustained and oscillatory. To define the problem in control system paradigm, modification in the existing mathematical model is performed to incorporate the effect of Nutlin. Attractor point analysis is carried out to select the suitable domain of attraction. A two-loop negative feedback control strategy is devised to drag the system trajectories to the attractor point and to regulate cellular concentration of Nutlin, respectively. An integrated framework is constituted to incorporate the pharmacokinetic effects of Nutlin in the cancerous cells. Bifurcation analysis is also performed on the p53 model to see the conditions for p53 oscillation.

Microbial Regulation of p53 Tumor Suppressor.

Directory of Open Access Journals (Sweden)

Alexander I Zaika

2015-09-01

Full Text Available p53 tumor suppressor has been identified as a protein interacting with the large T antigen produced by simian vacuolating virus 40 (SV40. Subsequent research on p53 inhibition by SV40 and other tumor viruses has not only helped to gain a better understanding of viral biology, but also shaped our knowledge of human tumorigenesis. Recent studies have found, however, that inhibition of p53 is not strictly in the realm of viruses. Some bacterial pathogens also actively inhibit p53 protein and induce its degradation, resulting in alteration of cellular stress responses. This phenomenon was initially characterized in gastric epithelial cells infected with Helicobacter pylori, a bacterial pathogen that commonly infects the human stomach and is strongly linked to gastric cancer. Besides H. pylori, a number of other bacterial species were recently discovered to inhibit p53. These findings provide novel insights into host-bacteria interactions and tumorigenesis associated with bacterial infections.

The nucleolus directly regulates p53 export and degradation.

Science.gov (United States)

Boyd, Mark T; Vlatkovic, Nikolina; Rubbi, Carlos P

2011-09-05

The correlation between stress-induced nucleolar disruption and abrogation of p53 degradation is evident after a wide variety of cellular stresses. This link may be caused by steps in p53 regulation occurring in nucleoli, as suggested by some biochemical evidence. Alternatively, nucleolar disruption also causes redistribution of nucleolar proteins, potentially altering their interactions with p53 and/or MDM2. This raises the fundamental question of whether the nucleolus controls p53 directly, i.e., as a site where p53 regulatory processes occur, or indirectly, i.e., by determining the cellular localization of p53/MDM2-interacting factors. In this work, transport experiments based on heterokaryons, photobleaching, and micronucleation demonstrate that p53 regulatory events are directly regulated by nucleoli and are dependent on intact nucleolar structure and function. Subcellular fractionation and nucleolar isolation revealed a distribution of ubiquitylated p53 that supports these findings. In addition, our results indicate that p53 is exported by two pathways: one stress sensitive and one stress insensitive, the latter being regulated by activities present in the nucleolus.

49 CFR 1242.73 - Cleaning car interiors and freight lost and damaged-all other (accounts XX-53-70 and 51-53-00).

Science.gov (United States)

2010-10-01

... 49 Transportation 9 2010-10-01 2010-10-01 false Cleaning car interiors and freight lost and damaged-all other (accounts XX-53-70 and 51-53-00). 1242.73 Section 1242.73 Transportation Other... freight lost and damaged—all other (accounts XX-53-70 and 51-53-00). Separate common expenses on basis of...

31 CFR 50.53 - Loss certifications.

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2010-07-01

... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Loss certifications. 50.53 Section 50.53 Money and Finance: Treasury Office of the Secretary of the Treasury TERRORISM RISK INSURANCE... Treasury, that includes basic information about each underlying insured loss. For purposes of this section...

48 CFR 53.111 - Contract clause.

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2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Contract clause. 53.111... AND FORMS FORMS General 53.111 Contract clause. Contracting officers shall insert the clause at 52.253-1, Computer Generated Forms, in solicitations and contracts that require the contractor to submit...

Immunohistochemical analysis of P53 protein in odontogenic cysts

Science.gov (United States)

Gaballah, Essam Taher M.A.; Tawfik, Mohamed A.

2010-01-01

The p53 is a well-known tumor suppressor gene, the mutations of which are closely related to the decreased differentiation of cells. Findings of studies on immunohistochemical P53 expression in odontogenic cysts are controversial. The present study was carried-out to investigate the immunohistochemical expression of P53 protein in odontogenic cysts. Thirty paraffin blocks of diagnosed odontogenic cysts were processed to determine the immunohistochemical expression of P53 protein. Nine of the 11 odontogenic keratocysts (81.8%) expressed P53, one of three dentigerous cyst cases expressed P53, while none of the 16 radicular cysts expressed P53 protein. The findings of the present work supported the reclassification of OKC as keratocystic odontogenic tumor. PMID:23960493

48 CFR 53.301-330 - Architect-Engineer Qualifications.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Architect-Engineer Qualifications. 53.301-330 Section 53.301-330 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS FORMS Illustrations of Forms 53.301-330 Architect-Engineer...

Analysis of p53- immunoreactivity in astrocytic brain tumors

Directory of Open Access Journals (Sweden)

Shinkarenko T.V.

2016-12-01

Full Text Available P53 is an antioncogene with the frequently occured mutations in human tumor cells, leading to corresponding protein overexpression which can be detected by immunohistochemistry. Researches dedicated to the investigation of possibilities of using this technique gave controversial results. The authors investigated features of p53 protein expression in astrocytic brain tumors with different degrees of malignancy. Analyzed the relationship of the expression level of p53 by tumor cells with clinical parameters and Ki-67 proliferation index (PI as well. Tissues were collected from 52 cases with diagnosed astrocytic brain tumors. The sections were immunohistochemically stained with p53 and Ki-67. For each marker, 1000 tumor cells were counted and the ratio of positive tumor cells was calculated using software package ImageJ 1,47v. In normal brain tissue p53- expression was not identified. p53-immunoreactive tumor cells were detected in 25% (1/4 pilocytic astrocytomas, 33.3% (2/6 of diffuse astrocytomas, 53.8% (7/13 anaplastic astrocytomas, 58.6% (17/29 glioblastomas. A high proportion of p53-immunoreactive cells (> 30% was observed only in glioblastomas. The level of p53-imunoreactivity was not related to the age, gender and Grade WHO (p> 0,05. Spearman correlation coefficient between the relative quantity of ki-67- and p53-immunoreactive nuclei showed weak direct correlation (0.023, but the one was not statistically significant (p> 0,05. The level of p53-imunoreactivity is not dependent from age and sex of patients, Grade (WHO and proliferative activity (p>0,05 but the high level of p53-immunoreactive cells (>30% is found in glioblastoma specimens only, that may be due to the accumulation of mutations in DNA of tumor cells. There is insignificant weak relationship between relative quantities of ki-67- and p53-immunoreactive tumor cells (p>0,05.

p53 downregulates the Fanconi anaemia DNA repair pathway.

Science.gov (United States)

Jaber, Sara; Toufektchan, Eléonore; Lejour, Vincent; Bardot, Boris; Toledo, Franck

2016-04-01

Germline mutations affecting telomere maintenance or DNA repair may, respectively, cause dyskeratosis congenita or Fanconi anaemia, two clinically related bone marrow failure syndromes. Mice expressing p53(Δ31), a mutant p53 lacking the C terminus, model dyskeratosis congenita. Accordingly, the increased p53 activity in p53(Δ31/Δ31) fibroblasts correlated with a decreased expression of 4 genes implicated in telomere syndromes. Here we show that these cells exhibit decreased mRNA levels for additional genes contributing to telomere metabolism, but also, surprisingly, for 12 genes mutated in Fanconi anaemia. Furthermore, p53(Δ31/Δ31) fibroblasts exhibit a reduced capacity to repair DNA interstrand crosslinks, a typical feature of Fanconi anaemia cells. Importantly, the p53-dependent downregulation of Fanc genes is largely conserved in human cells. Defective DNA repair is known to activate p53, but our results indicate that, conversely, an increased p53 activity may attenuate the Fanconi anaemia DNA repair pathway, defining a positive regulatory feedback loop.

48 CFR 53.232 - Contract financing (SF 1443).

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Contract financing (SF 1443). 53.232 Section 53.232 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS FORMS Prescription of Forms 53.232 Contract financing (SF 1443). SF 1443 (JUL...

7 CFR 1718.53 - Rights of other mortgagees.

Science.gov (United States)

2010-01-01

... 7 Agriculture 11 2010-01-01 2010-01-01 false Rights of other mortgagees. 1718.53 Section 1718.53 Agriculture Regulations of the Department of Agriculture (Continued) RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE LOAN SECURITY DOCUMENTS FOR ELECTRIC BORROWERS Mortgage for Distribution Borrowers § 1718.53...

Around and beyond 53BP1 Nuclear Bodies.

Science.gov (United States)

Fernandez-Vidal, Anne; Vignard, Julien; Mirey, Gladys

2017-12-05

Within the nucleus, sub-nuclear domains define territories where specific functions occur. Nuclear bodies (NBs) are dynamic structures that concentrate nuclear factors and that can be observed microscopically. Recently, NBs containing the p53 binding protein 1 (53BP1), a key component of the DNA damage response, were defined. Interestingly, 53BP1 NBs are visualized during G1 phase, in daughter cells, while DNA damage was generated in mother cells and not properly processed. Unlike most NBs involved in transcriptional processes, replication has proven to be key for 53BP1 NBs, with replication stress leading to the formation of these large chromatin domains in daughter cells. In this review, we expose the composition and organization of 53BP1 NBs and focus on recent findings regarding their regulation and dynamics. We then concentrate on the importance of the replication stress, examine the relation of 53BP1 NBs with DNA damage and discuss their dysfunction.

TP53 Mutations in Nonsmall Cell Lung Cancer

Directory of Open Access Journals (Sweden)

Akira Mogi

2011-01-01

Full Text Available The tumor suppressor gene TP53 is frequently mutated in human cancers. Abnormality of the TP53 gene is one of the most significant events in lung cancers and plays an important role in the tumorigenesis of lung epithelial cells. Human lung cancers are classified into two major types, small cell lung cancer (SCLC and nonsmall cell lung cancer (NSCLC. The latter accounts for approximately 80% of all primary lung cancers, and the incidence of NSCLC is increasing yearly. Most clinical studies suggest that NSCLC with TP53 alterations carries a worse prognosis and may be relatively more resistant to chemotherapy and radiation. A deep understanding of the role of TP53 in lung carcinogenesis may lead to a more reasonably targeted clinical approach, which should be exploited to enhance the survival rates of patients with lung cancer. This paper will focus on the role of TP53 in the molecular pathogenesis, epidemiology, and therapeutic strategies of TP53 mutation in NSCLC.

Around and beyond 53BP1 Nuclear Bodies

Directory of Open Access Journals (Sweden)

Anne Fernandez-Vidal

2017-12-01

Full Text Available Within the nucleus, sub-nuclear domains define territories where specific functions occur. Nuclear bodies (NBs are dynamic structures that concentrate nuclear factors and that can be observed microscopically. Recently, NBs containing the p53 binding protein 1 (53BP1, a key component of the DNA damage response, were defined. Interestingly, 53BP1 NBs are visualized during G1 phase, in daughter cells, while DNA damage was generated in mother cells and not properly processed. Unlike most NBs involved in transcriptional processes, replication has proven to be key for 53BP1 NBs, with replication stress leading to the formation of these large chromatin domains in daughter cells. In this review, we expose the composition and organization of 53BP1 NBs and focus on recent findings regarding their regulation and dynamics. We then concentrate on the importance of the replication stress, examine the relation of 53BP1 NBs with DNA damage and discuss their dysfunction.

9 CFR 3.53 - Primary enclosures.

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Primary enclosures. 3.53 Section 3.53 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL... maintained in good repair to protect the rabbits from injury, to contain them, and to keep predators out. (2...

The LiHCOO-Sc(HCOO)3-H2O system at 25 and 50 deg C

International Nuclear Information System (INIS)

Petrova, E.V.; Itkina, L.S.

1980-01-01

Solubility in the LiHCOO-Sc(HCOO) 3 -H 2 O system at 25 and 50 deg C has been investigated using the isothermal method It has been ascertainedy s stem is a simple eutonic one. Solubility isotherms consist of two crystallization branches: lithium formate monohydrate and scandium formate. Scandium formate salts-out lithium formate from the solution. Lithium formate increases the solubility of scandium formate (in the eutonic solution more than 2 times as compared to its solubility in the pure water)

PC communication world and Yiyagi 5.3

International Nuclear Information System (INIS)

1992-11-01

This book is comprised of four parts about Yiyagi 5.3. It describes how to use Yiyagi 5.3 : the way to save 5.3 into floppy disk and Hard disk, to store modem, how to communicate with Hitel and PC-serve in the first part, how to use the various function : function key, control key, alt key, text editor of Yiyagi 5.3 and mouse in the second part, to be good at using communication : Modem, screen control, RS-232C and Null Modem, script and Multitasking in the third part. It has an appendix about compression and decompression of file, BBS list, PC application such as VGA graphic, UNIX/ XENIX and DOS, RS-232C and Modem and GR.exe.

Mutant p53 protein localized in the cytoplasm inhibits autophagy.

Science.gov (United States)

Morselli, Eugenia; Tasdemir, Ezgi; Maiuri, Maria Chiara; Galluzzi, Lorenzo; Kepp, Oliver; Criollo, Alfredo; Vicencio, José Miguel; Soussi, Thierry; Kroemer, Guido

2008-10-01

The knockout, knockdown or chemical inhibition of p53 stimulates autophagy. Moreover, autophagy-inducing stimuli such as nutrient depletion, rapamycin or lithium cause the depletion of cytoplasmic p53, which in turn is required for the induction of autophagy. Here, we show that retransfection of p53(-/-) HCT 116 colon carcinoma cells with wild type p53 decreases autophagy down to baseline levels. Surprisingly, one third among a panel of 22 cancer-associated p53 single amino acid mutants also inhibited autophagy when transfected into p53(-/-) cells. Those variants of p53 that preferentially localize to the cytoplasm effectively repressed autophagy, whereas p53 mutants that display a prominently nuclear distribution failed to inhibit autophagy. The investigation of a series of deletion mutants revealed that removal of the DNA-binding domain from p53 fails to interfere with its role in the regulation of autophagy. Altogether, these results identify the cytoplasmic localization of p53 as the most important feature for p53-mediated autophagy inhibition. Moreover, the structural requirements for the two biological activities of extranuclear p53, namely induction of apoptosis and inhibition of autophagy, are manifestly different.

[Punish or cherish: p53, metabolism and tumor suppression].

Science.gov (United States)

Albagli, Olivier

2015-10-01

The p53 gene is essential for tumor suppression, but how it does so remains unclear. Upon genotoxic or oncogenic stresses, increased p53 activity induces transient cell cycle arrest, senescence or apoptosis, the three cornerstones of the so-called triumvirate. Accordingly, it has long been thought that p53 suppresses tumorigenesis by somehow counteracting cell proliferation or survival. However, several recently described genetically modified mice indicate that p53 can suppress tumorigenesis without triggering these three responses. Rather, as an important mechanism for tumor suppression, these mutant mice point to the ability of p53 to prevent the Warburg effect, that is to dampen glycolysis and foster mitochondrial respiration. Interestingly, these metabolic functions of p53 rely, in part, on its "unstressed" (basal) expression, a feature shared by its mechanistically linked anti-oxydant function. Together, these "conservative" activities of p53 may prevent tumor initiation by promoting and maintaining a normal oxidative metabolism and hence underly the "daily" tumor suppression by p53 in most cells. Conversely, destructive activities elicited by high p53 levels and leading to senescence or apoptosis provide a shield against partially or overtly transformed cells. This last situation, although relatively infrequent throughout life, is usual in experimental settings, which could explain the disproportionally high number of data implicating the triumvirate in tumor suppression by p53. © 2015 médecine/sciences – Inserm.

19 CFR 210.53 - Motion filed after complaint.

Science.gov (United States)

2010-04-01

... 19 Customs Duties 3 2010-04-01 2010-04-01 false Motion filed after complaint. 210.53 Section 210.53 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION INVESTIGATIONS OF UNFAIR PRACTICES IN IMPORT TRADE ADJUDICATION AND ENFORCEMENT Temporary Relief § 210.53 Motion filed after complaint. (a) A...

N-methylpurine DNA glycosylase inhibits p53-mediated cell cycle arrest and coordinates with p53 to determine sensitivity to alkylating agents.

Science.gov (United States)

Song, Shanshan; Xing, Guichun; Yuan, Lin; Wang, Jian; Wang, Shan; Yin, Yuxin; Tian, Chunyan; He, Fuchu; Zhang, Lingqiang

2012-08-01

Alkylating agents induce genome-wide base damage, which is repaired mainly by N-methylpurine DNA glycosylase (MPG). An elevated expression of MPG in certain types of tumor cells confers higher sensitivity to alkylation agents because MPG-induced apurinic/apyrimidic (AP) sites trigger more strand breaks. However, the determinant of drug sensitivity or insensitivity still remains unclear. Here, we report that the p53 status coordinates with MPG to play a pivotal role in such process. MPG expression is positive in breast, lung and colon cancers (38.7%, 43.4% and 25.3%, respectively) but negative in all adjacent normal tissues. MPG directly binds to the tumor suppressor p53 and represses p53 activity in unstressed cells. The overexpression of MPG reduced, whereas depletion of MPG increased, the expression levels of pro-arrest gene downstream of p53 including p21, 14-3-3σ and Gadd45 but not proapoptotic ones. The N-terminal region of MPG was specifically required for the interaction with the DNA binding domain of p53. Upon DNA alkylation stress, in p53 wild-type tumor cells, p53 dissociated from MPG and induced cell growth arrest. Then, AP sites were repaired efficiently, which led to insensitivity to alkylating agents. By contrast, in p53-mutated cells, the AP sites were repaired with low efficacy. To our knowledge, this is the first direct evidence to show that a DNA repair enzyme functions as a selective regulator of p53, and these findings provide new insights into the functional linkage between MPG and p53 in cancer therapy.

7 CFR 985.53 - Allotment base.

Science.gov (United States)

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Allotment base. 985.53 Section 985.53 Agriculture... Allotment base. (a) Initial issuance. Each producer desiring an allotment base for one or more classes of..., and of 1979, which is the representative base period, and the number of pounds of each class of oil...

Expression of Androgen Receptor Is Negatively Regulated By p53

Directory of Open Access Journals (Sweden)

Fatouma Alimirah

2007-12-01

Full Text Available Increased expression of androgen receptor (AR in prostate cancer (PC is associated with transition to androgen independence. Because the progression of PC to advanced stages is often associated with the loss of p53 function, we tested whether the p53 could regulate the expression of AR gene. Here we report that p53 negatively regulates the expression of AR in prostate epithelial cells (PrECs. We found that in LNCaP human prostate cancer cells that express the wild-type p53 and AR and in human normal PrECs, the activation of p53 by genotoxic stress or by inhibition of p53 nuclear export downregulated the expression of AR. Furthermore, forced expression of p53 in LNCaP cells decreased the expression of AR. Conversely, knockdown of p53 expression in LNCaP cells increased the AR expression. Consistent with the negative regulation of AR expression by p53, the p53-null HCT116 cells expressed higher levels of AR compared with the isogenic HCT116 cells that express the wildtype p53. Moreover, we noted that in etoposide treated LNCaP cells p53 bound to the promoter region of the AR gene, which contains a potential p53 DNA-binding consensus sequence, in chromatin immunoprecipitation assays. Together, our observations provide support for the idea that the loss of p53 function in prostate cancer cells contributes to increased expression of AR.

7 CFR 58.53 - Supervisor of packaging required.

Science.gov (United States)

2010-01-01

... 7 Agriculture 3 2010-01-01 2010-01-01 false Supervisor of packaging required. 58.53 Section 58.53... Packaging Products with Official Identification § 58.53 Supervisor of packaging required. The official....54 through 58.57, shall be done only under the supervision of a supervisor of packaging. The...

1 CFR 5.3 - Publication of other documents.

Science.gov (United States)

2010-01-01

... 1 General Provisions 1 2010-01-01 2010-01-01 false Publication of other documents. 5.3 Section 5.3 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER THE FEDERAL REGISTER GENERAL § 5.3 Publication of other documents. Whenever the Director of the Federal Register considers that publication of a...

The Role of Tumor Protein 53 Mutations in Common Human Cancers and Targeting the Murine Double Minute 2–P53 Interaction for Cancer Therapy

Directory of Open Access Journals (Sweden)

Tayebeh Hamzehloie

2012-03-01

Full Text Available The gene TP53 (also known as protein 53 or tumor protein 53, encoding transcription factor P53, is mutated or deleted in half of human cancers, demonstrating the crucial role of P53 in tumor suppression. There are reports of nearly 250 independent germ line TP53 mutations in over 100 publications. The P53 protein has the structure of a transcription factor and, is made up of several domains. The main function of P53 is to organize cell defense against cancerous transformation. P53 is a potent transcription factor that is activated in response to diverse stresses, leading to the induction of cell cycle arrest, apoptosis or senescence. The P53 tumor suppressor is negatively regulated in cells by the murine double minute 2 (MDM2 protein. Murine double minute 2 favors its nuclear export, and stimulates its degradation. Inhibitors of the P53-MDM2 interaction might be attractive new anticancer agents that could be used to activate wild-type P53 in tumors. Down regulation of MDM2 using an small interfering RNA (siRNA approach has recently provided evidence for a new role of MDM2 in the P53 response, by modulating the inhibition of the cyclin dependent kinase 2 (cdk2 by P21/WAF1 (also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1.

p53-competent cells and p53-deficient cells display different susceptibility to oxygen functionalized graphene cytotoxicity and genotoxicity.

Science.gov (United States)

Petibone, Dayton M; Mustafa, Thikra; Bourdo, Shawn E; Lafont, Andersen; Ding, Wei; Karmakar, Alokita; Nima, Zeid A; Watanabe, Fumiya; Casciano, Daniel; Morris, Suzanne M; Dobrovolsky, Vasily N; Biris, Alexandru S

2017-11-01

Due to the distinctive physical, electrical, and chemical properties of graphene nanomaterials, numerous efforts pursuing graphene-based biomedical and industrial applications are underway. Oxidation of pristine graphene surfaces mitigates its otherwise hydrophobic characteristic thereby improving its biocompatibility and functionality. Yet, the potential widespread use of oxidized graphene derivatives raises concern about adverse impacts on human health. The p53 tumor suppressor protein maintains cellular and genetic stability after toxic exposures. Here, we show that p53 functional status correlates with oxygen functionalized graphene (f-G) cytotoxicity and genotoxicity in vitro. The f-G exposed p53-competent cells, but not p53-deficient cells, initiated G 0 /G 1 phase cell cycle arrest, suppressed reactive oxygen species, and entered apoptosis. There was p53-dependent f-G genotoxicity evident as increased structural chromosome damage, but not increased gene mutation or chromatin loss. In conclusion, the cytotoxic and genotoxic potential for f-G in exposed cells was dependent on the p53 functional status. These findings have broad implications for the safe and effective implementation of oxidized graphene derivatives into biomedical and industrial applications. Published 2017. This article has been contributed to by US Government employees and their work is in the public domain in the USA. Published 2017. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

34 CFR 104.53 - Drug and alcohol addicts.

Science.gov (United States)

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false Drug and alcohol addicts. 104.53 Section 104.53... ASSISTANCE Health, Welfare, and Social Services § 104.53 Drug and alcohol addicts. A recipient to which this... or treatment against a drug or alcohol abuser or alcoholic who is suffering from a medical condition...

45 CFR 84.53 - Drug and alcohol addicts.

Science.gov (United States)

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Drug and alcohol addicts. 84.53 Section 84.53... Social Services § 84.53 Drug and alcohol addicts. A recipient to which this subpart applies that operates... drug or alcohol abuser or alcoholic who is suffering from a medical condition, because of the person's...

Friend or Foe: MicroRNAs in the p53 network.

Science.gov (United States)

Luo, Zhenghua; Cui, Ri; Tili, Esmerina; Croce, Carlo

2018-04-10

The critical tumor suppressor gene TP53 is either lost or mutated in more than half of human cancers. As an important transcriptional regulator, p53 modulates the expression of many microRNAs. While wild-type p53 uses microRNAs to suppress cancer development, microRNAs that are activated by gain-of-function mutant p53 confer oncogenic properties. On the other hand, the expression of p53 is tightly controlled by a fine-tune machinery including microRNAs. MicroRNAs can target the TP53 gene directly or other factors in the p53 network so that expression and function of either the wild-type or the mutant forms of p53 is downregulated. Therefore, depending on the wild-type or mutant p53 context, microRNAs contribute substantially to suppress or exacerbate tumor development. Copyright © 2018. Published by Elsevier B.V.

45 CFR 605.53 - Drug and alcohol addicts.

Science.gov (United States)

2010-10-01

... 45 Public Welfare 3 2010-10-01 2010-10-01 false Drug and alcohol addicts. 605.53 Section 605.53..., Welfare, and Social Services § 605.53 Drug and alcohol addicts. A recipient to which this subpart applies... against a drug or alcohol abuser or alcoholic who is suffering from a medical condition, because of the...

The genetic alteration of p53 in esophageal cancer

Energy Technology Data Exchange (ETDEWEB)

Cho, Jae Il; Baik, Hee Jong; Kim, Chang Min; Kim, Mi Hee [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

1996-01-01

Genetic alterations in the p53 gene have been detected in various human malignancies, and its alterations inactive the function of p53 as a tumor suppressor. Point mutation and gene deletion are the main mechanisms of p53 inactivation. To determine the incidence of genetic alteration of p53 and their clinical implications in Korean patients of esophageal cancer, we investigated p53 alterations in 26 esophageal cancer tissues paired with its normal tissue by Southern blot analysis, PCR-SSCP, and direct sequencing. Allelic loss of chromosome 17p occurred in 12 out of 21 informative cases(57%) by Southern blot analysis, and 16 cases showed mobility shift in PCR-SSCP, so overall incidence of p53 gene alterations was 77%(20/26). The mutations detected was randomly dispersed over exon4-8 and was frequently G-T transversion and C:T transitions. Three identical mutations were clustered at codon 213 suggested the same etiologic agents in this cases. The p53 gene alterations play a significant role in the development of esophageal cancers, however, no relationship between p53 mutation and clinical data was detected so far. 9 refs. (Author).

Tobacco, alcohol, and p53 overexpression in early colorectal neoplasia

International Nuclear Information System (INIS)

Terry, Mary Beth; Neugut, Alfred I; Mansukhani, Mahesh; Waye, Jerome; Harpaz, Noam; Hibshoosh, Hanina

2003-01-01

The p53 tumor suppressor gene is commonly mutated in colorectal cancer. While the effect of p53 mutations on colorectal cancer prognosis has been heavily studied, less is known about how epidemiologic risk factors relate to p53 status, particularly in early colorectal neoplasia prior to clinically invasive colorectal cancer (including adenomas, carcinoma in situ (CIS), and intramucosal carcinoma). We examined p53 status, as measured by protein overexpression, in 157 cases with early colorectal neoplasia selected from three New York City colonoscopy clinics. After collecting paraffin-embedded tissue blocks, immunohistochemistry was performed using an anti-p53 monoclonal mouse IgG 2 a [BP53-12-1] antibody. We analyzed whether p53 status was different for risk factors for colorectal neoplasia relative to a polyp-free control group (n = 508). p53 overexpression was found in 10.3%, 21.7%, and 34.9%, of adenomatous polyps, CIS, and intramucosal cases, respectively. Over 90% of the tumors with p53 overexpression were located in the distal colon and rectum. Heavy cigarette smoking (30+ years) was associated with cases not overexpressing p53 (OR = 1.8, 95% CI = 1.1–2.9) but not with those cases overexpressing p53 (OR = 1.0, 95% CI = 0.4–2.6). Heavy beer consumption (8+ bottles per week) was associated with cases overexpressing p53 (OR = 4.0, 95% CI = 1.3–12.0) but not with cases without p53 overexpression (OR = 1.6, 95% CI = 0.7–3.7). Our findings that p53 overexpression in early colorectal neoplasia may be positively associated with alcohol intake and inversely associated with cigarette smoking are consistent with those of several studies of p53 expression and invasive cancer, and suggest that there may be relationships of smoking and alcohol with p53 early in the adenoma to carcinoma sequence

Static dipole polarizabilities of Scn (n ≤ 15) clusters

International Nuclear Information System (INIS)

Xi-Bo, Li; Jiang-Shan, Luo; Wei-Dong, Wu; Yong-Jian, Tang; Hong-Yan, Wang; Yun-Dong, Guo

2009-01-01

The static dipole polarizabilities of scandium clusters with up to 15 atoms are determined by using the numerically finite field method in the framework of density functional theory. The electronic effects on the polarizabilities are investigated for the scandium clusters. We examine a large highest occupied molecular orbital — the lowest occupied molecular orbital (HOMO–LUMO) gap of a scandium cluster usually corresponds to a large dipole moment. The static polarizability per atom decreases slowly and exhibits local minimum with increasing cluster size. The polarizability anisotropy and the ratio of mean static polarizability to the HOMO–LUMO gap can also reflect the cluster stability. The polarizability of the scandium cluster is partially related to the HOMO–LUMO gap and is also dependent on geometrical characteristics. A strong correlation between the polarizability and ionization energy is observed. (atomic and molecular physics)

Combining Oncolytic Virotherapy with p53 Tumor Suppressor Gene Therapy

Directory of Open Access Journals (Sweden)

Christian Bressy

2017-06-01

Full Text Available Oncolytic virus (OV therapy utilizes replication-competent viruses to kill cancer cells, leaving non-malignant cells unharmed. With the first U.S. Food and Drug Administration-approved OV, dozens of clinical trials ongoing, and an abundance of translational research in the field, OV therapy is poised to be one of the leading treatments for cancer. A number of recombinant OVs expressing a transgene for p53 (TP53 or another p53 family member (TP63 or TP73 were engineered with the goal of generating more potent OVs that function synergistically with host immunity and/or other therapies to reduce or eliminate tumor burden. Such transgenes have proven effective at improving OV therapies, and basic research has shown mechanisms of p53-mediated enhancement of OV therapy, provided optimized p53 transgenes, explored drug-OV combinational treatments, and challenged canonical roles for p53 in virus-host interactions and tumor suppression. This review summarizes studies combining p53 gene therapy with replication-competent OV therapy, reviews preclinical and clinical studies with replication-deficient gene therapy vectors expressing p53 transgene, examines how wild-type p53 and p53 modifications affect OV replication and anti-tumor effects of OV therapy, and explores future directions for rational design of OV therapy combined with p53 gene therapy.

TP53 dysfunction in CLL: Implications for prognosis and treatment.

Science.gov (United States)

Te Raa, Gera D; Kater, Arnon P

2016-03-01

Despite the availability of novel targeted agents, TP53 defects remain the most important adverse prognostic factor in chronic lymphocytic leukemia (CLL). Detection of deletion of TP53 locus (17p deletion) by fluorescent in situ hybridization (FISH) has become standard and performed prior to every line of treatment as the incidence dramatically increases as relapses occur. As monoallelic mutations of TP53 equally affect outcome, novel methods are being developed to improve detection of TP53 defects and include next-generation sequencing (NGS) and functional assays. TP53 defects highly affect outcome of immunochemotherapy but also alter response durations of tyrosine kinase inhibitors. Although BCR-targeting agents and Bcl-2-inhibitos have achieved durable responses in some patients with TP53 defects, long-term follow-up is currently lacking. In this review biological and clinical consequences of TP53 dysfunction as well as applicability of currently available methods to detect TP53 defects are described. In addition, proposed novel therapeutic strategies specifically for patients with TP53 dysfunction are discussed. In summary, the only curative treatment option for TP53-defective CLL is still allogeneic hematopoietic stem cell transplantation. Other treatment strategies such as rationale combinations of agents with different (TP53 independent) targets, including kinase inhibitors and inhibitors of anti-apoptotic molecules but also immunomodulatory agents need to be further explored. Copyright © 2016 Elsevier Ltd. All rights reserved.

A dual role of p53 in the control of autophagy.

Science.gov (United States)

Tasdemir, Ezgi; Chiara Maiuri, M; Morselli, Eugenia; Criollo, Alfredo; D'Amelio, Marcello; Djavaheri-Mergny, Mojgan; Cecconi, Francesco; Tavernarakis, Nektarios; Kroemer, Guido

2008-08-01

Genotoxic stress can induce autophagy in a p53-dependent fashion and p53 can transactivate autophagy-inducing genes. We have observed recently that inactivation of p53 by deletion, depletion or inhibition can trigger autophagy. Thus, human and mouse cells subjected to knockout, knockdown or pharmacological inhibition of p53 manifest signs of autophagy such as depletion of p62/SQSTM1, LC3 lipidation, redistribution of GFP-LC3 in cytoplasmic puncta, and accumulation of autophagosomes and autolysosomes, both in vitro and in vivo. Inhibition of p53 causes autophagy in enucleated cells, indicating that the cytoplasmic, non-nuclear pool of p53 can regulate autophagy. Accordingly, retransfection of p53(-/-) cells with wild-type p53 as well as a p53 mutant that is excluded from the nucleus (due to the deletion of the nuclear localization sequence) can inhibit autophagy, whereas retransfection with a nucleus-restricted p53 mutant (in which the nuclear localization sequence has been deleted) does not inhibit autophagy. Several distinct autophagy inducers (e.g., starvation, rapamycin, lithium, tunicamycin and thapsigargin) stimulate the rapid degradation of p53. In these conditions, inhibition of the p53-specific E3 ubiquitin ligase HDM2 can avoid p53 depletion and simultaneously prevent the activation of autophagy. Moreover, a p53 mutant that lacks the HDM2 ubiquitinylation site and hence is more stable than wild-type p53 is particularly efficient in suppressing autophagy. In conclusion, p53 plays a dual role in the control of autophagy. On the one hand, nuclear p53 can induce autophagy through transcriptional effects. On the other hand, cytoplasmic p53 may act as a master repressor of autophagy.

Mutations in p53, p53 protein overexpression and breast cancer survival

Czech Academy of Sciences Publication Activity Database

Rössner ml., Pavel; Gammon, M. D.; Zhang, Y.J.; Terry, M. B.; Hibshoosh, H.; Memeo, L.; Mansukhani, M.; Long, CH.M.; Gabrowski, G.; Agrawal, M.; Kalra, T.S.; Teitelbaum, S. L.; Neugut, A. I.; Santella, R. M.

2009-01-01

Roč. 13, č. 9B (2009), s. 3847-3857 ISSN 1582-1838 Institutional research plan: CEZ:AV0Z50390512 Keywords : Breast cancer * p53 mutations * Survival Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 5.228, year: 2009

15 CFR 700.53 - Criteria for assistance.

Science.gov (United States)

2010-01-01

... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Criteria for assistance. 700.53 Section 700.53 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE NATIONAL SECURITY INDUSTRIAL BASE REGULATIONS...

Knockdown of p53 suppresses Nanog expression in embryonic stem cells

Energy Technology Data Exchange (ETDEWEB)

Abdelalim, Essam Mohamed, E-mail: emohamed@qf.org.qa [Qatar Biomedical Research Institute, Qatar Foundation, Doha 5825 (Qatar); Molecular Neuroscience Research Center, Shiga University of Medical Science, Setatsukinowa-cho, Otsu, Shiga 520-2192 (Japan); Department of Cytology and Histology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia (Egypt); Tooyama, Ikuo [Molecular Neuroscience Research Center, Shiga University of Medical Science, Setatsukinowa-cho, Otsu, Shiga 520-2192 (Japan)

2014-01-10

Highlights: •We investigate the role of p53 in ESCs in the absence of DNA damage. •p53 knockdown suppresses ESC proliferation. •p53 knockdown downregulates Nanog expression. •p53 is essential for mouse ESC self-renewal. -- Abstract: Mouse embryonic stem cells (ESCs) express high levels of cytoplasmic p53. Exposure of mouse ESCs to DNA damage leads to activation of p53, inducing Nanog suppression. In contrast to earlier studies, we recently reported that chemical inhibition of p53 suppresses ESC proliferation. Here, we confirm that p53 signaling is involved in the maintenance of mouse ESC self-renewal. RNA interference-mediated knockdown of p53 induced downregulation of p21 and defects in ESC proliferation. Furthermore, p53 knockdown resulted in a significant downregulation in Nanog expression at 24 and 48 h post-transfection. p53 knockdown also caused a reduction in Oct4 expression at 48 h post-transfection. Conversely, exposure of ESCs to DNA damage caused a higher reduction of Nanog expression in control siRNA-treated cells than in p53 siRNA-treated cells. These data show that in the absence of DNA damage, p53 is required for the maintenance of mouse ESC self-renewal by regulating Nanog expression.

Hormonal control of p53 and chemoprevention

International Nuclear Information System (INIS)

Jerry, D Joseph; Minter, Lisa M; Becker, Klaus A; Blackburn, Anneke C

2002-01-01

Improvements in the detection and treatment of breast cancer have dramatically altered its clinical course and outcome. However, prevention of breast cancer remains an elusive goal. Parity, age of menarche, and age at menopause are major risk factors drawing attention to the important role of the endocrine system in determining the risk of breast cancer, while heritable breast cancer susceptibility syndromes have implicated tumor suppressor genes as important targets. Recent work demonstrating hormonal modulation of the p53 tumor suppressor pathway draws together these established determinants of risk to provide a model of developmental susceptibility to breast cancer. In this model, the mammary epithelium is rendered susceptible due to impaired p53 activity during specific periods of mammary gland development, but specific endocrine stimuli serve to activate p53 function and to mitigate this risk. The results focus attention on p53 as a molecular target for therapies to reduce the risk of breast cancer

48 CFR 53.301-1438 - Settlement Proposal (Short Form).

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Settlement Proposal (Short Form). 53.301-1438 Section 53.301-1438 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS FORMS Illustrations of Forms 53.301-1438 Settlement Proposal (Short...

48 CFR 53.301-1439 - Schedule of Accounting Information.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Schedule of Accounting Information. 53.301-1439 Section 53.301-1439 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS FORMS Illustrations of Forms 53.301-1439 Schedule of Accounting...

CLCA2 as a p53-Inducible Senescence Mediator

Directory of Open Access Journals (Sweden)

Chizu Tanikawa

2012-02-01

Full Text Available p53 is a tumor suppressor gene that is frequently mutated in multiple cancer tissues. Activated p53 protein regulates its downstream genes and subsequently inhibits malignant transformation by inducing cell cycle arrest, apoptosis, DNA repair, and senescence. However, genes involved in the p53-mediated senescence pathway are not yet fully elucidated. Through the screening of two genome-wide expression profile data sets, one for cells in which exogenous p53 was introduced and the other for senescent fibroblasts, we have identified chloride channel accessory 2 (CLCA2 as a p53-inducible senescence-associated gene. CLCA2 was remarkably induced by replicative senescence as well as oxidative stress in a p53-dependent manner. We also found that ectopically expressed CLCA2 induced cellular senescence, and the down-regulation of CLCA2 by small interfering RNA caused inhibition of oxidative stress-induced senescence. Interestingly, the reduced expression of CLCA2 was frequently observed in various kinds of cancers including prostate cancer, whereas its expression was not affected in precancerous prostatic intraepithelial neoplasia. Thus, our findings suggest a crucial role of p53/CLCA2-mediated senescence induction as a barrier for malignant transformation.

Infection with E1B-mutant adenovirus stabilizes p53 but blocks p53 acetylation and activity through E1A

DEFF Research Database (Denmark)

Savelyeva, I.; Dobbelstein, M.

2011-01-01

to the suppression of p21 transcription. Depending on the E1A conserved region 3, E1B-defective adenovirus impaired the ability of the transcription factor Sp1 to bind the p21 promoter. Moreover, the amino terminal region of E1A, binding the acetyl transferases p300 and CREB-binding protein, blocked p53 K382...... accumulation of p53, without obvious defects in p53 localization, phosphorylation, conformation and oligomerization. Nonetheless, p53 completely failed to induce its target genes in this scenario, for example, p21/CDKN1A, Mdm2 and PUMA. Two regions of the E1A gene products independently contributed...... acetylation in infected cells. Mutating either of these E1A regions, in addition to E1B, partially restored p21 mRNA levels. Our findings argue that adenovirus attenuates p53-mediated p21 induction, through at least two E1B-independent mechanisms. Other virus species and cancer cells may employ analogous...

Targeting p53 by small molecules in hematological malignancies

OpenAIRE

Saha, Manujendra N; Qiu, Lugui; Chang, Hong

2013-01-01

p53 is a powerful tumor suppressor and is an attractive cancer therapeutic target. A breakthrough in cancer research came from the discovery of the drugs which are capable of reactivating p53 function. Most anti-cancer agents, from traditional chemo- and radiation therapies to more recently developed non-peptide small molecules exert their effects by enhancing the anti-proliferative activities of p53. Small molecules such as nutlin, RITA, and PRIMA-1 that can activate p53 have shown their ant...

9 CFR 53.6 - Disinfection of animals.

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Disinfection of animals. 53.6 Section 53.6 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF... of animals. Animals of species not susceptible to the disease for which a quarantine has been...

40 CFR 53.64 - Test procedure: Static fractionator test.

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2010-07-01

... 40 Protection of Environment 5 2010-07-01 2010-07-01 false Test procedure: Static fractionator test. 53.64 Section 53.64 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Performance Characteristics of Class II Equivalent Methods for PM2.5 § 53.64 Test procedure: Static...

The IARC TP53 mutation database: a resource for studying the significance of TP53 mutations in human cancers

Directory of Open Access Journals (Sweden)

Magali Olivier

2007-02-01

Full Text Available

The tumor suppressor gene TP53 is frequently inactivated by gene mutations in many types of human sporadic cancers, and inherited TP53 mutations predispose to a wide spectrum of early-onset tumors (Li-Fraumeni et Li-Fraumenilike Syndromes. All TP53 gene variations (somatic and germline mutations, as well as polymorphisms that are reported in the scientific literature or in SNP databases are compiled in the IARC TP53 Database. This database provides structured data and analysis tools to study mutation patterns in human cancers and cell-lines and to investigate the clinical impact of mutations. It contains annotations related to the clinical and pathological characteristics of tumors, as well as the demographics and carcinogen exposure of patients. The IARC TP53 web site (53.iarc.fr/">http://www-p53.iarc.fr/ provides a search interface for the core database and includes a comprehensive user guide, a slideshow on TP53 mutations in human cancer, protocols and references for sequencing TP53 gene, and links to relevant publications and bioinformatics databases. The database interface allows download of entire data sets and propose various tools for the selection, analysis and downloads of specific sets of data according to user's query.

Recently, new annotations on the functional properties of mutant p53 proteins have been integrated in this database. Indeed, the most frequent TP53 alterations observed in cancers (75% are missense mutations that result in the production of a mutant protein that differ from the wildtype by one single amino-acid. The characterization of the biological activities of these mutant proteins is thus very important. Over the last ten years, a great amount of systematic data has been generated from experimental assays performed in

Actinomycin D synergistically enhances the cytotoxicity of CDDP on KB cells by activating P53 via decreasing P53-MDM2 complex.

Science.gov (United States)

Wang, Lin; Pang, Xiao-Cong; Yu, Zi-Ru; Yang, Sheng-Qian; Liu, Ai-Lin; Wang, Jin-Hua; Du, Guan-Hua

2017-06-01

The aim of this study is to investigate the synergism of low dose of actinomycin D (LDActD) to the cytotoxicity of cisplatin (CDDP) on KB cells. The role of P53 reactivation by LDActD in the synergism and its mechanism were further studied. Cell viability was determined by MTT assay. Apoptosis was determined by AnnexinV-FITC/PI staining. Mitochondrial membrane potential (MMP) was detected by JC-1 staining. Expression of proteins was detected by Western blotting (WB) and/or immunofluorescence (IF). Molecular docking of actinomycin D (ACTD) to Mouse double minute 2 homolog (MDM2) and Mouse double minute 2 homolog X (MDMX). MDMX was analyzed by Discovery Studio. The content of P53-MDM2 complex was detected by ELISA assay. The cytotoxicity of CDDP was increased by the combination of LDActD in kinds of cancer cells. Molecular docking showed strong interaction between ACTD and MDM2/MDMX. Meanwhile, LDActD significantly decreased P53-MDM2 complex. Significant increase of the apoptotic activity by the combination therapy in KB cells is P53 upregulated modulator of apoptosis (PUMA) dependent. In addition to the decrease in MMP, LDActD increased P53 regulated protein and decreased BCL-XL in KB cells. LDActD efficiently enhanced the cytotoxicity of CDDP in cancer cells and induced P53-PUMA-dependent and mitochondria-mediated apoptosis in KB cells. The reactivation of P53 was probably achieved by disturbing the interaction of P53 and MDM2/MDMX.

An adaptive molecular timer in p53-meidated cell fate decision

Science.gov (United States)

Zhang, Xiao-Peng; Wang, Ping; Liu, Feng; Wang, Wei

The tumor suppressor p53 decides cellular outcomes in the DNA damage response. It is intriguing to explore the link between p53 dynamics and cell fates. We developed a theoretical model of p53 signaling network to clarify the mechanism of cell fate decision mediated by its dynamics. We found that the interplay between p53-Mdm2 negative feedback loop and p53-PTEN-Mdm2 positive feedback loop shapes p53 dynamics. Depending on the intensity of DNA damage, p53 shows three modes of dynamics: persistent pulses, two-phase dynamics with pulses followed by sustained high levels and straightforward high levels. Especially, p53 shows two-phase dynamics upon moderated damage and the required number of p53 pulses before apoptosis induction decreases with increasing DNA damage. Our results suggested there exists an adaptive molecular timer that determines whether and when the apoptosis switch should be triggered. We clarified the mechanism behind the switching of p53 dynamical modes by bifurcation analysis. Moreover, we reproduced the experimental results that drug additions alter p53 pulses to sustained p53 activation and leads to senescence. Our work may advance the understanding the significance of p53 dynamics in tumor suppression. This work was supported by National Natural Science Foundation of China (Nos. 11175084, 11204126 and 31361163003).

Role of Tumor Suppressor P53 in Megakaryopoiesis and Platelet Function

Science.gov (United States)

Apostolidis, Pani A.; Woulfe, Donna S.; Chavez, Massiel; Miller, William M.; Papoutsakis, Eleftherios T.

2011-01-01

The pathobiological role of p53 has been widely studied, however its role in normophysiology is relatively unexplored. We previously showed that p53 knock-down increased ploidy in megakaryocytic cultures. This study aims to examine the effect of p53 loss on in vivo megakaryopoiesis, platelet production and function, and to investigate the basis for greater ploidy in p53−/− megakaryocytic cultures. Here, we used flow cytometry to analyze ploidy, DNA synthesis and apoptosis in murine cultured and bone marrow megakaryocytes following thrombopoietin administration and to analyze fibrinogen binding to platelets in vitro. Culture of p53−/− marrow cells for 6 days with thrombopoietin gave rise to 1.7-fold more megakaryocytes, 26.1±3.6% of which reached ploidy classes ≥64N compared to 8.2±0.9% of p53+/+ megakaryocytes. This was due to 30% greater DNA synthesis in p53−/− megakaryocytes and 31% greater apoptosis in p53+/+ megakaryocytes by day 4 of culture. Although the bone marrow and spleen steady-state megakaryocytic content and ploidy were similar in p53+/+ and p53−/− mice, thrombopoietin administration resulted in increased megakaryocytic polyploidization in p53−/− mice. Although their platelet counts were normal, p53−/− mice exhibited significantly longer bleeding times and p53−/− platelets were less sensitive than p53+/+ platelets to agonist-induced fibrinogen binding and P-selectin secretion. In summary, our in vivo and ex-vivo studies indicate that p53 loss leads to increased polyploidization during megakaryopoiesis. Our findings also suggest for the first time a direct link between p53 loss and the development of fully functional platelets resulting in hemostatic deficiencies. PMID:22024107

9 CFR 53.4 - Destruction of animals.

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2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Destruction of animals. 53.4 Section 53.4 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF... animals. (a) Except as provided in paragraph (b) of this section, animals infected with or exposed to...

Dopaminergic Neuron-Specific Deletion of p53 Gene Attenuates Methamphetamine Neurotoxicity.

Science.gov (United States)

Lu, Tao; Kim, Paul P; Greig, Nigel H; Luo, Yu

2017-08-01

p53 plays an essential role in the regulation of cell death in dopaminergic (DA) neurons and its activation has been implicated in the neurotoxic effects of methamphetamine (MA). However, how p53 mediates MA neurotoxicity remains largely unknown. In this study, we examined the effect of DA-specific p53 gene deletion in DAT-p53KO mice. Whereas in vivo MA binge exposure reduced locomotor activity in wild-type (WT) mice, this was significantly attenuated in DAT-p53KO mice and associated with significant differences in the levels of the p53 target genes BAX and p21 between WT and DAT-p53KO. Notably, DA-specific deletion of p53 provided protection of substantia nigra pars reticulata (SNpr) tyrosine hydroxylase (TH) positive fibers following binge MA, with DAT-p53KO mice having less decline of TH protein levels in striatum versus WT mice. Whereas DAT-p53KO mice demonstrated a consistently higher density of TH fibers in striatum compared to WT mice at 10 days after MA exposure, DA neuron counts within the substantia nigra pars compacta (SNpc) were similar. Finally, supportive of these results, administration of a p53-specific inhibitor (PFT-α) provided a similarly protective effect on MA binge-induced behavioral deficits. Neither DA specific p53 deletion nor p53 pharmacological inhibition affected hyperthermia induced by MA binge. These findings demonstrate a specific contribution of p53 activation in behavioral deficits and DA neuronal terminal loss by MA binge exposure.

48 CFR 53.301-28 - Affidavit of Individual Surety.

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2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Affidavit of Individual Surety. 53.301-28 Section 53.301-28 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS FORMS Illustrations of Forms 53.301-28 Affidavit of Individual Surety. ER22MY03...

48 CFR 53.301-33 - Solicitation, Offer and Award.

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2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Solicitation, Offer and Award. 53.301-33 Section 53.301-33 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS FORMS Illustrations of Forms 53.301-33 Solicitation, Offer and Award. ER09DE97...

30 CFR 203.53 - What relief will MMS grant?

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2010-07-01

... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What relief will MMS grant? 203.53 Section 203.53 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR MINERALS REVENUE...-Life Leases § 203.53 What relief will MMS grant? (a) If we approve your application and you meet...

7 CFR 301.53-2 - Regulated articles.

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2010-01-01

... 7 Agriculture 5 2010-01-01 2010-01-01 false Regulated articles. 301.53-2 Section 301.53-2... articles. The following are regulated articles: (a) The emerald ash borer; firewood of all hardwood (non... article, product, or means of conveyance not listed in paragraph (a) of this section may be designated as...

14 CFR 21.53 - Statement of conformity.

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2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Statement of conformity. 21.53 Section 21... CERTIFICATION PROCEDURES FOR PRODUCTS AND PARTS Type Certificates § 21.53 Statement of conformity. Link to an... conformity (FAA Form 317) to the Administrator for each aircraft engine and propeller presented to the...

Mitofusin-2 is a novel direct target of p53

International Nuclear Information System (INIS)

Wang, Weilin; Cheng, Xiaofei; Lu, Jianju; Wei, Jianfeng; Fu, Guanghou; Zhu, Feng; Jia, Changku; Zhou, Lin; Xie, Haiyang; Zheng, Shusen

2010-01-01

Research highlights: → Mfn2 is a novel target gene of p53. → Mfn2 mRNA and protein levels can be up-regulated in a p53-dependent manner. → Mfn2 promoter activity can be elevated by the p53 protein. → P53 protein binds the Mfn2 promoter directly both in vitro and in vivo. -- Abstract: The tumor suppressor p53 modulates transcription of a number of target genes involved in cell cycle arrest, apoptosis, DNA repair, and other important cellular responses. Mitofusin-2 (Mfn2) is a novel suppressor of cell proliferation that may also exert apoptotic effects via the mitochondrial apoptotic pathway. Through bioinformatics analysis, we identified a p53 binding site in the Mfn2 promoter. Consistent with this, we showed that the p53 protein binds the Mfn2 promoter directly both in vitro and in vivo. Additionally, we found that Mfn2 mRNA and protein levels are up-regulated in a p53-dependent manner. Furthermore, luciferase assays revealed that the activity of the wild-type Mfn2 promoter, but not a mutated version of the promoter, was up-regulated by p53. These results indicate that Mfn2 is a novel p53-inducible target gene, which provides insight into the regulation of Mfn2 and its associated activities in the inhibition of cell proliferation, promotion of apoptosis, and modulation of tumor suppression.

Expression of p53 and p21 in primary glioblastomas

International Nuclear Information System (INIS)

Gross, M.W.; Nashwan, K.; Engenhart-Cabillic, R.; Kraus, A.; Mennel, H.D.; Schlegel, J.

2005-01-01

Background and purpose: primary glioblastomas (GBMs) are highly radioresistant, and in contrast to secondary GBMs, they bear wild-type (wt) p53 protein, which is stabilized in a proportion of these tumors. Therefore, it was investigated in vivo whether p53 expression has prognostic value in patients undergoing radiochemotherapy. Additionally, the authors tried to identify, in vitro, subgroups of primary GBM with different susceptibilities to irradiation, on the basis of their p53 and p21 responses to ionizing radiation. Material and methods: tumor tissue samples from 31 patients suffering from primary GBM undergoing a combined radiochemotherapy with topotecan were investigated. The percentage of cells expressing p53 protein was determined immunohistochemically. Additionally, primary cultures from eleven primary GBMs were established and investigated. p53 and p21 expressions were evaluated before irradiation with 10 Gy and at 2 and 8 h after irradiation. p53 protein expression was measured by western analysis and p21 mRNA expression by reverse transcription-polymerase chain reaction (RT-PCR). Results: the percentage of p53-positive cells within the tumor specimens obtained from the 31 patients ranged from 0% to 28%, the median value being 4.3%. No significant correlation with disease-free survival or overall survival was found. In vitro, p53 protein was detected in seven of eleven cultures from primary GBM. After irradiation a decrease in p53 protein expression was seen in six of the seven p53-positive cultures. Half of the cultures (two of four) without basal p53 expression showed an increase in p53 expression after irradiation. Basal overexpression of p21 was detected in six of the eleven cultures; in four out of six irradiation led to a decrease in p21 expression. In all cell lines (five of eleven) initially showing absent p21 expression, irradiation induced p21 expression. Despite these responses, G1 arrest was not detectable in any of the GBM cultures

Hydride vapor phase epitaxy growth of GaN, InGaN, ScN, and ScAIN

NARCIS (Netherlands)

Bohnen, T.

2010-01-01

Chemical vapor deposition (CVD); hydride vapor phase epitaxy (HVPE); gallium nitride (GaN); indium gallium nitride (InGaN); scandium nitride (ScN); scandium aluminum nitride (ScAlN); semiconductors; thin films; nanowires; III nitrides; crystal growth - We studied the HVPE growth of different III

Kinetic phenomena in Sc films

International Nuclear Information System (INIS)

Stasyuk, Z.V.

1992-01-01

Size effects in electrical conductivity, thermoelectric power and Hall coefficient of thin scandium films have been investigated. An analysis of experimental data was made within the framework of Mayadas-Shatzkes and Tellier-Tosser-Pichard models. The transport parameters of scandium have been found. (author)

Post-translational regulation enables robust p53 regulation.

Science.gov (United States)

Shin, Yong-Jun; Chen, Kai-Yuan; Sayed, Ali H; Hencey, Brandon; Shen, Xiling

2013-08-30

The tumor suppressor protein p53 plays important roles in DNA damage repair, cell cycle arrest and apoptosis. Due to its critical functions, the level of p53 is tightly regulated by a negative feedback mechanism to increase its tolerance towards fluctuations and disturbances. Interestingly, the p53 level is controlled by post-translational regulation rather than transcriptional regulation in this feedback mechanism. We analyzed the dynamics of this feedback to understand whether post-translational regulation provides any advantages over transcriptional regulation in regard to disturbance rejection. When a disturbance happens, even though negative feedback reduces the steady-state error, it can cause a system to become less stable and transiently overshoots, which may erroneously trigger downstream reactions. Therefore, the system needs to balance the trade-off between steady-state and transient errors. Feedback control and adaptive estimation theories revealed that post-translational regulation achieves a better trade-off than transcriptional regulation, contributing to a more steady level of p53 under the influence of noise and disturbances. Furthermore, post-translational regulation enables cells to respond more promptly to stress conditions with consistent amplitude. However, for better disturbance rejection, the p53- Mdm2 negative feedback has to pay a price of higher stochastic noise. Our analyses suggest that the p53-Mdm2 feedback favors regulatory mechanisms that provide the optimal trade-offs for dynamic control.

Effect of metabolic syndrome on mitsugumin 53 expression and function.

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Hanley Ma

Full Text Available Metabolic syndrome is a cluster of risk factors, such as obesity, insulin resistance, and hyperlipidemia that increases the individual's likelihood of developing cardiovascular diseases. Patients inflicted with metabolic disorders also suffer from tissue repair defect. Mitsugumin 53 (MG53 is a protein essential to cellular membrane repair. It facilitates the nucleation of intracellular vesicles to sites of membrane disruption to create repair patches, contributing to the regenerative capacity of skeletal and cardiac muscle tissues upon injury. Since individuals suffering from metabolic syndrome possess tissue regeneration deficiency and MG53 plays a crucial role in restoring membrane integrity, we studied MG53 activity in mice models exhibiting metabolic disorders induced by a 6 month high-fat diet (HFD feeding. Western blotting showed that MG53 expression is not altered within the skeletal and cardiac muscles of mice with metabolic syndrome. Rather, we found that MG53 levels in blood circulation were actually reduced. This data directly contradicts findings presented by Song et. al that indict MG53 as a causative factor for metabolic syndrome (Nature 494, 375-379. The diminished MG53 serum level observed may contribute to the inadequate tissue repair aptitude exhibited by diabetic patients. Furthermore, immunohistochemical analyses reveal that skeletal muscle fibers of mice with metabolic disorders experience localization of subcellular MG53 around mitochondria. This clustering may represent an adaptive response to oxidative stress resulting from HFD feeding and may implicate MG53 as a guardian to protect damaged mitochondria. Therapeutic approaches that elevate MG53 expression in serum circulation may be a novel method to treat the degenerative tissue repair function of diabetic patients.

Effect of recombinant adenovirus encoding human p53 tumor suppressor gene (rAd-p53) on the growth and radiotherapeutic sensitivity of human lymphoma cell lines

International Nuclear Information System (INIS)

Yu Zeyang; Fan Wo; Li Dongqing; Zhu Ran; Wang Yongqing; Wu Jinchang

2008-01-01

Objective: To explore the inhibitory effect and radiation sensitization of recombinant adenovirus encoding human p53 tumor suppressor gene (rAd-p53) on human lymphoma cell lines. Methods: Human lymphoma cell lines Raji and Daudi were treated with rAd-p53, radiation therapy and combined treatment, respectively. The cell growth inhibition was assessed by MTT. The p53 protein expression was detected by Western blotting, and p53 mRNA was detected by BT-PCB. Results: The MTT results showed that the inhibitory effect and radiosensitivity enhancement of rAd-p53 on human lymphoma cell lines were not obvious [Raji: (27.5±4.1)%; Daudi: (28.1±1.6)%]. The results of Western blotting and BT-PCB showed that extrinsic p53 protein and p53 mRNA were expressed to some degree, but not at high-level. In addition, the results didn't demonstrate obvious radiosensitivity enhancement. Conclusions: The role of inhibition and radiosensitivity enhancement of rAd-p53 was not significant on human lymphoma cell lines. (authors)

Regulation of Metabolic Activity by p53

Directory of Open Access Journals (Sweden)

Jessica Flöter

2017-05-01

Full Text Available Metabolic reprogramming in cancer cells is controlled by the activation of multiple oncogenic signalling pathways in order to promote macromolecule biosynthesis during rapid proliferation. Cancer cells also need to adapt their metabolism to survive and multiply under the metabolically compromised conditions provided by the tumour microenvironment. The tumour suppressor p53 interacts with the metabolic network at multiple nodes, mostly to reduce anabolic metabolism and promote preservation of cellular energy under conditions of nutrient restriction. Inactivation of this tumour suppressor by deletion or mutation is a frequent event in human cancer. While loss of p53 function lifts an important barrier to cancer development by deleting cell cycle and apoptosis checkpoints, it also removes a crucial regulatory mechanism and can render cancer cells highly sensitive to metabolic perturbation. In this review, we will summarise the major concepts of metabolic regulation by p53 and explore how this knowledge can be used to selectively target p53 deficient cancer cells in the context of the tumour microenvironment.

Effect of p53 genotype on gene expression profiles in murine liver

International Nuclear Information System (INIS)

Morris, Suzanne M.; Akerman, Gregory S.; Desai, Varsha G.; Tsai, Chen-an; Tolleson, William H.; Melchior, William B.; Lin, Chien-Ju; Fuscoe, James C.; Casciano, Daniel A.; Chen, James J.

2008-01-01

The tumor suppressor protein p53 is a key regulatory element in the cell and is regarded as the 'guardian of the genome'. Much of the present knowledge of p53 function has come from studies of transgenic mice in which the p53 gene has undergone a targeted deletion. In order to provide additional insight into the impact on the cellular regulatory networks associated with the loss of this gene, microarray technology was utilized to assess gene expression in tissues from both the p53 -/- and p53 +/- mice. Six male mice from each genotype (p53 +/+ , p53 +/- , and p53 -/- ) were humanely killed and the tissues processed for microarray analysis. The initial studies have been performed in the liver for which the Dunnett test revealed 1406 genes to be differentially expressed between p53 +/+ and p53 +/- or between p53 +/+ and p53 -/- at the level of p ≤ 0.05. Both genes with increased expression and decreased expression were identified in p53 +/- and in p53 -/- mice. Most notable in the gene list derived from the p53 +/- mice was the significant reduction in p53 mRNA. In the p53 -/- mice, not only was there reduced expression of the p53 genes on the array, but genes associated with DNA repair, apoptosis, and cell proliferation were differentially expressed, as expected. However, altered expression was noted for many genes in the Cdc42-GTPase pathways that influence cell proliferation. This may indicate that alternate pathways are brought into play in the unperturbed liver when loss or reduction in p53 levels occurs

The antagonism between MCT-1 and p53 affects the tumorigenic outcomes

Directory of Open Access Journals (Sweden)

Lin Tai-Du

2010-12-01

Full Text Available Abstract Background MCT-1 oncoprotein accelerates p53 protein degradation via a proteosome pathway. Synergistic promotion of the xenograft tumorigenicity has been demonstrated in circumstance of p53 loss alongside MCT-1 overexpression. However, the molecular regulation between MCT-1 and p53 in tumor development remains ambiguous. We speculate that MCT-1 may counteract p53 through the diverse mechanisms that determine the tumorigenic outcomes. Results MCT-1 has now identified as a novel target gene of p53 transcriptional regulation. MCT-1 promoter region contains the response elements reactive with wild-type p53 but not mutant p53. Functional p53 suppresses MCT-1 promoter activity and MCT-1 mRNA stability. In a negative feedback regulation, constitutively expressed MCT-1 decreases p53 promoter function and p53 mRNA stability. The apoptotic events are also significantly prevented by oncogenic MCT-1 in a p53-dependent or a p53-independent fashion, according to the genotoxic mechanism. Moreover, oncogenic MCT-1 promotes the tumorigenicity in mice xenografts of p53-null and p53-positive lung cancer cells. In support of the tumor growth are irrepressible by p53 reactivation in vivo, the inhibitors of p53 (MDM2, Pirh2, and Cop1 are constantly stimulated by MCT-1 oncoprotein. Conclusions The oppositions between MCT-1 and p53 are firstly confirmed at multistage processes that include transcription control, mRNA metabolism, and protein expression. MCT-1 oncogenicity can overcome p53 function that persistently advances the tumor development.

Gene expression patterns associated with p53 status in breast cancer

International Nuclear Information System (INIS)

Troester, Melissa A; Herschkowitz, Jason I; Oh, Daniel S; He, Xiaping; Hoadley, Katherine A; Barbier, Claire S; Perou, Charles M

2006-01-01

Breast cancer subtypes identified in genomic studies have different underlying genetic defects. Mutations in the tumor suppressor p53 occur more frequently in estrogen receptor (ER) negative, basal-like and HER2-amplified tumors than in luminal, ER positive tumors. Thus, because p53 mutation status is tightly linked to other characteristics of prognostic importance, it is difficult to identify p53's independent prognostic effects. The relation between p53 status and subtype can be better studied by combining data from primary tumors with data from isogenic cell line pairs (with and without p53 function). The p53-dependent gene expression signatures of four cell lines (MCF-7, ZR-75-1, and two immortalized human mammary epithelial cell lines) were identified by comparing p53-RNAi transduced cell lines to their parent cell lines. Cell lines were treated with vehicle only or doxorubicin to identify p53 responses in both non-induced and induced states. The cell line signatures were compared with p53-mutation associated genes in breast tumors. Each cell line displayed distinct patterns of p53-dependent gene expression, but cell type specific (basal vs. luminal) commonalities were evident. Further, a common gene expression signature associated with p53 loss across all four cell lines was identified. This signature showed overlap with the signature of p53 loss/mutation status in primary breast tumors. Moreover, the common cell-line tumor signature excluded genes that were breast cancer subtype-associated, but not downstream of p53. To validate the biological relevance of the common signature, we demonstrated that this gene set predicted relapse-free, disease-specific, and overall survival in independent test data. In the presence of breast cancer heterogeneity, experimental and biologically-based methods for assessing gene expression in relation to p53 status provide prognostic and biologically-relevant gene lists. Our biologically-based refinements excluded genes

Phenotype specific analyses reveal distinct regulatory mechanism for chronically activated p53.

Directory of Open Access Journals (Sweden)

Kristina Kirschner

2015-03-01

Full Text Available The downstream functions of the DNA binding tumor suppressor p53 vary depending on the cellular context, and persistent p53 activation has recently been implicated in tumor suppression and senescence. However, genome-wide information about p53-target gene regulation has been derived mostly from acute genotoxic conditions. Using ChIP-seq and expression data, we have found distinct p53 binding profiles between acutely activated (through DNA damage and chronically activated (in senescent or pro-apoptotic conditions p53. Compared to the classical 'acute' p53 binding profile, 'chronic' p53 peaks were closely associated with CpG-islands. Furthermore, the chronic CpG-island binding of p53 conferred distinct expression patterns between senescent and pro-apoptotic conditions. Using the p53 targets seen in the chronic conditions together with external high-throughput datasets, we have built p53 networks that revealed extensive self-regulatory 'p53 hubs' where p53 and many p53 targets can physically interact with each other. Integrating these results with public clinical datasets identified the cancer-associated lipogenic enzyme, SCD, which we found to be directly repressed by p53 through the CpG-island promoter, providing a mechanistic link between p53 and the 'lipogenic phenotype', a hallmark of cancer. Our data reveal distinct phenotype associations of chronic p53 targets that underlie specific gene regulatory mechanisms.

40 Years of Research Put p53 in Translation

Science.gov (United States)

Marcel, Virginie; Nguyen Van Long, Flora; Diaz, Jean-Jacques

2018-01-01

Since its discovery in 1979, p53 has shown multiple facets. Initially the tumor suppressor p53 protein was considered as a stress sensor able to maintain the genome integrity by regulating transcription of genes involved in cell cycle arrest, apoptosis and DNA repair. However, it rapidly came into light that p53 regulates gene expression to control a wider range of biological processes allowing rapid cell adaptation to environmental context. Among them, those related to cancer have been extensively documented. In addition to its role as transcription factor, scattered studies reported that p53 regulates miRNA processing, modulates protein activity by direct interaction or exhibits RNA-binding activity, thus suggesting a role of p53 in regulating several layers of gene expression not restricted to transcription. After 40 years of research, it appears more and more clearly that p53 is strongly implicated in translational regulation as well as in the control of the production and activity of the translational machinery. Translation control of specific mRNAs could provide yet unsuspected capabilities to this well-known guardian of the genome.

TP53 gene status affects survival in advanced mycosis fungoides

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Gitte Wooler

2016-11-01

Full Text Available TP53 is frequently mutated in different types of neoplasms including leukemia and lymphomas. Mutations of TP53 have also been reported in mycosis fungoides (MF, the most common type of cutaneous lymphoma. However, little is known about the frequency, spectrum of mutations and their prognostic significance in MF. In this study we have optimized the protocol for Sanger sequencing of TP53 using DNA extracted from archival paraffin-embedded biopsies. Of 19 samples from patients with stage IIB MF or higher, 31% harboured mutations in TP53. Overall survival of the patients with mutated TP53 was significantly shorter than median survival in the age- and stage-matched patients treated in our Institution. Distribution of mutations was heterogenous in TP53 exons, however C>T transitions were common suggesting the causal role of ultraviolet radiation. We propose that TP53 mutation status would be useful for risk stratification of patients with advanced MF.

Tumor suppressor p53 biology, its role in radioresponse and the analysis of p53 mutation/expression among Filipino breast cancers

International Nuclear Information System (INIS)

Deocaris, Custer C.

2004-01-01

Ionizing radiation remains one of the most effective tools for the treatment of breast cancer. It combines properties of a potent DNA-damaging agent and high degree of spatial specificity to the target tissue. Nonetheless, there remain considerable differences in the outcome for treatment of tumors of differing histological type treated by radiotherapy. The identification of predictive indicators of radiosensitivity is crucial for selecting patients suited for preoperative radiotherapy as well as those unwarranted for postoperative treatments. To improve prognostication, numerous genes involved in the breast carcinogenesis have been studied and thus far over the last decade several multi-center researches converge on the role of tumor suppressor p53 in tumor biology. The p53 gene is located on the short arm of chromosome 17 and encodes a 53-kd nuclear protein, p-53, also referred to as 'the guardian of the genome', it orchestrates multiple cellular processes such as cell growth control, DNA repair and programmed cell death. During radiotherapy, genotoxic damage induces p53 overexpression in order to control the rate of proliferating damaged cells, repair damage or induce the apoptotic pathway. Its molecular inactivation in a tumor cell, typically by a point mutation, leads to chemo/radio resistance due to the inability of the molecule to trigger p53-dependent programmed cell death

Stimulation of autophagy by the p53 target gene Sestrin2.

Science.gov (United States)

Maiuri, Maria Chiara; Malik, Shoaib Ahmad; Morselli, Eugenia; Kepp, Oliver; Criollo, Alfredo; Mouchel, Pierre-Luc; Carnuccio, Rosa; Kroemer, Guido

2009-05-15

The oncosuppressor protein p53 regulates autophagy in a dual fashion. The pool of cytoplasmic p53 protein represses autophagy in a transcription-independent fashion, while the pool of nuclear p53 stimulates autophagy through the transactivation of specific genes. Here we report the discovery that Sestrin2, a novel p53 target gene, is involved in the induction of autophagy. Depletion of Sestrin2 by RNA interference reduced the level of autophagy in a panel of p53-sufficient human cancer cell lines responding to distinct autophagy inducers. In quantitative terms, Sestrin2 depletion was as efficient in preventing autophagy induction as was the depletion of Dram, another p53 target gene. Knockout of either Sestrin2 or Dram reduced autophagy elicited by nutrient depletion, rapamycin, lithium or thapsigargin. Moreover, autophagy induction by nutrient depletion or pharmacological stimuli led to an increase in Sestrin2 expression levels in p53-proficient cells. In strict contrast, the depletion of Sestrin2 or Dram failed to affect autophagy in p53-deficient cells and did not modulate the inhibition of baseline autophagy by a cytoplasmic p53 mutant that was reintroduced into p53-deficient cells. We conclude that Sestrin2 acts as a positive regulator of autophagy in p53-proficient cells.

46 CFR 53.01-5 - Scope (modifies HG-100).

Science.gov (United States)

2010-10-01

... 46 Shipping 2 2010-10-01 2010-10-01 false Scope (modifies HG-100). 53.01-5 Section 53.01-5... General Requirements § 53.01-5 Scope (modifies HG-100). (a) The regulations in this part apply to steam... governing various types of pressure vessels and boilers. (b) Modifies HG-100. The requirements of Part HG of...

29 CFR 570.53 - Coal-mine occupations (Order 3).

Science.gov (United States)

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Coal-mine occupations (Order 3). 570.53 Section 570.53... § 570.53 Coal-mine occupations (Order 3). (a) Finding and declaration of fact. All occupations in or about any coal mine, except the occupation of slate or other refuse picking at a picking table or...

Phylogenetic analysis of human Tp53 gene using computational ...

African Journals Online (AJOL)

The TP53 gene encoding p53 protein is involved in regulating a series of pathways. New discoveries about the function and control of p53 are still in progress and it is hoped to develop better therapeutics and diagnostics by exploiting this system. Evolutionary studies are of prime importance in the field of biological ...

Molecular mechanism of X-ray-induced p53-dependent apoptosis

Energy Technology Data Exchange (ETDEWEB)

Nakano, Hisako [Tokyo Metropolitan Inst. of Medical Center (Japan)

1999-03-01

Radiation-induced cell death has been classified into the interphase- and mitotic-ones, both of which apoptosis involving. This review described the molecular mechanism of the apoptosis, focusing on its p53-dependent process. It is known that there are genes regulating cell death either negatively or positively and the latter is involved in apoptosis. As an important factor in the apoptosis, p53 has become remarkable since it was shown that X-ray-induced apoptosis required RNA and protein syntheses in thymocytes and those cells of p53 gene-depleted mouse were shown to be resistant to gamma-ray-induced apoptosis. Radiation sensitivity of MOLT-4 cells derived from human T cell leukemia, exhibiting the typical X-ray-induced p53-dependent apoptosis, depends on the levels of p53 mRNA and protein. p53 is a gene suppressing tumor and also a transcription factor. Consequently, mutation of p53 conceivably leads to the failure of cell cycle regulation, which allows damaged cells to divide without both repair and exclusion due to loss of the apoptotic mechanism, and finally results in carcinogenesis. The radiation effect occurs in the order of the cell damage, inhibition of p53-Mdm2 binding, accumulation of p53, activation of mdm2 transcription, Mdm2 accumulation, p53-protein degradation and recovery to the steady state level. Here, the cystein protease (caspases) plays an important role as a disposing mechanism for cells scheduled to die. However, many are unknown to be solved in future. (K.H.) 119 refs.

Both p53-PUMA/NOXA-Bax-mitochondrion and p53-p21cip1 pathways are involved in the CDglyTK-mediated tumor cell suppression

International Nuclear Information System (INIS)

Yu, Zhendong; Wang, Hao; Zhang, Libin; Tang, Aifa; Zhai, Qinna; Wen, Jianxiang; Yao, Li; Li, Pengfei

2009-01-01

CDglyTK fusion suicide gene has been well characterized to effectively kill tumor cells. However, the exact mechanism and downstream target genes are not fully understood. In our study, we found that CDglyTK/prodrug treatment works more efficiently in p53 wild-type (HONE1) cells than in p53 mutant (CNE1) cells. We then used adenovirus-mediated gene delivery system to either knockdown or overexpress p53 and its target genes in these cells. Consistent results showed that both p53-PUMA/NOXA/Bcl2-Bax and p53-p21 pathways contribute to the CDglyTK induced tumor cell suppression. Our work for the first time addressed the role of p53 related genes in the CDglyTK/prodrug system.

Both p53-PUMA/NOXA-Bax-mitochondrion and p53-p21cip1 pathways are involved in the CDglyTK-mediated tumor cell suppression

Energy Technology Data Exchange (ETDEWEB)

Yu, Zhendong, E-mail: zdyu@hotmail.com [Department of Clinical laboratory, Peking University Shenzhen Hospital, Guangdong (China); Wang, Hao [Department of pathology, The Chinese University of Hong Kong, Hong Kong (China); Zhang, Libin; Tang, Aifa; Zhai, Qinna; Wen, Jianxiang; Yao, Li [Department of Clinical laboratory, Peking University Shenzhen Hospital, Guangdong (China); Li, Pengfei, E-mail: lipengfei@cuhk.edu.hk [Department of pathology, The Chinese University of Hong Kong, Hong Kong (China)

2009-09-04

CDglyTK fusion suicide gene has been well characterized to effectively kill tumor cells. However, the exact mechanism and downstream target genes are not fully understood. In our study, we found that CDglyTK/prodrug treatment works more efficiently in p53 wild-type (HONE1) cells than in p53 mutant (CNE1) cells. We then used adenovirus-mediated gene delivery system to either knockdown or overexpress p53 and its target genes in these cells. Consistent results showed that both p53-PUMA/NOXA/Bcl2-Bax and p53-p21 pathways contribute to the CDglyTK induced tumor cell suppression. Our work for the first time addressed the role of p53 related genes in the CDglyTK/prodrug system.

HMGB1-mediated DNA bending: Distinct roles in increasing p53 binding to DNA and the transactivation of p53-responsive gene promoters.

Science.gov (United States)

Štros, Michal; Kučírek, Martin; Sani, Soodabeh Abbasi; Polanská, Eva

2018-03-01

HMGB1 is a chromatin-associated protein that has been implicated in many important biological processes such as transcription, recombination, DNA repair, and genome stability. These functions include the enhancement of binding of a number of transcription factors, including the tumor suppressor protein p53, to their specific DNA-binding sites. HMGB1 is composed of two highly conserved HMG boxes, linked to an intrinsically disordered acidic C-terminal tail. Previous reports have suggested that the ability of HMGB1 to bend DNA may explain the in vitro HMGB1-mediated increase in sequence-specific DNA binding by p53. The aim of this study was to reinvestigate the importance of HMGB1-induced DNA bending in relationship to the ability of the protein to promote the specific binding of p53 to short DNA duplexes in vitro, and to transactivate two major p53-regulated human genes: Mdm2 and p21/WAF1. Using a number of HMGB1 mutants, we report that the HMGB1-mediated increase in sequence-specific p53 binding to DNA duplexes in vitro depends very little on HMGB1-mediated DNA bending. The presence of the acidic C-terminal tail of HMGB1 and/or the oxidation of the protein can reduce the HMGB1-mediated p53 binding. Interestingly, the induction of transactivation of p53-responsive gene promoters by HMGB1 requires both the ability of the protein to bend DNA and the acidic C-terminal tail, and is promoter-specific. We propose that the efficient transactivation of p53-responsive gene promoters by HMGB1 depends on complex events, rather than solely on the promotion of p53 binding to its DNA cognate sites. Copyright © 2018 Elsevier B.V. All rights reserved.

Gene expression and apoptosis induction in p53-heterozygous irradiated mice

International Nuclear Information System (INIS)

Di Masi, Alessandra; Antoccia, Antonio; Dimauro, Ivan; Argentino-Storino, Alberta; Mosiello, Alberto; Mango, Ruggiero; Novelli, Giuseppe; Tanzarella, Caterina

2006-01-01

The role of the p53-genetic background in the expression of genes involved in either cell cycle checkpoint activation or apoptosis was evaluated in p53+/+ and p53+/- mouse strains at both basal levels and after DNA-induced damage. The spleen, colon, kidneys, lungs and liver of both strains were harvested from untreated animals and from mice exposed to 7.5 Gy of X-rays and sacrificed after 5 h. No significant differences were observed in the basal levels of p53 protein, CDKN1A and bax mRNA and spontaneous apoptosis, neither among the different organs within the same strain, nor between the same organ in the p53+/+ and p53+/- strains. After X-ray exposure, p53-dependent regulation was strikingly tissue-specific. In wild-type irradiated mice, p53 protein level increased after radiation treatment in all the organs analysed, whereas both CDKN1A and bax genes transcription increased in the spleen, colon and lungs, as assessed by means of quantitative RT-PCR. In p53+/- irradiated mice, on the contrary, a significant p53 induction was detected only in the spleen, while CDKN1A and bax genes levels increased in the spleen, colon and lungs, revealing the existence of different mechanisms of gene regulation in different organs. Apoptosis induction was observed in the spleen and colon of both strains, even if to lower extent in p53+/- mice compared to p53+/+ animals. In conclusion, in the spleen and colon, target gene transcription and apoptosis may be related to p53 genotype after DNA damage-induction. Moreover, our findings highlight the selectivity of p53 in transactivation following DNA damage in vivo, resulting in tissue-specific responses

Gene expression and apoptosis induction in p53-heterozygous irradiated mice

Energy Technology Data Exchange (ETDEWEB)

Di Masi, Alessandra [Department of Biology, University of Rome ' Roma Tre' , Viale G. Marconi, 446, 00146 Rome (Italy); Antoccia, Antonio [Department of Biology, University of Rome ' Roma Tre' , Viale G. Marconi, 446, 00146 Rome (Italy); Dimauro, Ivan [Department of Biology, University of Rome ' Roma Tre' , Viale G. Marconi, 446, 00146 Rome (Italy); Argentino-Storino, Alberta [Research Toxicology Centre S.p.A., Via Tito Speri, 18, 00040 Pomezia (RM) (Italy); Mosiello, Alberto [Research Toxicology Centre S.p.A., Via Tito Speri, 18, 00040 Pomezia (RM) (Italy); Mango, Ruggiero [Centre of Excellence for Genomic Risk Assessment in Multifactorial and Complex Diseases, School of Medicine, University of Rome ' Tor Vergata' , Rome (Italy); Novelli, Giuseppe [Centre of Excellence for Genomic Risk Assessment in Multifactorial and Complex Diseases, School of Medicine, University of Rome ' Tor Vergata' , Rome (Italy); Tanzarella, Caterina [Department of Biology, University of Rome ' Roma Tre' , Viale G. Marconi, 446, 00146 Rome (Italy)]. E-mail: tanzarel@uniroma3.it

2006-02-22

The role of the p53-genetic background in the expression of genes involved in either cell cycle checkpoint activation or apoptosis was evaluated in p53+/+ and p53+/- mouse strains at both basal levels and after DNA-induced damage. The spleen, colon, kidneys, lungs and liver of both strains were harvested from untreated animals and from mice exposed to 7.5 Gy of X-rays and sacrificed after 5 h. No significant differences were observed in the basal levels of p53 protein, CDKN1A and bax mRNA and spontaneous apoptosis, neither among the different organs within the same strain, nor between the same organ in the p53+/+ and p53+/- strains. After X-ray exposure, p53-dependent regulation was strikingly tissue-specific. In wild-type irradiated mice, p53 protein level increased after radiation treatment in all the organs analysed, whereas both CDKN1A and bax genes transcription increased in the spleen, colon and lungs, as assessed by means of quantitative RT-PCR. In p53+/- irradiated mice, on the contrary, a significant p53 induction was detected only in the spleen, while CDKN1A and bax genes levels increased in the spleen, colon and lungs, revealing the existence of different mechanisms of gene regulation in different organs. Apoptosis induction was observed in the spleen and colon of both strains, even if to lower extent in p53+/- mice compared to p53+/+ animals. In conclusion, in the spleen and colon, target gene transcription and apoptosis may be related to p53 genotype after DNA damage-induction. Moreover, our findings highlight the selectivity of p53 in transactivation following DNA damage in vivo, resulting in tissue-specific responses.

The p53 gene with emphasis on its paralogues in mosquitoes

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Tien-Huang Chen

2017-12-01

Full Text Available The p53 gene is highly important in human cancers, as it serves as a tumor-suppressor gene. Subsequently, two p53 homologues, i.e., p73 and p63, with high identity of amino acids were identified, leading to construction of the p53 family. The p53 gene is highly important in human cancer because it usually transcribes genes that function by causing apoptosis in mammalian cells. In contrast, p63 and p73 tend to be more important in modulating development than inducing cell death, even though they share similar protein structures. Relatively recently, p53 was also identified in mosquitoes and many other insect species. Uniquely, its structure lacks the sterile alpha motif domain which is a putative protein-protein interaction domain and exclusively exists at the C-terminal region in p73 and p63 in mammals. A phylogenetic analysis revealed that the p53 gene derived from mosquitoes is composed of two paralogues, p53-1 and p53-2. Of these, only p53-2 is responsively upregulated by dengue 2 virus (DENV2 in C6/36 cells which usually survive the infection. This indicates that the p53 gene is closely related to DENV infection in mosquito cells. The specific significance of p53-2's involvement in cell survival from virus-induced stress is described and briefly discussed in this report. Keywords: p53 homologue, Paralogue, Mosquitoes, Phylogeny, Cell survival

Visualization of RELAP5-3D best estimate code

International Nuclear Information System (INIS)

Mesina, G.L.

2004-01-01

The Idaho National Engineering Laboratory has developed a number of nuclear plant analysis codes such as RELAP5-3D, SCDAP/RELAP5-3D, and FLUENT/RELAP5-3D that have multi-dimensional modeling capability. The output of these codes is very difficult to analyze without the aid of visualization tools. The RELAP5-3D Graphical User Interface (RGUI) displays these calculations on plant images, functional diagrams, graphs, and by other means. These representations of the data enhance the analysts' ability to recognize plant behavior visually and reduce the difficulty of analyzing complex three-dimensional models. This paper describes the Graphical User Interface system for the RELAP5-3D suite of Best Estimate codes. The uses of the Graphical User Interface are illustrated. Examples of user problems solved by use of this interface are given. (author)

The role of p53 molecule in radiation and hyperthermic therapies

International Nuclear Information System (INIS)

Yasumoto, Jun-ichi; Takahashi, Akihisa; Ohnishi, Ken; Ohnishi, Takeo

2003-01-01

In recent years, cancer-related genes have been analyzed at the molecular level as predictive indicators for cancer therapy. Among those genes, the tumor suppressor gene p53 is worthy of notice in cancer therapy, because the p53 molecule prevents the malignant degeneration of non-cancer cells by regulating cell-cycle arrest, apoptosis, and DNA repair. An abnormality of the p53 gene introduces a genetic instability and increases the incidence of carcinogenesis and teratogenesis. Therefore, p53 is called a guardian of the genome. Mutations of p53 are observed at a high frequency in human tumors, and are recognized in about half of all malignant tumors in human head and neck cancers. We previously reported that radio- and heat-sensitivities of human cultured tongue squamous cell carcinoma cells are p53-dependent, and are closely correlated with the induction of apoptosis. In a human cell culture system, the interactive hyperthermic enhancement of radiosensitivity was observed in wild-type p53 cells, but not in mutated p53 cells. In a transplanted tumor system, the combination therapies of radiation and hyperthermia induced efficient tumor growth depression and apoptosis in the wild-type p53 tumors. In this review, we discuss the p53 activation signaling pathways through the modification of p53 molecules, such as phosphorylation after radiation and hyperthermia treatments. (author)

Pigmentation, Melanocyte Colonization, and p53 Status in Basal Cell Carcinoma

International Nuclear Information System (INIS)

Frey, L. M.; Houben, R.; Brocker, E. B.

2011-01-01

Basal cell carcinoma (BCC) is the most common neoplasm in the Caucasian population. Only a fraction of BCC exhibits pigmentation. Lack of melanocyte colonization has been suggested to be due to p53-inactivating mutations in the BCC cells interfering with the p53-proopiomelanocortin pathway and the production of alpha melanocyte-stimulating hormone in the tumor. To evaluate this, we determined tumor pigmentation as well as expression of melan-A and of p53 in 49 BCC tissues by means of immunohistochemistry. As expected, we observed a positive relation between tumor pigmentation and melan-A positive intra-tumoral melanocytes. Melanocyte colonization and, to a lesser extent, p53 overexpression showed intraindividual heterogeneity in larger tumors. p53 overexpression, which is indicative of p53 mutations, was not correlated to melanocyte colonization of BCC. Sequencing of exon 5-8 of the p53 gene in selected BCC cases revealed that colonization by melanocytes and BCC pigmentation is neither ablated by p53 mutations nor generally present in BCCs with wild-type p53.

Therapeutic targeting of the p53 pathway in cancer stem cells

Science.gov (United States)

Prabhu, Varun V.; Allen, Joshua E.; Hong, Bo; Zhang, Shengliang; Cheng, Hairong; El-Deiry, Wafik S.

2013-01-01

Introduction Cancer stem cells are a high profile drug target for cancer therapeutics due to their indispensable role in cancer progression, maintenance, and therapeutic resistance. Restoring wild-type p53 function is an attractive new therapeutic approach for the treatment of cancer due to the well-described powerful tumor suppressor function of p53. As emerging evidence intimately links p53 and stem cell biology, this approach also provides an opportunity to target cancer stem cells. Areas covered Therapeutic approaches to restore the function of wild-type p53, cancer and normal stem cell biology in relation to p53, and the downstream effects of p53 on cancer stem cells. Expert opinion The restoration of wild-type p53 function by targeting p53 directly, its interacting proteins, or its family members holds promise as a new class of cancer therapies. This review examines the impact that such therapies may have on normal and cancer stem cells based on the current evidence linking p53 signaling with these populations. PMID:22998602

Paracrine Apoptotic Effect of p53 Mediated by Tumor Suppressor Par-4

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Ravshan Burikhanov

2014-01-01

Full Text Available The guardian of the genome, p53, is often mutated in cancer and may contribute to therapeutic resistance. Given that p53 is intact and functional in normal tissues, we harnessed its potential to inhibit the growth of p53-deficient cancer cells. Specific activation of p53 in normal fibroblasts selectively induced apoptosis in p53-deficient cancer cells. This paracrine effect was mediated by p53-dependent secretion of the tumor suppressor Par-4. Accordingly, the activation of p53 in normal mice, but not p53−/− or Par-4−/− mice, caused systemic elevation of Par-4, which induced apoptosis of p53-deficient tumor cells. Mechanistically, p53 induced Par-4 secretion by suppressing the expression of its binding partner, UACA, which sequesters Par-4. Thus, normal cells can be empowered by p53 activation to induce Par-4 secretion for the inhibition of therapy-resistant tumors.

p53 and the Viral Connection: Back into the Future ‡

Directory of Open Access Journals (Sweden)

Ronit Aloni-Grinstein

2018-06-01

Full Text Available The discovery of the tumor suppressor p53, through its interactions with proteins of tumor-promoting viruses, paved the way to the understanding of p53 roles in tumor virology. Over the years, accumulating data suggest that WTp53 is involved in the viral life cycle of non-tumor-promoting viruses as well. These include the influenza virus, smallpox and vaccinia viruses, the Zika virus, West Nile virus, Japanese encephalitis virus, Human Immunodeficiency Virus Type 1, Human herpes simplex virus-1, and more. Viruses have learned to manipulate WTp53 through different strategies to improve their replication and spreading in a stage-specific, bidirectional way. While some viruses require active WTp53 for efficient viral replication, others require reduction/inhibition of WTp53 activity. A better understanding of WTp53 functionality in viral life may offer new future clinical approaches, based on WTp53 manipulation, for viral infections.

Hypoxia-induced p53 modulates both apoptosis and radiosensitivity via AKT

Science.gov (United States)

Leszczynska, Katarzyna B.; Foskolou, Iosifina P.; Abraham, Aswin G.; Anbalagan, Selvakumar; Tellier, Céline; Haider, Syed; Span, Paul N.; O’Neill, Eric E.; Buffa, Francesca M.; Hammond, Ester M.

2015-01-01

Restoration of hypoxia-induced apoptosis in tumors harboring p53 mutations has been proposed as a potential therapeutic strategy; however, the transcriptional targets that mediate hypoxia-induced p53-dependent apoptosis remain elusive. Here, we demonstrated that hypoxia-induced p53-dependent apoptosis is reliant on the DNA-binding and transactivation domains of p53 but not on the acetylation sites K120 and K164, which, in contrast, are essential for DNA damage–induced, p53-dependent apoptosis. Evaluation of hypoxia-induced transcripts in multiple cell lines identified a group of genes that are hypoxia-inducible proapoptotic targets of p53, including inositol polyphosphate-5-phosphatase (INPP5D), pleckstrin domain–containing A3 (PHLDA3), sulfatase 2 (SULF2), B cell translocation gene 2 (BTG2), cytoplasmic FMR1-interacting protein 2 (CYFIP2), and KN motif and ankyrin repeat domains 3 (KANK3). These targets were also regulated by p53 in human cancers, including breast, brain, colorectal, kidney, bladder, and melanoma cancers. Downregulation of these hypoxia-inducible targets associated with poor prognosis, suggesting that hypoxia-induced apoptosis contributes to p53-mediated tumor suppression and treatment response. Induction of p53 targets, PHLDA3, and a specific INPP5D transcript mediated apoptosis in response to hypoxia through AKT inhibition. Moreover, pharmacological inhibition of AKT led to apoptosis in the hypoxic regions of p53-deficient tumors and consequently increased radiosensitivity. Together, these results identify mediators of hypoxia-induced p53-dependent apoptosis and suggest AKT inhibition may improve radiotherapy response in p53-deficient tumors. PMID:25961455

AHP 4: na53 mʑi53 Tibetan Songs, Engagement Chants, and Flute Music

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LIBU LAKHI (LI JIANFU 李建富, DAWA TENZIN ཟླ་བ་བསྟན་འཛིན།

2010-06-01

Full Text Available The present study is a straightforward, pragmatic attempt to document the particulars of na53 mi53 song and musical traditions comprising the local 'performance-scape'. The primary researcher, Libu Lakhi, is a native of the community who was trained in a specialized mode of auto-ethnography developed by Charles Kevin Stuart and Gerald Roche at Qinghai Normal University 青海师范大学, Xining City 西宁市, Qinghai Province 青海省. Drawing on ethnomusicology, socio-linguistics, and the 'performance' school of folkloristics, the model is intended to enable local peoples to document and display their own traditions in a form available to scholars and interested persons on a global scale.

Differential sensitivity of p53+ and p53- cells to caffeine-induced radiosensitization and override of G2 delay

International Nuclear Information System (INIS)

Powell, S.N.; DeFrank, J.S.; Connell, P.; Eogan, M.; Preffer, F.; Dombkowski, D.; Tang, W.; Friend, S.H.

1995-01-01

Purpose: Most drug discovery efforts have focused on finding new DNA damaging agents to kill tumor cells preferentially. An alternative approach is to find ways to increase tumor specific killing by modifying tumor specific responses to that damage. We asked whether cells lacking the G1/S arrest in response to X-rays are more sensitive to X-ray damage when treated with agents that override G2/M arrest. Materials and Methods: Mouse embryonic fibroblasts genetically matched to be (+/+) or (-/-) p53 and rat embryonic fibroblasts (REF) made (+) or (-) for wild-type p53 function by transfection were irradiated with and without caffeine, a known checkpoint inhibitor. Caffeine treatment was maintained for 24 hours from 1 hour prior to irradiation. Cell survival following ionizing radiation was measured by clonogenic assay. For cell-cycle analysis, cells were in exponential asynchronous growth at the time of irradiation. The proportion of cells in G1, S and G2/M phases of the cell cycle were recorded immediately before and following irradiation and subsequently at 3,6,9,12,24 and 48 hours following irradiation. Results: Caffeine was found to cause radiosensitzation at low dose (0.5mM) in (-/-) cells but not in (+/+) cells. The sensitization enhancement ratio (SER) was 1.45 at 0.1 survival and 1.56 at 0.01 survival. At this dose of caffeine, this SER reflected therapeutic gain as there was no detectable effect on (+/+) cells. At 1mM caffeine, sensitization of (-/-) cells was 1.77, but (+/+) cells now also showed sensitization (SER=1.25). In (-/-) cells at 0.1mM caffeine the SER was 1.5 at 0.01 survival. The transfected REF cells (functionally null for p53) also exhibited caffeine-induced radiosensitization at both 0.5 and 2mM caffeine with a SER 1.45 for 2mM at 0.1 survival. No significant sensitization could be demonstrated for REF cells at the same doses of caffeine. The REF cells, with wild-type p53, transfected with pCMVneo alone showed no change in radiosensitivity or

44 CFR 204.53 - Certifying costs and payments.

Science.gov (United States)

2010-10-01

....21 and U. S. Treasury 31 CFR part 205, Cash Management Improvement Act. ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Certifying costs and payments. 204.53 Section 204.53 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY...

Pax3 stimulates p53 ubiquitination and degradation independent of transcription.

Directory of Open Access Journals (Sweden)

Xiao Dan Wang

Full Text Available Pax3 is a developmental transcription factor that is required for neural tube and neural crest development. We previously showed that inactivating the p53 tumor suppressor protein prevents neural tube and cardiac neural crest defects in Pax3-mutant mouse embryos. This demonstrates that Pax3 regulates these processes by blocking p53 function. Here we investigated the mechanism by which Pax3 blocks p53 function.We employed murine embryonic stem cell (ESC-derived neuronal precursors as a cell culture model of embryonic neuroepithelium or neural crest. Pax3 reduced p53 protein stability, but had no effect on p53 mRNA levels or the rate of p53 synthesis. Full length Pax3 as well as fragments that contained either the DNA-binding paired box or the homeodomain, expressed as GST or FLAG fusion proteins, physically associated with p53 and Mdm2 both in vitro and in vivo. In contrast, Splotch Pax3, which causes neural tube and neural crest defects in homozygous embryos, bound weakly, or not at all, to p53 or Mdm2. The paired domain and homeodomain each stimulated Mdm2-mediated ubiquitination of p53 and p53 degradation in the absence of the Pax3 transcription regulatory domains, whereas Splotch Pax3 did not stimulate p53 ubiquitination or degradation.Pax3 inactivates p53 function by stimulating its ubiquitination and degradation. This process utilizes the Pax3 paired domain and homeodomain but is independent of DNA-binding and transcription regulation. Because inactivating p53 is the only required Pax3 function during neural tube closure and cardiac neural crest development, and inactivating p53 does not require Pax3-dependent transcription regulation, this indicates that Pax3 is not required to function as a transcription factor during neural tube closure and cardiac neural crest development. These findings further suggest novel explanations for PAX3 functions in human diseases, such as in neural crest-derived cancers and Waardenburg syndrome types 1 and 3.

40 CFR 53.13 - Hearings.

Science.gov (United States)

2010-07-01

... MONITORING REFERENCE AND EQUIVALENT METHODS General Provisions § 53.13 Hearings. (a)(1) After granting a... officer of their authenticity, relevancy, and materiality, be received in evidence and shall constitute...

The flexibility of modified-linker MIL-53 materials.

Science.gov (United States)

Munn, Alexis S; Pillai, Renjith S; Biswas, Shyam; Stock, Norbert; Maurin, Guillaume; Walton, Richard I

2016-03-14

The flexibility of eight aluminium hydroxo terephthalates [Al(OH)(BDC-X)]·n(guest) (BDC = 1,4-benzene-dicarboxylate; X = -H, -CH3, -Cl, -Br, -NH2, -NO2, -(OH)2, -CO2H) crystallising in the MIL-53-type structure was investigated upon thermal dehydration of as-made samples, superhydration and methanol adsorption/desorption using in situ powder X-ray diffraction (PXRD). Profile fitting was used to determine lattice parameters as a function of time and/or temperature to describe their structural evolution. It has thus been shown that while methanol vapour adsorption induces an opening of all the modified frameworks, except the -NH2 material, superhydration only leads to open structures for Al-MIL-53-NO2, -Br and -(OH)2. All the MIL-53 solids, except Al-MIL-53-(OH)2 are present in the open structures upon thermal dehydration. In addition to the exploration of the breathing behavior of this MIL-53 series, the issue of disorder in the distribution of the functional groups between the organic linkers was explored. As a typical illustration, density functional theory calculations were carried out on different structures of Al-MIL-53-Cl, in which the distribution of -Cl within two adjacent BDC linkers is varied. The results show that the most energetically stable configuration leads to the best agreement with the experimental PXRD pattern. This observation supports that the distribution of the selected linker substituent in the functionalised solid is governed by energetics and that there is a preference for an ordering of this arrangement.

Acetylation Is Crucial for p53-Mediated Ferroptosis and Tumor Suppression

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Shang-Jui Wang

2016-10-01

Full Text Available Although previous studies indicate that loss of p53-mediated cell cycle arrest, apoptosis, and senescence does not completely abrogate its tumor suppression function, it is unclear how the remaining activities of p53 are regulated. Here, we have identified an acetylation site at lysine K98 in mouse p53 (or K101 for human p53. Whereas the loss of K98 acetylation (p53K98R alone has very modest effects on p53-mediated transactivation, simultaneous mutations at all four acetylation sites (p534KR: K98R+ 3KR[K117R+K161R+K162R] completely abolish its ability to regulate metabolic targets, such as TIGAR and SLC7A11. Notably, in contrast to p533KR, p534KR is severely defective in suppressing tumor growth in mouse xenograft models. Moreover, p534KR is still capable of inducing the p53-Mdm2 feedback loop, but p53-dependent ferroptotic responses are markedly abrogated. Together, these data indicate the critical role of p53 acetylation in ferroptotic responses and its remaining tumor suppression activity.

p53 tumor suppressor gene: significance in neoplasia - a review

International Nuclear Information System (INIS)

Alam, J.M.

2000-01-01

p53 is a tumor suppressor gene located on chromosome 17p13.1. Its function includes cell cycle control and apoptosis. Loss of p53 function, either due to decreased level or genetic transformation, is associated with loss of cell cycle control, decrease, apoptosis and genomic modification, such mutation of p53 gene is now assessed and the indicator of neoplasia of cancer of several organs and cell types, p53 has demonstrated to have critical role in defining various progressive stages of neoplasia, therapeutic strategies and clinical application. The present review briefly describes function of p53 in addition to its diagnostic and prognostic significance in detecting several types of neoplasia. (author)

41 CFR 105-53.134 - Office of Administration.

Science.gov (United States)

2010-07-01

... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Office of Administration. 105-53.134 Section 105-53.134 Public Contracts and Property Management Federal Property Management... Associate Administrator for Administration, participates in the executive leadership of the agency...

40 CFR 53.16 - Supersession of reference methods.

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2010-07-01

... 40 Protection of Environment 5 2010-07-01 2010-07-01 false Supersession of reference methods. 53... (CONTINUED) AMBIENT AIR MONITORING REFERENCE AND EQUIVALENT METHODS General Provisions § 53.16 Supersession of reference methods. (a) This section prescribes procedures and criteria applicable to requests that...

16 CFR 802.53 - Certain foreign banking transactions.

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2010-01-01

... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Certain foreign banking transactions. 802.53 Section 802.53 Commercial Practices FEDERAL TRADE COMMISSION RULES, REGULATIONS, STATEMENTS AND... foreign banking transactions. An acquisition which requires the consent or approval of the Board of...

POSTRANSLATIONAL MODIFICATIONS OF P53: UPSTREAM SIGNALING PATHWAYS.

Energy Technology Data Exchange (ETDEWEB)

ANDERSON,C.W.APPELLA,E.

2003-10-23

The p53 tumor suppressor is a tetrameric transcription factor that is posttranslational modified at >20 different sites by phosphorylation, acetylation, or sumoylation in response to various cellular stress conditions. Specific posttranslational modifications, or groups of modifications, that result from the activation of different stress-induced signaling pathways are thought to modulate p53 activity to regulate cell fate by inducing cell cycle arrest, apoptosis, or cellular senescence. Here we review recent progress in characterizing the upstream signaling pathways whose activation in response to various genotoxic and non-genotoxic stresses result in p53 posttranslational modifications.

p53-dependent non-coding RNA networks in chronic lymphocytic leukemia

NARCIS (Netherlands)

Blume, C. J.; Hotz-Wagenblatt, A.; Hüllein, J.; Sellner, L.; Jethwa, A.; Stolz, T.; Slabicki, M.; Lee, K.; Sharathchandra, A.; Benner, A.; Dietrich, S.; Oakes, C. C.; Dreger, P.; te Raa, D.; Kater, A. P.; Jauch, A.; Merkel, O.; Oren, M.; Hielscher, T.; Zenz, T.

2015-01-01

Mutations of the tumor suppressor p53 lead to chemotherapy resistance and a dismal prognosis in chronic lymphocytic leukemia (CLL). Whereas p53 targets are used to identify patient subgroups with impaired p53 function, a comprehensive assessment of non-coding RNA targets of p53 in CLL is missing. We

50 CFR 25.53 - Establishment of single visit entrance fees.

Science.gov (United States)

2010-10-01

... fees. 25.53 Section 25.53 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) THE NATIONAL WILDLIFE REFUGE SYSTEM ADMINISTRATIVE PROVISIONS Fees and Charges § 25.53 Establishment of single visit entrance fees. Entrance fees established for single visit...

48 CFR 53.235 - Research and Development Contracting (SF 298).

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Research and Development Contracting (SF 298). 53.235 Section 53.235 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS FORMS Prescription of Forms 53.235 Research and Development...

Germ-line mutations of the p53 tumor suppressor gene in patients with high risk for cancer inactivate the p53 protein.

Science.gov (United States)

Frebourg, T; Kassel, J; Lam, K T; Gryka, M A; Barbier, N; Andersen, T I; Børresen, A L; Friend, S H

1992-07-15

Germ-line mutations in the p53 tumor suppressor gene have been observed in patients with Li-Fraumeni syndrome, brain tumors, second malignancies, and breast cancers. It is unclear whether all of these mutations have inactivated p53 and thereby provide an increased risk for cancer. Therefore, it is necessary to establish the biological significance of these germ-line mutations by the functional and structural analysis of the resulting mutant p53 proteins. We analyzed the ability of seven germ-line mutant proteins observed in patients with Li-Fraumeni syndrome, second primary neoplasms, or familial breast cancer to block the growth of malignant cells and compared the structural properties of the mutant proteins to that of the wild-type protein. Six of seven missense mutations disrupted the growth inhibitory properties and structure of the wild-type protein. One germ-line mutation retained the features of the wild-type p53. Genetic analysis of the breast cancer family in which this mutation was observed indicated that this germ-line mutation was not associated with the development of cancer. These results demonstrate that germ-line p53 mutations observed in patients with Li-Fraumeni syndrome and with second malignancies have inactivated the p53 tumor suppressor gene. The inability of the germ-line p53 mutants to block the growth of malignant cells can explain why patients with these germ-line mutations have an increased risk for cancer. The observation of a functionally silent germ-line mutation indicates that, before associating a germ-line tumor suppressor gene mutation with cancer risk, it is prudent to consider its functional significance.

Germ-line mutations of the p53 tumor suppressor gene in patients with high risk for cancer inactivate the p53 protein.

Science.gov (United States)

Frebourg, T; Kassel, J; Lam, K T; Gryka, M A; Barbier, N; Andersen, T I; Børresen, A L; Friend, S H

1992-01-01

Germ-line mutations in the p53 tumor suppressor gene have been observed in patients with Li-Fraumeni syndrome, brain tumors, second malignancies, and breast cancers. It is unclear whether all of these mutations have inactivated p53 and thereby provide an increased risk for cancer. Therefore, it is necessary to establish the biological significance of these germ-line mutations by the functional and structural analysis of the resulting mutant p53 proteins. We analyzed the ability of seven germ-line mutant proteins observed in patients with Li-Fraumeni syndrome, second primary neoplasms, or familial breast cancer to block the growth of malignant cells and compared the structural properties of the mutant proteins to that of the wild-type protein. Six of seven missense mutations disrupted the growth inhibitory properties and structure of the wild-type protein. One germ-line mutation retained the features of the wild-type p53. Genetic analysis of the breast cancer family in which this mutation was observed indicated that this germ-line mutation was not associated with the development of cancer. These results demonstrate that germ-line p53 mutations observed in patients with Li-Fraumeni syndrome and with second malignancies have inactivated the p53 tumor suppressor gene. The inability of the germ-line p53 mutants to block the growth of malignant cells can explain why patients with these germ-line mutations have an increased risk for cancer. The observation of a functionally silent germ-line mutation indicates that, before associating a germ-line tumor suppressor gene mutation with cancer risk, it is prudent to consider its functional significance. Images PMID:1631137

Germ-line mutations of the p53 tumor suppressor gene in patients with high risk for cancer inactivate the p53 protein.

OpenAIRE

Frebourg, T; Kassel, J; Lam, K T; Gryka, M A; Barbier, N; Andersen, T I; Børresen, A L; Friend, S H

1992-01-01

Germ-line mutations in the p53 tumor suppressor gene have been observed in patients with Li-Fraumeni syndrome, brain tumors, second malignancies, and breast cancers. It is unclear whether all of these mutations have inactivated p53 and thereby provide an increased risk for cancer. Therefore, it is necessary to establish the biological significance of these germ-line mutations by the functional and structural analysis of the resulting mutant p53 proteins. We analyzed the ability of seven germ-...

1800MHz Microwave Induces p53 and p53-Mediated Caspase-3 Activation Leading to Cell Apoptosis In Vitro.

Directory of Open Access Journals (Sweden)

Fuqiang Xing

Full Text Available Recent studies have reported that exposure of mammalian cells to microwave radiation may have adverse effects such as induction of cell apoptosis. However, the molecular mechanisms underlying microwave induced mammalian cell apoptosis are not fully understood. Here, we report a novel mechanism: exposure to 1800MHz microwave radiation induces p53-dependent cell apoptosis through cytochrome c-mediated caspase-3 activation pathway. We first measured intensity of microwave radiation from several electronic devices with an irradiation detector. Mouse NIH/3T3 and human U-87 MG cells were then used as receivers of 1800MHz electromagnetic radiation (EMR at a power density of 1209 mW/m2. Following EMR exposure, cells were analyzed for viability, intracellular reactive oxygen species (ROS generation, DNA damage, p53 expression, and caspase-3 activity. Our analysis revealed that EMR exposure significantly decreased viability of NIH/3T3 and U-87 MG cells, and increased caspase-3 activity. ROS burst was observed at 6 h and 48 h in NIH/3T3 cells, while at 3 h in U-87 MG cells. Hoechst 33258 staining and in situ TUNEL assay detected that EMR exposure increased DNA damage, which was significantly restrained in the presence of N-acetyl-L-cysteine (NAC, an antioxidant. Moreover, EMR exposure increased the levels of p53 protein and p53 target gene expression, promoted cytochrome c release from mitochondrion, and increased caspase-3 activity. These events were inhibited by pretreatment with NAC, pifithrin-α (a p53 inhibitor and caspase inhibitor. Collectively, our findings demonstrate, for the first time, that 1800MHz EMR induces apoptosis-related events such as ROS burst and more oxidative DNA damage, which in turn promote p53-dependent caspase-3 activation through release of cytochrome c from mitochondrion. These findings thus provide new insights into physiological mechanisms underlying microwave-induced cell apoptosis.

Thymocyte apoptosis induced by p53-dependent and independent pathways

International Nuclear Information System (INIS)

Clarke, A.R.; Purdie, C.A.; Harrison, D.J.; Morris, R.G.; Bird, C.C.; Hooper, M.L.; Wyllie, A.H.

1993-01-01

The authors studied the dependence of apoptosis on p53 expression in cells from the thymus cortex. Short-term thymocyte cultures were prepared from mice constitutively heterozygous or homozygous for a deletion in the p53 gene introduced into the germ line after gene targeting. Wild-type thymocytes readily undergo apoptosis after treatment with ionizing radiation, the glucocorticoid methylprednisolone, or etoposide (an inhibitor of topoisomerase II), or after Ca 2+ -dependent activation by phorbol ester and a calcium ionophore. In contrast, homozygous null p53 thymocytes are resistant to induction of apoptosis by radiation or etoposide, but retain normal sensitivity to glucocorticoid and calcium. The time-dependent apoptosis that occurs in untreated cultures is unaffected by p53 status. Cells heterozygous for p53 deletion are partially resistant to radiation and etoposide. Results show that p53 exerts a significant and dose-dependent effect in the initiation of apoptosis, but only when it is induced by agents that cause DNA-strand breakage. (Author)

Regulation of Mdmx and its role in the p53 pathway

NARCIS (Netherlands)

Meulmeester, Erik

2006-01-01

The p53 protein is an important tumor suppressor that acts as a key regulator of the integrity of the genome. Two essential regulators of the p53 protein are Mdm2 and its homologue Mdmx. Like Mdm2, Mdmx represses p53-induced transcription. However, Mdmx cannot ubiquitinate or degrade p53 opposed to

Apoptosis in spermatogonia irradiated P53 null mice

International Nuclear Information System (INIS)

Streit-Bianchi, M.; Hendry, J.H.; Roberts, S.A.; Morris, J.D.; Durgaryan, A.A.

2007-01-01

Complete text of publication follows. The exposure of germ cells to ionizing radiations is of concern both from high-dose therapeutic exposures and from low doses causing deleterious trans-generational mutations. P53 protein plays an important role in cellular damage and is expressed in the testis normally during meiosis, its expression being localised to the preleptotene and early/mid pachytene spermatocytes. P53 null mice, heterozygotes possessing a 129 Sv/C57BL6 genetic background and B6D2F1 mice have been irradiated to 1 and 2 Gy single doses. Fractionated exposures of 1+1 Gy at 4 hours interval were also carried out. Apoptosis induction, spermatogonia and spermatocytes survival were assessed by microscope analysis of histological samples at 4 to 96 hours after irradiation in time-course experiments. The same end-points were also assessed at 72 and 96 hours after irradiation to single doses in the region between 20cGy to 2Gy. A dose dependent level of p53 expression was observed at 4 hours after irradiation to 1 and 2 Gy which returned to normal level by 24 hours. Our data support a two process mode of apoptosis with a first wave around 12 hours followed by a second wave at 2-3 days. The first wave apoptosis is substantially reduced in p53 null mice whereas the second wave is reduced in B6D2F1 mice. The initial increase in apoptosis was delayed in some stages of the of germ cells development which were identified by the spermatids shape. Clear correlation exists between apoptosis and survival assessed in stage XI-XII Tubules 72 hours after irradiation. The data are in agreement with other data in literature indicating that irradiated spermatogonia die through apoptosis. The lack of apoptosis observed in p53 null mice results in a very high survival rate of daughter cells assessed later. Theses spermatocytes and the following progenitor cells are likely to carry mutations as most will not die in the smaller second wave of apoptosis observed 3 days after

27 CFR 6.53 - Advertising in ballparks, racetracks, and stadiums.

Science.gov (United States)

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Advertising in ballparks, racetracks, and stadiums. 6.53 Section 6.53 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX... Advertising, Display Or Distribution Service § 6.53 Advertising in ballparks, racetracks, and stadiums. The...

27 CFR 53.143 - Special rules relating to further manufacture.

Science.gov (United States)

2010-04-01

... further manufacture. 53.143 Section 53.143 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX... AND AMMUNITION Exemptions, Registration, Etc. § 53.143 Special rules relating to further manufacture... the Code for use by it in further manufacture shall be treated as the manufacturer or producer of such...

DNA double strand break repair is enhanced by P53 following induction by DNA damage and is dependent on the C-terminal domain of P53

International Nuclear Information System (INIS)

Wei Tang; Powell, Simon N.

1996-01-01

Purpose: The tumor suppressor gene p53 can mediate cell cycle arrest or apoptosis in response to DNA damage. Accumulating evidence suggests that it may also directly or indirectly influence the DNA repair machinery. In the present study, we investigated whether p53, induced by DNA damage, could enhance the rejoining of double-strand DNA breaks. Materials and Methods: DNA double-strand breaks (dsb) were made by restriction enzyme digestion of a plasmid, between a promoter and a 'reporter' gene: luciferase (LUC) or chloramphenicol acetyl-transferase (CAT). Linear or circular plasmid DNA (LUC or CAT) was co-transfected with circular β-Gal plasmid (to normalize for uptake) into mouse embryonic fibroblasts genetically matched to be (+/+) or (-/-) for p53. Their ability to rejoin linearized plasmid was measured by the luciferase or CAT activity detected in rescued plasmids. The activity detected in cells transfected with linear plasmid was scored relative to the activity detected in cells transfected with circular plasmid. Results: Ionizing radiation (IR, 2 Gy) enhanced the dsb repair activity in wild type p53 cells; however, p53 null cells lose this effect, indicating that the enhancement of dsb repair was p53-dependent. REF cells with dominant-negative mutant p53 showed a similar induction compared with the parental REF cells with wild-type p53. This ala-143 mutant p53 prevents cell cycle arrest and transactivation of p21 WAF1/cip1) following IR, indicating that the p53-dependent enhancement of DNA repair is distinct from transactivation. Immortalized murine embryonic fibroblasts, 10(1)VasK1 cells, which express p53 cDNA encoding a temperature-sensitive mutant in the DNA sequence specific binding domain (ala135 to val135) with an alternatively spliced C-terminal domain (ASp53: amino-acids 360-381) and, 10(1)Val5 cells, which express the normal spliced p53 (NSp53) with the same temperature-sensitive mutant were compared. It was found that 10(1)VasK1 cells showed no DNA

Inactivation and inducible oncogenic mutation of p53 in gene targeted pigs.

Directory of Open Access Journals (Sweden)

Simon Leuchs

Full Text Available Mutation of the tumor suppressor p53 plays a major role in human carcinogenesis. Here we describe gene-targeted porcine mesenchymal stem cells (MSCs and live pigs carrying a latent TP53(R167H mutant allele, orthologous to oncogenic human mutant TP53(R175H and mouse Trp53(R172H, that can be activated by Cre recombination. MSCs carrying the latent TP53(R167H mutant allele were analyzed in vitro. Homozygous cells were p53 deficient, and on continued culture exhibited more rapid proliferation, anchorage independent growth, and resistance to the apoptosis-inducing chemotherapeutic drug doxorubicin, all characteristic of cellular transformation. Cre mediated recombination activated the latent TP53(R167H allele as predicted, and in homozygous cells expressed mutant p53-R167H protein at a level ten-fold greater than wild-type MSCs, consistent with the elevated levels found in human cancer cells. Gene targeted MSCs were used for nuclear transfer and fifteen viable piglets were produced carrying the latent TP53(R167H mutant allele in heterozygous form. These animals will allow study of p53 deficiency and expression of mutant p53-R167H to model human germline, or spontaneous somatic p53 mutation. This work represents the first inactivation and mutation of the gatekeeper tumor suppressor gene TP53 in a non-rodent mammal.

26 CFR 53.4943-10 - Business enterprise; definition.

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2010-04-01

... 26 Internal Revenue 17 2010-04-01 2010-04-01 false Business enterprise; definition. 53.4943-10...) MISCELLANEOUS EXCISE TAXES (CONTINUED) FOUNDATION AND SIMILAR EXCISE TAXES Taxes on Excess Business Holdings § 53.4943-10 Business enterprise; definition. (a) In general. (1) Except as provided in paragraph (b...

27 CFR 5.53 - Certificate of nonstandard fill.

Science.gov (United States)

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Certificate of nonstandard fill. 5.53 Section 5.53 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS LABELING AND ADVERTISING OF DISTILLED SPIRITS Requirements for Withdrawal...

Mutual interactions between P53 and growth factors in cancer

NARCIS (Netherlands)

Asschert, JGW; Vellenga, E; De Jong, S; De Vries, EGE

1998-01-01

The function of p53 armour suppressor protein is determined by various intrinsic properties of the protein. The effect of p53 DNA-binding, and platein-protein interactions are determined by the conformation of the protein. Thus p53 fulfils its role in cell cycle control and the onset of apoptotic

TP53 mutations in clinically normal mucosa adjacent to oral carcinomas

DEFF Research Database (Denmark)

Thode, Christenze; Bilde, Anders; von Buchwald, Christian

2010-01-01

BACKGROUND: The tumour-suppressor protein p53 often accumulates in histologically normal epithelium adjacent to oral squamous cell carcinomas (OSCC). We investigated whether this was associated with mutations in TP53, the gene for p53, and might implicate impending malignancy. METHODS: Specimens...... products were separated by denatured gradient gel electrophoresis. Fragments with a deviant DGEE pattern were sequenced. RESULTS: TP53 mutations were found in six of 18 tumours. Fourteen specimens contained histologically normal mucosa adjacent to the tumour; 13 of these showed small clusters of p53...

40 CFR 264.53 - Copies of contingency plan.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 25 2010-07-01 2010-07-01 false Copies of contingency plan. 264.53... Contingency Plan and Emergency Procedures § 264.53 Copies of contingency plan. A copy of the contingency plan... called upon to provide emergency services. [Comment: The contingency plan must be submitted to the...

48 CFR 53.236 - Construction and architect-engineer contracts.

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2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Construction and architect-engineer contracts. 53.236 Section 53.236 Federal Acquisition Regulations System FEDERAL ACQUISITION...-engineer contracts. ...

Restriction of human herpesvirus 6B replication by p53

DEFF Research Database (Denmark)

Øster, Bodil; Kofod-Olsen, Emil; Bundgaard, Bettina

2008-01-01

Human herpesvirus 6B (HHV-6B) induces significant accumulation of p53 in both the nucleus and cytoplasm during infection. Activation of p53 by DNA damage is known to induce either growth arrest or apoptosis; nevertheless, HHV-6B-infected cells are arrested in their cell cycle independently of p53...

Andrographolide induces degradation of mutant p53 via activation of Hsp70.

Science.gov (United States)

Sato, Hirofumi; Hiraki, Masatsugu; Namba, Takushi; Egawa, Noriyuki; Baba, Koichi; Tanaka, Tomokazu; Noshiro, Hirokazu

2018-05-22

The tumor suppressor gene p53 encodes a transcription factor that regulates various cellular functions, including DNA repair, apoptosis and cell cycle progression. Approximately half of all human cancers carry mutations in p53 that lead to loss of tumor suppressor function or gain of functions that promote the cancer phenotype. Thus, targeting mutant p53 as an anticancer therapy has attracted considerable attention. In the current study, a small-molecule screen identified andrographlide (ANDRO) as a mutant p53 suppressor. The effects of ANDRO, a small molecule isolated from the Chinese herb Andrographis paniculata, on tumor cells carrying wild-type or mutant p53 were examined. ANDRO suppressed expression of mutant p53, induced expression of the cyclin-dependent kinase inhibitor p21 and pro-apoptotic proteins genes, and inhibited the growth of cancer cells harboring mutant p53. ANDRO also induced expression of the heat-shock protein (Hsp70) and increased binding between Hsp70 and mutant p53 protein, thus promoting proteasomal degradation of p53. These results provide novel insights into the mechanisms regulating the function of mutant p53 and suggest that activation of Hsp70 may be a new strategy for the treatment of cancers harboring mutant p53.

Alterations of the TP53 Gene in Gastric and Esophageal Carcinogenesis

Directory of Open Access Journals (Sweden)

Marilanda Ferreira Bellini

2012-01-01

Full Text Available TP53 genes is one of more important tumor suppressor gene, which acts as a potent transcription factor with fundamental role in the maintenance of genetic stability. The development of esophageal and gastric cancers is a multistep process resulting in successive accumulation of genetic alterations that culminates in the malignant transformation. Thus, this study highlights the participation of the main genetic alterations of the TP53 gene in esophageal and gastric carcinogenesis. Among these changes, high frequency of TP53 mutations, loss of heterozygosity (LOH, overexpression of the p53 protein, and consequently loss of p53 function, which would be early events in esophageal and gastric cancers, as well as an important biomarker of the prognosis and treatment response. Furthermore, Single Nucleotide Polymorphisms (SNPs of TP53 have been implicated in the development and prognosis of several cancers, mainly TP53 codon 72 polymorphism whose role has been extensively studied in relation to susceptibility for esophageal and gastric cancer development.

40 CFR 265.53 - Copies of contingency plan.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 25 2010-07-01 2010-07-01 false Copies of contingency plan. 265.53... DISPOSAL FACILITIES Contingency Plan and Emergency Procedures § 265.53 Copies of contingency plan. A copy of the contingency plan and all revisions to the plan must be: (a) Maintained at the facility; and (b...

The 52Cr(p, γ)53Mn reaction

NARCIS (Netherlands)

Vuister, P.H.

The 52Cr(p, γ)53Mn reaction was investigated in the energy region Ep = 1.36–2.26 MeV. The resonance energies, the corresponding 53Mn excitation energies and the resonance strengths of 199 resonances, assigned to this reaction, are reported. The excitation energies and gamma-ray branchings of 13

40 CFR 53.65 - Test procedure: Loading test.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 5 2010-07-01 2010-07-01 false Test procedure: Loading test. 53.65... Characteristics of Class II Equivalent Methods for PM2.5 § 53.65 Test procedure: Loading test. (a) Overview. (1) The loading tests are designed to quantify any appreciable changes in a candidate method sampler's...

Autographa californica multiple nucleopolyhedrovirus ac53 plays a role in nucleocapsid assembly

International Nuclear Information System (INIS)

Liu Chao; Li Zhaofei; Wu Wenbi; Li Lingling; Yuan Meijin; Pan Lijing; Yang Kai; Pang Yi

2008-01-01

Autographa californica multiple nucleopolyhedrovirus (AcMNPV) orf53 (ac53) is a highly conserved gene existing in all sequenced Lepidoptera and Hymenoptera baculoviruses, but its function remains unknown. To investigate its role in the baculovirus life cycle, an ac53 deletion virus (vAc ac53KO-PH-GFP ) was generated through homologous recombination in Escherichia coli. Fluorescence and light microscopy and titration analysis revealed that vAc ac53KO-PH-GFP could not produce infectious budded virus in infected Sf9 cells. Real-time PCR demonstrated that the ac53 deletion did not affect the levels of viral DNA replication. Electron microscopy showed that many lucent tubular shells devoid of the nucleoprotein core are present in the virogenic stroma and ring zone, indicating that the ac53 knockout affected nucleocapsid assembly. With a recombinant virus expressing an Ac53-GFP fusion protein, we observed that Ac53 was distributed within the cytoplasm and nucleus at 24 h post-infection, but afterwards accumulated predominantly near the nucleus-cytoplasm boundary. These data demonstrate that ac53 is involved in nucleocapsid assembly and is an essential gene for virus production

Mutant Mice Lacking the p53 C-Terminal Domain Model Telomere Syndromes

Directory of Open Access Journals (Sweden)

Iva Simeonova

2013-06-01

Full Text Available Mutations in p53, although frequent in human cancers, have not been implicated in telomere-related syndromes. Here, we show that homozygous mutant mice expressing p53Δ31, a p53 lacking the C-terminal domain, exhibit increased p53 activity and suffer from aplastic anemia and pulmonary fibrosis, hallmarks of syndromes caused by short telomeres. Indeed, p53Δ31/Δ31 mice had short telomeres and other phenotypic traits associated with the telomere disease dyskeratosis congenita and its severe variant the Hoyeraal-Hreidarsson syndrome. Heterozygous p53+/Δ31 mice were only mildly affected, but decreased levels of Mdm4, a negative regulator of p53, led to a dramatic aggravation of their symptoms. Importantly, several genes involved in telomere metabolism were downregulated in p53Δ31/Δ31 cells, including Dyskerin, Rtel1, and Tinf2, which are mutated in dyskeratosis congenita, and Terf1, which is implicated in aplastic anemia. Together, these data reveal that a truncating mutation can activate p53 and that p53 plays a major role in the regulation of telomere metabolism.

Interaction of p53 with prolyl isomerases: Healthy and unhealthy relationships.

Science.gov (United States)

Mantovani, Fiamma; Zannini, Alessandro; Rustighi, Alessandra; Del Sal, Giannino

2015-10-01

The p53 protein family, comprising p53, p63 and p73, is primarily involved in preserving genome integrity and preventing tumor onset, and also affects a range of physiological processes. Signal-dependent modifications of its members and of other pathway components provide cells with a sophisticated code to transduce a variety of stress signaling into appropriate responses. TP53 mutations are highly frequent in cancer and lead to the expression of mutant p53 proteins that are endowed with oncogenic activities and sensitive to stress signaling. p53 family proteins have unique structural and functional plasticity, and here we discuss the relevance of prolyl-isomerization to actively shape these features. The anti-proliferative functions of the p53 family are carefully activated upon severe stress and this involves the interaction with prolyl-isomerases. In particular, stress-induced stabilization of p53, activation of its transcriptional control over arrest- and cell death-related target genes and of its mitochondrial apoptotic function, as well as certain p63 and p73 functions, all require phosphorylation of specific S/T-P motifs and their subsequent isomerization by the prolyl-isomerase Pin1. While these functions of p53 counteract tumorigenesis, under some circumstances their activation by prolyl-isomerases may have negative repercussions (e.g. tissue damage induced by anticancer therapies and ischemia-reperfusion, neurodegeneration). Moreover, elevated Pin1 levels in tumor cells may transduce deregulated phosphorylation signaling into activation of mutant p53 oncogenic functions. The complex repertoire of biological outcomes induced by p53 finds mechanistic explanations, at least in part, in the association between prolyl-isomerases and the p53 pathway. This article is part of a Special Issue entitled Proline-directed foldases: Cell signaling catalysts and drug targets. Copyright © 2015 Elsevier B.V. All rights reserved.

The critical role of catalase in prooxidant and antioxidant function of p53

Science.gov (United States)

Kang, M Y; Kim, H-B; Piao, C; Lee, K H; Hyun, J W; Chang, I-Y; You, H J

2013-01-01

The tumor suppressor p53 is an important regulator of intracellular reactive oxygen species (ROS) levels, although downstream mediators of p53 remain to be elucidated. Here, we show that p53 and its downstream targets, p53-inducible ribonucleotide reductase (p53R2) and p53-inducible gene 3 (PIG3), physically and functionally interact with catalase for efficient regulation of intracellular ROS, depending on stress intensity. Under physiological conditions, the antioxidant functions of p53 are mediated by p53R2, which maintains increased catalase activity and thereby protects against endogenous ROS. After genotoxic stress, high levels of p53 and PIG3 cooperate to inhibit catalase activity, leading to a shift in the oxidant/antioxidant balance toward an oxidative status, which could augment apoptotic cell death. These results highlight the essential role of catalase in p53-mediated ROS regulation and suggest that the p53/p53R2–catalase and p53/PIG3–catalase pathways are critically involved in intracellular ROS regulation under physiological conditions and during the response to DNA damage, respectively. PMID:22918438

46 CFR 53.05-3 - Materials (modifies HG-401.2).

Science.gov (United States)

2010-10-01

... 46 Shipping 2 2010-10-01 2010-10-01 false Materials (modifies HG-401.2). 53.05-3 Section 53.05-3... Pressure Relieving Devices (Article 4) § 53.05-3 Materials (modifies HG-401.2). Materials for valves must be in accordance with HG-401.2 of section IV of the ASME Boiler and Pressure Vessel Code...

The pro-survival function of p53 in HeLa cells

Energy Technology Data Exchange (ETDEWEB)

Kim, Jin Kyu; Kang, Mi Young; Jang, Eun Yeong; Kim, Jin Hong [Korea Atomic Energy Research Institute, Advanced Radiation Technology Institute, Jeongeup (Korea, Republic of)

2014-11-15

The rate of apoptosis and autophagy was variable with different p53 status after IR treatment of cells. The influence of p53 status on cell fate suggests a role of p53 in two fundamentally important cell biological pathways: autophagy and apoptosis. p53 coordinates cell cycle arrest and apoptosis to govern cell fate. This study was done to identify p53-mediated regulation of cell's fate. Autophagy induced by IR may prevent cells from undergoing apoptosis, implying an interlink modulation between autophagy and apoptosis. The rate of apoptosis and autophagy was determined with different p53 status after IR treatment of HeLa cells in this study. Our research on IR-induced cellular responses may provide new information about fate decision between the processes of apoptosis and autophagy.

40 CFR 53.66 - Test procedure: Volatility test.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 5 2010-07-01 2010-07-01 false Test procedure: Volatility test. 53.66... Characteristics of Class II Equivalent Methods for PM2.5 § 53.66 Test procedure: Volatility test. (a) Overview. This test is designed to ensure that the candidate method's losses due to volatility when sampling semi...

Phase composition of EhK 990-ID steel

International Nuclear Information System (INIS)

Rabinovich, A.V.; Milova, I.M.; Zaslavskij, Yu.B.; Neklyudov, I.M.; Chernyj, B.P.; Vanzha, A.F.; Zejdlits, M.P.; Kurasov, A.N.; Shmelev, Yu.S.

1990-01-01

The microstructure and phase composition of EhK99 steel have been investigated. It is shown that the scandium absolute concentration in solid solution of hot-deformed metal is directly proportional to their total content. It was established that the ratio between the scandium concentration in solid solution and the total content [Sc] ss/[Sc] s is not the function of the latter and constitutes (24.5±5.5) rel.%. The limiting scandium solubility in the EhK99 steel at temperature 1270 deg C was determined. It constitutes 0.07±0.005 mass%. In this paper proposed is the mechanism of intermetallide-and-second phase nucleation and growth during crystallization and homogenizing annealing. The recommendation for regimes of homogenizing annealing (1270 deg C, 12 hours) are given. It is shown that the homogenizing vacuum annealing may have an appreciable influence on the technique plasticity and production of good tubes of EhK99 steel with scandium content no more than 0.07wt%. 2 refs., 10 figs., 2 tabs

P53 function influences the effect of fractionated radiotherapy on glioblastoma tumors

International Nuclear Information System (INIS)

Haas-Kogan, Daphne A.; Kogan, Scott S.; Yount, Garret; Hsu, Jennie; Haas, Martin; Deen, Dennis F.; Israel, Mark A.

1999-01-01

Purpose: Glioblastoma multiforme brain tumors (GM) are treated with a spectrum of fractionation regimens based on the clinical and anatomical characteristics of the tumor but rarely based on the molecular characteristics of the individual neoplasm. This study tests the hypothesis that the response of cell lines derived from GM to fractionated radiotherapy depends on the function of wild-type p53 (wt p53), a tumor suppressor gene frequently mutated in GM tumors. Methods and Materials: Isogenic derivatives of glioblastoma cells differing only in p53 function were prepared using a retroviral vector expressing a dominant negative mutant of p53 (mt p53). Radiation survival in vitro was quantitated using linear quadratic and repair-saturation mathematical models. Apoptosis was assayed by a terminal deoxynucleotide transferase-labeling technique and chromatin morphology. Results: We have previously reported the generation of isogenic GM cell lines differing only in p53 function. U87-175.4, lacking wt p53 function, had a significantly lower α/β value than U87-LUX.8, expressing functional wt p53, leading us to hypothesize that fractionated irradiation would preferentially spare GM cells harboring mt p53 compared with those expressing functional, wt p53. Survival curves following either 2.0 Gy or 3.5 Gy/fraction demonstrated that lack of functional wt p53 was associated with resistance to fractionated irradiation. Radiation-induced apoptosis could not account for the observed differences in clonogenic survival. Rather, our data suggested that a deficit in the G1-checkpoint contributed to increased resistance to fractionated irradiation of cells expressing mutant p53. Conclusions: The effect of fractionated radiotherapy in GM may depend on the function of the tumor suppressor gene p53. A potential clinical consequence of these findings is that hyperfractionation regimens may provide a therapeutic advantage specifically for tumors expressing wt p53 whereas a radiotherapy

A nanobody modulates the p53 transcriptional program without perturbing its functional architecture

Science.gov (United States)

Bethuyne, Jonas; De Gieter, Steven; Zwaenepoel, Olivier; Garcia-Pino, Abel; Durinck, Kaat; Verhelle, Adriaan; Hassanzadeh-Ghassabeh, Gholamreza; Speleman, Frank; Loris, Remy; Gettemans, Jan

2014-01-01

The p53 transcription factor plays an important role in genome integrity. To perform this task, p53 regulates the transcription of genes promoting various cellular outcomes including cell cycle arrest, apoptosis or senescence. The precise regulation of this activity remains elusive as numerous mechanisms, e.g. posttranslational modifications of p53 and (non-)covalent p53 binding partners, influence the p53 transcriptional program. We developed a novel, non-invasive tool to manipulate endogenous p53. Nanobodies (Nb), raised against the DNA-binding domain of p53, allow us to distinctively target both wild type and mutant p53 with great specificity. Nb3 preferentially binds ‘structural’ mutant p53, i.e. R175H and R282W, while a second but distinct nanobody, Nb139, binds both mutant and wild type p53. The co-crystal structure of the p53 DNA-binding domain in complex with Nb139 (1.9 Å resolution) reveals that Nb139 binds opposite the DNA-binding surface. Furthermore, we demonstrate that Nb139 does not disturb the functional architecture of the p53 DNA-binding domain using conformation-specific p53 antibody immunoprecipitations, glutaraldehyde crosslinking assays and chromatin immunoprecipitation. Functionally, the binding of Nb139 to p53 allows us to perturb the transactivation of p53 target genes. We propose that reduced recruitment of transcriptional co-activators or modulation of selected post-transcriptional modifications account for these observations. PMID:25324313

Structural Basis of Competitive Recognition of p53 and MDM2 by HAUSP/USP7: Implications for the Regulation of the p53-MDM2 Pathway.

Directory of Open Access Journals (Sweden)

2006-01-01

Full Text Available Herpesvirus-associated ubiquitin-specific protease (HAUSP, also known as USP7, a deubiquitylating enzyme of the ubiquitin-specific processing protease family, specifically deubiquitylates both p53 and MDM2, hence playing an important yet enigmatic role in the p53-MDM2 pathway. Here we demonstrate that both p53 and MDM2 specifically recognize the N-terminal tumor necrosis factor-receptor associated factor (TRAF-like domain of HAUSP in a mutually exclusive manner. HAUSP preferentially forms a stable HAUSP-MDM2 complex even in the presence of excess p53. The HAUSP-binding elements were mapped to a peptide fragment in the carboxy-terminus of p53 and to a short-peptide region preceding the acidic domain of MDM2. The crystal structures of the HAUSP TRAF-like domain in complex with p53 and MDM2 peptides, determined at 2.3-A and 1.7-A resolutions, respectively, reveal that the MDM2 peptide recognizes the same surface groove in HAUSP as that recognized by p53 but mediates more extensive interactions. Structural comparison led to the identification of a consensus peptide-recognition sequence by HAUSP. These results, together with the structure of a combined substrate-binding-and-deubiquitylation domain of HAUSP, provide important insights into regulation of the p53-MDM2 pathway by HAUSP.

Cisplatinum and Taxol Induce Different Patterns of p53 Phosphorylation

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Giovanna Damia

2001-01-01

Full Text Available Posttranslational modifications of p53 induced by two widely used anticancer agents, cisplatinum (DDP and taxol were investigated in two human cancer cell lines. Although both drugs were able to induce phosphorylation at serine 20 (Ser20, only DDP treatment induced p53 phosphorylation at serine 15 (Ser15. Moreover, both drug treatments were able to increase p53 levels and consequently the transcription of waf1 and mdm-2 genes, although DDP treatment resulted in a stronger inducer of both genes. Using two ataxia telangiectasia mutated (ATM cell lines, the role of ATM in druginduced p53 phosphorylations was investigated. No differences in drug-induced p53 phosphorylation could be observed, indicating that ATM is not the kinase involved in these phosphorylation events. In addition, inhibition of DNA-dependent protein kinase activity by wortmannin did not abolish p53 phosphorylation at Ser15 and Ser20, again indicating that DNA-PK is unlikely to be the kinase involved. After both taxol and DDP treatments, an activation of hCHK2 was found and this is likely to be responsible for phosphorylation at Ser20. In contrast, only DDP was able to activate ATR, which is the candidate kinase for phosphorylation of Ser15 by this drug. This data clearly suggests that differential mechanisms are involved in phosphorylation and activation of p53 depending on the drug type.

49 CFR 192.53 - General.

Science.gov (United States)

2010-10-01

... Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY TRANSPORTATION OF NATURAL AND OTHER GAS BY PIPELINE: MINIMUM FEDERAL SAFETY STANDARDS Materials § 192.53 General. Materials for pipe and...

Morphological Heterogeneity of p53 Positive and p53 Negative Nuclei in Breast Cancers Stratified by Clinicopathological Variables

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Katrin Friedrich

1997-01-01

Full Text Available The study was aimed to detect differences in nuclear morphology between nuclear populations as well as between tumours with different p53 expression in breast cancers with different clinicopathological features, which also reflect the stage of tumour progression. The p53 immunohistochemistry was performed on paraffin sections from 88 tumour samples. After the cells had been localised by means of an image cytometry workstation and their immunostaining had been categorised visually, the sections were destained and stained by the Feulgen protocol. The nuclei were relocated and measured cytometrically by the workstation.

Mathematical Modeling of E6-p53 interactions in Cervical Cancer

Science.gov (United States)

Khattak, Faryal; Haseeb, Muhammad; Fazal, Sahar; Bhatti, A I; Ullah, Mukhtar

2017-04-01

Background: Cervical cancer is the third most common cancer in women throughout the world. The human papillomavirus (HPV) E6 viral protein plays an essential role in proteasomal degradation of the cancer suppressant protein p53. As a result, p53 negative regulation and apoptosis relevant activities are abrogated, facilitating development of cervical cancer. Methods: A mathematical model of E6-p53 interactions was developed using mathematical laws. In-silico simulations were carried out on CellDesigner and as a test case the small molecule drug RITA was considered for its ability to rescue the functions of tumor suppressor p53 by inhibiting E6 mediated proteasomal degradation. Results: Using a computational model we scrutinized how p53 responds to RITA, and chemical reactions of this small molecule drug were incorporated to perceive the full effects. The evolved strategy allowed the p53 response and rescue of its tumor suppressor function to be delineated, RITA being found to block p53 interactions with E6 associated proteins. Conclusion: We could develop a model of E6-p53 interactions with incorporation of actions of the small molecule drug RITA. Suppression of E6 associated proteins by RITA induces accumulation of tumor suppressant p53. Using CellDesigner to encode the model ensured that it can be easily modified and extended as more data become available. This strategy should play an effective role in the development of therapies against cancer. Creative Commons Attribution License

p53 Dependent Centrosome Clustering Prevents Multipolar Mitosis in Tetraploid Cells

Science.gov (United States)

Yi, Qiyi; Zhao, Xiaoyu; Huang, Yun; Ma, Tieliang; Zhang, Yingyin; Hou, Heli; Cooke, Howard J.; Yang, Da-Qing; Wu, Mian; Shi, Qinghua

2011-01-01

Background p53 abnormality and aneuploidy often coexist in human tumors, and tetraploidy is considered as an intermediate between normal diploidy and aneuploidy. The purpose of this study was to investigate whether and how p53 influences the transformation from tetraploidy to aneuploidy. Principal Findings Live cell imaging was performed to determine the fates and mitotic behaviors of several human and mouse tetraploid cells with different p53 status, and centrosome and spindle immunostaining was used to investigate centrosome behaviors. We found that p53 dominant-negative mutation, point mutation, or knockout led to a 2∼ 33-fold increase of multipolar mitosis in N/TERT1, 3T3 and mouse embryonic fibroblasts (MEFs), while mitotic entry and cell death were not significantly affected. In p53-/- tetraploid MEFs, the ability of centrosome clustering was compromised, while centrosome inactivation was not affected. Suppression of RhoA/ROCK activity by specific inhibitors in p53-/- tetraploid MEFs enhanced centrosome clustering, decreased multipolar mitosis from 38% to 20% and 16% for RhoA and ROCK, respectively, while expression of constitutively active RhoA in p53+/+ tetraploid 3T3 cells increased the frequency of multipolar mitosis from 15% to 35%. Conclusions p53 could not prevent tetraploid cells entering mitosis or induce tetraploid cell death. However, p53 abnormality impaired centrosome clustering and lead to multipolar mitosis in tetraploid cells by modulating the RhoA/ROCK signaling pathway. PMID:22076149

Stress-specific response of the p53-Mdm2 feedback loop

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Jensen Mogens H

2010-07-01

Full Text Available Abstract Background The p53 signalling pathway has hundreds of inputs and outputs. It can trigger cellular senescence, cell-cycle arrest and apoptosis in response to diverse stress conditions, including DNA damage, hypoxia and nutrient deprivation. Signals from all these inputs are channeled through a single node, the transcription factor p53. Yet, the pathway is flexible enough to produce different downstream gene expression patterns in response to different stresses. Results We construct a mathematical model of the negative feedback loop involving p53 and its inhibitor, Mdm2, at the core of this pathway, and use it to examine the effect of different stresses that trigger p53. In response to DNA damage, hypoxia, etc., the model exhibits a wide variety of specific output behaviour - steady states with low or high levels of p53 and Mdm2, as well as spiky oscillations with low or high average p53 levels. Conclusions We show that even a simple negative feedback loop is capable of exhibiting the kind of flexible stress-specific response observed in the p53 system. Further, our model provides a framework for predicting the differences in p53 response to different stresses and single nucleotide polymorphisms.

DWARF 53 acts as a repressor of strigolactone signalling in rice

Science.gov (United States)

Jiang, Liang; Liu, Xue; Xiong, Guosheng; Liu, Huihui; Chen, Fulu; Wang, Lei; Meng, Xiangbing; Liu, Guifu; Yu, Hong; Yuan, Yundong; Yi, Wei; Zhao, Lihua; Ma, Honglei; He, Yuanzheng; Wu, Zhongshan; Melcher, Karsten; Qian, Qian; Xu, H. Eric; Wang, Yonghong; Li, Jiayang

2013-12-01

Strigolactones (SLs) are a group of newly identified plant hormones that control plant shoot branching. SL signalling requires the hormone-dependent interaction of DWARF 14 (D14), a probable candidate SL receptor, with DWARF 3 (D3), an F-box component of the Skp-Cullin-F-box (SCF) E3 ubiquitin ligase complex. Here we report the characterization of a dominant SL-insensitive rice (Oryza sativa) mutant dwarf 53 (d53) and the cloning of D53, which encodes a substrate of the SCFD3 ubiquitination complex and functions as a repressor of SL signalling. Treatments with GR24, a synthetic SL analogue, cause D53 degradation via the proteasome in a manner that requires D14 and the SCFD3 ubiquitin ligase, whereas the dominant form of D53 is resistant to SL-mediated degradation. Moreover, D53 can interact with transcriptional co-repressors known as TOPLESS-RELATED PROTEINS. Our results suggest a model of SL signalling that involves SL-dependent degradation of the D53 repressor mediated by the D14-D3 complex.

p53 expression in biopsies from children with Langerhans cell histiocytosis

DEFF Research Database (Denmark)

Bank, Micha I; Lundegaard, Pia Rengtved; Carstensen, Henrik

2002-01-01

based on CD1a positivity. The slides were stained with p53 antibody and semiquantitatively evaluated using a grading system from 1 to 5 as an estimate for 0% to 20%, 20% to 40%, 40% to 60%, 60% to 80%, and 80% to 100% p53-positive for pathologic Langerhans cells (pLC), respectively. RESULTS: The p53...... protein was expressed in various degrees in pLC in all lesions. The degree of p53 expression could not be correlated to either clinical manifestation or outcome. CONCLUSIONS: An increased expression of p53 in pLC indicates an altered DNA repair control with or without abnormal control of apoptosis....

Mitochondrial localization of the low level p53 protein in proliferative cells

Energy Technology Data Exchange (ETDEWEB)

Ferecatu, Ioana; Bergeaud, Marie; Rodriguez-Enfedaque, Aida; Le Floch, Nathalie [Laboratoire de Genetique et Biologie Cellulaire - CNRS UMR 8159, Universite de Versailles Saint-Quentin-en-Yvelines, Versailles, France and Laboratoire de Genetique Moleculaire et Physiologique, Ecole Pratique des Hautes Etudes, Versailles (France); Oliver, Lisa [INSERM U601, Universite de Nantes, Faculte de Medecine, Nantes Cedex (France); Rincheval, Vincent; Renaud, Flore [Laboratoire de Genetique et Biologie Cellulaire - CNRS UMR 8159, Universite de Versailles Saint-Quentin-en-Yvelines, Versailles, France and Laboratoire de Genetique Moleculaire et Physiologique, Ecole Pratique des Hautes Etudes, Versailles (France); Vallette, Francois M. [INSERM U601, Universite de Nantes, Faculte de Medecine, Nantes Cedex (France); Mignotte, Bernard [Laboratoire de Genetique et Biologie Cellulaire - CNRS UMR 8159, Universite de Versailles Saint-Quentin-en-Yvelines, Versailles, France and Laboratoire de Genetique Moleculaire et Physiologique, Ecole Pratique des Hautes Etudes, Versailles (France); Vayssiere, Jean-Luc, E-mail: jean-luc.vayssiere@uvsq.fr [Laboratoire de Genetique et Biologie Cellulaire - CNRS UMR 8159, Universite de Versailles Saint-Quentin-en-Yvelines, Versailles, France and Laboratoire de Genetique Moleculaire et Physiologique, Ecole Pratique des Hautes Etudes, Versailles (France)

2009-10-02

p53 protein plays a central role in suppressing tumorigenesis by inducing cell cycle arrest or apoptosis through transcription-dependent and -independent mechanisms. Emerging publications suggest that following stress, a fraction of p53 translocates to mitochondria to induce cytochrome c release and apoptosis. However, the localization of p53 under unstressed conditions remains largely unexplored. Here we show that p53 is localized at mitochondria in absence of apoptotic stimuli, when cells are proliferating, localization observed in various cell types (rodent and human). This is also supported by acellular assays in which p53 bind strongly to mitochondria isolated from rat liver. Furthermore, the mitochondria subfractionation study and the alkaline treatment of the mitochondrial p53 revealed that the majority of mitochondrial p53 is present in the membranous compartments. Finally, we identified VDAC, a protein of the mitochondrial outer-membrane, as a putative partner of p53 in unstressed/proliferative cells.

p53 Maintains Genomic Stability by Preventing Interference between Transcription and Replication

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Constance Qiao Xin Yeo

2016-04-01

Full Text Available p53 tumor suppressor maintains genomic stability, typically acting through cell-cycle arrest, senescence, and apoptosis. We discovered a function of p53 in preventing conflicts between transcription and replication, independent of its canonical roles. p53 deficiency sensitizes cells to Topoisomerase (Topo II inhibitors, resulting in DNA damage arising spontaneously during replication. Topoisomerase IIα (TOP2A-DNA complexes preferentially accumulate in isogenic p53 mutant or knockout cells, reflecting an increased recruitment of TOP2A to regulate DNA topology. We propose that p53 acts to prevent DNA topological stress originating from transcription during the S phase and, therefore, promotes normal replication fork progression. Consequently, replication fork progression is impaired in the absence of p53, which is reversed by transcription inhibition. Pharmacologic inhibition of transcription also attenuates DNA damage and decreases Topo-II-DNA complexes, restoring cell viability in p53-deficient cells. Together, our results demonstrate a function of p53 that may underlie its role in tumor suppression.

Mitochondrial localization of the low level p53 protein in proliferative cells

International Nuclear Information System (INIS)

Ferecatu, Ioana; Bergeaud, Marie; Rodriguez-Enfedaque, Aida; Le Floch, Nathalie; Oliver, Lisa; Rincheval, Vincent; Renaud, Flore; Vallette, Francois M.; Mignotte, Bernard; Vayssiere, Jean-Luc

2009-01-01

p53 protein plays a central role in suppressing tumorigenesis by inducing cell cycle arrest or apoptosis through transcription-dependent and -independent mechanisms. Emerging publications suggest that following stress, a fraction of p53 translocates to mitochondria to induce cytochrome c release and apoptosis. However, the localization of p53 under unstressed conditions remains largely unexplored. Here we show that p53 is localized at mitochondria in absence of apoptotic stimuli, when cells are proliferating, localization observed in various cell types (rodent and human). This is also supported by acellular assays in which p53 bind strongly to mitochondria isolated from rat liver. Furthermore, the mitochondria subfractionation study and the alkaline treatment of the mitochondrial p53 revealed that the majority of mitochondrial p53 is present in the membranous compartments. Finally, we identified VDAC, a protein of the mitochondrial outer-membrane, as a putative partner of p53 in unstressed/proliferative cells.

Role of wild-type p53 in apoptotic and non-apoptotic cell death induced by X-irradiation and heat treatment in p53-mutated mouse M10 cells

International Nuclear Information System (INIS)

Ito, Atsushi; Nakano, Hisako; Shinohara, Kunio

2010-01-01

The sensitizing effects of wild-type p53 on X-ray-induced cell death and on heat-induced apoptosis in M10, a radiosensitive and Trp53 (mouse p53 gene)-mutated lymphoma cell line which dies through necrosis by X-irradiation, were investigated using three M10 derived transfectants with wild-type TP53 (human p53 gene). Cell death was determined by colony formation and/or dye exclusion test, and apoptosis was detected as the changes in nuclear morphology by Giemsa staining. Expression of wild-type p53 protein increased radiosensitivity of cell death as determined by both clonogenic and dye exclusion assays. This increase in radiosensitivity was attributable largely to apoptosis induction in addition to a small enhancement of necrosis. Interestingly neither pathway to cell death was accompanied by caspase-3 activation. On the other hand, heat-induced caspase-3 dependent apoptotic cell death without transfection was further increased by the transfection of wild-type p53. In conclusion, the introduction of wild-type p53 enhanced apoptotic cell death by X-rays or heat via different mechanisms that do or do not activate caspase-3, respectively. In addition, p53 also enhanced the X-ray-induced necrosis in M10 cells. (author)

40 CFR 53.2 - General requirements for a reference method determination.

Science.gov (United States)

2010-07-01

... part. Further, FRM samplers must be manufactured in an ISO 9001-registered facility, as defined in § 53... manufactured in an ISO 9001-registered facility, as defined in § 53.1 and as set forth in § 53.51. (b...

miR-34 and p53: New Insights into a Complex Functional Relationship.

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Francisco Navarro

Full Text Available miR-34, a tumor suppressor miRNA family transcriptionally activated by p53, is considered a critical mediator of p53 function. However, knockout of the mouse miR-34 family has little or no effect on the p53 response. The relative contribution of different miR-34 family members to p53 function or how much p53 relies on miR-34 in human cells is unclear. Here we show that miR-34a has a complex effect on the p53 response in human cells. In HCT116 cells miR-34a overexpression enhances p53 transcriptional activity, but the closely related family members, miR-34b and miR-34c, even when over-expressed, have little effect. Both TP53 itself and MDM4, a strong p53 transactivation inhibitor, are direct targets of miR-34a. The genes regulated by miR-34a also include four other post-translational inhibitors of p53. miR-34a overexpression leads to variable effects on p53 levels in p53-sufficient human cancer cell lines. In HCT116, miR-34a overexpression increases p53 protein levels and stability. About a quarter of all mRNAs that participate in the human p53 network bind to biotinylated miR-34a, suggesting that many are direct miR-34a targets. However, only about a fifth of the mRNAs that bind to miR-34a also bind to miR-34b or miR-34c. Two human cell lines knocked out for miR-34a have unimpaired p53-mediated responses to genotoxic stress, like mouse cells. The complex positive and negative effects of miR-34 on the p53 network suggest that rather than simply promoting the p53 response, miR-34a might act at a systems level to stabilize the robustness of the p53 response to genotoxic stress.

P53 expression in prostatic cancer: an immunohistochemical study

International Nuclear Information System (INIS)

Al-Nuaimy, W.M.; Al-Allaf, L.I.; Alnaimi, H.A.

2011-01-01

Prostate cancer is the most common malignancy in men and second leading cause of cancer death in the Western world. P53 alterations are the most frequent genetic changes in human cancers. Mutation of the p53 gene has been implicated in the development of >50% of all human cancer. The current study aims at evaluating the immuno-histochemical expression of p53 protein in patients with cancer of prostate, as prognostic parameter in correlation with other parameters including PSA receptors, and to correlate the results with those of other studies. (authors).

7 CFR 53.14 - Financial interest of official grader.

Science.gov (United States)

2010-01-01

... SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) REGULATIONS... (CONTINUED) LIVESTOCK (GRADING, CERTIFICATION, AND STANDARDS) Regulations Service § 53.14 Financial interest... 7 Agriculture 3 2010-01-01 2010-01-01 false Financial interest of official grader. 53.14 Section...

A combination of p53-activating APR-246 and phosphatidylserine-targeting antibody potently inhibits tumor development in hormone-dependent mutant p53-expressing breast cancer xenografts

Directory of Open Access Journals (Sweden)

Liang Y

2018-03-01

Full Text Available Yayun Liang,1 Benford Mafuvadze,1 Cynthia Besch-Williford,2 Salman M Hyder1 1Deparment of Biomedical Sciences and Dalton Cardiovascular Research Center, Columbia, MO, USA; 2IDEXX BioResearch, Columbia, MO, USA Background: Between 30 and 40% of human breast cancers express a defective tumor suppressor p53 gene. Wild-type p53 tumor suppressor protein promotes cell-cycle arrest and apoptosis and inhibits vascular endothelial growth factor–dependent angiogenesis, whereas mutant p53 protein (mtp53 lacks these functions, resulting in tumor cell survival and metastasis. Restoration of p53 function is therefore a promising drug-targeted strategy for combating mtp53-expressing breast cancer. Methods: In this study, we sought to determine whether administration of APR-246, a small-molecule drug that restores p53 function, in combination with 2aG4, an antibody that targets phosphatidylserine residues on tumor blood vessels and disrupts tumor vasculature, effectively inhibits advanced hormone-dependent breast cancer tumor growth. Results: APR-246 reduced cell viability in mtp53-expressing BT-474 and T47-D human breast cancer cells in vitro, and significantly induced apoptosis in a dose-dependent manner. However, APR-246 did not reduce cell viability in MCF-7 breast cancer cells, which express wild-type p53. We next examined APR-246’s anti-tumor effects in vivo using BT-474 and T47-D tumor xenografts established in female nude mice. Tumor-bearing mice were treated with APR-246 and/or 2aG4 and tumor volume followed over time. Tumor growth was more effectively suppressed by combination treatment than by either agent alone, and combination therapy completely eradicated some tumors. Immunohistochemistry analysis of tumor tissue sections demonstrated that combination therapy more effectively induced apoptosis and reduced cell proliferation in tumor xenografts than either agent alone. Importantly, combination therapy dramatically reduced the density of blood

Hypoxia-induced p53 modulates both apoptosis and radiosensitivity via AKT

NARCIS (Netherlands)

Leszczynska, K.B.; Foskolou, I.P.; Abraham, A.G.; Anbalagan, S.; Tellier, C.; Haider, S.; Span, P.N.; O'Neill, E.E.; Buffa, F.M.; Hammond, E.M.

2015-01-01

Restoration of hypoxia-induced apoptosis in tumors harboring p53 mutations has been proposed as a potential therapeutic strategy; however, the transcriptional targets that mediate hypoxia-induced p53-dependent apoptosis remain elusive. Here, we demonstrated that hypoxia-induced p53-dependent

P53 suppresses expression of the 14-3-3gamma oncogene

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Qi Wenqing

2011-08-01

Full Text Available Abstract Background 14-3-3 proteins are a family of highly conserved proteins that are involved in a wide range of cellular processes. Recent evidence indicates that some of these proteins have oncogenic activity and that they may promote tumorigenesis. We previously showed that one of the 14-3-3 family members, 14-3-3gamma, is over expressed in human lung cancers and that it can induce transformation of rodent cells in vitro. Methods qRTPCR and Western blot analysis were performed to examine 14-3-3gamma expression in non-small cell lung cancers (NSCLC. Gene copy number was analyzed by qPCR. P53 mutations were detected by direct sequencing and also by western blot. CHIP and yeast one hybrid assays were used to detect p53 binding to 14-3-3gamma promoter. Results Quantitative rtPCR results showed that the expression level of 14-3-3gamma was elevated in the majority of NSCLC that we examined which was also consistent with protein expression. Further analysis of the expression pattern of 14-3-3gamma in lung tumors showed a correlation with p53 mutations suggesting that p53 might suppress 14-3-3 gamma expression. Analysis of the gamma promoter sequence revealed the presence of a p53 consensus binding motif and in vitro assays demonstrated that wild-type p53 bound to this motif when activated by ionizing radiation. Deletion of the p53 binding motif eliminated p53's ability to suppress 14-3-3gamma expression. Conclusion Increased expression of 14-3-3gamma in lung cancer coincides with loss of functional p53. Hence, we propose that 14-3-3gamma's oncogenic activities cooperate with loss of p53 to promote lung tumorigenesis.

Mutant Mice Lacking the p53 C-Terminal Domain Model Telomere Syndromes

NARCIS (Netherlands)

Simeonova, I.; Jaber, S.; Draskovic, I.; Bardot, B.; Fang, M.; Bouarich-Bourimi, R.; Lejour, V.; Charbonnier, L.; Soudais, C.; Bourdon, J.C.; Huerre, M.; Londono-Vallejo, A.; Toledo, F.

2013-01-01

Mutations in p53, although frequent in human cancers, have not been implicated in telomere-related syndromes. Here, we show that homozygous mutant mice expressing p53(Delta31), a p53 lacking the C-terminal domain, exhibit increased p53 activity and suffer from aplastic anemia and pulmonary fibrosis,

Bioluminescence Detection of Cells Having Stabilized p53 in Response to a Genotoxic Event

Directory of Open Access Journals (Sweden)

Alnawaz Rehemtulla

2004-01-01

Full Text Available Inactivation of p53 is one of the most frequent molecular events in neoplastic transformation. Approximately 60% of all human tumors have mutations in both p53 alleles. Wild-type p53 activity is regulated in large part by the proteosome-dependent degradation of p53, resulting in a short p53 half-life in unstressed and untransformed cells. Activation of p53 by a variety of stimuli, including DNA damage induced by genotoxic drugs or radiation, is accomplished by stabilization of wild-type p53. The stabilized and active p53 can result in either cell-cycle arrest or apoptosis. Surprisingly, the majority of tumor-associated, inactivating p53 mutations also result in p53 accumulation. Thus, constitutive elevation of p53 levels in cells is a reliable measure of p53 inactivation, whereas transiently increased p53 levels reflect a recent genotoxic stress. In order to facilitate noninvasive imaging of p53 accumulation, we here describe the construction of a p53-luciferase fusion protein. Induction of DNA damage in cells expressing the fusion protein resulted in a time-dependent accumulation of the fusion that was noninvasively detected using bioluminescence imaging and validated by Western blot analysis. The p53-Luc protein retains p53 function because its expression in HCT116 cells lacking functional p53 resulted in activation of p21 expression as well as induction of apoptosis in response to a DNA damaging event. Employed in a transgenic animal model, the proposed p53-reporter fusion protein will be useful for studying p53 activation in response to exposure to DNA-damaging carcinogenic agents. It could also be used to study p53 stabilization as a result of inactivating p53 mutations. Such studies will further our understanding of p53's role as the “guardian of the genome” and its function in tumorigenesis.

HEXIM1, a New Player in the p53 Pathway

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Lew, Qiao Jing; Chu, Kai Ling; Chia, Yi Ling; Cheong, Nge [Expression Engineering Group, Bioprocessing Technology Institute, A*STAR (Agency for Science, Technology and Research), 20 Biopolis Way, #06-01, Singapore 138668 (Singapore); Chao, Sheng-Hao, E-mail: jimmy_chao@bti.a-star.edu.sg [Expression Engineering Group, Bioprocessing Technology Institute, A*STAR (Agency for Science, Technology and Research), 20 Biopolis Way, #06-01, Singapore 138668 (Singapore); Department of Microbiology, National University of Singapore, Singapore 117597 (Singapore)

2013-07-04

Hexamethylene bisacetamide-inducible protein 1 (HEXIM1) is best known as the inhibitor of positive transcription elongation factor b (P-TEFb), which controls transcription elongation of RNA polymerase II and Tat transactivation of human immunodeficiency virus. Besides P-TEFb, several proteins have been identified as HEXIM1 binding proteins. It is noteworthy that more than half of the HEXIM1 binding partners are involved in cancers. P53 and two key regulators of the p53 pathway, nucleophosmin (NPM) and human double minute-2 protein (HDM2), are among the factors identified. This review will focus on the functional importance of the interactions between HEXIM1 and p53/NPM/HDM2. NPM and the cytoplasmic mutant of NPM, NPMc+, were found to regulate P-TEFb activity and RNA polymerase II transcription through the interaction with HEXIM1. Importantly, more than one-third of acute myeloid leukemia (AML) patients carry NPMc+, suggesting the involvement of HEXIM1 in tumorigenesis of AML. HDM2 was found to ubiquitinate HEXIM1. The HDM2-mediated ubiquitination of HEXIM1 did not lead to protein degradation of HEXIM1 but enhanced its inhibitory activity on P-TEFb. Recently, HEXIM1 was identified as a novel positive regulator of p53. HEXIM1 prevented p53 ubiquitination by competing with HDM2 in binding to p53. Taken together, the new evidence suggests a role of HEXIM1 in regulating the p53 pathway and tumorigenesis.

Biological activity and safety of adenoviral vector-expressed wild-type p53 after intratumoral injection in melanoma and breast cancer patients with p53-overexpressing tumors

NARCIS (Netherlands)

Dummer, R; Bergh, J; Karlsson, Y; Horovitz, JA; Mulder, NH; Huinin, DT; Burg, G; Hofbauer, G; Osanto, S

p53 mutations are common genetic alterations in human cancer. Gene transfer of a wild-type (wt) p53 gene reverses the loss of normal p53 function in vitro and in vivo. A phase I dose escalation study of single intratumoral (i.t.) injection of a replication-defective adenoviral expression vector

Drosophila Cbp53E Regulates Axon Growth at the Neuromuscular Junction.

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Kimberly R Hagel

Full Text Available Calcium is a primary second messenger in all cells that functions in processes ranging from cellular proliferation to synaptic transmission. Proper regulation of calcium is achieved through numerous mechanisms involving channels, sensors, and buffers notably containing one or more EF-hand calcium binding domains. The Drosophila genome encodes only a single 6 EF-hand domain containing protein, Cbp53E, which is likely the prototypic member of a small family of related mammalian proteins that act as calcium buffers and calcium sensors. Like the mammalian homologs, Cbp53E is broadly though discretely expressed throughout the nervous system. Despite the importance of calcium in neuronal function and growth, nothing is known about Cbp53E's function in neuronal development. To address this deficiency, we generated novel null alleles of Drosophila Cbp53E and examined neuronal development at the well-characterized larval neuromuscular junction. Loss of Cbp53E resulted in increases in axonal branching at both peptidergic and glutamatergic neuronal terminals. This overgrowth could be completely rescued by expression of exogenous Cbp53E. Overexpression of Cbp53E, however, only affected the growth of peptidergic neuronal processes. These findings indicate that Cbp53E plays a significant role in neuronal growth and suggest that it may function in both local synaptic and global cellular mechanisms.

Chronology of p53 protein accumulation in gastric carcinogenesis

NARCIS (Netherlands)

Craanen, M. E.; Blok, P.; Dekker, W.; Offerhaus, G. J.; Tytgat, G. N.

1995-01-01

p53 Protein accumulation in early gastric carcinoma was studied in relation to the histological type (Lauren classification) and the type of growth pattern, including the chronology of p53 protein accumulation during carcinogenesis. Forty five, paraffin embedded gastrectomy specimens from early

41 CFR 105-53.141 - Office of Policy Analysis.

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2010-07-01

... Management Regulations System (Continued) GENERAL SERVICES ADMINISTRATION 53-STATEMENT OF ORGANIZATION AND FUNCTIONS Central Offices § 105-53.141 Office of Policy Analysis. The Office of Policy Analysis, headed by..., independent, objective information concerning management policies and programs, and technical and analytical...

P53 autoantibodies in 1006 patients followed up for breast cancer

International Nuclear Information System (INIS)

Metcalfe, Su; Wheeler, Terence K; Picken, Sheila; Negus, Susanne; Jo Milner, A

2000-01-01

Serial plasma samples from 1006 patients with breast cancer revealed: (i) no correlation of p53 autoantibody status with disease status at the time of sample collection, or with menopausal status at time of primary diagnosis of breast cancer; (ii) 155 out of 1006 (15%) of patients were positive for p53 autoantibodies, and these patients tended to have a persistent autoantibody status throughout follow up, irrespective of disease behaviour; and (iii) where a negative autoantibody status was found at primary diagnosis of breast cancer, this negative status persisted throughout follow up, irrespective of later disease behaviour. We conclude that screening for p53 autoantibody status is not informative on residual tumour activity nor on therapeutic responsiveness. Dysfunction of the tumour-suppressor protein, p53, may be due to either mutational or epigenetic factors, each of which may lead to accumulation of cytoplasmic p53. Abnormal accumulation of p53 in breast cancer tissue is predictive of poor prognosis [1,2]. Humoral studies [3,4] have shown that cancer patients may develop immunity to abnormally expressed p53, as revealed by p53 autoantibodies in the blood. Again, prognostic correlates have been noted, with presence of circulating p53 autoantibodies at diagnosis of breast cancer being associated with reduced overall survival [5,6] and with poor prognostic factors such as high histological grade and the absence of hormone receptors [5,7,8]. Little is known of the potential value of p53 autoantibody in follow up of cancer. In lung cancer there is evidence that autoantibodies to p53 may provide a useful tool to monitor response to therapy [9,10], whereas serial measurements of autoantibodies to p53 in 40 patients with advanced ovarian cancer were not found to be clinically useful [11]. In breast cancer some 30% of node-negative patients will relapse within 5 years, but there is no current means to predict those who are at risk. We performed the present study to

Stabilization and activation of p53 are regulated independently by different phosphorylation events

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Chernov, Mikhail V.; Ramana, Chilakamarti V.; Adler, Victor V.; Stark, George R.

1998-01-01

Treatment of mouse or human cells with the protein kinase C (PKC) inhibitors H7 or bisindolylmaleimide I induced an increase in the lifetime of p53, leading to its accumulation. In inhibitor-treated cells, p53 translocated to the nuclei and bound to DNA but was not competent to induce transcription. However, transactivation could be induced by subsequent DNA damage. Phorbol ester, a potent activator of PKC, significantly inhibited the accumulation of p53 after DNA damage. Therefore, constitutive PKC-dependent phosphorylation of p53 itself, or of a protein that interacts with p53, is required for the rapid degradation of p53 in untreated cells. Furthermore, an increase in the lifetime of p53 is not accompanied necessarily by its activation. Treatment with the PKC inhibitors decreased the overall level of p53 phosphorylation but led to the appearance of a phosphopeptide not seen in tryptic digests of p53 from untreated cells. Therefore, the lifetime and activities of p53 are likely to be regulated by distinct alterations of the phosphorylation pattern of p53, probably caused by the actions of different kinases. PMID:9482877

Pre-irradiation at a low dose-rate blunted p53 response

International Nuclear Information System (INIS)

Takahashi, Akihisa

2002-01-01

We investigated whether chronic irradiation at a low dose-rate interferes with the p53-centered signal transduction pathyway induced by radiation in human cultured cells and C57BL/6N mice. In in vitro experiments, we found that a challenge with X-ray irradiation immediately after chronic irradiation resulted in lower levels of p53 than those observed after the challenge alone in glioblastoma cells (A-172). In addition, the levels of p53-centered apoptosis and its related proteins after the challenge were strongly correlated with the above-mentioned phenomena in squamous cell carcinoma cells (SAS/neo). In in vivo experiments, the accumulation of p53 and Bax, and the induction of apoptosis were observed dose-dependently in mouse spleen at 12 h after a challenge with X-rays (3.0 Gy). However, we found significant suppression of p53 and Bax accumulation and the induction of apoptosis 12 h after challenge irradiation at 3.0 Gy with a high doses-rate following chronic pre-irradiation (1.5 Gy, 0.001 Gy/min). These findings suggest that chronic pre-irradiation suppressed the p53 function through radiation-induced signaling and/or p53 stability. (author)

Bibliography on Cold Regions Science and Technology Volume 53, Part 2

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1999-12-01

Arctic snow cover information for hydrological investiga - Wright, J.R.53-3036Designing network partitions to improve maintenance Tout- Wohtman,53-3036...832 [1998,eng] 53-1703 Amazonia Effect of dissolved NaCI on freezing curves of kaolinite, moat- Ice complex and cryoplanation terraces on Big Lyakhovsky

Functions of MDMX in the Modulation of the p53-Response

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Kristiaan Lenos

2011-01-01

Full Text Available The MDM family proteins MDM2 and MDMX are two critical regulators of the p53 tumor suppressor protein. Expression of both proteins is necessary for allowing the embryonal development by keeping the activity of p53 in check. Upon stresses that need to activate p53 to perform its function as guardian of the genome, p53 has to be liberated from these two inhibitors. In this review, we will discuss the various mechanisms by which MDMX protein levels are downregulated upon various types of stress, including posttranslational modifications of the MDMX protein and the regulation of mdmx mRNA expression, including alternative splicing. In addition, the putative function(s of the described MDMX splice variants, particularly in tumor development, will be discussed. Lastly, in contrast to common belief, we have recently shown the existence of a p53-MDMX feedback loop, which is important for dampening the p53-response at later phases after genotoxic stress.

The prognostic value of p53 mutation in pediatric marrow hypoplasia

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Sharaf Alzahraa EA

2011-06-01

Full Text Available Abstract Background The tumor suppressor gene p53 is involved in the control of cell proliferation, particularly in stressed cells. p 53 gene mutations are the most frequent genetic event found in human cancers. Fanconi Anemia (FA is the most common representative of inherited bone marrow failure syndromes (IBMFS with a leukemic propensity. P 53 DNA alteration has not been studied before in Egyptian children with FA. Patients and methods we investigated p53 mutation in the bone marrow and peripheral blood of forty children, FA (n = 10, acquired aplastic anemia (AAA (n = 10, and immune thrombocytopenia (ITP as a control (n = 20, using real-time PCR by TaqMan probe assay Results Mutation of p53 gene was demonstrated in the BM of 90% (9/10 of children with FA, compared to 10% (1/10 in AAA (p Conclusion mutation of p53 gene in hypoplastic marrow especially FA may represent an early indicator of significant DNA genetic alteration with cancer propensity.

Increased Arf/p53 activity in stem cells, aging and cancer.

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Carrasco-Garcia, Estefania; Moreno, Manuel; Moreno-Cugnon, Leire; Matheu, Ander

2017-04-01

Arf/p53 pathway protects the cells against DNA damage induced by acute stress. This characteristic is the responsible for its tumor suppressor activity. Moreover, it regulates the chronic type of stress associated with aging. This is the basis of its anti-aging activity. Indeed, increased gene dosage of Arf/p53 displays elongated longevity and delayed aging. At a cellular level, it has been recently shown that increased dosage of Arf/p53 delays age-associated stem cell exhaustion and the subsequent decline in tissue homeostasis and regeneration. However, p53 can also promote aging if constitutively activated. In this context, p53 reduces tissue regeneration, which correlates with premature exhaustion of stem cells. We discuss here the current evidence linking the Arf/p53 pathway to the processes of aging and cancer through stem cell regulation. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

41 CFR 109-26.501-53 - Acquisitions by transfer.

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2010-07-01

... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Acquisitions by transfer. 109-26.501-53 Section 109-26.501-53 Public Contracts and Property Management Federal Property Management Regulations System (Continued) DEPARTMENT OF ENERGY PROPERTY MANAGEMENT REGULATIONS SUPPLY AND...

Discrimination of p53 immunohistochemistry-positive tumors by its staining pattern in gastric cancer

International Nuclear Information System (INIS)

Ando, Koji; Oki, Eiji; Saeki, Hiroshi; Yan, Zhao; Tsuda, Yasuo; Hidaka, Gen; Kasagi, Yuta; Otsu, Hajime; Kawano, Hiroyuki; Kitao, Hiroyuki; Morita, Masaru; Maehara, Yoshihiko

2015-01-01

Immunohistochemistry staining of p53 is a cheap and simple method to detect aberrant function of p53. However, there are some discrepancies between the result of immunohistochemistry staining and mutation analysis. This study attempted to find a new definition of p53 staining by its staining pattern. Immunohistochemistry staining of p53 and TP53 gene mutation analysis were performed in 148 gastric cancer patients. Also SNP-CGH array analysis was conducted to four cases. Positive staining of p53 was observed in 88 (59.5%) tumors. Tumors with positive p53 staining showed malignant features compared to negative tumors. Mutation of TP53 gene was observed in 29 (19.6%) tumors with higher age and differentiated type. In positive p53 tumors, two types could be distinguished; aberrant type and scattered type. With comparison to TP53 gene mutation analysis, all the scattered type had wild-type TP53 gene (P = 0.0003). SNP-CGH array showed that scattered-type tumors had no change in the structure of chromosome 17. P53-scattered-type staining tumors may reflect a functionally active nonmutated TP53 gene. In interpretation of p53 immunohistochemistry staining, distinguishing p53-positive tumors by their staining pattern may be important in gastric cancer

Correlation between p53 expression and clinical-pathological characteristics of gastric cancer

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Radovanović Dragče

2011-01-01

Full Text Available Backgraund/Aim. Gene p53, or “cell genome keeper”, has a preventive effect on the occurrence of genetic aberrations and prevents abnormal expansion of (tumor cells. In gastric cancer cells in most cases we register high expression of mutated p53 gene, which correlates with prognosis and specific clinicalpathological characteristics of gastric cancer. Methods. Using the imunohistochemical method we determined the level of expression of p53 protein in 62 gastric cancers and 30 precancerous conditions (intestinal metaplasia of the stomach. We analyzed the relationship of the level of p53 expression and clinical pathological characteristics of gastric cancer. Results. Expression of p53 was positive in 42 (67.7% tumor cases and in 7 (14.3% cases of intestinal metaplasia. Expression of P53 and stomach cancer were in direct correlation (p = 0.000. Sensitivity for p53 in stomach cancer cases was 67.7% (42/62, and specifility was 76.7% (23/30. Expression of mutated p53 protein was in direct correlation with the invasion of lymph nodes (p = 0.034 and with invasion of blood vessels by carcinoma cells (p = 0.042. Conclusion. There is a direct correlation between p53 expression and gastric cancer and it indicates the ability of carcinoma cells to invade blood vessels.

Divergent evolution of human p53 binding sites: cell cycle versus apoptosis.

Directory of Open Access Journals (Sweden)

Monica M Horvath

2007-07-01

Full Text Available The p53 tumor suppressor is a sequence-specific pleiotropic transcription factor that coordinates cellular responses to DNA damage and stress, initiating cell-cycle arrest or triggering apoptosis. Although the human p53 binding site sequence (or response element [RE] is well characterized, some genes have consensus-poor REs that are nevertheless both necessary and sufficient for transactivation by p53. Identification of new functional gene regulatory elements under these conditions is problematic, and evolutionary conservation is often employed. We evaluated the comparative genomics approach for assessing evolutionary conservation of putative binding sites by examining conservation of 83 experimentally validated human p53 REs against mouse, rat, rabbit, and dog genomes and detected pronounced conservation differences among p53 REs and p53-regulated pathways. Bona fide NRF2 (nuclear factor [erythroid-derived 2]-like 2 nuclear factor and NFkappaB (nuclear factor of kappa light chain gene enhancer in B cells binding sites, which direct oxidative stress and innate immunity responses, were used as controls, and both exhibited high interspecific conservation. Surprisingly, the average p53 RE was not significantly more conserved than background genomic sequence, and p53 REs in apoptosis genes as a group showed very little conservation. The common bioinformatics practice of filtering RE predictions by 80% rodent sequence identity would not only give a false positive rate of approximately 19%, but miss up to 57% of true p53 REs. Examination of interspecific DNA base substitutions as a function of position in the p53 consensus sequence reveals an unexpected excess of diversity in apoptosis-regulating REs versus cell-cycle controlling REs (rodent comparisons: p < 1.0 e-12. While some p53 REs show relatively high levels of conservation, REs in many genes such as BAX, FAS, PCNA, CASP6, SIVA1, and P53AIP1 show little if any homology to rodent sequences. This

The expanding regulatory universe of p53 in gastrointestinal cancer.

Science.gov (United States)

Fesler, Andrew; Zhang, Ning; Ju, Jingfang

2016-01-01

Tumor suppresser gene TP53 is one of the most frequently deleted or mutated genes in gastrointestinal cancers. As a transcription factor, p53 regulates a number of important protein coding genes to control cell cycle, cell death, DNA damage/repair, stemness, differentiation and other key cellular functions. In addition, p53 is also able to activate the expression of a number of small non-coding microRNAs (miRNAs) through direct binding to the promoter region of these miRNAs.  Many miRNAs have been identified to be potential tumor suppressors by regulating key effecter target mRNAs. Our understanding of the regulatory network of p53 has recently expanded to include long non-coding RNAs (lncRNAs). Like miRNA, lncRNAs have been found to play important roles in cancer biology.  With our increased understanding of the important functions of these non-coding RNAs and their relationship with p53, we are gaining exciting new insights into the biology and function of cells in response to various growth environment changes. In this review we summarize the current understanding of the ever expanding involvement of non-coding RNAs in the p53 regulatory network and its implications for our understanding of gastrointestinal cancer.

Depression of p53-independent Akt survival signals in human oral cancer cells bearing mutated p53 gene after exposure to high-LET radiation

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Nakagawa, Yosuke [Department of Oral and Maxillofacial Surgery, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Takahashi, Akihisa [Advanced Scientific Research Leader Development Unit, Gunma University, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan); Kajihara, Atsuhisa; Yamakawa, Nobuhiro; Imai, Yuichiro [Department of Oral and Maxillofacial Surgery, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Ota, Ichiro; Okamoto, Noritomo [Department of Otorhinolaryngology, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Mori, Eiichiro [Department of Radiation Oncology, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Noda, Taichi [Department of Dermatology, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Furusawa, Yoshiya [Heavy-ion Radiobiology Research Group, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Kirita, Tadaaki [Department of Oral and Maxillofacial Surgery, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Ohnishi, Takeo, E-mail: tohnishi@naramed-u.ac.jp [Department of Radiation Oncology, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan)

2012-07-13

Highlights: Black-Right-Pointing-Pointer High-LET radiation induces efficiently apoptosis regardless of p53 gene status. Black-Right-Pointing-Pointer We examined whether high-LET radiation depresses the Akt-survival signals. Black-Right-Pointing-Pointer High-LET radiation depresses of survival signals even in the mp53 cancer cells. Black-Right-Pointing-Pointer High-LET radiation activates Caspase-9 through depression of survival signals. Black-Right-Pointing-Pointer High-LET radiation suppresses cell growth through depression of survival signals. -- Abstract: Although mutations and deletions in the p53 tumor suppressor gene lead to resistance to low linear energy transfer (LET) radiation, high-LET radiation efficiently induces cell lethality and apoptosis regardless of the p53 gene status in cancer cells. Recently, it has been suggested that the induction of p53-independent apoptosis takes place through the activation of Caspase-9 which results in the cleavage of Caspase-3 and poly (ADP-ribose) polymerase (PARP). This study was designed to examine if high-LET radiation depresses serine/threonine protein kinase B (PKB, also known as Akt) and Akt-related proteins. Human gingival cancer cells (Ca9-22 cells) harboring a mutated p53 (mp53) gene were irradiated with 2 Gy of X-rays or Fe-ion beams. The cellular contents of Akt-related proteins participating in cell survival signaling were analyzed with Western Blotting 1, 2, 3 and 6 h after irradiation. Cell cycle distributions after irradiation were assayed with flow cytometric analysis. Akt-related protein levels decreased when cells were irradiated with high-LET radiation. High-LET radiation increased G{sub 2}/M phase arrests and suppressed the progression of the cell cycle much more efficiently when compared to low-LET radiation. These results suggest that high-LET radiation enhances apoptosis through the activation of Caspase-3 and Caspase-9, and suppresses cell growth by suppressing Akt-related signaling, even in mp

NGF-mediated transcriptional targets of p53 in PC12 neuronal differentiation

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Labhart Paul

2007-05-01

Full Text Available Abstract Background p53 is recognized as a critical regulator of the cell cycle and apoptosis. Mounting evidence also suggests a role for p53 in differentiation of cells including neuronal precursors. We studied the transcriptional role of p53 during nerve growth factor-induced differentiation of the PC12 line into neuron-like cells. We hypothesized that p53 contributed to PC12 differentiation through the regulation of gene targets distinct from its known transcriptional targets for apoptosis or DNA repair. Results Using a genome-wide chromatin immunoprecipitation cloning technique, we identified and validated 14 novel p53-regulated genes following NGF treatment. The data show p53 protein was transcriptionally activated and contributed to NGF-mediated neurite outgrowth during differentiation of PC12 cells. Furthermore, we describe stimulus-specific regulation of a subset of these target genes by p53. The most salient differentiation-relevant target genes included wnt7b involved in dendritic extension and the tfcp2l4/grhl3 grainyhead homolog implicated in ectodermal development. Additional targets included brk, sdk2, sesn3, txnl2, dusp5, pon3, lect1, pkcbpb15 and other genes. Conclusion Within the PC12 neuronal context, putative p53-occupied genomic loci spanned the entire Rattus norvegicus genome upon NGF treatment. We conclude that receptor-mediated p53 transcriptional activity is involved in PC12 differentiation and may suggest a contributory role for p53 in neuronal development.

27 CFR 53.186 - Accounting procedures for like articles.

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2010-04-01

... like articles. 53.186 Section 53.186 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND... Accounting procedures for like articles. (a) Identification of manufacturer. In applying section 6416 of the Code and the regulations thereunder, a person who has purchased like articles from various...

28 CFR 90.53 - Eligibility of Indian tribal governments.

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2010-07-01

...: (i) The cost associated with filing criminal charges against a domestic violence offender, or (ii.... 90.53 Section 90.53 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) VIOLENCE AGAINST WOMEN... meeting the requirements of § 90.14(b). (c) Filing costs for criminal charges requirement. An Indian...

22 CFR 51.53 - Refunds.

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2010-04-01

... DEPARTMENT OF STATE NATIONALITY AND PASSPORTS PASSPORTS Fees § 51.53 Refunds. (a) The Department will refund the passport application fee and the security surcharge to any person exempt from payment of passport... expedited passport processing fee if the Department fails to provide expedited passport processing as...

p53 regulates cytoskeleton remodeling to suppress tumor progression.

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Araki, Keigo; Ebata, Takahiro; Guo, Alvin Kunyao; Tobiume, Kei; Wolf, Steven John; Kawauchi, Keiko

2015-11-01

Cancer cells possess unique characteristics such as invasiveness, the ability to undergo epithelial-mesenchymal transition, and an inherent stemness. Cell morphology is altered during these processes and this is highly dependent on actin cytoskeleton remodeling. Regulation of the actin cytoskeleton is, therefore, important for determination of cell fate. Mutations within the TP53 (tumor suppressor p53) gene leading to loss or gain of function (GOF) of the protein are often observed in aggressive cancer cells. Here, we highlight the roles of p53 and its GOF mutants in cancer cell invasion from the perspective of the actin cytoskeleton; in particular its reorganization and regulation by cell adhesion molecules such as integrins and cadherins. We emphasize the multiple functions of p53 in the regulation of actin cytoskeleton remodeling in response to the extracellular microenvironment, and oncogene activation. Such an approach provides a new perspective in the consideration of novel targets for anti-cancer therapy.

2-Sulfonylpyrimidines: Mild alkylating agents with anticancer activity toward p53-compromised cells.

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Bauer, Matthias R; Joerger, Andreas C; Fersht, Alan R

2016-09-06

The tumor suppressor p53 has the most frequently mutated gene in human cancers. Many of p53's oncogenic mutants are just destabilized and rapidly aggregate, and are targets for stabilization by drugs. We found certain 2-sulfonylpyrimidines, including one named PK11007, to be mild thiol alkylators with anticancer activity in several cell lines, especially those with mutationally compromised p53. PK11007 acted by two routes: p53 dependent and p53 independent. PK11007 stabilized p53 in vitro via selective alkylation of two surface-exposed cysteines without compromising its DNA binding activity. Unstable p53 was reactivated by PK11007 in some cancer cell lines, leading to up-regulation of p53 target genes such as p21 and PUMA. More generally, there was cell death that was independent of p53 but dependent on glutathione depletion and associated with highly elevated levels of reactive oxygen species and induction of endoplasmic reticulum (ER) stress, as also found for the anticancer agent PRIMA-1(MET)(APR-246). PK11007 may be a lead for anticancer drugs that target cells with nonfunctional p53 or impaired reactive oxygen species (ROS) detoxification in a wide variety of mutant p53 cells.

Doxycyclin induces p53 expression in SaOs (osteosarcoma) cell line ...

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The p53 tumour suppressor gene plays an important role in preventing cancer development. This study determined if p53 can be induced in osteosarcoma cell line upon treatment ... represent an important component of the p53 tumor suppressor pathway. Keywords: Tumor suppressor, oncogene, mdm2, cyclinE, apoptosis ...

27 CFR 53.91 - Charges to be included in sale price.

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2010-04-01

... or display of the article, for sales promotion programs, or otherwise. With respect to the rules... sale price. 53.91 Section 53.91 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND... AMMUNITION Special Provisions Applicable to Manufacturers Taxes § 53.91 Charges to be included in sale price...

41 CFR 105-53.140 - Office of Operations and Industry Relations.

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2010-07-01

... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Office of Operations and Industry Relations. 105-53.140 Section 105-53.140 Public Contracts and Property Management Federal Property... FUNCTIONS Central Offices § 105-53.140 Office of Operations and Industry Relations. The Office of Operations...

R248Q mutation--Beyond p53-DNA binding.

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Ng, Jeremy W K; Lama, Dilraj; Lukman, Suryani; Lane, David P; Verma, Chandra S; Sim, Adelene Y L

2015-12-01

R248 in the DNA binding domain (DBD) of p53 interacts directly with the minor groove of DNA. Earlier nuclear magnetic resonance (NMR) studies indicated that the R248Q mutation resulted in conformation changes in parts of DBD far from the mutation site. However, how information propagates from the mutation site to the rest of the DBD is still not well understood. We performed a series of all-atom molecular dynamics (MD) simulations to dissect sterics and charge effects of R248 on p53-DBD conformation: (i) wild-type p53 DBD; (ii) p53 DBD with an electrically neutral arginine side-chain; (iii) p53 DBD with R248A; (iv) p53 DBD with R248W; and (v) p53 DBD with R248Q. Our results agree well with experimental observations of global conformational changes induced by the R248Q mutation. Our simulations suggest that both charge- and sterics are important in the dynamics of the loop (L3) where the mutation resides. We show that helix 2 (H2) dynamics is altered as a result of a change in the hydrogen bonding partner of D281. In turn, neighboring L1 dynamics is altered: in mutants, L1 predominantly adopts the recessed conformation and is unable to interact with the major groove of DNA. We focused our attention the R248Q mutant that is commonly found in a wide range of cancer and observed changes at the zinc-binding pocket that might account for the dominant negative effects of R248Q. Furthermore, in our simulations, the S6/S7 turn was more frequently solvent exposed in R248Q, suggesting that there is a greater tendency of R248Q to partially unfold and possibly lead to an increased aggregation propensity. Finally, based on the observations made in our simulations, we propose strategies for the rescue of R248Q mutants. © 2015 Wiley Periodicals, Inc.

TP53 and lacZ mutagenesis induced by 3-nitrobenzanthrone in Xpa-deficient human TP53 knock-in mouse embryo fibroblasts.

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Kucab, Jill E; Zwart, Edwin P; van Steeg, Harry; Luijten, Mirjam; Schmeiser, Heinz H; Phillips, David H; Arlt, Volker M

2016-03-01

3-Nitrobenzanthrone (3-NBA) is a highly mutagenic compound and possible human carcinogen found in diesel exhaust. 3-NBA forms bulky DNA adducts following metabolic activation and induces predominantly G:CT:A transversions in a variety of experimental systems. Here we investigated the influence of nucleotide excision repair (NER) on 3-NBA-induced mutagenesis of the human tumour suppressor gene TP53 and the reporter gene lacZ. To this end we utilised Xpa -knockout (Xpa-Null) human TP53 knock-in (Hupki) embryo fibroblasts (HUFs). As Xpa is essential for NER of bulky DNA adducts, we hypothesized that DNA adducts induced by 3-NBA would persist in the genomes of Xpa-Null cells and lead to an increased frequency of mutation. The HUF immortalisation assay was used to select for cells harbouring TP53 mutations following mutagen exposure. We found that Xpa-Null Hupki mice and HUFs were more sensitive to 3-NBA treatment than their wild-type (Xpa-WT) counterparts. However, following 3-NBA treatment and immortalisation, a similar frequency of TP53-mutant clones arose from Xpa-WT and Xpa-Null HUF cultures. In cells from both Xpa genotypes G:CT:A transversion was the predominant TP53 mutation type and mutations exhibited bias towards the non-transcribed strand. Thirty-two percent of 3-NBA-induced TP53 mutations occurred at CpG sites, all of which are hotspots for mutation in smokers' lung cancer (codons 157, 158, 175, 245, 248, 273, 282). We also examined 3-NBA-induced mutagenesis of an integrated lacZ reporter gene in HUFs, where we again observed a similar mutant frequency in Xpa-WT and Xpa-Null cells. Our findings suggest that 3-NBA-DNA adducts may evade removal by global genomic NER; the persistence of 3-NBA adducts in DNA may be an important factor in its mutagenicity. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

The expression of p53 protein in patients with multiple myeloma

Directory of Open Access Journals (Sweden)

Marković Olivera

2007-01-01

Full Text Available Introduction: Although mutations of p53 are one of the most often acquired genetic changes in malignant tumors, these mutations are rare events in patients with newly diagnosed multiple myeloma (MM. Moreover, there are a few literature data about clinical significance of p53 overexpression in multiple myeloma. Objective The aim of our study was to evaluate the clinical significance of p53 immunoexpression in multiple myeloma. Method A total of 58 patients with newly diagnosed MM (26 females and 32 males, mean age 62 years were enrolled in the study. The diagnosis of MM was made according to criteria of Chronic Leukemia-Myeloma Task Force. Clinical staging was done according to Durie and Salmon classification (4 patients had disease stage I, 15 patients stage II and 39 patients stage III. The histological grade and histological stage were determined according to predominant plasma cell morphology and volume of myeloma infiltration, respectively. Standard immunohistochemical analysis with p53 antibody in B5-fixed and paraffin- embedded bone marrow specimens was used to evaluate the expression of p53 in myeloma cells. The specimens were considered positive when ≥5% of plasma cells exhibited clear nuclear positivity. Results Out of 58 patients, p53 expression was detected in 9 (15.52%. No significant correlation was found between p53 expression and clinical stage (I+II vs. III, Я2-microglobulin level (≤6 mg/L vs. >6mg/L, histological grade (I vs. II+III, histological stage (<20% vs. 21-50% vs. >50% and the extent of osteolytic lesions (≤3 vs. >3 lesions. Median survival of patients with p53 immunoreactivity in =>5% of plasma cells was 10 months, whilst median survival of patients with p53 immunoreactivity in <5% of plasma cells was 36 months. However, such difference was not significant (p=0.2. Conclusion The frequency of p53 immunoexpression in our group of newly diagnosed MM was relatively low. Although p53 immunoexpression was not

p53 functions as a cell cycle control protein in osteosarcomas.

OpenAIRE

Diller, L; Kassel, J; Nelson, C E; Gryka, M A; Litwak, G; Gebhardt, M; Bressac, B; Ozturk, M; Baker, S J; Vogelstein, B

1990-01-01

Mutations in the p53 gene have been associated with a wide range of human tumors, including osteosarcomas. Although it has been shown that wild-type p53 can block the ability of E1a and ras to cotransform primary rodent cells, it is poorly understood why inactivation of the p53 gene is important for tumor formation. We show that overexpression of the gene encoding wild-type p53 blocks the growth of osteosarcoma cells. The growth arrest was determined to be due to an inability of the transfect...

Relationship between P53 and bystander effect induced by radiated hepatoma cells

International Nuclear Information System (INIS)

Zhao Meijia; Shen Bo; Yuan Dexiao; Cheng Honghong; Shao Chunlin

2009-01-01

The role of p53 in bystander responses on normal liver cells were investigated by co-culturing irradiated hepatoma cells with non-irradiated bystander Chang liver cells. It was found that radiosensitivity of the hepatoma cells was relative to p53. HepG2 cells with wtp53 had the highest radiosensitivity followed by PLC/PRF/5 cells with mtp53 and Hep3B cells with null-p53. The induction of bystander micronucleus(MN) was observed only in the Chang liver cells that had been co-cultured with HepG2 cells but not co-cultured with PLC/PRF/5 or Hep3B. Also, this bystander MN was relative to the irradiation dose and the cell co-culture rime. When the hepatoma cells were treated with pifithrin-α, a p53 inhibitor, their radiosensitivities were reduced, and the bystander effect was diminished. The results indicate that p53 could regulate not only the radiosensitivity but also the bystander response. (authors)

RITA displays anti-tumor activity in medulloblastomas independent of TP53 status.

Science.gov (United States)

Gottlieb, Aline; Althoff, Kristina; Grunewald, Laura; Thor, Theresa; Odersky, Andrea; Schulte, Marc; Deubzer, Hedwig E; Heukamp, Lukas; Eggert, Angelika; Schramm, Alexander; Schulte, Johannes H; Künkele, Annette

2017-04-25

Current therapy of medulloblastoma, the most common malignant brain tumor of childhood, achieves 40-70% survival. Secondary chemotherapy resistance contributes to treatment failure, where TP53 pathway dysfunction plays a key role. MDM2 interaction with TP53 leads to its degradation. Reactivating TP53 functionality using small-molecule inhibitors, such as RITA, to disrupt TP53-MDM2 binding may have therapeutic potential. We show here that RITA decreased viability of all 4 analyzed medulloblastoma cell lines, regardless of TP53 functional status. The decrease in cell viability was accompanied in 3 of the 4 medulloblastoma cell lines by accumulation of TP53 protein in the cells and increased CDKN1A expression. RITA treatment in mouse models inhibited medulloblastoma xenograft tumor growth. These data demonstrate that RITA treatment reduces medulloblastoma cell viability in both in vitro and in vivo models, and acts independently of cellular TP53 status, identifying RITA as a potential therapeutic agent to treat medulloblastoma.

Inhibition of Endothelial p53 Improves Metabolic Abnormalities Related to Dietary Obesity

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Masataka Yokoyama

2014-06-01

Full Text Available Accumulating evidence has suggested a role for p53 activation in various age-associated conditions. Here, we identified a crucial role of endothelial p53 activation in the regulation of glucose homeostasis. Endothelial expression of p53 was markedly upregulated when mice were fed a high-calorie diet. Disruption of endothelial p53 activation improved dietary inactivation of endothelial nitric oxide synthase that upregulated the expression of peroxisome proliferator-activated receptor-γ coactivator-1α in skeletal muscle, thereby increasing mitochondrial biogenesis and oxygen consumption. Mice with endothelial cell-specific p53 deficiency fed a high-calorie diet showed improvement of insulin sensitivity and less fat accumulation, compared with control littermates. Conversely, upregulation of endothelial p53 caused metabolic abnormalities. These results indicate that inhibition of endothelial p53 could be a novel therapeutic target to block the vicious cycle of cardiovascular and metabolic abnormalities associated with obesity.

9 CFR 53.9 - Mortgage against animals or materials.

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2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Mortgage against animals or materials. 53.9 Section 53.9 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT....9 Mortgage against animals or materials. When animals or materials have been destroyed pursuant to...

19 CFR 148.53 - Exemption for tools of trade.

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2010-04-01

... 19 Customs Duties 2 2010-04-01 2010-04-01 false Exemption for tools of trade. 148.53 Section 148.53 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF... tools of trade. (a) Exemption. Professional books, implements, instruments, or tools of trade...

Basal p53 expression is indispensable for mesenchymal stem cell integrity.

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Boregowda, Siddaraju V; Krishnappa, Veena; Strivelli, Jacqueline; Haga, Christopher L; Booker, Cori N; Phinney, Donald G

2018-03-01

Marrow-resident mesenchymal stem cells (MSCs) serve as a functional component of the perivascular niche that regulates hematopoiesis. They also represent the main source of bone formed in adult bone marrow, and their bifurcation to osteoblast and adipocyte lineages plays a key role in skeletal homeostasis and aging. Although the tumor suppressor p53 also functions in bone organogenesis, homeostasis, and neoplasia, its role in MSCs remains poorly described. Herein, we examined the normal physiological role of p53 in primary MSCs cultured under physiologic oxygen levels. Using knockout mice and gene silencing we show that p53 inactivation downregulates expression of TWIST2, which normally restrains cellular differentiation to maintain wild-type MSCs in a multipotent state, depletes mitochondrial reactive oxygen species (ROS) levels, and suppresses ROS generation and PPARG gene and protein induction in response to adipogenic stimuli. Mechanistically, this loss of adipogenic potential skews MSCs toward an osteogenic fate, which is further potentiated by TWIST2 downregulation, resulting in highly augmented osteogenic differentiation. We also show that p53 - /- MSCs are defective in supporting hematopoiesis as measured in standard colony assays because of decreased secretion of various cytokines including CXCL12 and CSF1. Lastly, we show that transient exposure of wild-type MSCs to 21% oxygen upregulates p53 protein expression, resulting in increased mitochondrial ROS production and enhanced adipogenic differentiation at the expense of osteogenesis, and that treatment of cells with FGF2 mitigates these effects by inducing TWIST2. Together, these findings indicate that basal p53 levels are necessary to maintain MSC bi-potency, and oxygen-induced increases in p53 expression modulate cell fate and survival decisions. Because of the critical function of basal p53 in MSCs, our findings question the use of p53 null cell lines as MSC surrogates, and also implicate dysfunctional

40 CFR 53.1 - Definitions.

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2010-07-01

... followed by a gravimetric mass determination, but which is not a Class I equivalent method because of... MONITORING REFERENCE AND EQUIVALENT METHODS General Provisions § 53.1 Definitions. Terms used but not defined... slope of a linear plot fitted to corresponding candidate and reference method mean measurement data...

17 CFR 200.53 - Preamble.

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2010-04-01

... ETHICS; AND INFORMATION AND REQUESTS Canons of Ethics § 200.53 Preamble. (a) Members of the Securities and Exchange Commission are entrusted by various enactments of the Congress with powers and duties of... possible abuses and injustice which, if left unchecked, might jeopardize the strength of our economic...

p53 functions as a cell cycle control protein in osteosarcomas.

Science.gov (United States)

Diller, L; Kassel, J; Nelson, C E; Gryka, M A; Litwak, G; Gebhardt, M; Bressac, B; Ozturk, M; Baker, S J; Vogelstein, B

1990-11-01

Mutations in the p53 gene have been associated with a wide range of human tumors, including osteosarcomas. Although it has been shown that wild-type p53 can block the ability of E1a and ras to cotransform primary rodent cells, it is poorly understood why inactivation of the p53 gene is important for tumor formation. We show that overexpression of the gene encoding wild-type p53 blocks the growth of osteosarcoma cells. The growth arrest was determined to be due to an inability of the transfected cells to progress into S phase. This suggests that the role of the p53 gene as an antioncogene may be in controlling the cell cycle in a fashion analogous to the check-point control genes in Saccharomyces cerevisiae.

p53 functions as a cell cycle control protein in osteosarcomas.

Science.gov (United States)

Diller, L; Kassel, J; Nelson, C E; Gryka, M A; Litwak, G; Gebhardt, M; Bressac, B; Ozturk, M; Baker, S J; Vogelstein, B

1990-01-01

Mutations in the p53 gene have been associated with a wide range of human tumors, including osteosarcomas. Although it has been shown that wild-type p53 can block the ability of E1a and ras to cotransform primary rodent cells, it is poorly understood why inactivation of the p53 gene is important for tumor formation. We show that overexpression of the gene encoding wild-type p53 blocks the growth of osteosarcoma cells. The growth arrest was determined to be due to an inability of the transfected cells to progress into S phase. This suggests that the role of the p53 gene as an antioncogene may be in controlling the cell cycle in a fashion analogous to the check-point control genes in Saccharomyces cerevisiae. Images PMID:2233717

Conformational detection of p53's oligomeric state by FlAsH Fluorescence

OpenAIRE

Webber, Tawnya M.; Allen, Andrew C.; Ma, Wai Kit; Molloy, Rhett G.; Kettelkamp, Charisse N.; Dow, Caitlin A.; Gage, Matthew J.

2009-01-01

The p53 tumor suppressor protein is a critical checkpoint in prevention of tumor formation, and the function of p53 is dependent on proper formation of the active tetramer. In vitro studies have shown that p53 binds DNA most efficiently as a tetramer, though inactive p53 is predicted to be monomeric in vivo. We demonstrate that FlAsH binding can be used to distinguish between oligomeric states of p53, providing a potential tool to explore p53 oligomerization in vivo. The FlAsH tetra-cysteine ...

P53 and Rb tumor suppressor gene alterations in gastric cancer Alterações dos genes supressores tumorais p53 e Rb no câncer gástrico

Directory of Open Access Journals (Sweden)

Rejane Mattar

2004-01-01

Full Text Available Inactivation of tumor suppressor genes has been frequently observed in gastric carcinogenesis. Our purpose was to study the involvement of p53, APC, DCC, and Rb genes in gastric carcinoma. METHOD: Loss of heterozygosity of the p53, APC, DCC and Rb genes was studied in 22 gastric cancer tissues using polymerase chain reaction; single-strand conformation polymorphism of the p53 gene exons 5-6 and exons 7-8 was studied using 35S-dATP, and p53 expression was detected using a histological immunoperoxidase method with an anti-p53 clone. RESULTS AND DISCUSSION: No loss of heterozygosity was observed in any of these tumor suppressor genes; homozygous deletion was detected in the Rb gene in 23% (3/13 of the cases of intestinal-type gastric carcinoma. Eighteen (81.8% cases showed band mobility shifts in exons 5-6 and/or 7-8 of the p53 gene. The presence of the p53 protein was positive in gastric cancer cells in 14 cases (63.6%. Normal gastric mucosa showed negative staining for p53; thus, the immunoreactivity was likely to represent mutant forms. The correlation of band mobility shift and the immunoreactivity to anti-p53 was not significant (P = .90. There was no correlation of gene alterations with the disease severity. CONCLUSIONS: The inactivation of Rb and p53 genes is involved in gastric carcinogenesis in our environment. Loss of the Rb gene observed only in the intestinal-type gastric cancer should be further evaluated in association with Helicobacter pylori infection. The p53 gene was affected in both intestinal and diffuse histological types of gastric cancer.A inativação de genes supressores tumorais tem sido freqüentemente observada na carcinogênese gástrica. O nosso objetivo foi estudar o envolvimento dos genes p53, APC, DCC e Rb no câncer gástrico. MÉTODO: Vinte e dois casos de câncer gástrico foram estudados por PCR-LOH (reação de polimerase em cadeia- perda de alelo heterozigoto dos genes p53, APC, DCC e Rb; e por PCR-SSCP (rea

Robustness of the p53 network and biological hackers.

Science.gov (United States)

Dartnell, Lewis; Simeonidis, Evangelos; Hubank, Michael; Tsoka, Sophia; Bogle, I David L; Papageorgiou, Lazaros G

2005-06-06

The p53 protein interaction network is crucial in regulating the metazoan cell cycle and apoptosis. Here, the robustness of the p53 network is studied by analyzing its degeneration under two modes of attack. Linear Programming is used to calculate average path lengths among proteins and the network diameter as measures of functionality. The p53 network is found to be robust to random loss of nodes, but vulnerable to a targeted attack against its hubs, as a result of its architecture. The significance of the results is considered with respect to mutational knockouts of proteins and the directed attacks mounted by tumour inducing viruses.

Menin and p53 have non-synergistic effects on tumorigenesis in mice

International Nuclear Information System (INIS)

Loffler, Kelly A; Mould, Arne W; Waring, Paul M; Hayward, Nicholas K; Kay, Graham F

2012-01-01

While it is now more than a decade since the first description of the gene mutation underlying the tumour predisposition syndrome multiple endocrine neoplasia type 1 (MEN1), the mechanism by which its protein product menin acts to prevent development of tumours is still poorly understood. We undertook a genetic experiment to assess whether menin synergises with p53. Mice carrying various combinations of Men1 and Trp53 mutations were generated then survival and pathology assessed. While homozygous loss of Trp53 in mice resulted in early onset, aggressive tumours and profoundly reduced lifespan, heterozygous loss of either Trp53 or Men1 caused later onset disease, with a spectrum of tumours characteristic of each tumour suppressor gene. Loss of one copy of Men1 in animals also lacking both alleles of Trp53 did not exacerbate phenotype, based on survival, animal weight or sites of pathology, compared to Trp53 deletion alone. Dual heterozygous deletion of Men1 and Trp53 resulted in a small reduction in lifespan compared to the individual mutations, without new tumour sites. In the adrenal, we observed development of cortical tumours in dual heterozygous animals, as we have previously seen in Men1 +/− animals, and there was loss of heterozygosity at the Men1 allele in these tumours. Median number of pathology observations per animal was increased in dual heterozygous animals compared with heterozygous loss of Trp53 alone. Simultaneous heterozygous deletion of Men1 in animals with either heterozygous or homozygous deletion of Trp53 did not result in formation of tumours at any new sites, implying additive rather than synergistic effects of these pathways. Mice that were Men1 +/− in addition to Trp53 +/− had tumours in endocrine as well as other sites, implying that increase in total tumour burden, at sites typically associated with either Men1 or Trp53 loss, contributed to the slight decrease in survival in Men1 +/− : Trp53 +/− animals in comparison with their

9 CFR 53.3 - Appraisal of animals or materials.

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2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Appraisal of animals or materials. 53.3 Section 53.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF... animals or materials. (a) Animals affected by or exposed to disease, and materials required to be...

24 CFR 576.53 - Use as an emergency shelter.

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2010-04-01

... URBAN DEVELOPMENT COMMUNITY FACILITIES EMERGENCY SHELTER GRANTS PROGRAM: STEWART B. McKINNEY HOMELESS ASSISTANCE ACT Program Requirements § 576.53 Use as an emergency shelter. (a)(1) Restrictions and definition... 24 Housing and Urban Development 3 2010-04-01 2010-04-01 false Use as an emergency shelter. 576.53...

Disruption of the MDM2-p53 interaction strongly potentiates p53-dependent apoptosis in cisplatin-resistant human testicular carcinoma cells via the Fas/FasL pathway

NARCIS (Netherlands)

Koster, R.; Timmer-Bosscha, H.; Bischoff, R.; Gietema, J. A.; de Jong, S.

Wild-type p53 has a major role in the response and execution of apoptosis after chemotherapy in many cancers. Although high levels of wild-type p53 and hardly any TP53 mutations are found in testicular cancer (TC), chemotherapy resistance is still observed in a significant subgroup of TC patients.

Vulture News - Vol 53 (2005)

African Journals Online (AJOL)

Poisoning of seventeen Eurasian Griffons by carbofuran on the Island of Rab, Croatia, in December 2004 · EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. Gordana Pavokovic, Goran Susic, 24-25. http://dx.doi.org/10.4314/vulnew.v53i1.37632 ...

19 CFR 145.53 - Firearms and munitions of war.

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2010-04-01

... 19 Customs Duties 2 2010-04-01 2010-04-01 false Firearms and munitions of war. 145.53 Section 145.53 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF... munitions of war. Importations of firearms, munitions of war, and related articles are subject to the import...