High Mutability of the Tumor Suppressor Genes RASSF1 and RBSP3 (CTDSPL) in Cancer

BACKGROUND:Many different genetic alterations are observed in cancer cells. Individual cancer genes display point mutations such as base changes, insertions and deletions that initiate and promote cancer growth and spread. Somatic hypermutation is a powerful mechanism for generation of different mutations. It was shown previously that somatic hypermutability of proto-oncogenes can induce development of lymphomas. METHODOLOGY/PRINCIPAL FINDINGS:We found an exceptionally high incidence of single-base mutations in the tumor suppressor genes RASSF1 and RBSP3 (CTDSPL) both located in 3p21.3 regions, LUCA and AP20 respectively. These regions contain clusters of tumor suppressor genes involved in multiple cancer types such as lung, kidney, breast, cervical, head and neck, nasopharyngeal, prostate and other carcinomas. Altogether in 144 sequenced RASSF1A clones (exons 1-2), 129 mutations were detected (mutation frequency, MF = 0.23 per 100 bp) and in 98 clones of exons 3-5 we found 146 mutations (MF = 0.29). In 85 sequenced RBSP3 clones, 89 mutations were found (MF = 0.10). The mutations were not cytidine-specific, as would be expected from alterations generated by AID/APOBEC family enzymes, and appeared de novo during cell proliferation. They diminished the ability of corresponding transgenes to suppress cell and tumor growth implying a loss of function. These high levels of somatic mutations were found both in cancer biopsies and cancer cell lines. CONCLUSIONS/SIGNIFICANCE:This is the first report of high frequencies of somatic mutations in RASSF1 and RBSP3 in different cancers suggesting it may underlay the mutator phenotype of cancer. Somatic hypermutations in tumor suppressor genes involved in major human malignancies offer a novel insight in cancer development, progression and spread

Selective laser spectroscopy of the bixbyite-type yttrium scandate doped by rare-earth ions

Yttrium scandate crystals doped by Nd3+ and Tm3+ ions have been obtained in the form of a fiber through the laser-heated pedestal growth (LHPG) method. Three types of optical centers of Nd3+ and Tm3+ have been recorded by the selective laser spectroscopy methods. Two dominant centers form due to substitution of the rare-earth ions for Y3+ and Sc3+ in the structural site of C2. In the case of Nd3+:YScO3, the third one is aggregate pair center Nd3+ - Nd3+ which forms due to substitution of basic ions (Y3+ or Sc3+) in neighboring MO6 polyhedra shared the edge. In the case of Tm3+:YScO3, the third optical center form due to substitution of Tm3+ for Y3+ or Sc3+ in the octahedra MO6 with symmetry site of C3i. The lifetime have been estimated for Nd3+ and Tm3+ ions occupied MO6 polyhedra with symmetry sites of C2 and C3i in the YScO3 crystal fibers. Stark level schematic of 2F3/2, 4I11/2, and 4I9/2 multiplets of Nd3+ ions have been built for both centers of C2 in the YScO3 crystal fibe

Dynamics of Hydrogen Isotope Absorption and Emission of Neutron-Irradiated Tungsten

This overview presents recent results regarding hydrogen isotope absorption and emission dynamics in neutron-irradiated tungsten (W) using our recently developed Compact Diverter Plasma Simulator (CDPS), a linear plasma device in a radiation-controlled area. Neutron irradiation to 0.016 - 0.06 displacement per atom resulted in a significant increase in deuterium (D) retention due to trapping effects of radiation-induced defects. We analyzed the dependency of D retention on the D plasma fluence by exposing neutron-irradiated pure W to D plasma at 563 K over a range of D fluence values. The total retention was revealed to be proportional to the square root of D fluence, indicating that the implanted D atoms first occupy the defects caused by neutron-irradiation near the surface and then the defects located in deeper regions. We further investigated the effects of post-plasma annealing on D emission; neutron-irradiated pure W was exposed to D plasma at 573 K and was then annealed at the same temperature for 30 hours. Approximately 10% of the absorbed D was released by annealing, suggesting that a heat treatment of the plasma-facing component of a fusion reactor at moderately elevated temperatures could contribute to the removal of accumulated hydrogen isotopes. The experimental results obtained in this study were only available by investigating neutron-irradiated specimens with the CDPS system, which will be essential for future studies of material behavior and plasma-wall interactions in the fusion reactor environment

Development of Mass Spectrometry Selected Reaction Monitoring Method for Quantitation and Pharmacokinetic Study of Stepharine in Rabbit Plasma

Highly sensitive liquid chromatography mass spectrometry method on triple quadrupole (QQQ) mass spectrometer was successfully applied for pharmacokinetic study of stepharine in rabbit plasma. Specific ion transitions of stepharine protonated precursor ion were selected and recorded in the certain retention time employing dynamic selected reaction monitoring mode. The developed method facilitated quantitative measurements of stepharine in plasma samples in linear range of five orders of magnitude with high accuracy and low standard deviation coefficient and pharmacokinetics parameters were calculated. The apparent volume of stepharine distribution (estimated as ratio of clearance to elimination rate constant, data not shown) allows us to assume that stepharine was extensively distributed throughout the body

Structural and Spectroscopic Features of the Bixbyite-Type Yttrium Scandate Doped by Rare-Earth Ions

Yttrium scandate crystal fiber has been obtained through laser-heated pedestal growth. The crystal belongs to a bixbyite crystal structure and crystallizes in Ia3¯ space group. X-ray diffraction method shows a lattice parameter of a = 10.228(1) Å. Factor-group analysis of YScO3 Raman spectra points to high degree of disorder in crystal structure of the new compound. Spectral-kinetic investigation of the crystal fibers doped by rare-earth ions points to the presence of two independent active optical centers of rare-earth ions. Moreover, the character of rare-earth impurities’ distribution is independent on a rare-earth ionic radius size

Structural and Spectroscopic Features of the Bixbyite-Type Yttrium Scandate Doped by Rare-Earth Ions

Yttrium scandate crystal fiber has been obtained through laser-heated pedestal growth. The crystal belongs to a bixbyite crystal structure and crystallizes in Ia3¯ space group. X-ray diffraction method shows a lattice parameter of a = 10.228(1) Å. Factor-group analysis of YScO3 Raman spectra points to high degree of disorder in crystal structure of the new compound. Spectral-kinetic investigation of the crystal fibers doped by rare-earth ions points to the presence of two independent active optical centers of rare-earth ions. Moreover, the character of rare-earth impurities’ distribution is independent on a rare-earth ionic radius size

Performance and characterization of the FinEstBeAMS beamline at the MAX IV Laboratory

Abstract FinEstBeAMS (Finnish–Estonian Beamline for Atmospheric and Materials Sciences) is a multidisciplinary beamline constructed at the 1.5 GeV storage ring of the MAX IV synchrotron facility in Lund, Sweden. The beamline covers an extremely wide photon energy range, 4.5–1300 eV, by utilizing a single elliptically polarizing undulator as a radiation source and a single grazing-incidence plane grating monochromator to disperse the radiation. At photon energies below 70 eV the beamline operation relies on the use of optical and thin-film filters to remove higher-order components from the monochromated radiation. This paper discusses the performance of the beamline, examining such characteristics as the quality of the gratings, photon energy calibration, photon energy resolution, available photon flux, polarization quality and focal spot size