Epigenetic silencing of UBXN8 contributes to leukemogenesis in t(8;21) acute myeloid leukemia

The formation of the RUNX1-RUNX1T1 fusion protein, resulting from the t(8;21) translocation, is considered to be one of the initiating events of t(8;21) acute myeloid leukemia (AML). However, the mechanisms of the oncogenic mechanism of RUNX1-RUNX1T1 remain unclear. In this study, we found that RUNX1-RUNX1T1 triggers the heterochromatic silencing of UBXN8 by recognizing the RUNX1-binding sites and recruiting chromatin-remodeling enzymes to the UBXN8 promoter region. Decitabine, a specific inhibitor of DNA methylation, upregulated the expression of UBXN8 in RUNX1-RUNX1T1⁺ AML cell lines. Overexpression of UBXN8 inhibited the proliferation and colony-forming ability of and promoted cell cycle arrest in t(8;21) AML cell lines. Enhancing UBXN8 levels can significantly inhibit tumor proliferation and promote the differentiation of RUNX1-RUNX1T1⁺ cells in vivo. In conclusion, our results indicated that epigenetic silencing of UBXN8 via methylation of its promoter region mediated by the RUNX1-RUNX1T1 fusion protein contributes to the leukemogenesis of t(8;21) AML and that UBXN8 targeting may be a potential therapeutic strategy for t(8;21) AML.Subject terms: Acute myeloid leukaemia, Tumour heterogeneity     

Enhancing the phase profile and contrast of an interferogram by polarization recording in bacteriorhodopsin

Interferometry is a technique for reconstructing the profiles of phase objects. We present a novel interferometric setup for generating interferograms with doubled phase profile and enhanced contrast compared with the standard interferogram. The proposed system consists of a two-beam interferometer in which the reference and test waves are circularly polarized orthogonally to each other. They are superposed upon a bacteriorhodopsin film, creating a polarization grating that is distorted by the phase of the test object. This polarization pattern is read by a polarized He-Ne beam. We show analytically and experimentally that, when the zero diffraction order is removed, an interferogram with doubled phase profile and enhanced contrast is obtained.     

Alternating current tast-polarographic determination of surface activity of lung surfactant

It is demonstrated that lung surfactant, like DL-α-lecithin, acts as a typical surface active substance in phase-selected alternating current tast-polarography. It lowers both the electrical double-layer capacity and the surface tension on the mercury electrode/saline interface and gives rise to characteristic adsorption-desorption capacity peaks. Capacity decrease, peak height, and diminution of the supporting electrolyte hump are controlled by the quantity, i.e. surface activity, of lung surfactant. A linear relationship between the logarithm of capacity values and surface activity measured with the de Noüy ring method is derived. Based on these facts it is possible to express surface activity of lung surfactant in capacity terms and to use the phase-selected alternating current tast-polarography in surface activity studies of lung surfactant.     

Sulfides: chemical ionization induced fragmentation studied with Proton Transfer Reaction‐Mass Spectrometry and density functional calculations

We report the energy‐dependent fragmentation patterns upon protonation of eight sulfides (organosulfur compounds) in Proton Transfer Reaction‐Mass Spectrometry (PTR‐MS). Studies were carried out, both, experimentally with PTR‐MS, and with theoretical quantum‐chemical methods. Charge retention usually occurred at the sulfur‐containing fragment for short chain sulfides. An exception to this is found in the unsaturated monosulfide allylmethyl sulfide (AMS), which preferentially fragmented to a carbo‐cation at m/z 41, C₃H₅⁺. Quantum chemical calculations (DFT with the M062X functional 6‐31G(d,p) basis sets) for the fragmentation reaction pathways of AMS indicated that the most stable protonated AMS cation at m/z 89 is a protonated (cyclic) thiirane, and that the fragmentation reaction pathways of AMS in the drift tube are kinetically controlled. The protonated parent ion MH⁺ is the predominant product in PTR‐MS, except for diethyl disulfide at high collisional energies. The saturated monosulfides R‐S‐R’ (with R<R’) have little or no fragmentation, at the same time the most abundant fragment ion is the smaller R‐S⁺ fragment. The saturated disulfides R‐S‐S‐R display more fragmentation than the saturated monosulfides, the most common fragments are disulfide containing fragments or long‐chain carbo‐cations. The results rationalize fragmentation data for saturated monosulfides and disulfides and represent a detailed analysis of the fragmentation of an unsaturated sulfide. Apart from the theoretical interest, the results are in support of the quantitative analysis of sulfides with PTR‐MS, all the more so as PTR‐MS is one of a few techniques that allow for ultra‐low quantitative analysis of sulfides. Copyright © 2013 John Wiley & Sons, Ltd.