122 research outputs found
Mdm2 Induces Mono-Ubiquitination of FOXO4
Background: The Forkhead box O (FOXO) class of transcription factors are involved in the regulation of several cellular responses including cell cycle progression and apoptosis. Furthermore, in model organisms FOXOs act as tumor suppressors and affect aging. Previously, we noted that FOXOs and p53 are remarkably similar within their spectrum of regulatory proteins [1]. For example, the de-ubiquitinating enzyme USP7 removes ubiquitin from both FOXO and p53. However, Skp2 has been identified as E3 ligase for FOXO1, whereas Mdm2 is the prime E3 ligase for p53. Principal Findings/Methodology: Here we provide evidence that Mdm2 acts as an E3 ligase for FOXO as well. In vitro incubation of Mdm2 and FOXO results in ATP-dependent (multi)mono-ubiquitination of FOXO similar to p53. Furthermore, in vivo co-expression of Mdm2 and FOXO induces FOXO mono-ubiquitination and consistent with this result, siRNAmediated depletion of Mdm2 inhibits mono-ubiquitination of FOXO induced by hydrogen peroxide. Regulation of FOXO ubiquitination by Mdm2 is likely to be direct since Mdm2 and FOXO co-immunoprecipitate. In addition, Mdm2-mediated ubiquitination regulates FOXO transcriptional activity. Conclusions/Significance: These data identify Mdm2 as a novel E3 ligase for FOXOs and extend the analogous mode o
Adsorption and two-body recombination of atomic hydrogen on He-He mixture films
We present the first systematic measurement of the binding energy of
hydrogen atoms to the surface of saturated He-He mixture films.
is found to decrease almost linearly from 1.14(1) K down to 0.39(1) K, when the
population of the ground surface state of He grows from zero to
cm, yielding the value K cm
for the mean-field parameter of H-He interaction in 2D. The experiments
were carried out with overall He concentrations ranging from 0.1 ppm to 5 %
as well as with commercial and isotopically purified He at temperatures
70...400 mK. Measuring by ESR the rate constants and for
second-order recombination of hydrogen atoms in hyperfine states and we
find the ratio to be independent of the He content and to
grow with temperature.Comment: 4 pages, 4 figures, all zipped in a sigle file. Submitted to Phys.
Rev. Let
Wannier-function description of the electronic polarization and infrared absorption of high-pressure hydrogen
We have constructed maximally-localized Wannier functions for prototype
structures of solid molecular hydrogen under pressure, starting from LDA and
tight-binding Bloch wave functions. Each occupied Wannier function can be
associated with two paired protons, defining a ``Wannier molecule''. The sum of
the dipole moments of these ``molecules'' always gives the correct macroscopic
polarization, even under strong compression, when the overlap between nearby
Wannier functions becomes significant. We find that at megabar pressures the
contributions to the dipoles arising from the overlapping tails of the Wannier
functions is very large. The strong vibron infrared absorption experimentally
observed in phase III, above ~ 150 GPa, is analyzed in terms of the
vibron-induced fluctuations of the Wannier dipoles. We decompose these
fluctuations into ``static'' and ``dynamical'' contributions, and find that at
such high densities the latter term, which increases much more steeply with
pressure, is dominant.Comment: 17 pages, two-column style with 14 postscript figures embedded. Uses
REVTEX and epsf macro
HDAC inhibition increases HLA class I expression in uveal melanoma
The treatment of uveal melanoma (UM) metastases or adjuvant treatment may imply immunological approaches or chemotherapy. It is to date unknown how epigenetic modifiers affect the expression of immunologically relevant targets, such as the HLA Class I antigens, in UM. We investigated the expression of HDACs and the histone methyl transferase EZH2 in a set of 64 UMs, using an Illumina HT12V4 array, and determined whether a histone deacetylase (HDAC) inhibitor and EZH2 inhibitor modified the expression of HLA Class I on three UM cell lines. Several HDACs (HDAC1, HDAC3, HDAC4, and HDAC8) showed an increased expression in high-risk UM, and were correlated with an increased HLA expression. HDAC11 had the opposite expression pattern. While in vitro tests showed that Tazemetostat did not influence cell growth, Quisinostat decreased cell sur
Is biotechnology (more) acceptable when it enables a reduction in phytosanitary treatments? A European comparison of the acceptability of transgenesis and cisgenesis
Reduced pesticide use is one of the reasons given by Europeans for accepting new genetic engineering techniques. According to the advocates of these techniques, consumers are likely to embrace the application of cisgenesis to apple trees. In order to verify the acceptability of these techniques, we estimate a Bayesian multilevel structural equation model, which takes into account the multidimensional nature of acceptability and individual, national, and European effects, using data from the Eurobarometer 2010 73.1 on science. The results underline the persistence of clear differences between European countries and whilst showing considerable defiance, a relatively wider acceptability of vertical gene transfer as a means of reducing phytosanitary treatments, compared to horizontal transfer
Moral issues in mentoring sessions
This article describes the results of research that investigated whether student nurses identified the moral aspects of everyday nursing care situations and, if so, how they dealt with them. We intended to elucidate the role of mentoring situations in moral development. Student written documents reflecting discussions during mentoring situations were analysed quantitatively and qualitatively. The students studied in one of the three nursing schools involved in the research. In only a small proportion of cases
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