De status van het menselijk embryo

VakpublicatieFaculteit der Wijsbegeert

Adsorption and two-body recombination of atomic hydrogen on 3^3He-4^4He mixture films

We present the first systematic measurement of the binding energy $E_a$ of hydrogen atoms to the surface of saturated $^3$He-$^4$He mixture films. $E_a$ 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 $^3$He grows from zero to $6\times10^{14}$ cm$^{-2}$, yielding the value $1.2(1)\times 10^{-15}$ K cm$^2$ for the mean-field parameter of H-$^3$He interaction in 2D. The experiments were carried out with overall $^3$He concentrations ranging from 0.1 ppm to 5 % as well as with commercial and isotopically purified $^4$He at temperatures 70...400 mK. Measuring by ESR the rate constants $K_{aa}$ and $K_{ab}$ for second-order recombination of hydrogen atoms in hyperfine states $a$ and $b$ we find the ratio $K_{ab}/K_{aa}$ to be independent of the $^3$He content and to grow with temperature.Comment: 4 pages, 4 figures, all zipped in a sigle file. Submitted to Phys. Rev. Let

HDMX-L is expressed from a functional P53-responsive promoter in the first intron of the HDMX gene, and participates in an auto-regulatory feedback loop to control P53 activity.

The p53 regulatory network is critically involved in preventing the initiation of cancer. In unstressed cells p53 is maintained at low levels and is largely inactive, mainly through the action of its two essential negative regulators, HDM2 and HDMX. p53 abundance and activity are upregulated in response to various stresses including DNA damage and oncogene activation. Active p53 initiates transcriptional and transcription-independent programs that result in cell cycle arrest, cellular senescence or apoptosis. p53 also activates transcription of HDM2, which initially leads to the degradation of HDMX, creating a positive feedback loop to obtain maximal activation of p53. Subsequently, when stress-induced post-translational modifications start to decline, HDM2 becomes effective in targeting p53 for degradation, thus attenuating the p53 response. To date, no clear function for HDMX in this critical attenuation phase has been demonstrated experimentally. Like HDM2, the HDMX gene contains a promoter (P2) in its first intron that is potentially inducible by p53. We show that p53 activation in response to a plethora of p53-activating agents induces the transcription of a novel HDMX mRNA transcript from the HDMX-P2 promoter. This mRNA is more efficiently translated than that expressed from the constitutive HDMX-P1 promoter, and it encodes a long form of HDMX protein, HDMX-L. Importantly, we demonstrate that HDMX-L cooperates with HDM2 to promote the ubiquitination of p53, and that p53-induced HDMX transcription from the P2 promoter can play a key role in the attenuation phase of the p53-response, to effectively diminish p53 abundance as cells recover from stress

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