The novel MKL target gene myoferlin modulates expansion and senescence of hepatocellular carcinoma.

Megakaryoblastic Leukemia 1 and 2 (MKL1/2) are transcriptional coactivators of Serum Response Factor (SRF) with an essential role for hepatocellular carcinoma (HCC) growth and oncogene-induced senescence. In this report, we identified myoferlin as a novel MKL/SRF target gene by gene expression profiling and verification in vivo in HCC xenografts. Myoferlin was overexpressed in human and murine HCCs triggered by conditional expression of constitutively active SRF-VP16 protein in hepatocytes. Furthermore, myoferlin was required for HCC cell invasion, proliferation and anchorage-independent cell growth. We provide evidence that myoferlin is a crucial gene target of MKL1/2 mediating its effect on oncogene-induced senescence by modulating the activation state of the EGFR and downstream MAPK and p16-/Rb pathways. Depletion of myoferlin in tumour cells from SRF-VP16-derived murine HCCs induced a senescence phenotype. These findings identify MKL1/2 and myoferlin as novel therapeutic targets to treat human HCC by a senescence-inducing strategy.

X-ray absorption from large molecules at metal surfaces: theoretical and experimental results for Co-OEP on Ni(100).

Metal octaethylporphyrins (M-OEP), M-N(4)C(20)H(4)(C(2)H(5))(8), adsorbed at a metallic substrate are promising candidates to provide spin dependent electric transport. Despite these systems having been studied extensively by experiment, details of the adsorbate geometry and surface binding are still unclear. We have carried out density functional theory calculations for cobalt octaethyl porphyrin (Co-OEP) adsorbate at clean and oxygen-covered Ni(100) surfaces as well as for the free Co-OEP molecule where equilibrium structures were obtained by corresponding energy optimizations. These geometries were then used in calculations of Co-OEP carbon and nitrogen 1s core excitations yielding theoretical excitation spectra to be compared with corresponding K-edge x-ray absorption fine structure (NEXAFS) measurements. The experimental NEXAFS spectra near the carbon K-edge of Co-OEP bulk material show large intensity close to the ionization threshold and a triple-peak structure at lower energies, which can be reproduced by the calculations on free Co-OEP. The experimental nitrogen K-edge spectra of adsorbed Co-OEP layers exhibit always a double-peak structure below ionization threshold, independent of the layer thickness. The peaks are shifted slightly and their separation varies with adsorbate-substrate distance. This can be explained by hybridization of N 2p with corresponding 3d contributions of the Ni substrate in the excited final state orbitals as a result of adsorbate-substrate binding via N-Ni bond formation.

Switching the electronic properties of Co-octaethylporphyrin molecules on oxygen-covered Ni films by NO adsorption.

Using x-ray absorption spectroscopy, we demonstrate that the electronic properties of Co-octaethylporphyrin (CoOEP) molecules on oxygen-covered ultrathin Ni films can be reversibly manipulated by a chemical stimulus. This is achieved by adsorption of nitrogen monoxide (NO), leading to the formation of a NO-CoOEP nitrosyl complex, and subsequent thermal desorption of the NO from the Co ions. The integration of the absorption spectra of the Co L(2,3) edges reveals a partial oxidation of the Co ions after dosing with NO compared to the pristine sample, for which a valency of 2+ and a low-spin state of the Co ions can be deduced from the Co L(2,3) XAS line shape. By means of x-ray magnetic circular dichroism the magnetic moments of the Co ions were found to be coupled parallel to the magnetization of the Ni films across the intermediate layer of atomic oxygen, before and after NO uptake.

Ferromagnetic coupling of mononuclear Fe centers in a self-assembled metal-organic network on Au(111).

The magnetic state and magnetic coupling of individual atoms in nanoscale structures relies on a delicate balance between different interactions with the atomic-scale surroundings. Using scanning tunneling microscopy, we resolve the self-assembled formation of highly ordered bilayer structures of Fe atoms and organic linker molecules (T4PT) when deposited on a Au(111) surface. The Fe atoms are encaged in a three-dimensional coordination motif by three T4PT molecules in the surface plane and an additional T4PT unit on top. Within this crystal field, the Fe atoms retain a magnetic ground state with easy-axis anisotropy, as evidenced by x-ray absorption spectroscopy and x-ray magnetic circular dichroism. The magnetization curves reveal the existence of ferromagnetic coupling between the Fe centers.

Potential energy landscape for hot electrons in periodically nanostructured graphene.

We explore the spatial variations of the unoccupied electronic states of graphene epitaxially grown on Ru(0001) and observed three unexpected features: the first graphene image state is split in energy; unlike all other image states, the split state does not follow the local work function modulation, and a new interfacial state at +3 eV appears on some areas of the surface. First-principles calculations explain the observations and permit us to conclude that the system behaves as a self-organized periodic array of quantum dots.