Acetylation-dependent regulation of endothelial Notch signalling by the SIRT1 deacetylase

Notch signalling is a key intercellular communication mechanism that is essential for cell specification and tissue patterning, and which coordinates critical steps of blood vessel growth. Although subtle alterations in Notch activity suffice to elicit profound differences in endothelial behaviour and blood vessel formation, little is known about the regulation and adaptation of endothelial Notch responses. Here we report that the NAD(+)-dependent deacetylase SIRT1 acts as an intrinsic negative modulator of Notch signalling in endothelial cells. We show that acetylation of the Notch1 intracellular domain (NICD) on conserved lysines controls the amplitude and duration of Notch responses by altering NICD protein turnover. SIRT1 associates with NICD and functions as a NICD deacetylase, which opposes the acetylation-induced NICD stabilization. Consequently, endothelial cells lacking SIRT1 activity are sensitized to Notch signalling, resulting in impaired growth, sprout elongation and enhanced Notch target gene expression in response to DLL4 stimulation, thereby promoting a non-sprouting, stalk-cell-like phenotype. In vivo, inactivation of Sirt1 in zebrafish and mice causes reduced vascular branching and density as a consequence of enhanced Notch signalling. Our findings identify reversible acetylation of the NICD as a molecular mechanism to adapt the dynamics of Notch signalling, and indicate that SIRT1 acts as rheostat to fine-tune endothelial Notch responses.     

Atomic structure of Cu{0 0 1}c(2 × 2)-Cl

A LEED intensity analysis of Cu{0 0 1}c(2 × 2)-Cl has given an excellent fit of theory to experiment with Cl in the fourfold symmetrical hollows in a simple overlayer structure with a Cu-Cl bond length of 2.38 Å. This structure is consistent with an analysis of angle-resolved photoemission measurements made in the same experiments and published elsewhere. These results help confirm the LEED analysis of the analogous system Ag{0 0 1}c(2 × 2)-Cl which gave the same structure, but had been rejected by an independent photoemission analysis.     

Study of the neutron quantum states in the gravity field

We have studied neutron quantum states in the potential well formed by the earths gravitational field and a horizontal mirror. The estimated characteristic sizes of the neutron wave functions in the two lowest quantum states correspond to expectations with an experimental accuracy. A position-sensitive neutron detector with an extra-high spatial resolution of m was developed and tested for this particular experiment, to be used to measure the spatial density distribution in a standing neutron wave above a mirror for a set of some of the lowest quantum states. The present experiment can be used to set an upper limit for an additional short-range fundamental force. We studied methodological uncertainties as well as the feasibility of improving further the accuracy of this experiment.Received: 31 July 2004, Published online: 7 March 2005PACS: 03.65, 28.20 Correspondence to: V. Nesvizhevsky     

Potential allergenicity of novel proteins in murine models

Bioengineered crops represent an important advancement for farmers who want to avoid losses caused by insect infestations or adverse environmental conditions. However, the use of modern biotechnology has raised questions regarding the safety of bioengineered foods because of the potential allergenicity of proteins expressed by the newly introduced genes. Standard approaches for safety assessment of these foods are still evolving. Animal models have been suggested as a tool that could help evaluate the potential allergenicity of such compounds. Several investigators are developing animal models to evaluate novel proteins, but none of these have yet been validated. This article reviews the published murine models, rat and mouse in particular, and the different methods used to evaluate parameters related to allergy. It also addresses the factors involved in the development of a model. Finally, it raises some questions that should be considered by the international community so that financial and intellectual efforts can be addressed in a unified manner.     

Buried interfaces studied by photoelectron diffraction

Angle- and energy-scanned photoelectron diffraction data can be used to investigate structures below surfaces. The modulations in photoelectron intensity result from diffraction of the emitted electron wave at neighbor atoms. In the past, scanned-energy photoelectron diffraction had been mainly used to determine the adsorption site of molecules at surfaces. Recent data show, however, that the technique can also be employed to obtain information about the upper substrate layer(s). At low kinetic energies, backward scattering is strong and in scanned-angle photoelectron diffraction the recorded patterns result from backward- and multiple-scattering effects. For a structural analysis, the intensity modulations have to be compared with the results for simulations performed for model clusters. As an example, recent angle-scanned photoelectron diffraction patterns recorded for the technologically important silicon oxide/silicon interface were compared with simulations. At the Si(001) surface orientation, the interface is extended over a few layers, whereas at the Si(111) surface orientation the transition is rather abrupt and occurs within one or two layers. Received: 9 September 2002 / Accepted: 2 October 2002 / Published online: 5 February 2003 RID="*" ID="*"Corresponding author. Fax: +49-231/755-3657, E-mail: carsten.westphal@physik.uni-dortmund.de     

Local atomic environment of Si suboxides at the SiO2/Si(111) interface determined by angle-scanned photoelectron diffraction

Local environments of Si suboxides at the interface between a thermally grown SiO2 film and Si(111) were studied by angle-scanned photoelectron diffraction. Si 2p core-level spectra containing chemically shifted components were recorded. The components were deconvoluted by least squares fitting and assigned to different Si oxidation states. The obtained diffraction patterns of the various suboxides exhibit different features. Comparison of these patterns with multiple scattering calculations including a multipole R-factor analysis shows that a simple chemical abrupt interface model describes well the environment of the suboxides and indicates ordered SiO2 close to the interface.     

Experimental results on neutrino-electron scattering

A determination of sin² θ _w based on measurements of elastic scattering of muon-neutrinos and muon-anti-neutrinos on atomic electrons is described. These purely leptonic processes were studied using the CHARM calorimeter exposed to neutrino and antineutrino wide-band beams at the CERN super proton synchrotron. A total of 83±16 neutrino-electron and 112±21 antineutrino-electron events have been detected. From the measurement of the ratio of muon-neutrino and muon-antineutrino cross-sections a value of sin² θ _w =0.211±0.037 was obtained.     

Near-field turbulence properties of single- and two-stream plane mixing layers

Detailed mean flow and turbulence measurements have been made in the near-field of two plane mixing layers in air with a maximum velocity of 21 m/s. The experimental rig enabled mixing layers of velocity ratios 0 and 0.46 to be generated simultaneously. Cases with both tripped and untripped initial boundary layers were studied. In all cases, it was found that the two-stream layer developed to the self-preserving state in a distance much shorter than the single-stream layer, which followed accepted criteria for the development distance. The asymptotic levels of the turbulence quantities in the two-stream layer and the development of the single-stream layer showed agreement with existing data. The results suggest that the two-stream mixing layer should provide a better test case for the development of turbulence models and calculation methods than the single-stream mixing layer.     

Polycatenar liquid crystals based on bent-shaped chalcone and cyanopyridine molecules

In this study, the synthesis, structural characterisation and mesomorphic and optical properties of seven new bent-shaped and polycatenar bent-shaped compounds derived from chalcone and cyanopyridine are reported. The mesomorphic behaviour was investigated by differential scanning calorimetry (DSC), polarised optical microscopy (POM) and X-ray diffraction (XRD) and correlated with the molecular structure. Two bent-core hexacatenars molecules (Ic and IIc) presented liquid crystalline properties, showing a hexagonal columnar (Col_h) phases at room temperature, being each disc constituted by two mesogens. Optical studies were also performed for the final molecules, being conducted by ultraviolet-visible and fluorescence spectrometry. The cyanopyridine derivatives show moderate luminescence quantum yields, ranging between 18% and 27%, with emission maxima around 371 nm. It is also shown that while the chalcone central unit favours a calamitic liquid crystalline behaviour in molecules with lower number of aliphatic chains, a polycatenar structure with cyanopyridine as the central unit favours a Col_h arrangement, also providing luminescence properties to the molecule.