C. Chauvet

The gene encoding human retinoic acid-receptor-related orphan receptor α is a target for hypoxia-inducible factor 1

Retinoic acid-receptor-related orphan receptor (ROR) alpha is a nuclear receptor involved in many pathophysiological processes such as cerebellar ataxia, inflammation, atherosclerosis and angiogenesis. In the present study we first demonstrate that hypoxia increases the amount of Rora transcripts in a wide panel of cell lines derived from diverse tissues. In addition, we identified a functional promoter sequence upstream of the first exon of the human Rora gene, spanning -487 and -45 from the translation initiation site of RORalpha1. When cloned in a luciferase reporter vector, this sequence allowed the efficient transcription of the luciferase gene in several cell lines. Interestingly, the activity of the Rora promoter was enhanced by hypoxia in HepG2 human hepatoma cells, and this effect was dependent on an HRE (hypoxia response element) spanning from -229 to -225. Using electrophoretic-mobility-shift assays, we showed that HIF-1 (hypoxia-inducible factor 1), which plays a key role in the transcriptional response to hypoxia, bound to this HRE. Overexpression of HIF-1alpha increased the activity of the Rora promoter through the HRE. Overexpression of a dominant-negative form of HIF-1alpha producing transcriptionally inactive HIF-1alpha/HIF-1beta dimers abolished hypoxic activation of the Rora promoter. This indicated that HIF-1 is involved in the response of RORalpha to hypoxia. Taken together, our data reveal Rora as a new HIF-1 target gene. This illustrates, at the molecular level, the existence of cross-talk between signalling pathways mediated by HIF-1 and those mediated by nuclear receptors.

Retinoic acid receptor-related orphan receptor (ROR) α4 is the predominant isoform of the nuclear receptor RORα in the liver and is up-regulated by hypoxia in HepG2 human hepatoma cells

The retinoic acid receptor-related orphan receptor alpha (RORalpha) is critically involved in many physiological functions in several organs. We find that the main RORalpha isoform in the mouse liver is the RORalpha4 isoform, in terms of both mRNA and protein levels, while the RORalpha1 isoform is less abundant. Because hypoxia is a major feature of liver physiology and pathology, we examined the effect of this stress on Rora gene expression and RORalpha transcriptional activity. HepG2 human hepatoma cells were cultured for 24 h under normoxia (20% O2) or hypoxia (10, 2, and 0.1% O2) and the abundance of the Rora transcripts measured by Northern blot and semi-quantitative RT-PCR. Hypoxic HepG2 cells contained more Rora mRNA than controls. This was also observed in rat hepatocytes in primary culture. Cobalt chloride and desferrioxamine also increased the amount of Rora mRNA in HepG2 cells. It is likely that these treatments increase the amount of the RORalpha4 protein in HepG2 cells as evidenced by Western blotting in the case of desferrioxamine. Transient transfection experiments indicated that hypoxia, cobalt chloride, and desferrioxamine all stimulate RORalpha transcriptional activity in HepG2 cells. Hence, we believe that RORalpha participates in the control of gene transcription in hepatic cells and modulates gene expression in response to hypoxic stress.

HETEROEPITAXIAL GROWTH OF BESE ON VICINAL SI(001) SURFACES

The growth of BeSe on vicinal Si(001) substrates has been investigated by molecular beam epitaxy. Reflection high energy electron diffraction was used to study the initial growth mode and the surface structure. Efforts have been done at the early steps of the growth in order to optimize the interface quality. Transmission electron microscopy revealed a BeSe layer relaxed with misfit dislocations and stacking faults that are mainly confined near the heterointerface. These results are promising in view of the growth of Zn0.55Be0.45Se alloy that is lattice matched to silicon. There will be many potential applications of this alloy—in the case of a direct band gap—in the frame of Si-based optoelectronic devices.

Raman study of ZnxBe1−xSe alloy (100) epitaxial layers

Long wavelength longitudinal optical (LO) and transverse optical (TO) phonons of BeSe and ZnxBe1−xSe layers are identified in a wide composition range by using Raman spectroscopy. A two-mode behavior is clearly evidenced. As predicted by the dielectric model of Hon and Faust, the eigenfrequencies of the BeSe- and ZnSe-like LO modes correspond to the maxima of Im〈−e(ω, x)−1〉. Excellent agreement is obtained with a model where the calculations are performed by using the equations of motion and polarization derived from the modified random element isodisplacement model. Besides, the TO and LO frequencies for BeSe are determined to be 501 and 579 cm−1, respectively.

Raman study of Zn1−xBexSe/GaAs systems with low Be content (x⩽0.20)

We present an experimental and theoretical investigation of the Raman line shape of long-wavelength phonons with longitudinal optical (LO) symmetry from both sides of Zn1−xBexSe/GaAs (001) heterojunctions with special emphasis on samples with low Be content (x⩽0.20). First the built-in p-type LO phonon–plasmon (LO–P) coupled mode at the near-interfacial substrate is used as a sensitive probe to investigate the interfacial quality. The corresponding hole gas is reinforced when the ZnBeSe layers are nominally p doped by nitrogen. This provides clear evidence for effective hole transfer across the junction, and thereby indicates a minimized density of interfacial defects. In the nitrogen-doped layers hole densities as high as 1017 cm−3, in accordance with capacitance–voltage measurements, are directly inferred from clear weakening of the ZnSe-like LO mode due to LO–P coupling. Concerning the intrinsic properties of the alloys, we demonstrate that the asymmetric broadening of the ZnSe-like LO mode is determin...

Vibrational Evidence for Percolative Behavior in ZnBeSe

We propose a picture based on simple percolative concepts for the basic understanding of vibrational properties in the new attractive class of ternary semiconductor alloys made of materials with highly contrasted bond stiffness. In Zn 1-x Be x Se this accounts for the activation of a strong extra BeSe-like optical mode for x between the percolation thresholds of the Be-Se and Zn-Se bonds. Latter mode is attributed to Be-Se bonds within the quasi-continuous Be-rich hard-like cluster which forms above the percolation threshold.

Raman study of ZnxBe1−xSe solid solutions

Raman spectroscopy is used to identify the LO phonons of Zn x Be 1 . x Se/GaAs systems in a wide composition range. On the layer side a two-mode behavior is evidenced. The eigenfrequencies of the BeSe- and ZnSe-like LO modes correspond to the maxima of Im[-e(ω,x) -1 ]. Excellent agreement is obtained with a model based upon the modified random element isodisplacement (MREI) model. On the substrate side the LO mode couples with a plasmon (P) at the near-interface. The resulting LO-P mode is very sensitive to limit conditions at the junction. Below x ∼ 45% strong coupling is observed; above x ∼ 45% coupling is relaxed. The first behavior appears to be a marker for clean interfaces while the second one goes with the deposition of a thin highly disordered layer before the nominal Zn x Be 1-x Se is grown up to the surface.

LO phonon-plasmon coupling in N-doped Zn1-xBex Se/GaAs (x ≤ 0.15)

The study of p-type doping in low-Be content Zn 1-x Be x Se layers deposited on GaAs is transferred from the layer to the substrate side where a built-in dense hole gas is evidenced. The idea is to use the extreme sensibility of the associated LO-P mode to give evidence for large hole transfer from Zn 1-x Be x Se to GaAs in case of even moderate p-doping of Zn 1-x Be x Se. As a matter of fact the built-in hole accumulation in GaAs appears to be systematically reinforced. Moreover, in some N-doped layers hole densities as high as 10 17 cm in accordance with C-V results could be directly inferred from a clear weakening of the ZnSe-like longitudinal optical (LO) mode. Quantitative treatment of the LO phonon-plasmon lineshapes in ternary Zn 1-x Be x Se alloy is developed within the dielectric approach of Hon and Faust, by using equations of motion and polarization derived from the MREI model.

Raman study of Zn1−xBexSe/GaAs systems with low Be-content (x≤0.31)

Abstract By Raman spectroscopy we investigate the substitutional disorder in (001) Zn 1− x Be x Se/GaAs epitaxial layers with low Be-content ( x ≤0.31). We demonstrate that the asymmetric broadening of the ZnSe-like longitudinal optical mode (LO Zn–Se ) is determined by topological disorder and not by other possible mechanism such as structural disorder, non-homogeneity in the alloy composition, distribution of tensile strain or Fano-type interference. This reveals that Zn 1− x Be x Se can be grown of high structural quality. For allowed phonons topological disorder results basically in the breaking of the translational symmetry, which leads to the contribution of q ≠0 phonons to Raman scattering. Quantitative information upon latter finite-size effects is obtained via a spatial correlation model with Gaussian distribution to describe the relation between disorder and the lineshape of the allowed LO Zn–Se phonon.