Hif1a inactivation rescues photoreceptor degeneration induced by a chronic hypoxia-like stress

Reduced choroidal blood flow and tissue changes in the ageing human eye impair oxygen delivery to photoreceptors and the retinal pigment epithelium. As a consequence, mild but chronic hypoxia may develop and disturb cell metabolism, function and ultimately survival, potentially contributing to retinal pathologies such as age-related macular degeneration (AMD). Here, we show that several hypoxia-inducible genes were expressed at higher levels in the aged human retina suggesting increased activity of hypoxia-inducible transcription factors (HIFs) during the physiological ageing process. To model chronically elevated HIF activity and investigate ensuing consequences for photoreceptors, we generated mice lacking von Hippel Lindau (VHL) protein in rods. This activated HIF transcription factors and led to a slowly progressing retinal degeneration in the ageing mouse retina. Importantly, this process depended mainly on HIF1 with only a minor contribution of HIF2. A gene therapy approach using AAV-mediated RNA interference through an anti-Hif1a shRNA significantly mitigated the degeneration suggesting a potential intervention strategy that may be applicable to human patients

Polymorphism in protein-stabilized lipid nanoparticles as food bioactive carriers: A synchrotron SAXS/WAXS/DSC study

International audienc

Nanostructures and polymorphisms in protein stabilised lipid nanoparticles, as food bioactive carriers: contribution of particle size and adsorbed materials.

International audienc

Caractérisation structurale et contraintes résiduelles de films d'AIN par diffraction des rayons X

L'état mécanique des couches minces influence considérablement leurs propriétés macroscopiques et notamment leur comportement tribologique. Ainsi, outre les caractéristiques structurales, la détermination des microdéformations et des contraintes résiduelles apparaît comme essentielle. Cette étude porte donc sur la caractérisation par diffraction des rayons X de l'état microstructural et mécanique de couches de nitrure d'aluminium élaborées par deux types de procédé : la nitruration d'aluminium par plasma induit par laser et le dépôt par pulvérisation cathodique. Les résultats montrent l'absence d'orientation préférentielle et de contraintes résiduelles dans les couches d'AIN laser-plasma, alors que les dépôts présentent une direction de croissance privilégiée et de fortes contraintes d'origine thermique.The mechanical state in thin films considerably influences their macroscopic properties, especially their tribological behaviour. It is the reason why microstrains and residual stresses determination is very important. This paper deals with the characterization by X-ray diffraction of the microstructural and mechanical state of aluminum nitride layers elaborated by two kinds of processing : laser induced plasma aluminum nitriding and magnetron sputtering deposition. Results show no preferential orientation and residual stresses in laser-plasma AIN films while deposits offer preferential growth direction and high stresses from thermal ones

Experimental observation of double-walled peptide nanotubes and monodispersity modeling of the number of walls

Self-assembled nanoarchitectures based on biological molecules are attractive because of the simplicity and versatility of the building blocks. However, size control is still a challenge. This control is only possible when a given system is deeply understood. Such is the case with the lanreotide acetate, an octapeptide salt that spontaneously forms monodisperse nanotubes when dissolved into pure water. Following a structural approach, we have in the past demonstrated the possibility to tune the diameter of these nanotubes while keeping a strict monodispersity, either by chemical modification of one precise amino acid on the peptide sequence or by changing the size of the counterions. On the basis of these previous studies, we replaced monovalent counterions by divalent ones to vary the number of walls. Indeed, in the present work, we show that lanreotide associated with a divalent counterion forms double-walled nanotubes while keeping the average diameter constant. However, the strict monodispersity of the number of walls was unexpected. We propose that the divalent counterions create an adhesion force that can drive the wall packing. This adhesion force is counterbalanced by a mechanical one that is related to the stiffness of the peptide wall. By taking into account these two opposite forces, we have built a general model that fully explains why the lanreotide nanotubes formed with divalent counterions possess two walls and not more

Synthesis and characterisation of small ZnS particles

Small ZnS particles, prepared at room temperature in an alcoholic medium using a zinc salt and thioacetamide as sulphur source, have been characterised using a suite of techniques which includes XRD, TEM and Zn K-edge EXAFS. The investigation suggests that aggregates of small sphalerite particles (cubic lattice), with average size of 3.5 nm and well-defined morphology are obtained and the particle size appears not to change with increase in the reaction time from 2 to 24 h. Zn K-edge EXAFS experiments were performed at 10 K, in order to reduce thermal disorder and the refinement of the EXAFS data resulted in very small second shell coordination numbers with respect to the bulk samples. The result is in good agreement with SEM and XRD data about the presence of nanosized particles, having a large number of surface atoms with low second shell coordination number

Shear-Induced Crystallization in blends of Model Linear and Long-Chain Branched Hydrogenated Polybutadienes

Quiescent and shear-induced crystallizations were performed on several well-defined linear monodisperse hydrogenated polybutadiene blends with a high-molecular-weight long-chain branched (LCB) combshaped additive. The connection between microscopic molecular motion and crystallization kinetics has been quantitatively studied with respect to the formation of either isotropic or oriented shish kebab crystal morphology using time-resolved X-ray scattering techniques. Using a constant preshear rate, the addition of small amounts of LCB combs to the sample blends, at concentrations below and just above the overlap concentration c*, has significantly increased the crystallization rates compared to quiescent conditions. However, only one blend showed the formation of an oriented shish kebab morphology. Also, for these model blends, the transition between isotropic and oriented crystals occurs quite sharply between 5 and 10%, which is around c*. We explain these data by using a shish formation mechanism in which, to form shish kebabs, the combs must be mutually overlapping and the comb Weissenberg number must be in the strong stretch regime