66 research outputs found

    Mastering disorder in a first-order transition by ion irradiation

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    The effect of ion bombardment on MnAs single crystalline thin films is studied. The role of elastic collisions between ions and atoms of the material is singled-out as the main process responsible for modifying the properties of the material. Thermal hysteresis suppression, and the loss of sharpness of the magneto-structural phase transition are studied as a function of different irradiation conditions. While the latter is shown to be associated with the ion induced disorder at the scale of the transition correlation length, the former is related to the coupling between disorder and the large-scale elastic field associated with the phase coexistence pattern

    PEDF and GDNF are key regulators of photoreceptor development and retinal neurogenesis in reaggregates from chick embryonic retina

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    Here, role(s) of pigment epithelial-derived factor (PEDF) and glial-derived neurotrophic factor (GDNF) on photoreceptor development in three-dimensional reaggregates from the retinae of the E6 chick embryo (rosetted spheroids) was investigated. Fully dispersed cells were reaggregated under serum-reduced conditions and supplemented with 50 ng/ml PEDF alone or in combination with 50 ng/ml GDNF. The spheroids were analyzed for cell growth, differentiation, and death using proliferating cell nuclear antigen, terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling, and other immunocytochemical stainings and semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) methods. PEDF strongly promoted synthesis of the messenger RNAs for blue and violet cone opsins and to a lesser extent on the red and green cone opsins. This correlated with an increase in the number of cone photoreceptors, as determined by the cone cell marker CERN906. Likewise, PEDF nearly completely inhibited rod differentiation, as detected by immunostaining with anti-rho4D2 and RT-PCR. Furthermore, PEDF accelerated proliferation of cells in the spheroids and inhibited apoptosis. As negative effects, PEDF inhibited the normal histotypic tissue formation of retinal aggregates and reduced the frequency of photoreceptor rosettes and IPL-like areas. Noticeably, supplementation of PEDF-treated cultures with GDNF reversed the effects of PEDF on spheroid morphology and on rod differentiation. This study establishes that PEDF strongly affects three-dimensional retinogenesis in vitro, most notably by inhibiting rod development and supporting proliferation and differentiation of cones, effects which are partially counteracted by GDNF

    Quantifying the Proteolytic Release of Extracellular Matrix-Sequestered VEGF with a Computational Model

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    BACKGROUND: VEGF proteolysis by plasmin or matrix metalloproteinases (MMPs) is believed to play an important role in regulating vascular patterning in vivo by releasing VEGF from the extracellular matrix (ECM). However, a quantitative understanding of the kinetics of VEGF cleavage and the efficiency of cell-mediated VEGF release is currently lacking. To address these uncertainties, we develop a molecular-detailed quantitative model of VEGF proteolysis, used here in the context of an endothelial sprout. METHODOLOGY AND FINDINGS: To study a cell's ability to cleave VEGF, the model captures MMP secretion, VEGF-ECM binding, VEGF proteolysis from VEGF165 to VEGF114 (the expected MMP cleavage product of VEGF165) and VEGF receptor-mediated recapture. Using experimental data, we estimated the effective bimolecular rate constant of VEGF165 cleavage by plasmin to be 328 M(-1) s(-1) at 25 degrees C, which is relatively slow compared to typical MMP-ECM proteolysis reactions. While previous studies have implicated cellular proteolysis in growth factor processing, we show that single cells do not individually have the capacity to cleave VEGF to any appreciable extent (less than 0.1% conversion). In addition, we find that a tip cell's receptor system will not efficiently recapture the cleaved VEGF due to an inability of cleaved VEGF to associate with Neuropilin-1. CONCLUSIONS: Overall, VEGF165 cleavage in vivo is likely to be mediated by the combined effect of numerous cells, instead of behaving in a single-cell-directed, autocrine manner. We show that heparan sulfate proteoglycans (HSPGs) potentiate VEGF cleavage by increasing the VEGF clearance time in tissues. In addition, we find that the VEGF-HSPG complex is more sensitive to proteases than is soluble VEGF, which may imply its potential relevance in receptor signaling. Finally, according to our calculations, experimentally measured soluble protease levels are approximately two orders of magnitude lower than that needed to reconcile levels of VEGF cleavage seen in pathological situations

    Low Temperature Synthesis of Nanocrystallized Titanium Oxides with Layered or Tridimensional Frameworks, from [Ti8O12(H2O)24]Cl8·HCl·7H2O Hydrolysis

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    International audienceA low-temperature aqueous chemical growth process was developed to produce nanometric titanium oxide with controlled size and structural variety. Gentle hydrolysis of a commercial TiOCl2 solution, in a controlled relative humidity, leads to the formation of single crystals of [Ti8O12(H2O)24]Cl8·HCl·7H2O. Under autogenous pressure at 120 °C, the hydrolysis of the latter by tetramethylammonium hydroxide (noted TMAOH) is mainly governed by the R = Ti/TMAOH molar ratio and thus by the pH value. Two values are particularly important: R = 8/9 and 8/17. The former corresponds to the balance of the Cl− ions of the titanium oxychloride hydrate by TMA+ cations and the latter to the stoichiometric ratio for the formation of a layered oxo-hydroxide (TMA)2Ti2O4−x(CO3)x(OH)2·nH2O, x = 0.7, which is obtained under basic conditions. Above R = 8/9, that is, in an acidic medium, the solvothermal treatment at 120 °C directly leads to the crystallization of anatase and then rutile when the pH decreases. For intermediate R values, the amorphous dried solid is required to be rinsed and dried at 110 °C to lead to the crystallization of nanometric titania, either anatase or brookite. TEM studies show that titania nanoparticles exhibit superstructures involving a doubling of the cell parameters that could originate from the adsorption of carbonate, hydrogen carbonate, or hydroxyl groups on the nanocrystallite surface. During evaporation of the solvent, these crystallites can self-assemble to form micrometric platelets
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