Resveratrol Targeting of Carcinogen-Induced Brain Endothelial Cell Inflammation Biomarkers MMP-9 and COX-2 is Sirt1-Independent

The occurrence of a functional relationship between the release of metalloproteinases (MMPs) and the expression of cyclooxygenase (COX)-2, two inducible pro-inflammatory biomarkers with important pro-angiogenic effects, has recently been inferred. While brain endothelial cells play an essential role as structural and functional components of the blood-brain barrier (BBB), increased BBB breakdown is thought to be linked to neuroinflammation. Chemopreventive mechanisms targeting both MMPs and COX-2 however remain poorly investigated. In this study, we evaluated the pharmacological targeting of Sirt1 by the diet-derived and antiinflammatory polyphenol resveratrol. Total RNA, cell lysates, and conditioned culture media from human brain microvascular endothelial cells (HBMEC) were analyzed using qRT-PCR, immunoblotting, and zymography respectively. Tissue scan microarray analysis of grade I–IV brain tumours cDNA revealed increased gene expression of Sirt-1 from grade I–III but surprisingly not in grade IV brain tumours. HBMEC were treated with a combination of resveratrol and phorbol 12-myristate 13-acetate (PMA), a carcinogen known to increase MMP-9 and COX-2 through NF-κB. We found that resveratrol efficiently reversed the PMA-induced MMP-9 secretion and COX-2 expression. Gene silencing of Sirt1, a critical modulator of angiogenesis and putative target of resveratrol, did not lead to significant reversal of MMP-9 and COX-2 inhibition. Decreased resveratrol inhibitory potential of carcinogen-induced IκB phosphorylation in siSirt1-transfected HBMEC was however observed. Our results suggest that resveratrol may prevent BBB disruption during neuroinflammation by inhibiting MMP-9 and COX-2 and act as a pharmacological NF-κB signal transduction inhibitor independent of Sirt1

Direct Measurements of Colloidal Solvophoresis under Imposed Solvent and Solute Gradients

We describe a microfluidic system that enables direct visualization and measurement of diffusiophoretic migration of colloids in response to imposed solution gradients. Such measurements have proven difficult or impossible in macroscopic systems due to difficulties in establishing solution gradients that are sufficiently strong yet hydrodynamically stable. We validate the system with measurements of the concentration-dependent diffusiophoretic mobility of polystyrene colloids in NaCl gradients, confirming that diffusiophoretic migration velocities are proportional to gradients in the logarithm of electrolyte concentration. We then perform the first direct measurement of the concentration-dependent "solvophoretic" mobility of colloids in ethanol-water gradients, whose dependence on concentration and gradient strength was not known either theoretically or experimentally, but which our measurements reveal to be proportional to the gradient in the logarithm of ethanol mole fraction. Finally, we examine solvophoretic migration under a variety of qualitatively distinct chemical gradients, including solvents that are miscible or have finite solubility with water, an electrolyte for which diffusiophoresis proceeds down concentration gradients (unlike for most electrolytes), and a nonelectrolyte (sugar). Our technique enables the direct characterization of diffusiophoretic mobilities of various colloids under various solvent and solute gradients, analogous to the electrophoretic ζ-potential measurements that are routinely used to characterize suspensions. We anticipate that such measurements will provide the feedback required to test and develop theories for solvophoretic and diffusiophoretic migration and ultimately to the conceptual design and engineering of particles that respond in a desired way to their chemical environments

Osmotic manipulation of particles for microfluidic applications

International audienceDiffusiophoresis, i.e. the movement of macromolecules along a molecular gradient, is shown to be an efficient means to drive particles in microchannels. By using a generic microfluidic setup, we assess the displacement of silica particles under a controlled salt gradient and provide experimental evidence for a strongly enhanced migration process, the amplitude of which depends on the nature of the salt. A theoretical description shows quantitative agreement with the observed experimental features. Furthermore, we describe a set of microfluidic operations such as separation, sorting or focusing of a colloidal assembly which can be efficiently performed using diffusiophoresis

Boosting migration of large particles by solute contrasts

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Microarray-Based Method for Combinatorial Library Sequence Mapping and Characterization

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Luminescence Dynamics of Single Self-Assembled Chains of Förster (FRET)-Coupled CdSe Nanoplatelets

International audienceSelf-assembled linear chains of CdSe nanoplatelets are known to exhibit highly efficient Förster resonant energy transfer (FRET) leading to fast exciton diffusion between platelets. Here, we compare the luminescence decay dynamics of single nanoplatelets, clusters of a few platelets, and selfassembled chains. As the number of stacked platelets is increased, we show that the luminescence decay becomes faster, which can be interpreted as FRET-mediated effect of quenchers: excitons may diffuse to nearby quenchers so that their decay rate is increased. On the other hand, a minor slow decay component is also observed for single platelets, corresponding to trapping-detrapping mechanisms in nearby trap states. The contribution of the slow component is enhanced for the platelet chains. This is consistent with a FRET-mediated trapping mechanism where the excitons would diffuse from platelet to platelet until they reach a trap state. Finally, we develop toy models for the FRETmediated quenching and trapping effects on the decay curves and analyze the relevant parameters

Re-expression of DNA methylation-silenced CD44 gene in a resistant NB4 cell line: rescue of CD44-dependent cell death by cAMP.: Restoration of CD44-mediated cell death by cAMP

International audienceIn the acute promyelocytic leukemia cell line, NB4, activation of the CD44 receptor triggers apoptosis. This pathway does not operate in the retinoid-maturation-resistant NB4-LR1 subclone. In this work, we show that the CD44 gene is silenced in these cells. The molecular defect involves DNA methylation of cytosine phosphate guanine (CpG) island and underacetylation of histone H3 at CD44 promoter. The methylating inhibitor 5-aza-CdR and cyclic AMP (cAMP) reverse the CD44 gene silencing. Contrary to 5-aza-CdR, cAMP does not induce DNA demethylation or histone modification at the CD44 promoter, whereas an H3pS10/AcK14 dual modification is observed on a global level. cAMP also induces the expression of c-Jun transcription factor and its recruitment at the CD44 promoter. Chromatin immunoprecipitation assays further show the association of brahma (Brm), a subunit of SWI/SNF chromatin-remodelling complex involved in the crosstalk between transcription and RNA polymerase II (RNA Pol II) processing, as well as the binding of phosphorylated RNA Pol II to the proximal promoter region of CD44. Finally, our study reveals that cAMP re-establishes the CD44-mediated cell death signalling. We propose that one of the actions of cAMP in restoring normal cell phenotype of leukaemia cells may consist in a broad trans-reactivation of silenced genes, despite marked hypermethylation of their promoters, as illustrated here with CD44 re-expression

L’éducation en Égypte

En consacrant cette livraison de la revue Égypte/Monde arabe à l’enseignement, nous avons tiré profit de la rencontre de trois éléments : les préoccupations d’une équipe dont les intérêts convergent au-delà des appartenances disciplinaires ; un « air du temps » qui, en Égypte comme ailleurs, a propulsé le sujet au rang des grands questionnements à travers lesquels des sociétés réfléchissent sur elles-mêmes — tant sur leur présent et leur avenir que sur leur passé ; enfin, le renouvellement des problématiques et des perspectives permettant d’aborder dans des termes rajeunis un domaine où, tant les savoirs accumulés que les enjeux du temps présent pèsent lourdement sur qui veut réfléchir sur la question éducative autrement que les acteurs ou les experts. […