UA62784 Is a Cytotoxic Inhibitor of Microtubules, not CENP-E

SummaryA recent screen for compounds that selectively targeted pancreatic cancer cells isolated UA62784. We found that UA62784 inhibits microtubule polymerization in vitro. UA62784 interacts with tubulin dimers ten times more potently than colchicine, vinblastine, or nocodazole. Competition experiments revealed that UA62784 interacts with tubulin at or near the colchicine-binding site. Nanomolar doses of UA62784 promote the accumulation of mammalian cells in mitosis, due to aberrant mitotic spindles, as shown by immunofluorescence and live cell imaging. Treatment of cancerous cell lines with UA62784 is lethal, following activation of apoptosis signaling. By monitoring mitotic spindle perturbations and apoptosis, we found that the effects of UA62784 and of some known microtubule-depolymerizing drugs are additive. Finally, high content screening of H2B-GFP HeLa cells revealed that low doses of UA62784 and vinblastine potentiate each other to inhibit proliferation

Bueil – Le Pelleret, rue du Puits

Dans le cadre de travaux de pose d’une nouvelle conduite d’assainissement entre Bueil et le hameau de Chanu (commune de Villiers-en-Desœuvre), l’entreprise EHTP a fait la découverte de trois sépultures. Suite à un arrêt de chantier, une opération de fouille urgente consécutive à cette découverte fortuite a pu être engagée. Seine-Normandie-Agglomération, maître d’ouvrage des travaux, a accepté de prendre en charge le financement de l’intervention. Des sondages ponctuels ont été réalisés sur le..

Direct Translocation as Major Cellular Uptake for CADY Self-Assembling Peptide-Based Nanoparticles

Cell penetrating peptides constitute a potent approach to overcome the limitations of in vivo siRNA delivery. We recently proposed a peptide-based nanoparticle system, CADY, for efficient delivery of siRNA into numerous cell lines. CADY is a secondary amphipathic peptide that forms stable complexes with siRNA thereby improving both their cellular uptake and biological response. With the aim of understanding the cellular uptake mechanism of CADY:siRNA complexes, we have combined biochemical, confocal and electron microscopy approaches. In the present work, we provide evidence that the major route for CADY:siRNA cellular uptake involves direct translocation through the membrane but not the endosomal pathway. We have demonstrated that CADY:siRNA complexes do not colocalize with most endosomal markers and remain fully active in the presence of inhibitors of the endosomal pathway. Moreover, neither electrostatic interactions with cell surface heparan sulphates nor membrane potential are essential for CADY:siRNA cell entry. In contrast, we have shown that CADY:siRNA complexes clearly induce a transient cell membrane permeabilization, which is rapidly restored by cell membrane fluidity. Therefore, we propose that direct translocation is the major gate for cell entry of CADY:siRNA complexes. Membrane perturbation and uptake are driven mainly by the ability of CADY to interact with phospholipids within the cell membrane, followed by rapid localization of the complex in the cytoplasm, without affecting cell integrity or viability

Étude microtopographique des fortifications de terre de Haute-Normandie

Date de l'opération : 2006 (PC) ; 2006 (PI) Inventeur(s) : Flambard-Hérichier Anne-Marie (ENS SUP) ; Lepeuple Bruno ; Etienne Daniel ; Deshayes Gilles (GAVS) ; Lefèvre Sébastien (SAR) ; Mouchard Jimmy (ENS SUP) ; Guérin Thomas ; Painchault Aude L’objectif du groupe de travail qui s’est constitué à l’université de Rouen, au sein du GRHIS (EA 3831), avec l’appui du service régional de l’Archéologie de Haute-Normandie, sous la direction d’Anne-Marie Flambard-Héricher est de pratiquer de façon sy..

Étude microtopographique des fortifications de terre de Haute-Normandie

Date de l'opération : 2006 (PC) ; 2006 (PI) Inventeur(s) : Flambard-Hérichier Anne-Marie (ENS SUP) ; Lepeuple Bruno ; Etienne Daniel ; Deshayes Gilles (GAVS) ; Lefèvre Sébastien (SAR) ; Mouchard Jimmy (ENS SUP) ; Guérin Thomas ; Painchault Aude L’objectif du groupe de travail qui s’est constitué à l’université de Rouen, au sein du GRHIS (EA 3831), avec l’appui du service régional de l’Archéologie de Haute-Normandie, sous la direction d’Anne-Marie Flambard-Héricher est de pratiquer de façon sy..

Precipitation in original Duralumin A-U4G versus modern 2017A alloy

Precipitation in Duralumin, a historic quaternary alloy of the type: Al–Cu–Mg–Si, was never fully studied nor observed by current electron microscopy techniques. This article presents the full characterization and comparison of two alloys: a Duralumin (A-U4G) from the 1950s collected on a vintage aircraft and its modern equivalent: a 2017A alloy. The as-received and peak-aging states were analysed with DSC, SAXS and TEM advanced techniques. It is shown that old Duralumin and modern 2017A present a similar nanoprecipitation in the as-received state and behave similarly upon artificial aging. As opposed to what has been reported in the past, three types of precipitates participating in hardening were found upon aging: θ’-Al2Cu, Q’(Q)-AlCuMgSi and Ω-Al2Cu

Approche historique, topographique et archéologique des fortifications des comtes de Beaumont-Meulan en Basse-Seine (XIe-XIIe siècle)

International audienc

Le Landin (Eure), ‘La motte'

BSR 2005, DRAC-SRA, 2007, p. 43-4

La motte du Landin

National audienc