Nouvelles données sur la séquence culturelle du site de Brassempouy (Landes) : Fouilles 1997-2002

National audienceThe field of Brassempouy is situated in the south of the Landes departement, two kilometres away from the village and forty kilometres south-east of Mont-de-Marsan in Chalosse. It holds several cavities (cave of the Pope, cave of the Hyenas, Dubalen gallery, Megaceros gallery) which belong to a complex karstic network, dug in a limestone formation of the Eocene, a few metres bellow the natural soil. The purpose of this article is to present the cultural sequence as it appears after the excavations 1997-2002.Le gisement de Brassempouy est localisé au sud du département des Landes (France), à deux kilomètres du village de Brassempouy et à quarante kilomètres au sud-ouest de Mont-de-Marsan, en Chalosse. Il comprend plusieurs cavités (grotte du Pape, grotte des Hyènes, galerie Dubalen, galerie du Mégacéros) qui appartiennent à un réseau karstique complexe creusé dans une formation calcaire de l'Eocène à quelques mètres sous le sol naturel. L'objectif de cet article est de présenter la séquence culturelle telle qu'elle apparaît à l'issue des fouilles 1997-2002

Targeted Disruption of the PME-1 Gene Causes Loss of Demethylated PP2A and Perinatal Lethality in Mice

Phosphoprotein phosphatase 2A (PP2A), a major serine-threonine protein phosphatase in eukaryotes, is an oligomeric protein comprised of structural (A) and catalytic (C) subunits to which a variable regulatory subunit (B) can associate. The C subunit contains a methyl ester post-translational modification on its C-terminal leucine residue, which is removed by a specific methylesterase (PME-1). Methylesterification is thought to control the binding of different B subunits to AC dimers, but little is known about its physiological significance in vivo.Here, we show that targeted disruption of the PME-1 gene causes perinatal lethality in mice, a phenotype that correlates with a virtually complete loss of the demethylated form of PP2A in the nervous system and peripheral tissues. Interestingly, PP2A catalytic activity over a peptide substrate was dramatically reduced in PME-1(-/-) tissues, which also displayed alterations in phosphoproteome content.These findings suggest a role for the demethylated form of PP2A in maintenance of enzyme function and phosphorylation networks in vivo

High rate of intestinal absorption of the phospholipid analogue 1-dodecyl 2-(1-14C) octanamido-sn-2-deoxy-glycero-3-phosphocholine in the rat

International audienc

Studies on lipidomimetic derivatives of α-difluoromethylornithine (DFMO) to enhance the bioavailability in a

DFMO, a trypanostatic drug, presents a satisfactory intestinal absorption but its elimination from the blood is rapid so that high doses are necessary to obtain a therapeutic effect. In this study, we propose a strategy to enhance the bioavailability of DFMO by using lipidomimetic derivatives. Three lipidomimetic DFMO derivatives called ODFMO, S-DFMO and Chol-DFMO were designed to reach easily the plasma and to be cleaved preferentially by plasma esterases progressively liberating free DFMO. Chol-DFMO only could be cleaved partially whereas the other compounds appeared to be stable in a reconstituted intestinal medium and mouse plasma. Nevertheless, the use of DFMO derivatives in T. b. brucei experimental chemotherapy appeared as an interesting approach. Thus, ODFMO was trypanocidal in vitro whereas DFMO, the active principle, was only trypanostatic. Nevertheless, this compound did not release DFMO in mouse blood as expected and acted therefore not as a prodrug. Oral treatment using low doses of compound O-DFMO was able to cure 40 % mice while the active principle (eflornithine) administered at 50 fold higher molarity failed to cure any mice. This indicates that compound ODFMO acts by a specific mechanism which remains to be investigated. S-DFMO was less active and Chol-DFMO had no in vitro activity but released small amounts of DFMO in mice, however, too slight to obtain a therapeutic effect

Dissociate arachidonic acid release from eicosanoid synthesis in rat peritoneal macrophages is possible using concomitantly eicosapentanoic acid and a phospholipid analogue

International audienc

Uptake of the phospholipase A2 inhibitor 1-dodecyl 2-(1-14C) octanamido-sn-2-deoxyglycero-3-phosphocholine by peritoneal macrophages

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Synthesis and in vitro study of a diglyceride prodrug of a peptide

A diglyceride derivative of a pentapeptide renin inhibitor, the 1,3-dipalmitoyl-[Iva-Phe-Nle-Sta-Ala-Sta-acetyl]-glycerol was synthesized and tested in vitro as a potential prodrug for oral administration. The ability of the diglyceride analog to inhibit the renin activity was equivalent to that of the parent peptide after predigestion with pancreatic lipase. Furthermore, the presence of the palmitoyl groups was found to induce, in vitro, an efficient protection of the peptide from gastric and intestinal hydrolysis. During incubation with intestinal and gastric fluids, and with alpha-chymotrypsin and pancreatic lipase, the glycerolipidic derivative was more stable than the peptide alone. These results support the use of glycerolipidic prodrug for oral administration of peptides