sox9b Is a Key Regulator of Pancreaticobiliary Ductal System Development

The pancreaticobiliary ductal system connects the liver and pancreas to the intestine. It is composed of the hepatopancreatic ductal (HPD) system as well as the intrahepatic biliary ducts and the intrapancreatic ducts. Despite its physiological importance, the development of the pancreaticobiliary ductal system remains poorly understood. The SRY-related transcription factor SOX9 is expressed in the mammalian pancreaticobiliary ductal system, but the perinatal lethality of Sox9 heterozygous mice makes loss-of-function analyses challenging. We turned to the zebrafish to assess the role of SOX9 in pancreaticobiliary ductal system development. We first show that zebrafish sox9b recapitulates the expression pattern of mouse Sox9 in the pancreaticobiliary ductal system and use a nonsense allele of sox9b, sox9bfh313, to dissect its function in the morphogenesis of this structure. Strikingly, sox9bfh313 homozygous mutants survive to adulthood and exhibit cholestasis associated with hepatic and pancreatic duct proliferation, cyst formation, and fibrosis. Analysis of sox9bfh313 mutant embryos and larvae reveals that the HPD cells appear to mis-differentiate towards hepatic and/or pancreatic fates, resulting in a dysmorphic structure. The intrahepatic biliary cells are specified but fail to assemble into a functional network. Similarly, intrapancreatic duct formation is severely impaired in sox9bfh313 mutants, while the embryonic endocrine and acinar compartments appear unaffected. The defects in the intrahepatic and intrapancreatic ducts of sox9bfh313 mutants worsen during larval and juvenile stages, prompting the adult phenotype. We further show that Sox9b interacts with Notch signaling to regulate intrahepatic biliary network formation: sox9b expression is positively regulated by Notch signaling, while Sox9b function is required to maintain Notch signaling in the intrahepatic biliary cells. Together, these data reveal key roles for SOX9 in the morphogenesis of the pancreaticobiliary ductal system, and they cast human Sox9 as a candidate gene for pancreaticobiliary duct malformation-related pathologies

Nouvelles réactions multicomposants avec des isonitriles

First, a Ugi-Smiles reaction with ammonia equivalent is presented. Post-condensations to this reaction are proposed. In a second part, new variants of the Passerini reaction with acyl phosphonate are described. At last, an original keteneimine synthesis and its applications in heterocyclic synthesis are exposed.Dans une première partie est décrite une réaction de Ugi-Smiles avec des équivalents d'ammoniaque ainsi que des post-condensations à cette réaction. Dans une seconde partie, des nouvelles réactions de Passerini entre des isonitriles, des phosphonates d'acyle et différents partenaires acides ont été décrites. Dans une dernière partie, une synthèse originale de cétène-imines basée sur une séquence Nef-Perkow ainsi que des applications en synthèse hétérocyclique sont présentées

Nouvelles réactions multicomposants avec des isonitriles

Dans une première partie est décrite une réaction de Ugi-Smiles avec des équivalents d'ammoniaque ainsi que des post-condensations à cette réaction. Dans une seconde partie, des nouvelles réactions de Passerini entre des isonitriles, des phosphonates d'acyle et différents partenaires acides ont été décrites. Dans une dernière partie, une synthèse originale de cétène-imines basée sur une séquence Nef-Perkow ainsi que des applications en synthèse hétérocyclique sont présentées.First, a Ugi-Smiles reaction with ammonia equivalent is presented. Post-condensations to this reaction are proposed. In a second part, new variants of the Passerini reaction with acyl phosphonate are described. At last, an original keteneimine synthesis and its applications in heterocyclic synthesis are exposedPALAISEAU-Polytechnique (914772301) / SudocSudocFranceF

Isocyanide-Based Two-Step Three-Component Keteneimine Formation

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New Benzotriazole and Benzimidazole Scaffolds from Ugi−Smiles Couplings of Isocyanides

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Isocyanide Addition to Acylphosphonates: A Formal Passerini Reaction of Acyl Chlorides

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Direct amination of hydrogen-terminated boron doped diamond surfaces

This paper reports on direct amination of hydrogen-terminated polycrystalline boron doped electrode. The technique consists of NH3 plasma treatment of hydrogenated diamond substrate to generate surface terminal amino groups. The aminated diamond surface was further investigated for its ability to bind gold nanoparticles. Homogeneous and well-distributed gold nanoparticles were obtained by simple exposure of the amine-terminated surface to an aqueous solution of gold colloid. The resulting surfaces were characterized using X-ray spectroscopy (XPS), scanning electron microscopy (SEM) and cyclic voltammetry (CV). The presence of gold nanoparticles led to more reversible electron transfer process on the modified electrode. Keywords: Boron-doped polycrystalline diamond, Amination, Plasma treatment, Gold nanoparticles, Electron transfe

Covalent linking of peptides onto oxygen-terminated boron-doped diamond surfaces.

International audienceThis paper reports on the formation of semicarbazide boron-doped diamond surfaces and their use for the prepn. of peptide microarrays through site-specific a-oxo semicarbazone ligation. Hydrogen-terminated diamond substrates were first photochem. oxidized and the resulting surface hydroxyl groups were coupled with (aminopropyl)triethoxysilane to yield amine-terminated surfaces. Chem. reaction of the terminal amino groups with triphosgene and Fmoc-protected hydrazine, followed by a deprotection step led to the formation of a semicarbazide termination. Peptides bearing a glyoxylyl group were linked to the semicarbazide-terminated BDD surfaces through site-specific ligation. XPS and fluorescence measurements were used to characterize the resulting surfaces

A new multicomponent reaction for the synthesis of pyridines via cycloaddition of azadienes and ketenimines

The ketenimines resulting from a Nef isocyanide/Perkow sequence react with 1-azadienes to form pyridines or pyrimidines depending on their substitution pattern. The reaction is most efficient with ester-substituted ketenimines which leads to pyridines after elimination of the phosphate group. © 2011 Elsevier Ltd. All rights reserved

Peptide immobilization on amine-terminated boron-doped diamond surfaces.

International audienceThis paper reports on the formation and characterization of semicarbazide termination on aminated boron-doped diamond (BDD) surfaces, and further prepn. of peptide microarray through site-specific a-oxo semicarbazone ligation. Hydrogen-terminated BDD electrodes were first aminated using NH3 plasma treatment and then reacted with triphosgene and Fmoc-protected (Fmoc = 9-fluorenylmethoxycarbonyl) hydrazine to yield a protected semicarbazide termination. Subsequent deprotection and chem. reaction with glyoxylyl peptides led to the covalent immobilization of the peptides on the surface through site-specific ligation. The resulting surfaces were characterized using XPS and fluorescence measurements