Radical-Mediated Anti-Markovnikov Hydrophosphonation of Olefins

The radical-mediated addition of triphenylphosphonium tetrafluoroborate to olefins (hydrophosphonation) is reported. Both standard radical initiators and photochemical conditions are effective, up to the gram scale. The phosphonium salts are shown to serve as Z-selective Wittig olefination reagents, even without purification

Pancreatic Cancer Cell Lines Can Induce Prostaglandin E2 Production from Human Blood Mononuclear Cells

Accumulating evidence suggests an important role for cyclooxygenase-2 (COX-2) in the pathogenesis of a wide range of malignancies. The protumorigenic properties of COX-2 are generally thought to be mediated by its product, PGE2, which is shown to promote tumor spread and growth by multiple mechanisms but most importantly through modulation of the local immune response in the tumor. Pancreatic tumor cells produce various amounts of PGE2, some of them being even deficient in COX enzymes or other PGE2 synthases. Here we describe that, beside pancreatic tumor cells or stromal fibroblasts, human peripheral blood mononuclear cells can also produce PGE2 upon coculture with pancreatic cancer cells. Stimulating of cellular cPLA2 within PBMCs by secreted factors, presumably sPLA2, from tumor cells appeared crucial, while the direct contact between PBMCs and PDACs seemed to be dispensable for this effect. Our data is emphasizing the complex interactions participating in the formation of the tolerogenic immune milieu within pancreatic tumors

Functionally Important Aromatic–Aromatic and Sulfur−π Interactions in the D2 Dopamine Receptor

The recently published crystal structure of the D3 dopamine receptor shows a tightly packed region of aromatic residues on helices 5 and 6 in the space bridging the binding site and what is thought to be the origin of intracellular helical motion. This highly conserved region also makes contacts with residues on helix 3, and here we use double mutant cycle analysis and unnatural amino acid mutagenesis to probe the functional role of several residues in this region of the closely related D2 dopamine receptor. Of the eight mutant pairs examined, all show significant functional coupling (Ω > 2), with the largest coupling coefficients observed between residues on different helices, C3.36/W6.48, T3.37/S5.46, and F5.47/F6.52. Additionally, three aromatic residues examined, F5.47, Y5.48, and F5.51, show consistent trends upon progressive fluorination of the aromatic side chain. These trends are indicative of a functionally important electrostatic interaction with the face of the aromatic residue examined, which is likely attributed to aromatic–aromatic interactions between residues in this microdomain. We also propose that the previously determined fluorination trend at W6.48 is likely due to a sulfur−π interaction with the side chain of C3.36. We conclude that these residues form a tightly packed structural microdomain that connects helices 3, 5, and 6, thus forming a barrier that prevents dopamine from binding further toward the intracellular surface. Upon activation, these residues likely do not change their relative conformation, but rather act to translate agonist binding at the extracellular surface into the large intracellular movements that characterize receptor activation

Plouharnel – L’épave Plouharnel 1 (EA 3655)

Par suite d’épisodes climatiques exceptionnels, le littoral atlantique a profondément souffert de l’érosion littorale, d’amaigrissement de plages engendrant la destruction de vestiges anthropiques conservés en contexte d’estran. Ainsi à la mi-février 2014, la présence d’un fond de carène dérivant entre deux eaux aux abords de la commune de Plouharnel a été signalé par la presse (fig. 1). Ces vestiges d’une charpente axiale de navire et d’une série de membrures ont été rapidement récupérés par..

Plonévez-Porzay – L’épave Trez Malaouen 2 (EA 842)

Les premiers sondages menés sur l’épave Trez Malaouen 2 par Jean René Donguy avaient conclu à son importance scientifique et à la nécessité de conduire une étude plus approfondie. Daté du début du xvie s., il s’agit d’un navire construit à franc-bord en chêne et orme probablement d’une vingtaine de mètres. La campagne de fouille 2014, conduite durant une semaine, a mis en évidence le bon état de conservation de ce site d’estran. Celui-ci montre en effet peu de différence avec la documentation..

Du bois, de terre et d’eau : patrimoine archéologique, historique et culturel autour de la forêt de Cerisy

Depuis 2015, ce PCR se propose d’étudier sur la longue durée les transformations et les aménagements d’un territoire forestier situé autour de la forêt domaniale de Cerisy (Calvados et Manche), couvrant une quarantaine de communes et correspondant aux anciennes forêts médiévales de Bur-le-Roy. L’aménagement de cet espace boisé a généré des activités économiques particulières : potiers, charbonniers, sabotiers, charpentiers de maison et de moulin, forge industrielle, mine de charbon de terre. ..

Functional Evaluation of Key Interactions Evident in the Structure of the Eukaryotic Cys-Loop Receptor GluCl

The publication of the first high-resolution crystal structure of a eukaryotic Cys-loop receptor, GluClα, has provided valuable structural information on this important class of ligand-gated ion channels (LGIC). However, limited functional data exist for the GluCl receptors. Before applying the structural insights from GluCl to mammalian Cys-loop receptors such as nicotinic acetylcholine and GABA receptors, it is important to ensure that established functional features of mammalian Cys-loop receptors are present in the more distantly related GluCl receptors. Here, we seek to identify ligand-binding interactions that are generally associated with Cys-loop receptors, including the frequently observed cation−π interaction. Our studies were performed on the highly homologous GluClβ receptor, because GluClα is not activated by glutamate in Xenopus laevis oocytes. Mutagenesis of the signal peptide and pore lining helix was performed to enhance functional expression and sensitivity to applied ligand, respectively. Conventional and unnatural amino acid mutagenesis indicate a strong cation−π interaction between Y206 and the protonated amine of glutamate, as well as other important ionic and hydrogen bond interactions between the ligand and the binding site, consistent with the crystal structure

Rapid, regioselective living ring-opening metathesis polymerization of bio-derivable asymmetric tricyclic oxanorbornenes

The synthesis of a range of alkyl esters (methyl, n-butyl, and n-decyl) prepared via Steglich esterification of the thermodynamically controlled exo, exo Diels���Alder adduct of furfuryl alcohol and maleic anhydride is reported. Subsequent ring-opening metathesis polymerization of these bio-derivable tricyclic oxanorbornene analogs delivers polymers with targeted molar mass and low molar mass dispersity. The polymerizations are rapid with complete monomer conversion achieved within 15 min. Significantly, the presence of the cyclic lactone at the bridgehead of these monomers leads to polymers with high regioregularity (>85% head-to-tail) and high stereoregularity (>75% trans). The resultant polymers display both high thermal stability and high glass transition temperatures. This new class of oxanorbornene monomer, accessed from bio-derivable furfuryl alcohol and maleic anhydride, may be further tailored to incorporate a range of functional moieties. Furthermore, the exceptional properties of the derived polymers indicate potential in a range of applications

Calvi – Port de plaisance (épave Calvi 2)

Découverte en 1987 à l’extérieur du départ de la jetée du port de plaisance, l’épave repose sur un fond de sable par environ 2 m de profondeur. Elle a fait l’objet en 1988 et 1989 de sondages intéressant la partie avant du navire qui fut dégagée sur environ 5 m sur 5 m. Ces sondages ont permis de s’assurer de l’excellent état de conservation du navire préservé presque intégralement. La structure de la coque se caractérise par des bordages de 4,5 cm d’épaisseur fixés par des clous de fer sur l..