Décolleté | EPFL Graph Search

Le décolleté est une encolure très large de certains vêtements, qui laisse dénudée une partie de la gorge et des épaules à partir de celle-ci, ainsi que du haut de la poitrine, de manière plus ou moins prononcée. Le haut du dos peut aussi être révélé. Les décolletés sont courants sur les robes, notamment les tenues de soirée, et se présentent également sur d'autres types de vêtements (débardeur, chemisier, etc.). Le décolleté désigne également la partie du corps ainsi montrée ; il est ainsi courant de parler d'un « beau décolleté. » Les décolletés mettent en valeur la poitrine, en la révélant plus ou moins, ainsi que les épaules et la nuque. Les formes les plus courantes sont le décolleté bateau, en forme de V, carré, en collier ou en tube. Influençant les contacts sociaux en Occident, les décolletés sont fréquents sur les tenues de soirée et de vacances mais sont plus rares dans la vie professionnelle. Ils sont considérés comme choquants et provocants dans certaines régions du mon

Synthese und Paarungseigenschaften von pDNA und deren Anwendung bei der Entwicklung funktionalisierter Ribozyme

Damian Ackermann

Within this project methods for the preparation of the unnatural nucleic acids 3'-O-Methyl-pRNA and pDNA (3'-Desoxy-pRNA) were developed. The pairing properties of these two systems have been examined and compared with that of pRNA. All of the three systems do follow the same pairing rules. Pairing has been observed only on the Watson-Crick side forming duplexes in antiparallel direction. All three systems are autonomous pairing systems that do not interact with RNA or DNA. In this series pRNA forms the most stable duplexes. Nucleobase 9H-purin-2,6-diamin instead of adenin and 5-methyl-cytosine instead of cytosine were introduced to increase the stability of pDNA duplexes. A solution structure of the self-complementary pDNA sequence [MGAATTMG]2 was elucidated by NMR. It shows an antiparallel duplex twisted against the major groove with sligthly lefthanded helicity. In analogy to pRNA the interstrand stacking predominates with a inclination angel of approximately 45°. Proceeding form the NMR structure a MD simulation was performed, in which the duplex has strongly bent after a regeneration time of 1.5 ns; this bent shape was conserved during the remaining simulation time of 4.0 ns. Using automated solid phase synthesis pDNA/RNA hybrid sequences were prepared. Examining the pairing strength, the RNA-2'—>4'-pDNA linkage at the pDNA/RNA interface was observed to lead to more stable duplexes than the RNA-3'—>4'-pDNA linkage did. This kind of pDNA/RNA structures have been used to replace structure defining elements like hairpins or stem motifs by pDNA-duplexes in complex RNA structures. From the FMN binding RNA aptamer an analogous pDNA/RNA construct has been prepared, that was built of two hybrid sequences. The binding of FMN in the pDNA/RNA construct was shown by fluorescence spectroscopy and the dissociation constant K0 = 2.6·10-7 M was calculated. Using the same strategy a pDNA/RNA construct of the hammerhead ribozyme was prepared, having substrate cleavage activity in analogy to the natural ribozyme. Cleavage properties of the pDNA/RNA construct at different Mg2+ and Mn2+ concentrations and at different reaction temperatures showed the same trend as those from the natural ribozyme did. Under all measured conditions, the natural ribozyme was about 1.5 times as active as the pDNA/RNA construct. Additional functional groups were introduced at different positions of the pDNA/RNA hybrid sequences using a pre-functionalized 6'-bromopentyl allofuranosyl building bloc on which the bromide was substituted with MeNH2 resp. EtSH after solid phase synthesis. 25 different functionalized pDNA/RNA ribozyme constructs could be built up in a combinatorial way. From 17 out of the 25 constructs, the cleavage kinetics was measured and the cleavage rate evaluated. The substitution pattern of the most active pDNA/RNA ribozyme analogue was applied on the hammerhead RNA sequence and the doubly methylamino-substituted construct prepared. Compared to the natural hammerhead ribozyme, the cleavage rates of this construct were higher with a factor of 2.0 - 3.3 under all measured conditions.

EPFL2004

Caspase-2-mediated cleavage of Mdm2 creates a p53-induced positive feedback loop

Etienne Meylan

Caspase-2 is an evolutionarily conserved caspase, yet its biological function and cleavage targets are poorly understood. Caspase-2 is activated by the p53 target gene product PIDD (also known as LRDD) in a complex called the Caspase-2-PIDDosome. We show that PIDD expression promotes growth arrest and chemotherapy resistance by a mechanism that depends on Caspase-2 and wild-type p53. PIDD-induced Caspase-2 directly cleaves the E3 ubiquitin ligase Mdm2 at Asp 367, leading to loss of the C-terminal RING domain responsible for p53 ubiquitination. As a consequence, N-terminally truncated Mdm2 binds p53 and promotes its stability. Upon DNA damage, p53 induction of the Caspase-2-PIDDosome creates a positive feedback loop that inhibits Mdm2 and reinforces p53 stability and activity, contributing to cell survival and drug resistance. These data establish Mdm2 as a cleavage target of Caspase-2 and provide insight into a mechanism of Mdm2 inhibition that impacts p53 dynamics upon genotoxic stress.

2011

Cleavage of mitochondrial antiviral signaling protein in the liver of patients with chronic hepatitis C correlates with a reduced activation of the endogenous interferon system

Etienne Meylan

Hepatitis C virus (HCV) infection induces the endogenous interferon (IFN) system in the liver in some but not all patients with chronic hepatitis C (CHC). Patients with a pre-activated IFN system are less likely to respond to the current standard therapy with pegylated IFN-alpha. Mitochondrial antiviral signaling protein (MAVS) is an important adaptor molecule in a signal transduction pathway that senses viral infections and transcriptionally activates IFN-beta. The HCV NS3-4A protease can cleave and thereby inactivate MAVS in vitro, and, therefore, might be crucial in determining the activation status of the IFN system in the liver of infected patients. We analyzed liver biopsies from 129 patients with CHC to investigate whether MAVS is cleaved in vivo and whether cleavage prevents the induction of the endogenous IFN system. Cleavage of MAVS was detected in 62 of the 129 samples (48%) and was more extensive in patients with a high HCV viral load. MAVS was cleaved by all HCV genotypes (GTs), but more efficiently by GTs 2 and 3 than by GTs 1 and 4. The IFN-induced Janus kinase (Jak)-signal transducer and activator of transcription protein (STAT) pathway was less frequently activated in patients with cleaved MAVS, and there was a significant inverse correlation between cleavage of MAVS and the expression level of the IFN-stimulated genes IFI44L, Viperin, IFI27, USP18, and STAT1. We conclude that the pre-activation status of the endogenous IFN system in the liver of patients with CHC is in part regulated by cleavage of MAVS.

2010

Synthese und Paarungseigenschaften von pDNA und deren Anwendung bei der Entwicklung funktionalisierter Ribozyme

Damian Ackermann

EPFL2004