Altération et bifurcation : l’écho est-il neutre ?

L’écho ne se contente pas de reproduire ce qu’il entend comme le souligne la tradition latine. Figure d’Écho, l’écho fait tout ce qu’il peut pour refuser la transparence et la neutralité. Il se venge de la malédiction qu’il porte en altérant tout ce qu’il touche. Sa vengeance est l’expression de son existence. Mais, au-delà de l’écho, c’est toute la question de ces expressions et formes qui vivent en retrait et en attente qui est posée ; la question du suiveur : « qui me précède ? » ; la question de l’ombre : « suis-je une ressemblance ? » ; la question du miroir : « quelle image dois-je renvoyer ? ». La figure de l’écho offre ainsi l’occasion de s’interroger sur la guerre que se livrent l’original et la copie tout en se demandant si l’existence d’un énoncé sans origine est envisageable. À cette question, l’écho répond par la seule arme en sa possession : l’altération. C’est toute la question de la neutralité de l’écho que nous poserons en réfléchissant sur l’altération que la voix d’Écho profère.Far from reproducing what it hears, as the Latin tradition would have it, the echo resists transparency and neutrality. It avenges itself for the curse it carries by distorting everything it touches. Its revenge is the expression of its existence. However, the main concern here has to do with the expressions and forms that live in withdrawal and on standby; the question of the follower: “who precedes me ?”, the question of the shade: “am I a resemblance?”, the question of the mirror: “what image should I return?”... The echo thus offers the opportunity to wonder about the war between the original and the copy, while wondering if the existence of a statement without origin is possible. The echo answers this question with the only weapon in its possession: distortion. I will examine the question of the neutrality of the echo while reflecting on the distortion made by the voice of Echo

Adhesive factor/rabbit 2, a new fimbrial adhesin and a virulence factor from Escherichia coli O103, a serogroup enteropathogenic for rabbits

Enteropathogenic Escherichia coli-like E. coli strains belonging to serovar O103:K-:H2 and rhamnose-negative biotypes are highly pathogenic diarrhea-inducing strains for weaned European rabbits. We describe here the cloning and sequencing of the major subunit gene of a new fimbrial adhesin, adhesive factor/rabbit 2 (AF/R2), which confers on these strains the ability to attach to rabbit enterocytes and to HeLa cells in a diffuse manner and which is associated with in vivo virulence. The chromosomal operon that encodes functional AF/R2 has been cloned from strain B10. The major subunit gene afr2G, as well as an adjacent open reading frame, afr2H, has been sequenced. The Afr2G protein shows homologies with FaeG and ClpG, which are the respective major subunits of fimbrial adhesin K88 (F4) and afimbrial adhesin CS31A. Plasmid carrying the operon transcomplements an AF/R2-negative TnphoA mutant for its ability to express AF/R2. As a whole, AF/R2 is a new member of the E. coli K88 adhesin family which is associated with virulence and which may serve in the design of vaccines

Structure et dynamique de la dynorphine et de son recepteur

International audienceDynorphin is a neuropeptide involved in pain, addiction and mood regulation. It exerts its activity by binding to the kappa opioid receptor (KOP) which belongs to the large family of G-protein coupled receptors. The dynorphin peptide was discovered in 1975, while its receptor was cloned in 1993. This review will describe: a) the activities and physiological functions of dynorphin and its receptor, b) early structure-activity relationship studies performed before cloning of the receptor (mostly pharmacological and biophysical studies of peptide analogues), c) structure-activity relationship studies performed after cloning of the receptor via receptor mutagenesis and the development of recombinant receptor expression systems, d) structural biology of the opiate receptors culminating in X-ray structures of the four opioid receptors in their inactive state and structures of MOP and KOP receptors in their active state. X-ray and EM structures are combined with NMR data, which gives complementary insight into receptor and peptide dynamics. Molecular modelling greatly benefited from the availability of atomic resolution 3D structures of receptor-ligand complexes and an example of the strategy used to model a dynorphin-KOP receptor complex using NMR data will be described. These achievements have led to a better understanding of the complex dynamics of KOP receptor activation and to the development of new ligands and drugs

L’acte de création comme mouvement de déformation

In this article, we approach, in the footsteps of Maurice Blanchot's works, the intimacy of the bond which links the word to the thing, bond inscribed in a double relation, reality / thought and possibility / impossibility. There is no question of assessing their adequacy, but of digging into the intimacy of what exists between them. The between interrogates both the (im)possible of the real to exist and of the thought to designate. His/her writing illustrates this impossibility of the word to translate a real which is, itself, impossible to become true. Does it mean that the real only exists as a transformed reality, in the same way that the word would only exist as an impossible designation? The deformation of thought through the word and of reality through the thing might be connected to a movement which we interrogate beginning with the question of the (im)possible deformation of real through writing

Expression and pharmacological characterization of the human μ-opioid receptor in the methylotrophic yeast Pichia pastoris

AbstractThe human μ-opioid receptor cDNA from which the 32 amino-terminal codons were substituted by the Saccharomyces cerevisiae α-mating factor signal sequence has been expressed in the methylotrophic yeast Pichia pastoris using the host promoter of the alcohol oxidase-1 gene. Cell membranes exhibited specific and saturable binding of the opioid antagonist [3H]diprenorphine (Kd = 0.2 nM and Bmax = 400 fmol/mg protein or 800 sites/cell). Competition studies with non-selective, and μ-, δ- and κ-selective opioid agonists and antagonists revealed a typical μ-opioid receptor binding profile, suggesting proper folding of the protein in yeast membranes

Protection against myxomatosis and rabbit viral hemorrhagic disease with recombinant myxoma viruses expressing rabbit hemorrhagic disease virus capsid protein

Two myxoma virus-rabbit hemorrhagic disease virus (RHDV) recombinant viruses were constructed with the SG33 strain of myxoma virus to protect rabbits against myxomatosis and rabbit viral hemorrhagic disease. These recombinant viruses expressed the RHDV capsid protein (VP60). The recombinant protein, which is 60 kDa in size, was antigenic, as revealed by its reaction in immunoprecipitation with antibodies raised against RHDV. Both recombinant viruses induced high levels of RHDV- and myxoma virus-specific antibodies in rabbits after immunization. Inoculations by the intradermal route protected animals against virulent RHDV and myxoma virus challenges

Testing the efficacy of medium chain fatty acids against rabbit colibacillosis

Enteropathogenic Escherichia coli (EPEC) represents a major cause of lethal diarrhea in young mammals. Although the pathogenicity mechanisms of EPEC are now well understood, the intrinsic and environmental factors that control the expression of EPEC virulence remain largely unknown. In the rabbit, suckling reduces pups’ sensitivity to EPEC infection. Hence, we have hypothesized that uncharacterized factors present in doemilkmay mediate this protection. Medium chain fatty acids (MCFA), known to possess antimicrobial properties, are highly abundant in doe milk.We demonstrate that caprylic acid exhibits a clear bacteriostatic effect in vitro against the rabbit EPEC strain E22 (O103:H2:K-), in a dose-dependent manner. In vivo, the dietary inclusion of triglycerides of MCFA did not however reduce the sensitivity of young rabbits challenged with this EPEC strain. The mortality and fecal excretion of EPEC were not reduced, and the bacterial adhesion to ileum was not inhibited. Amount of MCFA reaching the ileal level might have been too low and/or their association to other milk antimicrobials may have been required to observe a positive effect on disease evolution in a context of a highly virulent challenge

Structural insights on the pamoic acid and the 8 kDa domain of DNA polymerase beta complex: Towards the design of higher-affinity inhibitors

<p>Abstract</p> <p>Background</p> <p>DNA polymerase beta (pol beta), the error-prone DNA polymerase of single-stranded DNA break repair as well as base excision repair pathways, is overexpressed in several tumors and takes part in chemotherapeutic agent resistance, like that of cisplatin, through translesion synthesis. For this reason pol beta has become a therapeutic target. Several inhibitors have been identified, but none of them presents a sufficient affinity and specificity to become a drug. The fragment-based inhibitor design allows an important improvement in affinity of small molecules. The initial and critical step for setting up the fragment-based strategy consists in the identification and structural characterization of the first fragment bound to the target.</p> <p>Results</p> <p>We have performed docking studies of pamoic acid, a 9 micromolar pol beta inhibitor, and found that it binds in a single pocket at the surface of the 8 kDa domain of pol beta. However, docking studies provided five possible conformations for pamoic acid in this site. NMR experiments were performed on the complex to select a single conformation among the five retained. Chemical Shift Mapping data confirmed pamoic acid binding site found by docking while NOESY and saturation transfer experiments provided distances between pairs of protons from the pamoic acid and those of the 8 kDa domain that allowed the identification of the correct conformation.</p> <p>Conclusion</p> <p>Combining NMR experiments on the complex with docking results allowed us to build a three-dimensional structural model. This model serves as the starting point for further structural studies aimed at improving the affinity of pamoic acid for binding to DNA polymerase beta.</p

Structure et dynamique de neuropeptides liés à leur récepteur

International audienc