Bradykinin receptors : agonists, antagonists, expression, signaling and adaptation to sustained stimulation

Bradykinin-related peptides, the kinins, are blood-derived peptides that stimulate 2 G protein–coupled receptors, the B1 and B2 receptors (B1R, B2R). The pharmacologic and molecular identities of these 2 receptor subtypes will be succinctly reviewed, with emphasis on drug development, receptor expression, signaling, and adaptation to persistent stimulation. Peptide and nonpeptide antagonists and fluorescent ligands have been produced for each receptor. The B2R is widely and constitutively expressed in mammalian tissues, whereas the B1R is mostly inducible under the effect of cytokines during infection and immunopathology. Both receptor subtypes mediate the vascular aspects of inflammation (vasodilation, edema formation). On this basis, icatibant, a peptide antagonist of the B2R, is approved in the management of hereditary angioedema attacks. Other clinical applications are still elusive despite the maturity of the medicinal chemistry efforts applied to kinin receptors. While both receptor subtypes are mainly coupled to the Gq protein and related second messengers, the B2R is temporarily desensitized by a cycle of phosphorylation/endocytosis followed by recycling, whereas the nonphosphorylable B1R is relatively resistant to desensitization and translocated to caveolae on activation

Vascular smooth muscle contractility assays for inflammatory and immunological mediators

The blood vessels are one of the important target tissues for the mediators of inflammation and allergy; further cytokines affect them in a number of ways. We review the use of the isolated blood vessel mounted in organ baths as an important source of pharmacological information. While its use in the bioassay of vasoactive substances tends to be replaced with modern analytical techniques, contractility assays are effective to evaluate novel synthetic drugs, generating robust potency and selectivity data about agonists, partial agonists and competitive or insurmountable antagonists. For instance, the human umbilical vein has been used extensively to characterize ligands of the bradykinin B2 receptors. Isolated vascular segments are live tissues that are intensely reactive, notably with the regulated expression of gene products relevant for inflammation (e.g., the kinin B1 receptor and inducible nitric oxide synthase). Further, isolated vessels can be adapted as assays of unconventional proteins (cytokines such as interleukin-1, proteases of physiopathological importance, complement-derived anaphylatoxins and recombinant hemoglobin) and to the gene knockout technology. The well known cross-talks between different cell types, e.g., endothelium-muscle and nerve terminal-muscle, can be extended (smooth muscle cell interaction with resident or infiltrating leukocytes and tumor cells). Drug metabolism and distribution problems can be modeled in a useful manner using the organ bath technology, which, for all these reasons, opens a window on an intermediate level of complexity relative to cellular and molecular pharmacology on one hand, and in vivo studies on the other

The impact of language co-activation on L1 and L2 speech fluency

Fluent speech depends on the availability of well-established linguistic knowledge and routines for speech planning and articulation. A lack of speech fluency in late second-language (L2) learners may point to a deficiency of these representations, due to incomplete acquisition. Experiments on bilingual language processing have shown, however, that there are strong reasons to believe that multilingual speakers experience co-activation of the languages they speak. We have studied to what degree language co-activation affects fluency in the speech of bilinguals, comparing a monolingual German control group with two bilingual groups: 1) first-language (L1) attriters, who have fully acquired German before emigrating to an L2 English environment, and 2) immersed L2 learners of German (L1: English). We have analysed the temporal fluency and the incidence of disfluency markers (pauses, repetitions and self-corrections) in spontaneous film retellings. Our findings show that learners to speak more slowly than controls and attriters. Also, on each count, the speech of at least one of the bilingual groups contains more disfluency markers than the retellings of the control group. Generally speaking, both bilingual groups-learners and attriters-are equally (dis)fluent and significantly more disfluent than the monolingual speakers. Given that the L1 attriters are unaffected by incomplete acquisition, we interpret these findings as evidence for language competition during speech production

Analyse des défaillances et modélisation du comportement du logiciel d'un autocommutateur téléphonique.

International audienc

Software dependability of a telephone switching system.

International audienc

Analyse des défaillances et évaluation de la sûreté de fonctionnement du logiciel d'un autocommutateur téléphonique

International audienc

Emulsifying and Antioxidant Properties of a Shrimp (Pandalus borealis) Hydrolysate Conjugated With Xylose or Dextran Through the Maillard Reaction by Dry-Heating in Mild Conditions

Maillard Reaction (MR) was performed in ‘dry’ conditions at 50 °C for 48 h between native shrimp hydrolysate (HN) and xylose or dextran. Resulting emulsifying and antioxidant properties were assessed. HN was compared with a native sodium caseinate (CN) and its glycoconjugates, obtained in the same conditions. Compared to dextran, xylose resulted in significant browning after MR with HN or CN, but HN-xylose conjugates showed the most functional modifications. Increasing xylose/HN ratios led to significant molecular rearrangements in the peptide populations and intermediate aromatic compounds of the MR detected at 220 and 294 nm, respectively. Consequently, HN-xylose conjugates had higher reducing power than HN. Conversely, at 0.5% (w/w), a sharp increase in consistency index and apparent viscosity of emulsions after a 4-h ageing period was obtained with the lowest xylose/HN ratio. These results confirm that MR is a promising process for the production of new natural food ingredients from marine-derived protein sources

Evaluation de la fiabilite du logiciel d'un autocommutateur telephonique

SIGLECNRS T Bordereau / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc