1,247 research outputs found

    Characterization of three vasopressin receptor 2 variants: an apparent polymorphism (V266A) and two loss-of-function mutations (R181C and M311V).

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    Arginine vasopressin (AVP) is released from the posterior pituitary and controls water homeostasis. AVP binding to vasopressin V2 receptors (V2Rs) located on kidney collecting duct epithelial cells triggers activation of Gs proteins, leading to increased cAMP levels, trafficking of aquaporin-2 water channels, and consequent increased water permeability and antidiuresis. Typically, loss-of-function V2R mutations cause nephrogenic diabetes insipidus (NDI), whereas gain-of-function mutations cause nephrogenic syndrome of inappropriate antidiuresis (NSIAD). Here we provide further characterization of two mutant V2Rs, R181C and M311V, reported to cause complete and partial NDI respectively, together with a V266A variant, in a patient diagnosed with NSIAD. Our data in HEK293FT cells revealed that for cAMP accumulation, AVP was about 500- or 30-fold less potent at the R181C and M311V mutants than at the wild-type receptor respectively (and about 4000- and 60-fold in COS7 cells respectively). However, in contrast to wild type V2R, the R181C mutant failed to increase inositol phosphate production, while with the M311V mutant, AVP exhibited only partial agonism in addition to a 37-fold potency decrease. Similar responses were detected in a BRET assay for β-arrestin recruitment, with the R181C receptor unresponsive to AVP, and partial agonism with a 23-fold decrease in potency observed with M311V in both HEK293FT and COS7 cells. Notably, the V266A V2R appeared functionally identical to the wild-type receptor in all assays tested, including cAMP and inositol phosphate accumulation, β-arrestin interaction, and in a BRET assay of receptor ubiquitination. Each receptor was expressed at comparable levels. Hence, the M311V V2R retains greater activity than the R181C mutant, consistent with the milder phenotype of NDI associated with this mutant. Notably, the R181C mutant appears to be a Gs protein-biased receptor incapable of signaling to inositol phosphate or recruiting β-arrestin. The etiology of NSIAD in the patient with V266A V2R remains unknown

    Prediction during simultaneous interpreting:Evidence from the visual-world paradigm

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    We report the results of an eye-tracking study which used the Visual World Paradigm (VWP) to investigate the time-course of prediction during a simultaneous interpreting task. Twenty-four L1 French professional conference interpreters and twenty-four L1 French professional translators untrained in simultaneous interpretation listened to sentences in English and interpreted them simultaneously into French while looking at a visual scene. Sentences contained a highly predictable word (e.g., The dentist asked the man to open his mouth a little wider). The visual scene comprised four objects, one of which depicted either the target object (mouth; bouche), an English phonological competitor (mouse; souris), a French phonological competitor (cork; bouchon), or an unrelated word (bone; os). We considered 1) whether interpreters and translators predict upcoming nouns during a simultaneous interpreting task, 2) whether interpreters and translators predict the form of these nouns in English and in French and 3) whether interpreters and translators manifest different predictive behaviour. Our results suggest that both interpreters and translators predict upcoming nouns, but neither group predicts the word-form of these nouns. In addition, we did not find significant differences between patterns of prediction in interpreters and translators. Thus, evidence from the visual-world paradigm shows that prediction takes place in simultaneous interpreting, regardless of training and experience. However, we were unable to establish whether word-form was predicted

    Magnetic characterization of the frustrated three-leg ladder compound [(CuCl2tachH)3Cl]Cl2

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    We report the magnetic features of a new one-dimensional stack of antiferromagnetically coupled equilateral copper(II) triangles. High-field magnetization measurements show that the interaction between the copper triangles is of the same order of magnitude as the intra-triangle exchange although only coupled via hydrogen bonds. The infinite chain turns out to be an interesting example of a frustrated cylindrical three-leg ladder with competing intra- and inter-triangle interactions. We demonstrate that the ground state is a spin singlet which is gaped from the triplet excitation.Comment: 6 pages, 9 figures, revised version submitted to Phys. Rev. B. More information at http://obelix.physik.uni-osnabrueck.de/~schnack

    Student interpreters predict meaning while simultaneously interpreting - even before training

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    Prediction has long been considered advantageous in simultaneous interpreting, as it may allow interpreters to comprehend more rapidly and focus on their own production. However, evidence of prediction in simultaneous interpreting to date is relatively limited. In addition, it is unclear whether training in simultaneous interpreting influences predictive processing during a simultaneous interpreting task. We report on a longitudinal eyetracking study which measured the timing and extent of prediction in students before and after two semesters of training in simultaneous interpreting. The students simultaneously interpreted sentences containing a highly predictable word as they viewed a screen containing four pictures, one of which depicted a highly predictable object. They made predictive eye movements to the highly predictable object both before and after their training in simultaneous interpreting. However, we did not find evidence that training influenced the timing or the magnitude of their prediction

    Correlating the Energetics and Atomic Motions of the Metal-Insulator Transition of M1 Vanadium Dioxide

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    Materials that undergo reversible metal-insulator transitions are obvious candidates for new generations of devices. For such potential to be realised, the underlying microscopic mechanisms of such transitions must be fully determined. In this work we probe the correlation between the energy landscape and electronic structure of the metal-insulator transition of vanadium dioxide and the atomic motions occurring using first principles calculations and high resolution X-ray diffraction. Calculations find an energy barrier between the high and low temperature phases corresponding to contraction followed by expansion of the distances between vanadium atoms on neighbouring sub-lattices. X-ray diffraction reveals anisotropic strain broadening in the low temperature structure's crystal planes, however only for those with spacings affected by this compression/expansion. GW calculations reveal that traversing this barrier destabilises the bonding/anti-bonding splitting of the low temperature phase. This precise atomic description of the origin of the energy barrier separating the two structures will facilitate more precise control over the transition characteristics for new applications and devices.Comment: 11 Pages, 8 Figure

    A voluntary association in a formal bureaucracy: the case of the county council on aging in Kansas

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    Call number: LD2668 .T4 1979 S44Master of Art

    New insights on the interaction between thiophene derivatives and Au surfaces: the case of 3,4-ethylenedioxythiophene and the relevant polymer.

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    The nature of the interface between electrogenerated poly(3,4-ethylenedioxythiophene) and the Au substrate is studied in detail. In particular, the adsorption of the relevant monomer, namely, 3,4-ethylenedioxythiophene, is investigated and compared with that of other thiophene derivatives. Different deposition procedures have been adopted: very thin films of the thiophene derivatives have been obtained through chemisorption processes from vapor and liquid phases, on Au polycrystalline substrates, Au nano particles possessing different size, and a Au(111) single crystal. Different techniques, operating both in situ and ex situ, have been employed for the characterization of these deposits, that is, X-ray photoemission and surface enhanced Raman spectroscopy. The results show that the poly(3,4-ethylenedioxythiophene)/metal interface is far from being simply constituted by unreacted molecules in contact with the substrate; rather, the formation of oligothiophene species and sulfur atoms at the interface has been ascertained

    Electropolymerisation of 3,4-ethylenedioxythiophene in aqueous solutions

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    The potentiostatic electrosynthesis of poly(3,4-ethylenedioxythiophene) (PEDOT) in aqueous media without addition to the solution of any kind of surfactant has been studied by electrochemical quartz crystal microbalance (EQCM) and by spectroelectrochemistry. These tandem techniques have given valuable new information about the electropolymerisation process, allowing us to relate absorbance-charge and frequency-charge relationships to: (i) oligomers generation and chain propagation, as far as the length leading to precipitation is reached; (ii) growing of the polymer deposit and concomitant p-doping, and even (iii) overoxidation of the polymer film. An analysis of the whole of the data, in fact, shows that the charge spent is not necessarily totally involved in thepolymer deposit formation, growth, and p-doping, so that it is necessary to be particularly careful in the fitting of the experimental data to linear models

    Bidimensional chronoabsorptometric study of electropolymerisation of 4,4 '-bis(2-methylbutylthio)-2,2 '-bithiophene

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    Bidimensional chronoabsorptometry is a novel spectroelectrochemical technique that monitors simultaneously three different signals: current and absorbance both normal to the electrode plane and parallel to this plane during a time in which a fixed potential is imposed. This technique is applied in the visible range to the study of the electropolymerisation of 4,4'-bis(2-methylbutylthio)2,2'-bithiophene (MBTBT). Experiments are performed in a spectroelectrochemical cell under finite diffusion conditions (thin layer cell) with the aim of interpreting the processes taking place both at the electrode surface and in the adjacent solution during the potentiostatic electrogeneration and deposition of the polymer. Correlations are drawn out among the trends of the oligomers concentration in solution, the polymer electrodeposition and charging, and the current flow, on the time scales of the different steps of the process. (C) 2002 Elsevier Science B.V. All rights reserved

    BCKDH: the missing link in apicomplexan mitochondrial metabolism is required for full virulence of Toxoplasma gondii and Plasmodium berghei

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    While the apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii are thought to primarily depend on glycolysis for ATP synthesis, recent studies have shown that they can fully catabolize glucose in a canonical TCA cycle. However, these parasites lack a mitochondrial isoform of pyruvate dehydrogenase and the identity of the enzyme that catalyses the conversion of pyruvate to acetyl-CoA remains enigmatic. Here we demonstrate that the mitochondrial branched chain ketoacid dehydrogenase (BCKDH) complex is the missing link, functionally replacing mitochondrial PDH in both T. gondii and P. berghei. Deletion of the E1a subunit of T. gondii and P. berghei BCKDH significantly impacted on intracellular growth and virulence of both parasites. Interestingly, disruption of the P. berghei E1a restricted parasite development to reticulocytes only and completely prevented maturation of oocysts during mosquito transmission. Overall this study highlights the importance of the molecular adaptation of BCKDH in this important class of pathogens
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