517 research outputs found

    Structural basis of control of inward rectifier Kir2 channel gating by bulk anionic phospholipids

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    Inward rectifier potassium (Kir) channel activity is controlled by plasma membrane lipids. Phosphatidylinositol-4,5-bisphosphate (PIP(2)) binding to a primary site is required for opening of classic inward rectifier Kir2.1 and Kir2.2 channels, but interaction of bulk anionic phospholipid (PL(−)) with a distinct second site is required for high PIP(2) sensitivity. Here we show that introduction of a lipid-partitioning tryptophan at the second site (K62W) generates high PIP(2) sensitivity, even in the absence of PL(−). Furthermore, high-resolution x-ray crystal structures of Kir2.2[K62W], with or without added PIP(2) (2.8- and 2.0-Å resolution, respectively), reveal tight tethering of the C-terminal domain (CTD) to the transmembrane domain (TMD) in each condition. Our results suggest a refined model for phospholipid gating in which PL(−) binding at the second site pulls the CTD toward the membrane, inducing the formation of the high-affinity primary PIP(2) site and explaining the positive allostery between PL(−) binding and PIP(2) sensitivity

    Pathogenicity and antigenicity of a new variant of Korean nephropathogenic infectious bronchitis virus

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    Despite the existence of an active vaccination program, recently emerged strains of nephropathogenic infectious bronchitis virus (IBV) in Korea have caused significant economic losses in the poultry industry. In this study, we assessed the pathogenic and antigenic characteristics of a K-IIb type field strain of IBV that emerged in Korea since 2003, such as Kr/Q43/06. Specific pathogen free 1-week-old chickens exhibited severe respiratory symptoms (dyspnea) and nephropathogenic lesions (swollen kidneys with nephritis and urate deposits) following challenge with the recent IBV field strain. The antigenic relatedness (R value), based on a calculated virus neutralization index, of the K-IIb type field strain and K-IIa type strain KM91 (isolated in 1991) was 30%, which indicated that the recent strain, Kr/Q43/06, is a new variant that is antigenically distinct from strain KM91. This report is the first to document the emergence of a new antigenic variant of nephropathogenic IBV in chicken from Korea

    Quasi 3D ECE imaging system for study of MHD instabilities in KSTAR

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    A second electron cyclotron emission imaging (ECEI) system has been installed on the KSTAR tokamak, toroidally separated by 1/16th of the torus from the first ECEI system. For the first time, the dynamical evolutions of MHD instabilities from the plasma core to the edge have been visualized in quasi-3D for a wide range of the KSTAR operation (B0 = 1.7???3.5 T). This flexible diagnostic capability has been realized by substantial improvements in large-aperture quasi-optical microwave components including the development of broad-band polarization rotators for imaging of the fundamental ordinary ECE as well as the usual 2nd harmonic extraordinary ECE.open1

    Protective efficacy of commercial inactivated Newcastle disease virus vaccines in chickens against a recent Korean epizootic strain

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    Despite the intensive vaccination policy that has been put in place to control Newcastle disease virus (NDV), the recent emergence of NDV genotype VII strains in Korea has led to significant economic losses in the poultry industry. We assessed the ability of inactivated, oil-emulsion vaccines derived from La Sota or Ulster 2C NDV strains to protect chickens from challenge with Kr-005/00, which is a recently isolated Korean epizootic genotype VII strain. Six-week-old SPF chickens were vaccinated once and challenged three weeks later via the eye drop/intranasal route. All vaccinated birds were fully protected from disease, regardless of the vaccine strains used. All vaccinated and challenged groups showed significant sero-conversion 14 days after challenge. However, some vaccinated birds, despite being protected from disease, shed the challenge virus from their oro-pharynx and cloaca, albeit at significantly lower titers than the unvaccinated challenged control birds. The virological, serological, and epidemiological significance of our observations with regard to NDV disease eradication is discussed

    The Medicinal Chemistry of 5-HT6 Receptor Ligands with a Focus on Arylsulfonyltryptamine Analogs

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    Arylsulfonyl analogs of aminopyrimidines (e.g. Ro 04-6790; 2), aminopyridines (e.g. Ro 63-0563; 3), 1-phenylpiperazines (e.g. SB-271046; 4), and tryptamines (e.g. MS-245; 5) were described as the first examples of selective 5-HT6 receptor antagonists only ten years ago. Today, hundreds of compounds of seemingly diverse structure have been reported. The early antagonists featured an arylsulfonyl group leading to the widespread assumption that an arylsulfonyl moiety might be critical for binding and antagonist action. With respect to the arylsulfonyltryptamines, it seems that neither the “arylsulfonyl” nor the “tryptamine” portion of these compounds is essential for binding or for antagonist action, and some such derivatives even display agonist action. The present review describes many of the currently available 5-HT6 receptor ligands and, unlike prior reviews, provides a narrative of the thinking (where possible) that led to their design, synthesis, and evaluation. The arylsulfonyltryptamines are also used as the structural basis of attempts to relate various structure-types to one another to afford a better understanding of the overall structural requirements for 5-HT6 receptor binding

    Broadband Multichannel Radiometer for ECE Measurements on KSTAR

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    A broadband heterodyne radiometer system has been developed and installed on KSTAR to measure second harmonic electron cyclotron emission (ECE) at the magnetic field of 3 T. The system consisting of two radiometers (110-162 GHz and 164-196 GHz) can cover a frequency range of 110-196 GHz. The unique and key components to construct this ECE diagnostic instrument are specially-designed detector modules and a diplexer for splitting ECE radiation with high efficiency. The minimum detectable electron temperature with a time response of 1 ?s is about 0.23 eV. The observed signal intensity is roughly consistent with the value estimated by using characteristics of various components (waveguide components, sub-harmonic mixers, amplifiers, and intermediate frequency detectors). In this article, design considerations and preliminary ECE measurements will be described

    Linkages between sediment composition, wave climate and beach profile variability at multiple timescales

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    The paper analyses, compares and contrasts cross-shore morphodynamic behaviour of four diverse beaches that have very different regional settings, wave climates and sediment characteristics, with the aid of rarely available long term measurements of beach profiles and incident waves. The beaches investigated are Narrabeen Beach, New South Wales, Australia; Milford-on-Sea Beach, Christchurch Bay, UK; Hasaki Coast, Ibaraki Prefecture, Japan; and Joetsu-Ogata Coast, Niigata Prefecture, Japan. A statistical analysis, equilibrium beach profile analysis and Empirical Orthogonal Function analysis are used to investigate, compare and contrast spatial and temporal variability of cross shore beach profiles of the selected beaches at short-, medium- and long-term timescales. All beaches show evidence of multi-timescale morphodynamic change. Narrabeen Beach profile has the highest sensitivity to local weather patterns. Milford-on-Sea, Joetsu-Ogata and Hasaki profiles are sensitive to seasonal variation of the wave climate however, they also show some correlations with regional climate variabilities. The nature of sediment exchange across the profile, which contributes to profile shape change with time, is found to be related to sediment characteristics across the profile. At Milford-on-Sea and Joetsu-Ogata, both of which have composite profiles, sediment exchange between the upper beach and the inter-tidal zone dominates profile change, irrespective of the distinct differences in sediment composition found in the two beaches. On the other hand in Narrabeen and Hasaki where beach sediment comprises medium to find sand, sediment exchange and hence profile change occur mainly in intertidal and subtidal zones
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