628 research outputs found

    Health Reform 2007: Impact on the Valley

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    Provides a summary of California's health reform debate, background information on recent legislative action, and an overview of the major healthcare proposals pending in the state

    Ballots and plane trees

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    AbstractThe correspondence of certain plane trees and binary sequences reported by D. A. Klarner in [1], and a ballot interpretation of the latter, are used to make an independent evaluation of the number of classes of isomorphic, (k + 1)-valent, planted plane trees with kn + 2 points. This provides an interesting multivariable identity for binomial coefficients

    Search for proteins with similarity to the CFTR R domain using an optimized RDBMS solution, mBioSQL

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    The cystic fibrosis transmembrane conductance regulator (CFTR) comprises ATP binding and transmembrane domains, and a unique regulatory (R) domain not found in other ATP binding cassette proteins. Phosphorylation of the R domain at different sites by PKA and PKC is obligatory for the chloride channel function of CFTR. Sequence similarity searches on the R domain were uninformative. Furthermore, R domains from different species show low sequence similarity. Since these R domains resemble each other only in the location of the phosphorylation sites, we generated different R domain patterns masking amino acids between these sites. Because of the high number of the generated patterns we expected a large number of matches from the UniProt database. Therefore, a relational database management system (RDBMS) was set up to handle the results. During the software development our system grew into a general package which we term Modular BioSQL (mBioSQL). It has higher performance than other solutions and presents a generalized method for the storage of biological result-sets in RDBMS allowing convenient further analysis. Application of this approach revealed that the R domain phosphorylation pattern is most similar to those in nuclear proteins, including transcription and splicing factors

    Regulation of CFTR ion channel gating by MgATP

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    AbstractSingle channel currents of wild-type CFTR reconstituted in lipid bilayers were recorded to study the temperature dependence of channel gating between +20°C and +40°C. The opening of the channel was highly temperature dependent and required an activation energy of about 100 kJ/mol. Closing of the channel was only weakly temperature dependent with an activation energy close to that of diffusion in water. We found no significant difference in the free energy between the open and closed states. Most of the excess energy needed to activate channel opening is used to diminish the entropy of the open state. This structural reorganization is initiated by ATP binding followed by interconversion to the open channel structure as the CFTR-ATP-Mg complex passes to the transition state for hydrolysis. The energy of the CFTR-ATP-Mg interaction in the transition state is responsible for the CFTR ion channel opening rather than the energy of ATP hydrolysis. Channel closing is a diffusion limited process and does not require additional ATP binding

    Dual Effects of Adp and Adenylylimidodiphosphate on Cftr Channel Kinetics Show Binding to Two Different Nucleotide Binding Sites

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    The CFTR chloride channel is regulated by phosphorylation by protein kinases, especially PKA, and by nucleotides interacting with the two nucleotide binding domains, NBD-A and NBD-B. Giant excised inside-out membrane patches from Xenopus oocytes expressing human epithelial cystic fibrosis transmembrane conductance regulator (CFTR) were tested for their chloride conductance in response to the application of PKA and nucleotides. Rapid changes in the concentration of ATP, its nonhydrolyzable analogue adenylylimidodiphosphate (AMP-PNP), its photolabile derivative ATP-P3-[1-(2-nitrophenyl)ethyl]ester, or ADP led to changes in chloride conductance with characteristic time constants, which reflected interaction of CFTR with these nucleotides. The conductance changes of strongly phosphorylated channels were slower than those of partially phosphorylated CFTR. AMP-PNP decelerated relaxations of conductance increase and decay, whereas ATP-P3-[1-(2-nitrophenyl)ethyl]ester only decelerated the conductance increase upon ATP addition. ADP decelerated the conductance increase upon ATP addition and accelerated the conductance decay upon ATP withdrawal. The results present the first direct evidence that AMP-PNP binds to two sites on the CFTR. The effects of ADP also suggest two different binding sites because of the two different modes of inhibition observed: it competes with ATP for binding (to NBD-A) on the closed channel, but it also binds to channels opened by ATP, which might either reflect binding to NBD-A (i.e., product inhibition in the hydrolysis cycle) or allosteric binding to NBD-B, which accelerates the hydrolysis cycle at NBD-A

    Toward CFTR Structural Dynamics During Ion Channel Gating

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    G89-925 \u27Helminthosporium\u27 Leaf Spot and Melting Out Diseases of Turfgrass (Revised December 1995)

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    Symptoms and controls for Helminthosporium leaf spot and melting out are discussed. Leaf spot and melting out are two fungal diseases of turfgrass within the Helminthosporium leaf, crown and root disease complex. They are the most common and serious groups of cool season turfgrass diseases in North America
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