15 research outputs found

    frystreet + friends

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    A performance of the Fry Street Quartet and others at the Performance Hall at Utah State University, performed on November 8, 2012.https://digitalcommons.usu.edu/music_programs/1174/thumbnail.jp

    Caine Chamber Ensembles

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    Caine Chamber Ensembles featuring the Brass Quintet, Woodwind Quintet, Percussion Ensemble and Saxophone Quartet.https://digitalcommons.usu.edu/music_programs/1030/thumbnail.jp

    Caine Chamber Ensembles

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    Caine Chamber Ensembles featuring the Brass Quintet, Woodwind Quintet, Percussion Ensemble and Saxophone Quartet.https://digitalcommons.usu.edu/music_programs/1030/thumbnail.jp

    Caine Chamber Ensembles

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    Join us for a concert performed by the Caine Chamber Ensembles.https://digitalcommons.usu.edu/music_programs/1102/thumbnail.jp

    Cellular Ser/Thr-Kinase Assays Using Generic Peptide Substrates

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    High-throughput cellular profiling has successfully stimulated early drug discovery pipelines by facilitating targeted as well as opportunistic lead finding, hit annotation and SAR analysis. While automation-friendly universal assay formats exist to address most established drug target classes like GPCRs, NHRs, ion channels or Tyr-kinases, no such cellular assay technology is currently enabling an equally broad and rapid interrogation of the Ser/Thr-kinase space. Here we present the foundation of an emerging cellular Ser/Thr-kinase platform that involves a) coexpression of targeted kinases with promiscuous peptide substrates and b) quantification of intracellular substrate phosphorylation by homogeneous TR-FRET. Proof-of-concept data is provided for cellular AKT, B-RAF and CamK2δ assays. Importantly, comparable activity profiles were found for well characterized B-Raf inhibitors in TR-FRET assays relying on either promiscuous peptide substrates or a MEK1(WT) protein substrate respectively. Moreover, IC50-values correlated strongly between cellular TR-FRET assays and a gold standard Ba/F3 proliferation assay for B-Raf activity. Finally, we expanded our initial assay panel by screening a kinase-focused cDNA library and identified starting points for >20 cellular Ser/Thr-kinase assays

    Caine Chamber Ensembles

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    The USU Caine Chamber Ensembles preform a concert featuring the Caine String Quartet, Caine Woodwind Quintet, Caine Saxophone Quartet, Caine Brass Quintet, and Caine Percussion Ensemble.https://digitalcommons.usu.edu/music_programs/1037/thumbnail.jp

    Homogeneous high-throughput screening assays for HIV-1 integrase 3beta-processing and strand transfer activities.

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    HIV-1 integrase (HIV-IN) is a well-validated antiviral drug target catalyzing a multistep reaction to incorporate the HIV-1 provirus into the genome of the host cell. Small molecule inhibitors of HIV-1 integrase that specifically target the strand transfer step have demonstrated efficacy in the suppression of virus propagation. However, only few specific strand transfer inhibitors have been identified to date, and the need to screen for novel compound scaffolds persists. Here, the authors describe 2 homogeneous time-resolved fluorescent resonance energy transfer-based assays for the measurement of HIV-1 integrase 3'-processing and strand transfer activities. Both assays were optimized for high-throughput screening formats, and a diverse library containing more than 1 million compounds was screened in 1536-well plates for HIV-IN strand transfer inhibitors. As a result, compounds were found that selectively affect the enzymatic strand transfer reaction over 3beta processing. Moreover, several bioactive molecules were identified that inhibited HIV-1 reporter virus infection in cellular model systems. In conclusion, the assays presented herein have proven their utility for the identification of mechanistically interesting and biologically active inhibitors of HIV-1 integrase that hold potential for further development into potent antiviral drugs

    Chemical activation of the mechanotransduction channel Piezo1

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    Piezo ion channels are activated by various types of mechanical stimuli and function as biological pressure sensors in both vertebrates and invertebrates. To date mechanical stimuli are the only means to activate Piezo ion channels and whether other modes of activation exist is not known. Here, we screened ~3.25 million compounds using a cell-based fluorescence assay and identified a synthetic small molecule we termed Yoda1 that acts as an agonist for both human and mouse Piezo1. Functional studies in cells revealed that Yoda1 affects the sensitivity and the inactivation kinetics of mechanically induced responses. Characterization of Yoda1 in artificial droplet lipid bilayers showed that Yoda1 activates purified Piezo1 channels in the absence of other cellular components. Our studies demonstrate that Piezo1 is amenable to chemical activation, and raise the possibility that endogenous Piezo1 agonists might exist. Yoda1 will serve as a key tool compound to study Piezo1 regulation and function
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