Browsing by Author "Wang, Ping"

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    The cell division protein MinD from Pseudomonas aeruginosa dominates the assembly of the MinC-MinD copolymers.
    (The Journal of biological chemistry, 2018-04-02) Huang, Haiyan; Wang, Ping; Bian, Li; Osawa, Masaki; Erickson, Harold P; Chen, Yaodong
    Cell division of rod-shaped bacteria requires the Z ring, a ring of FtsZ filaments associated with the inner-membrane wall. The MinCDE proteins help localize the Z ring to the center of the Escherichia coli cell. MinC, which inhibits Z-ring assembly, is a passenger on MinD. Previous studies have shown that MinC-MinD from E. coli and Aquifex aeolicus assemble in vitro into extended filaments with a 1:1 stoichiometry. However, a recent study has raised questions about the function of the MinC-MinD copolymer in vivo, since its assembly appears to require a high concentration of these two proteins, has a long lag time, and its blockade does not affect in vivo activities. Here, we found that MinC and MinD from Pseudomonas aeruginosa coassemble into filaments with a 1:1 stoichiometry. We also found that the minimal concentration of ~4 μM required for assembly applies only to MinD because above 4 μM MinD, even very low MinC concentrations sustained coassembly. As previously reported, the MinC-MinD coassembly exhibited a long lag of ~100 s when initiated by ATP. Premixing MinD with ATP eliminated this lag, suggesting that it may be due to slow MinD dimerization following ATP activation. We also discovered that MinC-MinD copolymers quickly bound and formed huge bundles with FtsZ filaments. Our results resolve previous questions about the low concentration of MinC and the lag time, insights that may inform future investigations into the exact role of the MinC-MinD copolymer in vivo.
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    ZFX Mediates Non-canonical Oncogenic Functions of the Androgen Receptor Splice Variant 7 in Castrate-Resistant Prostate Cancer
    (Molecular Cell, 2018-10) Cai, Ling; Tsai, Yi-Hsuan; Wang, Ping; Wang, Jun; Li, Dongxu; Fan, Huitao; Zhao, Yilin; Bareja, Rohan; Lu, Rui; Wilson, Elizabeth M; Sboner, Andrea; Whang, Young E; Zheng, Deyou; Parker, Joel S; Earp, H Shelton; Wang, Gang Greg
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    β-D-glucan surveillance with preemptive anidulafungin for invasive candidiasis in intensive care unit patients: a randomized pilot study.
    (PloS one, 2012-01) Hanson, Kimberly E; Pfeiffer, Christopher D; Lease, Erika D; Balch, Alfred H; Zaas, Aimee K; Perfect, John R; Alexander, Barbara D

    Background

    Invasive candidiasis (IC) is a devastating disease. While prompt antifungal therapy improves outcomes, empiric treatment based on the presence of fever has little clinical impact. Β-D-Glucan (BDG) is a fungal cell wall component detectable in the serum of patients with early invasive fungal infection (IFI). We evaluated the utility of BDG surveillance as a guide for preemptive antifungal therapy in at-risk intensive care unit (ICU) patients.

    Methods

    Patients admitted to the ICU for ≥ 3 days and expected to require at least 2 additional days of intensive care were enrolled. Subjects were randomized in 3:1 fashion to receive twice weekly BDG surveillance with preemptive anidulafungin in response to a positive test or empiric antifungal treatment based on physician preference.

    Results

    Sixty-four subjects were enrolled, with 1 proven and 5 probable cases of IC identified over a 2.5 year period. BDG levels were higher in subjects with proven/probable IC as compared to those without an IFI (117 pg/ml vs. 28 pg/ml; p<0.001). Optimal assay performance required 2 sequential BDG determinations of ≥ 80 pg/ml to define a positive test (sensitivity 100%, specificity 75%, positive predictive value 30%, negative predictive value 100%). In all, 21 preemptive and 5 empiric subjects received systemic antifungal therapy. Receipt of preemptive antifungal treatment had a significant effect on BDG concentrations (p< 0.001). Preemptive anidulafungin was safe and generally well tolerated with excellent outcome.

    Conclusions

    BDG monitoring may be useful for identifying ICU patients at highest risk to develop an IFI as well as for monitoring treatment response. Preemptive strategies based on fungal biomarkers warrant further study.

    Trial registration

    Clinical Trials.gov NCT00672841.