Browsing by Author "Beketskaia, Maria"

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    Phenotypic Association between the Outer Membrane Protein OmpW and the Small Multi-Drug Resistance Protein EmrE in Escherichia coli
    (2014-09-02) Beketskaia, Maria; Turner, Raymond
    In Escherichia coli, the small multidrug resistance (SMR) transporter protein EmrE confers host resistance to a broad range of toxic quaternary cationic compounds (QCCs) via proton motive force in the cytoplasmic membrane. Biologically produced QCCs also act as EmrE osmoprotectant substrates within the cell and participate in host pH regulation and osmotic tolerance. Although E. coli EmrE is one of the most well-characterized SMR members, it is unclear how the substrates that it transports into the periplasmic space escape across the outer membrane (OM) in Gram-negative bacteria. We tested the hypothesis that E. coli EmrE relies on an unidentified OM protein (OMP) to complete the extracellular release of its QCC. By conducting pH-based phenotypic growth screens, complementation and methyl viologen (MV) resistance assays, we have confirmed that EmrE relies on the presence of an OMP, specifically OmpW, to complete its extracellular substrate efflux across the OM.
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    Using magnetic resonance imaging in animal models to guide drug development in multiple sclerosis
    (2013-11-21) Nathoo, Nabeela; Yong, V Wee; Dunn, Jeffrey F.; Beketskaia, Maria
    Major advances are taking place in the development of therapeutics for multiple sclerosis (MS), with a move past traditional immunomodulatory/immunosuppressive therapies toward medications aimed at promoting remyelination or neuroprotection. With an increase in diversity of MS therapies comes the need to assess the effectiveness of such therapies. Magnetic resonance imaging (MRI) is one of the main tools used to evaluate the effectiveness of MS therapeutics in clinical trials. As all new therapeutics for MS are tested in animal models first, it is logical that MRI be incorporated into preclinical studies assessing therapeutics. Here, we review key papers showing how MR imaging has been combined with a range of animal models to evaluate potential therapeutics for MS. We also advise on how to maximize the potential for incorporating MRI into preclinical studies evaluating possible therapeutics for MS, which should improve the likelihood of discovering new medications for the condition.