196,002 research outputs found

    Antiproliferative effects of neuroprotective drugs targeting big Ca2+-activated K+ (BK) channel in the undifferentiated neuroblastoma cells

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    The big Ca2+-activated K+ (BK) channel has a role in regulating cell viability and survival in a variety of cells. The effects of drugs targeting the BK channels in neuronal and smooth muscle tissues in the human SH-SY5Y cell and mouse Neuro2A undifferentiated neuroblastoma cells have never been investigated. The expression/activity of BK channel subunits and the effects of the BK channel openers: acetazolamide (ACTZ) (10-7 - 2 × 10-4 M), resveratrol (RESV) (10-7 - 2 × 10-4 M), dichlorphenamide (DCP) (10-12 - 2 × 10-4 M), bendroflumethiazide (BFT) (10-9 - 10-5 M) and riluzole (RIL) (10-6 - 10-4 M) were evaluated by real time-polymerase chain reaction (RT-PCR)/patch-clamp experiments in SH-SY5Y cells and Neuro2a. Cell proliferation was evaluated by cell-dehydrogenase activity (CCK8-assay), cell impedentiometric (Scepter-counter) and clonogenic assays. An elevated expression/activity of the hslo1-BK channel subunit was observed in the SH-SY5Y, while a low expression/activity of this subunit was found in the Neuro2a. Tetraethylammonium (TEA) (1 - 5 x 10-3) and iberiotoxin (IbTX) (10-9 - 6 × 10-7 M) caused a marked inhibition of the whole-cell K+-currents in SH-SY5Y. A mild inhibition of the K+-currents was found in Neuro2a with these compounds. The application of ACTZ, DCP, RESV and BFT to the patches failed to activate the K+-currents but rather reduced it. The rank order of efficacy of the drugs as K+-current inhibitors at +30 mV (Vm) was: TEA > RESV ≥ IbTX > DCP > ACTZ > BFT. RESV and IbTX irreversibly reduced the K+-currents and the cell number in the enzymatic, clonogenic and impedentiometric assays with RESV being more effective than IbTX. TEA reversibly reduced the K+-currents without affecting cell proliferation. Whereas, RIL potentiated the BK current and reduced cell-dehydrogenases activity with no changes in the cell morphology and number. The observed irreversible BK channel-blocking action exerted by RESV and IbTX can be associated with anti-proliferative effects in cells overexpressing hslo1-BK channel subunit. This can be an additional mechanism contributing to the cytotoxic action of RESV in SH-SY5Y cells

    Dr. Duane M. Jackson, Morehouse College, July 2011

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    This video is a conversation with Dr. Duane M. Jackson. Dr. Jackson talks about his paper, "Recall and the Serial Position Effect: The Role of Primacy and Recency on Accounting Students' Performance." Jackie Daniel, AUC Woodruff Library, is the interviewer

    "Reflections on the subject of Emigration from Europe with a view to Settlement in the United States" By M. Carey.

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    "Reflections on the subject of Emigration from Europe with a view to Settlement in the United States: containing bried sketches of the moral and political character of those states. By M. Carey, member of the American philosophical, and of the American Antiquarian Society, and author of The Olive Branch, Cindiciae Hibernicae, essays on banking, on political economy, and on internal improvement. To which are now added the English editor's comments on the subject; together with Important Advice to Emigrants, and Cautions Against Impositions Practiced in the Outports

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    The alteration of calcium homeostasis in adult dystrophic mdx muscle fibers is worsened by a chronic exercise in vivo

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    Chronic exercise in vivo aggravates dystrophy in mdx mice. Calcium homeostasis was evaluated ex vivo by micro-spectrofluorometry on tendon-to-tendon dissected extensor digitorum longus (EDL) muscle fibers. Resting cytosolic calcium ([Ca2+]i) and sarcolemmal permeability through Gd3+-sensitive mechanosensitive calcium (MsCa) channel were significantly higher in mdx vs. wild-type fibers. The exercise further enhanced [Ca2+]i in mdx fibers and increased sarcolemmal permeability by activating nifedipine-sensitive leak calcium channels. The two genotypes did not differ in caffeine sensitivity and in the excitation-calcium release (ECaR) coupling mechanism by K+ depolarization. The exercise produced a similar adaptation of activation curve of ECaR and of sensitivity to caffeine. However, the inactivation of ECaR of mdx fibers did not adapt to exercise. No fiber phenotype transition occurred in exercised muscle. We provide the first evidence that an in vivo exercise worsens the impaired calcium homeostasis of dystrophic fibers, supporting the role of enhanced calcium entrance in dystrophic progression. © 2004 Elsevier Inc. All rights reserved
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