204 resultados para linton


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Preface signed: Anne Gilchrist.

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"Reproduced by Duopage process."

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Master microform held by: DLC.

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A novel.

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At head of title: University of Liverpool.

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WHEN MEDIA ARE NEW: UNDERSTANDING THE DYNAMICS OF NEW MEDIA ADOPTION AND USE, JOHN CAREY AND MARTIN C. J. ELTON (2010) Ann Arbor, MI: University of Michigan Press (374 pp.), ISBN 978-0-472-05085-7, $47.50 (paperback). YOU ARE NOT A GADGET: A MANIFESTO, JARON LANIER (2011) New York: Vintage (240 pp.), ISBN 978-0307389978, $15 (paperback) EXTRAORDINARY CANADIANS: MARSHALL McLUHAN, DOUGLAS COUPLAND (2010) Toronto, Canada: Penguin Canada (208 pp.), ISBN 9780670069224, $26 (hardback)

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Structural evidence has demonstrated that P-glycoprotein (P-gp) undergoes considerable conformational changes during catalysis, and these alterations are important in drug interaction. Knowledge of which regions in P-gp undergo conformational alterations will provide vital information to elucidate the locations of drug binding sites and the mechanism of coupling. A number of investigations have implicated transmembrane segment six (TM6) in drug-P-gp interactions, and a cysteine-scanning mutagenesis approach was directed to this segment. Introduction of cysteine residues into TM6 did not disturb basal or drug-stimulated ATPase activity per se. Under basal conditions the hydrophobic probe coumarin maleimide readily labeled all introduced cysteine residues, whereas the hydrophilic fluorescein maleimide only labeled residue Cys-343. The amphiphilic BODIPY-maleimide displayed a more complex labeling profile. The extent of labeling with coumarin maleimide did not vary during the catalytic cycle, whereas fluorescein maleimide labeling of F343C was lost after nucleotide binding or hydrolysis. BODIPY-maleimide labeling was markedly altered during the catalytic cycle and indicated that the adenosine 5'-(beta,gamma-imino)triphosphate-bound and ADP/vanadate-trapped intermediates were conformationally distinct. Our data are reconciled with a recent atomic scale model of P-gp and are consistent with a tilting of TM6 in response to nucleotide binding and ATP hydrolysis.