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第十五届国际药理学大会

作者： Komives Elizabeth A. taylor palmer Depart of Chemistry and Biochemistry Univ of Calif San Diego 9500 Gilman Drive La Jolla CA 92093-0636 Depart.of Pharmacology Univ of Calif San Diego 9500 Gilman Drive La Jolla CA 92093 - 0636

＜正＞ AChBP serves as a high resolution structural template for the ligand binding domains of the nicotinic acetylcholine receptor. To examine how changes in protein dynamics and flexibility contribute to ligand dependent activation of the nicotinic receptor, we have employed mass spectrometry to probe changes in hydrogen/ deuterium exchange in AChBP in the presence and absence of different classes of ligands. These include nicotinic agonists （epibatidine and lobeline）. partial agonists, alkaloid antagonists, short and long peptidic antagonists （alpha - conotoxinsand alpha - neurotoxins）. and non - competitive ligands （galanthamine）. In the apo - protein, two regions facing the active site at the subunit interface, loop C （175 - 193） and loop F （164 - 171）, adopt highly flexible conformations. The various ligands all protect loop C to varying extents and with distinctive exchange kinetics. The partial agonist, an anabaseine derivative, and small alkaloid antagonist, methyllycaconitine. also simultaneously protect residues on loop F （164 - 171）. on the complementary subunit interface. These data underscore the selective influence on dynamic state of AChBP by pharmacologically different classes of nicotinic ligands.

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Conformational States of AChBP revealed by X-ray crystal Structures of bound nAChR Agonists. Antagonists and Non- competitive ligands.

Conformational States of AChBP revealed by X-ray crystal Str...

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第十五届国际药理学大会

作者： Hansen Scott Sulzenbacher Gerlind Huxford Tom Marchot Pascale Bourne Yves taylor palmer Dept of Pharmacology UCSD CNRS Marseille Dept of Chemistry and Biochemistry UCSD CNRS Marseille CNRS Marseille Dept of Pharmacology UCSD

＜正＞ We use the acetylcholine binding protein （AChBP） from mollusks as a soluble surrogate for the extracellular ligand binding domain of nicotinic acetylcholine receptors （ nAChR）. Ligand binding in the nAChR extracellular domain induces conformational states that allosterically open an ion channel. nAChR states have not been studied at atomic resolution. We have solved X- ray crystal structures of receptor agonists, antagonists and non- competitive ligand bound to AChBP. These structures reveal large conformation changes in the ligand binding pocket and distinct interface binding surfaces. Conformational changes in loop C reveal a general mechanism for agonism and partial agonism. X- ray structures of noncompetitivereceptor ligands galanthamine. cocaine, and thienyl - cylohexylpiperidine（TCP） in complex with AChBP reveal valuable information for accurately describing non- competitive receptor modulation. A crystal structure of apo AChBP is presented and compared to that of bound agonists, lobeline and epibatidine. and antagonists, alpha-conotoxin Iml and methyllycaconitine.

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Recruitment and functionality traits as bioindicators of ecological restoration success in the Lurg Hills district,Victoria,Australia

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Ecological Processes 2013年第1期2卷 286-296页

作者： Kristin Monie Singarayer Florentine Grant palmer Centre for Environmental Management School of ScienceInformation Technology and EngineeringUniversity of BallaratPO Box 663BallaratVictoriaAustralia

Introduction:The Regent Honeyeater Project commenced ecological restoration in the Lurg district in 1994,with an aim to restore habitats for the critically endangered Regent Honeyeater Anthochaera phrygia and a range of other threatened and declining *** this context,our study aimed to explore whether plant reproduction can be an effective measure of ecological restoration ***:Evaluation involved comparing attributes at unrestored,restored and remnant sites to establish whether sites displayed evidence of a clear restoration *** age classes(unrestored,4–6 years old,8–10 years old,12–14 years old and remnant areas)and two landforms(upper hills and lower hills)were *** diversity of woody plant species—which have easily recognisable reproductive material and which all recruit seedlings—provides easily measured parameters that have the potential to allow the determination of early establishment success and long-term ecological development of restored ***:Restoration plantings developed in a hybrid state towards a benchmark in the lower hills;seedling species composition differed significantly among age classes,increasing in similarity with time since restoration,with some divergence from the target *** of functional groups with reproductive outputs was also significantly different among age classes;however,a restoration trajectory was only evident in the upper hills where sites converged towards the target ***:Divergence or deviation from the restoration trajectory was not deemed to be a restoration failure,as the variety of functional groups with fruits and diversity of seedlings recruiting indicated a potential increase in resilience in the future due to greater variability across the *** recruitment was effective in detecting development trends towards a restoration target in this study and therefore may be a useful measure that contributes to determining ecological

关键词： Restoration Assessment Ecological development Trajectory Monitoring

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