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971.
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973.
Dollé F Emond P Mavel S Demphel S Hinnen F Mincheva Z Saba W Valette H Chalon S Halldin C Helfenbein J Legaillard J Madelmont JC Deloye JB Bottlaender M Guilloteau D 《Bioorganic & medicinal chemistry》2006,14(4):1115-1125
LBT-999 (8-((E)-4-fluoro-but-2-enyl)-3beta-p-tolyl-8-aza-bicyclo[3.2.1]octane-2beta-carboxylic acid methyl ester), a cocaine derivative belonging to a new generation of highly selective dopamine transporter (DAT) ligands, and its corresponding carboxylic acid derivative, the latter used as precursor for labelling both with tritium and the positron-emitter carbon-11 (half-life: 20.38 min), were synthesized from (R)-cocaine. [(3)H]LBT-999 (>99% radiochemically pure, specific radioactivity of 3.1 TBq/mmol) was prepared from [(3)H]methyl iodide, allowing its in vitro pharmacological evaluation (K(D): 9 nM for DAT and IC(50) > 1000 nM for SERT and NET). Routine production batches of 4.5-9.0 GBq of iv injectable solutions of [(11)C]LBT-999 (with specific radioactivities ranging from 30 to 45 GBq/mumol) were prepared in 25-30 min (HPLC purification and formulation included) using the efficient methylation reagent [(11)C]methyl triflate. The preliminary in vivo pharmacological evaluation of [(11)C]LBT-999, using both biodistributions in rats and brain imaging in monkeys with positron emission tomography (PET), clearly illustrates that this ligand is an excellent candidate for quantification with PET of DAT in humans. 相似文献
974.
Nayak V Zhao K Wyce A Schwartz MF Lo WS Berger SL Marmorstein R 《Structure (London, England : 1993)》2006,14(3):477-485
The Snf1/AMPK kinases are intracellular energy sensors, and the AMPK pathway has been implicated in a variety of metabolic human disorders. Here we report the crystal structure of the kinase domain from yeast Snf1, revealing a bilobe kinase fold with greatest homology to cyclin-dependant kinase-2. Unexpectedly, the crystal structure also reveals a novel homodimer that we show also forms in solution, as demonstrated by equilibrium sedimentation, and in yeast cells, as shown by coimmunoprecipitation of differentially tagged intact Snf1. A mapping of sequence conservation suggests that dimer formation is a conserved feature of the Snf1/AMPK kinases. The conformation of the conserved alphaC helix, and the burial of the activation segment and substrate binding site within the dimer, suggests that it represents an inactive form of the kinase. Taken together, these studies suggest another layer of kinase regulation within the Snf1/AMPK family, and an avenue for development of AMPK-specific activating compounds. 相似文献
975.
976.
Yannis Guillemin Jonathan Lopez Diana Gimenez Gustavo Fuertes Juan Garcia Valero Lo?c Blum Philippe Gonzalo Jesùs Salgado Agnès Girard-Egrot Abdel Aouacheria 《PloS one》2010,5(2)
Background
The BCL-2 family of proteins includes pro- and antiapoptotic members acting by controlling the permeabilization of mitochondria. Although the association of these proteins with the outer mitochondrial membrane is crucial for their function, little is known about the characteristics of this interaction.Methodology/Principal Findings
Here, we followed a reductionist approach to clarify to what extent membrane-active regions of homologous BCL-2 family proteins contribute to their functional divergence. Using isolated mitochondria as well as model lipid Langmuir monolayers coupled with Brewster Angle Microscopy, we explored systematically and comparatively the membrane activity and membrane-peptide interactions of fragments derived from the central helical hairpin of BAX, BCL-xL and BID. The results show a connection between the differing abilities of the assayed peptide fragments to contact, insert, destabilize and porate membranes and the activity of their cognate proteins in programmed cell death.Conclusion/Significance
BCL-2 family-derived pore-forming helices thus represent structurally analogous, but functionally dissimilar membrane domains. 相似文献977.
Chun‐Yen Chen Kuei‐Ling Yeh Huei‐Meei Su Yung‐Chung Lo Wen‐Ming Chen Jo‐Shu Chang 《Biotechnology progress》2010,26(3):679-686
The autotrophic growth of an oil‐rich indigenous microalgal isolate, identified as Chlorella vulgaris C? C, was promoted by using engineering strategies to obtain the microalgal oil for biodiesel synthesis. Illumination with a light/dark cycle of 14/10 (i.e., 14 h light‐on and 10 h light‐off) resulted in a high overall oil production rate (voil) of 9.78 mg/L/day and a high electricity conversion efficiency (Ec) of 23.7 mg cell/kw h. When using a NaHCO3 concentration of 1,500 mg/L as carbon source, the voil and Ec were maximal at 100 mg/L/day and 128 mg/kw h, respectively. A Monod type model was used to describe the microalgal growth kinetics with an estimated maximum specific growth rate (μmax) of 0.605 day?1 and a half saturation coefficient (Ks) of 124.9 mg/L. An optimal nitrogen source (KNO3) concentration of 625 mg/L could further enhance the microalgal biomass and oil production, leading to a nearly 6.19 fold increase in voil value. © 2010 American Institute of Chemical Engineers Biotechnol. Prog., 2010 相似文献
978.
Lo JT 《Cognitive neurodynamics》2010,4(4):401-402
[This corrects the article DOI: 10.1007/s11571-010-9110-4.]. 相似文献
979.
980.
Siu-Kin Ng Wing-Sze Lo Frank W. Pun Cunyou Zhao Zhiliang Yu Jianhuan Chen Ka-Lok Tong Zhiwen Xu Shui-Ying Tsang Qiang Yang Weichuan Yu Vishwajit Nimgaonkar Gerald St?ber Mutsuo Harano Hong Xue 《PloS one》2010,5(3)