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1.
Flavin-containing monooxygenases (FMOs) are NADPH-dependent flavoenzymes that catalyze the oxidation of heteroatom centers in numerous drugs and xenobiotics. FMO2, or "pulmonary" FMO, one of five forms of the enzyme identified in mammals, is expressed predominantly in lung and differs from other FMOs in that it can catalyze the N-oxidation of certain primary alkylamines. We describe here the isolation and characterization of cDNAs for human FMO2. Analysis of the sequence of the cDNAs and of a section of the corresponding gene revealed that the major FMO2 allele of humans encodes a polypeptide that, compared with the orthologous protein of other mammals, lacks 64 amino acid residues from its C terminus. Heterologous expression of the cDNA revealed that the truncated polypeptide was catalytically inactive. The nonsense mutation that gave rise to the truncated polypeptide, a C --> T transition in codon 472, is not present in the FMO2 gene of closely related primates, including gorilla and chimpanzee, and must therefore have arisen in the human lineage after the divergence of the Homo and Pan clades. Possible mechanisms for the fixation of the mutation in the human population and the potential significance of the loss of functional FMO2 in humans are discussed.  相似文献   
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Dolphin GT  Ouberai M  Dumy P  Garcia J 《ChemMedChem》2007,2(11):1613-1623
Amyloid beta peptide (Abeta) fibril formation is widely believed to be the causative event of Alzheimer's disease pathogenesis. Therapeutic approaches are therefore in development that target various sites in the production and aggregation of Abeta. Herein we present a high-throughput screening tool to generate novel hit compounds that block Abeta fibril formation. This tool is an application for our fibril model (Abeta(16-37)Y(20)K(22)K(24))(4), which is a covalent assembly of four Abeta fragments. With this tool, screening studies are complete within one hour, as opposed to days with native Abeta(1-40). A Z' factor of 0.84+/-0.03 was determined for fibril formation and inhibition, followed by the reporter molecule thioflavin T. Herein we also describe the analysis of a broad range of reported inhibitors and non-inhibitors of Abeta fibril formation to test the validity of the system.  相似文献   
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Dolphin  Jack 《电脑》2010,(5):218-218
4月16—18日,世界一级方程式锦标赛中国大奖项在上海举行,飞利浦汽车影音组织了30人的观摩团,现场为F1及威廉姆斯车队加油助威。飞利浦是威廉姆斯车队的主要赞助商,因此本次中国大奖赛受到飞利浦汽车影音各级经销商和广大用户的普遍关注,为此飞利浦优质生活大中华区和华飞商贸有限公  相似文献   
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The second epidermal growth factor (EGF)-like domain of human coagulation factor VII is a potent inhibitor of the FVIIa/tissue factor complex, the predominant initiator of coagulation in vivo. This domain has now for the first time been cloned and expressed in Escherichia coli as an affinity fusion protein. The fusion protein was secreted into the periplasm of E. coli and purified by affinity chromatography. The purified protein consisted of a fusion protein with the expected molecular weight, and in addition, a significant fraction of oligomers cross-linked by intermolecular disulfide bonds. Despite the presence of oligomers, the purified protein was a potent inhibitor of the extrinsic blood coagulation pathway with an IC50 value of about 20 microM. The biological activity was retained after liberation of the EGF domain by proteolytic cleavage.  相似文献   
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Dolphin  Jack 《电脑》2010,(3):206-206,208
冬去春来又一年,对于广州来说春天的到来就代表了夏季的临近,气温的升高。此时,车内经常有令人不舒服的味道。尤其打开空调时,异味感更加严重。无奈中只得一边享受空调带来的清凉,一边忍受空调中难闻的气味。而随风带出来的霉菌、细菌更是对车内人士健康不利。  相似文献   
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Based on an attribute-by-treatment interaction paradigm, the determinants of 217 female college students' achievement were compared under conventional and self-paced mastery examination schedules in an anatomy and physiology course. Measures of general scholastic ability (e.g., Minnesota Scholastic Aptitude Test) did not interact with method, but prior preparation in science did. Ss with less science preparation showed greater achievement under self-paced mastery testing than their counterparts under conventional testing. This compensation was explained when study habits were explored. Under self-paced testing, study time was inversely related to amount of science background. Self-pacing Ss with less background reported greater textbook usage and indicated that unit test results aided in planning study effort. No such relationships were found for Ss in the conventional course. (38 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   
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The creation of molecular systems that can mimic some of the properties of natural macromolecules is one of the major endeavors in contemporary protein chemistry. However, the construction of artificial proteins with predetermined structure and function is difficult on account of complex folding pathways. The use of topological peptide templates has been suggested to induce and stabilize defined secondary and tertiary structures. This is because the recent advances in the chemistry of coupling reagents, protecting groups, and solid-phase synthesis have made the chemical synthesis of peptides with conformationally controlled and complex structures feasible. Besides their use as structure-inducing devices, these peptide templates can also be utilized to construct novel structures with tailor-made functions. Herein, we present recent advances in the field of peptide-template-based approaches with particular emphasis on the demonstrated utility of this approach in molecular recognition, along with related applications.  相似文献   
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