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171.
Kumar TS Mishra S Deflorian F Yoo LS Phan K Kecskés M Szabo A Shinkre B Gao ZG Trenkle W Jacobson KA 《Bioorganic & medicinal chemistry letters》2011,21(9):2740-2745
Pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine derivatives such as SCH 442416 display high affinity and selectivity as antagonists for the human A2A adenosine receptor (AR). We extended ether-linked chain substituents at the p-position of the phenyl group using optimized O-alkylation. The conjugates included an ester, carboxylic acid and amines (for amide condensation), an alkyne (for click chemistry), a fluoropropyl group (for 18F incorporation), and fluorophore reporter groups (e.g., BODIPY conjugate 14, Ki 15 nM). The potent and A2AAR-selective N-aminoethylacetamide 7 and N-[2-(2-aminoethyl)-aminoethyl]acetamide 8 congeners were coupled to polyamidoamine (PAMAM) G3.5 dendrimers, and the multivalent conjugates displayed high A2AAR affinity. Theoretical docking of an AlexaFluor conjugate to the receptor X-ray structure highlighted the key interactions between the heterocyclic core and the binding pocket of the A2AAR as well as the distal anchoring of the fluorophore. In conclusion, we have synthesized a family of high affinity functionalized congeners as pharmacological probes for studying the A2AAR. 相似文献
172.
Lambert W Koeck PJ Ahrman E Purhonen P Cheng K Elmlund D Hebert H Emanuelsson C 《Protein science : a publication of the Protein Society》2011,20(2):291-301
Unfolding proteins are prevented from irreversible aggregation by small heat shock proteins (sHsps) through interactions that depend on a dynamic equilibrium between sHsp subunits and sHsp oligomers. A chloroplast-localized sHsp, Hsp21, provides protection to client proteins to increase plant stress resistance. Structural information is lacking concerning the oligomeric conformation of this sHsp. We here present a structure model of Arabidopsis thaliana Hsp21, obtained by homology modeling, single-particle electron microscopy, and lysine-specific chemical crosslinking. The model shows that the Hsp21 subunits are arranged in two hexameric discs, similar to a cytosolic plant sHsp homolog that has been structurally determined after crystallization. However, the two hexameric discs of Hsp21 are rotated by 25° in relation to each other, suggesting a role for global dynamics in dodecamer function. 相似文献
173.
Image analysis of two-dimensional gel electrophoresis is a key step in proteomic workflow for identifying proteins that change under different experimental conditions. Since there are usually large amount of proteins and variations shown in the gel images, the use of software for analysis of 2D gel images is inevitable. We developed open-source software with graphical user interface for differential analysis of 2D gel images. The user-friendly software, RegStatGel, contains fully automated as well as interactive procedures. It was developed and has been tested under Matlab 7.01. AVAILABILITY: The database is available for free at http://www.mediafire.com/FengLi/2DGelsoftware. 相似文献
174.
目的:探讨无创检测心功能的指标—颈动脉瞬时减速度波强(W2)评价左心室舒张功能的价值。方法:测量40例高血压病患者和43例健康对照者的左、右侧颈总动脉W2,组织多普勒测定二尖瓣环运动速度和血清脑利钠肽前体(N-terminal probrain natriuretic peptide,NT-proBNP),分析W2与各参数间的相关性。结果:①高血压组W2低于对照组,以左侧明显(1126±996vs1690±1126 mmHg.m/s3,P〈0.01);②高血压组与对照组比较:E/Em(二尖瓣舒张早期峰值速度/二尖瓣环舒张早期纵向运动峰值速度)增大(9.37±3.32vs7.39±1.83,P〈0.01),NT-proB-NP升高(94.6±48.5vs45.2±13.8,P〈0.01);③相关性分析:W2与E/Em负相关(r=-0.46,P〈0.05),与NT-proBNP负相关(r=-0.21,P〈0.05)。结论:无创性评价血流动力学的新技术指标W2是反映早期左室舒张功能受损的敏感指标。 相似文献
175.
Trachymolgus purpureus Fisher & Dowling sp. n. is described from the Ozark highlands of North America. A diversity of imaging techniques are used to illustrate the species including low-temperature scanning electron microscopy (LT-SEM), stereomicrography, compound light micrography, and digitally created line drawings. Developmental stages (larva, nymphs, and adult) and morphology are illustrated and discussed, and terminological corrections are suggested. Trachymolgus recki Gomelauri, 1961 is regarded as being described from tritonymphs. A key to Trachymolgus is presented. 相似文献
176.
177.
Venzke D Domgall I Köcher T Féthière J Fischer S Böttcher B 《Journal of molecular biology》2005,349(3):659-669
V-ATPases are membrane protein complexes that pump protons in the lumen of various subcellular compartments at the expense of ATP. Proton pumping is done by a rotary mechanism that requires a static connection between the membrane pumping domain (V(0)) and the extrinsic catalytic head (V(1)). This static connection is composed of several known subunits of the V-ATPase, but their location and topological relationships are still a matter of controversy. Here, we propose a model for the V-ATPase of Neurospora crassa on the basis of single-particle analysis by electron microscopy. Comparison of the resulting map to that of the A-ATPase from Thermus thermophilus allows the positioning of two subunits in the static connecting region that are unique to eukaryotic V-ATPases (C and H). These two subunits seem to be located on opposite sides of a semicircular arrangement of the peripheral connecting elements, suggesting a role in stabilizing the stator in V-ATPases. 相似文献
178.
Fokine A Kostyuchenko VA Efimov AV Kurochkina LP Sykilinda NN Robben J Volckaert G Hoenger A Chipman PR Battisti AJ Rossmann MG Mesyanzhinov VV 《Journal of molecular biology》2005,352(1):117-124
The three-dimensional structure of the Pseudomonas aeruginosa bacteriophage phiKZ head has been determined by cryo-electron microscopy and image reconstruction to 18A resolution. The head has icosahedral symmetry measuring 1455 A in diameter along 5-fold axes and a unique portal vertex to which is attached an approximately 1800 A-long contractile tail. The 65 kDa major capsid protein, gp120, is organized into a surface lattice of hexamers, with T = 27 triangulation. The shape and size of the hexamers is similar to the hexameric building blocks of the bacteriophages T4, phi29, P22, and HK97. Pentameric vertices of the capsid are occupied by complexes composed of several special vertex proteins. The double-stranded genomic DNA is packaged into a highly condensed series of layers, separated by 24 A, that follow the contour of the inner wall of the capsid. 相似文献
179.
The eubacterial flagellar filament is an external, self-assembling, helical polymer approximately 220 A in diameter constructed from a highly conserved monomer, flagellin, which polymerizes externally at the distal end. The archaeal filament is only approximately 100 A in diameter, assembles at the proximal end and is constructed from different, glycosylated flagellins. Although the phenomenology of swimming is similar to that of eubacteria, the symmetry of the archebacterial filament is entirely different. Here, we extend our previous study on the flagellar coiled filament structure of strain R1M1 of Halobacterium salinarum. We use strain M175 of H.salinarum, which forms poly-flagellar bundles at high yield which, under conditions of relatively low ionic-strength (0.8 M versus 5 M) and low pH ( approximately 2.5 versus approximately 6.8), form straight filaments. We demonstrated previously that a single-particle approach to helical reconstruction has many advantages over conventional Fourier-Bessel methods when dealing with variable helical symmetry and heterogeneity. We show here that when this method is applied to the ordered helical structure of the archebacterial uncoiled flagellar filament, significant extensions in resolution can be obtained readily when compared to applying traditional helical techniques. The filament population can be separated into classes of different morphologies, which may represent polymorphic states. Using cryo-negatively stained images, a resolution of approximately 10-15 A has been achieved. Single alpha-helices can be fit into the reconstruction, supporting the proposed similarity of the structure to that of type IV bacterial pili. 相似文献
180.
Application of Image Analysis Techniques in Activated Sludge Wastewater Treatment Processes 总被引:1,自引:0,他引:1
Liwarska-Bizukojc E 《Biotechnology letters》2005,27(19):1427-1433
Image analytical techniques have been extensively developed to evaluate complex microbial aggregates such as sludge flocs
and biofilms. This review covers the latest contributions concerning the application of image analysis to the activated sludge
systems with respect to the most frequently used morphological parameters and relations between them and traditional wastewater
treatment parameters. Recent developments have indicated that image analysis can be successfully used for the quantification
of flocs and filamentous bacteria in the operating wastewater treatment plants, which enables prediction of bulking events
and pinpoint flocs formation. 相似文献