Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules

Phosphodiesterases (PDEs) are a superfamily of enzymes that degrade the intracellular second messengers cyclic AMP and cyclic GMP. As essential regulators of cyclic nucleotide signalling with diverse physiological functions, PDEs are drug targets for the treatment of various diseases, including heart failure, depression, asthma, inflammation and erectile dysfunction. Of the 12 PDE gene families, cGMP-specific PDE5 carries out the principal cGMP-hydrolysing activity in human corpus cavernosum tissue. It is well known as the target of sildenafil citrate (Viagra) and other similar drugs for the treatment of erectile dysfunction. Despite the pressing need to develop selective PDE inhibitors as therapeutic drugs, only the cAMP-specific PDE4 structures are currently available. Here we present the three-dimensional structures of the catalytic domain (residues 537-860) of human PDE5 complexed with the three drug molecules sildenafil, tadalafil (Cialis) and vardenafil (Levitra). These structures will provide opportunities to design potent and selective PDE inhibitors with improved pharmacological profiles.     

Chromosome cohesion is regulated by a clock gene paralogue TIM-1

Faithful transmission of the genome requires that a protein complex called cohesin establishes and maintains the regulated linkage between replicated chromosomes before their segregation. Here we report the unforeseen participation of Caenorhabditis elegans TIM-1, a paralogue of the Drosophila clock protein TIMELESS, in the regulation of chromosome cohesion. Our biochemical experiments defined the C. elegans cohesin complex and revealed its physical association with TIM-1. Functional relevance of the interaction was demonstrated by aberrant mitotic chromosome behaviour, embryonic lethality and defective meiotic chromosome cohesion caused by the disruption of either TIM-1 or cohesin. TIM-1 depletion prevented the assembly of non-SMC (structural maintenance of chromosome) cohesin subunits onto meiotic chromosomes; however, unexpectedly, a partial cohesin complex composed of SMC components still loaded. Further disruption of cohesin activity in meiosis by the simultaneous depletion of TIM-1 and an SMC subunit decreased homologous chromosome pairing before synapsis, revealing a new role for cohesin in metazoans. On the basis of comparisons between TIMELESS homologues in worms, flies and mice, we propose that chromosome cohesion, rather than circadian clock regulation, is the ancient and conserved function for TIMELESS-like proteins.     

红血球悬浮液流经平面狭缝的Fhraeus效应

本文论述了红血球悬浮液流经平面狭缝时其血球压积的变化规律,亦即片流Fahraeus效应。采用平面光学玻璃特制的二维狭缝装置、灌流管路、显微摄影记录及图象处理系统等组成实验系统。研究了厚度为4、7、12、25、36(μm)的五种狭缝中流过不同压积(H_f=2.00～31.00％)的红血球悬浮液时相对红血球压积的变化,发现了显著的片流Fahraeus效应及其规律并与管流Fahraeus效应进行了比较。本研究结论对“片流理论”及体液循环生理学具有重要意义。     

黄海周边河流的稀土元素地球化学及沉积物物源示踪

黄海周边的中韩主要河流悬浮沉积物中稀土元素组成不同, 韩国河流的稀土元素分异强于中国长江、黄河和鸭绿江, 表现为上陆壳标准化模式上明显的轻稀土相对富集. 不同级别的流域内源岩组成差异是形成这些河流稀土元素组成差异的主要因素. 稀土元素分异参数(La/Yb)_UCC和(Gd/Yb)_UCC, 以及稳定的La/Sc和Th/Sc元素比是识别进入黄海的中韩河流沉积物的可靠指标, 可以用于中国边缘海沉积物物源研究和古环境分析.     

Spatial aggregations for spatial based decision making in spatial data warehouses

For spatial based decision making such as choice of best place to construct a new department store, spatial data warehousing system is required more and more previous spatial data warehousing systems; however, provided decision making of non-spatial data on a map and so those cannot support enough spatial based decision making. The spatial aggregations are proposed for spatial based decision making in spatial data warehouses. The meaning of aggregation operators for applying spatial data was modified and new spatial aggregations were defined. These aggregations can support hierarchical concept of spatial measure. Using these aggregations, the spatial analysis classified by non-spatial data is provided. In case study, how to use these aggregations and how to support spatial based decision making are shown.     

One Dimensional Nanostructures for Lithium-ion Batteries, Gas Sensors and Optoelectronics Applications

1 Results One dimensional (1D) nanostructures such as nanowires,nanotubes,nanorods and nanoribbons have been extensively investigated for a wide range of applications[1].Here,we present the synthesis,characterization and technological applications of several 1D nanostructures including SnO2 nanowires,CuO nanoribbons,CdSe nanowires and In2O3 nanowires.SnO2 nanowires were synthesized by thermal evaporation combined with a self-catalyzed growth procedure.Scanning electron microscopy (SEM) observation shows...     

Study for the Forming Principle of Logix Gear Tooth Profile and Its Mesh Performance

In recent years, a new type of gear named Logix gea r was developed. Actually, the tooth profile of this new type of gear is composed of lots of micro-segment involute curves, and on the profile, there exist lots of points, which their relative curvatures are equal to zero. This can result in the sliding coefficient smaller between two meshed Logix gears, and the mesh ch aracteristic becomes almost rolling transmission from sliding transmission accor dingly. So, this new type of gear has lots of advanta...