Mutations that silence constitutive signaling activity in the allosteric ligand-binding site of the thyrotropin receptor

The thyrotropin receptor (TSHR) exhibits elevated cAMP signaling in the basal state and becomes fully activated by thyrotropin. Previously we presented evidence that small-molecule ligands act allosterically within the transmembrane region in contrast to the orthosteric extracellular hormone-binding sites. Our goal in this study was to identify positions that surround the allosteric pocket and that are sensitive for inactivation of TSHR. Homology modeling combined with site-directed mutagenesis and functional characterization revealed seven mutants located in the allosteric binding site that led to a decrease of basal cAMP signaling activity. The majority of these silencing mutations, which constrain the TSHR in an inactive conformation, are found in two clusters when mapped onto the 3D structural model. We suggest that the amino acid positions identified herein are indicating locations where small-molecule antagonists, both neutral antagonists and inverse agonists, might interfere with active TSHR conformations.     

Silane as Electrolyte Additives for Lithium Ion Batteries

1 Results In order to overcome the inherent incompatibility of PC with graphite in the lithium ion battery system, improve their electrochemical performance at low temperature,phenyl tris-2-methoxydiethoxy silane (PTMS) has been studied as an additive to the PC-based electrolyte of lithium ion batteries with graphite anode. From the cyclic voltammogram for the graphite anode in the PC-based electrolyte,we find that in the case of the electrolyte without the additive,there is a large irreversible peak ne...     

我所经历的5个物理实验

结合亲身经历的5个物理实验,讲解了从事科学研究的独到体会。     

“Without Ub I am nothing”: NEMO as a multifunctional player in ubiquitin-mediated control of NF-κB activation

Ubiquitination has emerged over the years as the most sophisticated way to modify proteins to affect their fate and function. In particular, it has been reported to be instrumental in regulating several steps of the NF-κB signalling pathway which controls inflammation, immunity, adhesion and cell survival. Integrating ubiquitination into NF-κB activation requires the regulatory subunit of IKK, NEMO, which not only displays affinity for polyubiquitin chains, but is also posttranslationally modified by a complex set of reactions involving ubiquitin. Here, we examine how studies of the NEMO/ubiquitin relationship have provided novel insights into the IKK activation process and have uncovered molecular mechanisms that should represent in the future attractive targets for specifically modulating NF-κB function.     

Early life history of the sheepnose (Plethobasus cyphyus) (Mollusca: Bivalvia: Unionoida)

Managing a rare species can be improved with knowledge of its natural history. The sheepnose (Plethobasus cyphyus) is a freshwater mussel recently listed by the US as federally endangered. We used standard methods to study P. cyphyus brooding behaviour, host fishes in the laboratory and under natural conditions, and glochidial morphology. We monitored a population of P. cyphyus in the Chippewa River, WI during spring and summer 2007–2009 and 2011 and found brooding animals between mid-May and early August. Gravid individuals ranged between 5 and 27 yr (mean age ± 1 s.d. = 13 ± 4 yr). Plethobasus cyphyus brooded glochidia in outer gills, which varied in colour from red, orange, pink, cream, or white. We observed mature glochidia more commonly in individuals with cream or white gills and these glochidia were released in a clear, adhesive, mucus matrix. In laboratory trials we found several minnow and topminnow species (29 spp.) served as productive suitable native hosts. The mean number of juvenile mussels released per cyprinid per day was significantly higher for trials conducted at 22–25°C compared with those at 18–20°C, and 83% of trials conducted at 18–20°C using suitable host species produced no juveniles. Glochidia had a unique outline and shell morphometrics that distinguished P. cyphyus from seven other Chippewa River mussel species that produce similar sized glochidia. Using morphometrics we determined that mimic shiners (Notropis volucellus) were natural hosts for P. cyphyus, round pigtoe (Pleurobema sintoxia), and Wabash pigtoe (Fusconaia flava). Releasing mucus-bound glochidia has evolved in a variety of mussel species and may be more common than is currently realized. Our data show that P. cyphyus is a cyprinid host specialist, and propagation efforts for this species can be strengthened through improved access to mature glochidia by using females with cream-coloured gills and increased juvenile production through warmer fish holding temperatures.     

混凝土板梁的有限条法简化分析

桥梁结构在各种荷载作用下产生的内力和弯矩影响着桥梁的性能.桥梁弯曲、扭转和挠度等过大时会导致结构的破坏,这在结构设计阶段就应加以分析.本文提出一种有限条简化分析方法,可以较好地分析桥梁的挠度、弯曲和扭转变形.通过对一座简支板梁桥模型的分析,与现行有限元方法的分析结果进行了比较.结果表明,本方法能够较好地处理边界条件,只需要很少的输入工作就可以得到正确的分析结果,从而为结构工程师提供了一种用于分析板梁桥在交通荷载作用下行为的有效工具.