Tricyclic dihydroquinazolinones as novel 5-HT2C selective and orally efficacious anti-obesity agents

Agonists of the 5-HT_2C receptor have been shown to suppress appetite and reduce body weight in animal models as well as in humans. However, agonism of the related 5-HT_2B receptor has been associated with valvular heart disease. Synthesis and biological evaluation of a series of novel and highly selective dihydroquinazolinone-derived 5-HT_2C agonists with no detectable agonism of the 5-HT_2B receptor is described. Among these, compounds (+)-2a and (+)-3c were identified as potent and highly selective agonists which exhibited weight loss in a rat model upon oral dosing.     

Generation and analysis of expressed sequence tags for microsatellite marker development in Calamus simplicifolius C. F. Wei

Rattans serve as an important source of raw non-wood materials for furniture and handicraft industries worldwide. However, their genomic sequence information in public databases is very limited. In this study, a set of 2,528 good-quality expressed sequence tags (ESTs) were generated from a full-length cDNA library constructed previously with root, stem and male inflorescence tissues of Calamus simplicifolius C. F. Wei, a rattan species native to Hainan Island, China. The ESTs were assembled into 1,588 unigenes, including 1,221 singletons and 367 contigs. BlastX searches against the GenBank non-redundant protein database revealed that 1,248 (78.6 %) unigenes had at least one significant match (E ≤ 10^?5). The gene ontology functional classification assigned 991, 669 and 977 of the unigenes to the cellular component, molecular function and biological process categories, respectively. A total of 71 simple sequence repeat (SSR) loci were developed among these ESTs, including 65 polymorphic across 19 rattan species representing three genera. High levels of cross-species/genus transferability were observed for the EST-SSRs. For the polymorphic EST-SSR markers, the number of alleles per locus and polymorphic information content ranged from 2 to 25 (mean 11.1) and from 0.135 to 0.949 (mean 0.695), respectively. The EST sequences and the EST-SSR primers have been deposited in GenBank databases of EST (IDs JK838364–40891) and Probe (IDs Pr16718978–9048, to be assigned).     

小兴安岭兴安落叶松泥炭藓沼泽植物的主要微量元素

小兴安岭兴安落叶松、泥炭藓沼泽是我国典型贫营养型沼泽。沼泽中树木生长发育不良,泥炭藓和常绿小灌木发育十分良好。这与沼泽水文状况和泥炭中营养元素和微量元素有关。各种植物的主要微量元素硼、铜、钴、锰、锌等含量不同,植物的不同器官中的含量亦不同,而且随季节而变化。狭叶杜香和甸杜的主要微量元素含量特点及其季节变化规律基本相似,两种泥炭藓相似,都与兴安落叶松有明显的区别。 本文重点探讨植物体内主要微量元素及其含量变化规律,为揭示贫营养型森林沼泽生态、为合理利用与改造沼泽提供依据。     

不同小麦品种茎秆特性及其与抗倒性的关系

以黄淮麦区优良品种矮抗58、周麦18、豫麦49、百农418为研究对象,采用田间试验与实验室分析相结合的方法,对不同小麦品种在不同生育时期的抗倒伏性状进行研究.结果表明: 茎秆机械强度在开花期至花后20 d处于较高水平,在花后30 d明显下降;倒伏指数在开花期最小,花后30 d最大,其余两个时期处于中间水平.相关分析表明,开花期机械强度与重心高度呈显著负相关,与纤维素、木质素含量呈显著正相关,倒伏指数与节长、株高、重心高度呈显著正相关,与纤维素、木质素含量呈显著负相关;花后10 d和花后20 d机械强度与节长、株高、重心高度呈显著负相关,与茎粗、纤维素、半纤维素、木质素含量呈显著正相关,倒伏指数这段时期正好与之相反;花后30 d机械强度与株高、重心高度呈显著负相关,倒伏指数与株高、重心高度呈显著正相关,与木质素含量呈显著负相关.因此,明确各个生育时期与抗倒性相关的茎秆特性,可为黄淮麦区高产抗倒性品种的选育提供依据.     

Morphological and molecular characterisation and differentiation of <Emphasis Type="Italic">Sargassum baccularia</Emphasis> and <Emphasis Type="Italic">S. polycystum</Emphasis> (Phaeophyta)

Two Sargassum species (S. baccularia and S. polycystum) collected from Teluk Kemang and Cape Rachado, Port Dickson, Negeri Sembilan, Malaysia, which are alike in morphology except for the rhizoidal system and vesicles, were characterised using random amplified polymorphism DNA (RAPD). The genomic DNA of both species was isolated from the leaves using a modified CTAB method. Four random primers, that is, OPA2, OPA3, OPA4 and OPA13, successfully amplified the DNA. The polymorphisms generated by these four primers were analysed using the Dice Coefficient of Similarity and cluster analysis was carried out using GelCompar II Version 2.0 (Applied Maths, Kortrijk, Belgium) based on UPGMA. DNA analysis showed that three primers were able to differentiate the two species. Morphological analysis using Principal Components Analysis (PCA) and discriminant function analysis supported the molecular data. Both species are characterised by heavily muricate main branches, oblong-lanceolate leaves with dentate margins and discoid holdfasts and spherical vesicles; both are dioecious. The only difference is that S. polycystum has secondary holdfasts transformed into stolons. This last characteristic is therefore a very important criterion and may contribute to the difference shown by DNA analysis.     

Hsp90 restrains ErbB-2/HER2 signalling by limiting heterodimer formation

ErbB-2/HER2 is an oncogenic tyrosine kinase that regulates a signalling network by forming ligand-induced heterodimers with several growth factor receptors of the ErbB family. Hsp90 and co-chaperones regulate degradation of ErbB-2 but not other ErbB members. Here, we report that the role of Hsp90 in modulating the ErbB network extends beyond regulation of protein stability. The capacity of ErbB-2 to recruit ligand-bound receptors into active heterodimers is limited by Hsp90, which is dissociated from ErbB-2 following ligand-induced heterodimerization. We show that Hsp90 binds a specific loop within the kinase domain of ErbB-2, thereby restraining heterodimer formation and catalytic function. These results define a role for Hsp90 as a molecular switch regulating the ErbB signalling network by limiting formation of ErbB-2-centred receptor complexes.