新生隐球菌嗜中枢性感染机制的研究进展

新生隐球菌是临床上最重要的侵袭性病原真菌之一,可感染免疫抑制和免疫正常人群引发具有致命威胁的隐球菌性脑膜脑炎.近年来,隐球菌嗜中枢神经系统感染的机制研究取得了长足的进展,隐球菌参与侵袭中枢神经系统的相关毒力因子及多条宿主细胞应答信号通路相继被发现.     

1-[2-[(Heteroarylmethoxy)aryl]carbamoyl]indolines are selective and orally active 5-HT2C receptor inverse agonists

Bisarylmethoxyethers have been identified with nanomolar 5-HT2C affinity and selectivity over both 5-HT2A and 5-HT2B receptors. Compounds such as 1, 2, 8, 12, 14 and 18 have potent oral activity in a centrally mediated pharmacodynamic model of 5-HT2C function and their therapeutic potential is currently under further investigation.     

Novel (4-piperazin-1-ylquinolin-6-yl) arylsulfonamides with high affinity and selectivity for the 5-HT(6) receptor

The discovery of (4-piperazin-1-ylquinolin-6-yl) arylsulfonamides and their binding affinities for a selection of 5-HT and dopamine subreceptors is described. Many compounds show high affinity (pK(i)>8) for the 5-HT(6) receptor and >100-fold selectivity against a range of other receptors. Structure-activity relationships of these compounds are discussed.     

Pleistocene climate change promoted rapid diversification of aquatic invertebrates in Southeast Australia

ABSTRACT: BACKGROUND: The Pleistocene Ice Ages were the most recent geohistorical event of major global impact, but their consequences for most parts of the Southern hemisphere remain poorly known. We investigate a radiation of ten species of Sternopriscus, the most species-rich genus of epigean Australian diving beetles. These species are distinct based on genital morphology but cannot be distinguished readily by mtDNA and nDNA because of genotype sharing caused by incomplete lineage sorting. Their genetic similarity suggests a Pleistocene origin. RESULTS: We use a dataset of 3858 bp of mitochondrial and nuclear DNA to reconstruct a phylogeny of Sternopriscus using gene and species trees. Diversification analyses support the finding of a recent rapid speciation event with estimated speciation rates of up to 2.40 species per MY, which is considerably higher than the proposed average rate of 0.16 species per MY for insects. Additionally, we use ecological niche modeling and analyze data on habitat preferences to test for niche divergence between species of the recent Sternopriscus radiation. These analyses show that the species can be characterized by a set of ecological variables referring to habitat, climate and altitude. CONCLUSIONS: Our results suggest that the repeated isolation of populations in glacial refugia might have led to divergent ecological adaptations and the fixation of morphological traits supporting reproductive isolation and therefore may have promoted speciation. The recent Sternopriscus radiation fulfills many characteristics of a species flock and would be the first described example of an aquatic insect species flock. We argue that the species of this group may represent a stage in speciation past the species flock condition because of their mostly broad and often non-overlapping ranges and preferences for different habitat types.     

Model studies on a synthetically facile series of N-substituted phenyl-N'-pyridin-3-yl ureas leading to 1-(3-pyridylcarbamoyl) indolines that are potent and selective 5-HT(2C/2B) receptor antagonists

A model series of 5-HT_2C antagonists have been prepared by rapid parallel synthesis. These N-substituted phenyl-N′-pyridin-3-yl ureas were found to have a range of 5-HT_2C receptor affinities and selectivities over the closely related 5-HT_2A receptor. Extrapolation of simple SAR, derived from this set of compounds, to the more active but synthetically more complex 1-(3-pyridyl-carbamoyl)indoline series allowed us to target optimal substitution patterns and identify potent and selective 5-HT_2C/2B antagonists.     

N-(indol-3-ylglyoxylyl)piperidines: high affinity agonists of human GABA-A receptors containing the alpha1 subunit

A new class of N-(indol-3-ylglyoxylyl)piperidines are high affinity agonists at the benzodiazepine binding site of human GABA-A receptor ion-channels, with modest selectivity for receptors containing the alpha1 subunit over alpha2 and alpha3. All three receptor subtypes discriminate substantially between the two enantiomers of the chiral ligand 10.     

敦煌西湖湿地鸟类栖息地重要性模糊综合评判

根据2007～2008年在甘肃敦煌西湖国家级自然保护区进行的湿地鸟类调查种类和数量数据,运用模糊综合评判法对保护区内的8块湿地进行了湿地鸟类栖息地重要性评价. 评判中隶属度的确定采用最佳因子值法,并分春、秋两种最佳因子值进行评判.结果表明:(1)春季各湿地均比秋季的重要性程度高,春季是管理的重点;(2)春秋两季南湖湿地重要性(0.938和0.966)都要远大于其它的湿地.春季盐池湾、羊水海子、南大湖的结果较相近,重要性程度次之,可持有相同程度的管理水平.党河水库、墩子湾、马圈湾、南园湖的重要性程度较低,只需一般水平的管理;(3)秋季各湿地水平除了南湖外普遍较低,羊水海子和盐池湾的重要性(0.340和0.269)相对较高些,但也只需一般水平的管理.     

多基因模型在肝细胞癌预后中的应用

利用较少分子信息预测肝细胞癌类型对患者的个性化治疗十分关键。探索已知的与肝细胞癌预后相关的信号通路,共发现41个关键基因。随后,运用机器学习的方法对其构建风险预测模型,并在4个肝细胞癌数据集上进行验证。结果显示,该模型能将肝细胞癌患者分成两个预后差异显著的类型:癌症基因图谱(The cancer genome atlas,TCGA)数据集交叉验证的平均log rank P值为0.03;其他测试数据集的log rank P 值分别为0.000 38、0.002 1和0.01。生物信息学分析显示肝细胞癌的预后与细胞周期等信号通路显著相关,并筛选出12个潜在的肝细胞癌分子标志物。研究结果表明,基于41个基因构建的肝细胞癌预后模型具有较好的稳健性和准确的风险预测能力。