Primary amides as selective inhibitors of cathepsin K

The nitrile warhead used in a series of cathepsin K inhibitors can be replaced by a less electrophilic primary amide. The accompanying loss of potency can be partially recovered by introducing a substituent alpha to the amide. The potency gain resulting from this addition is not achieved with the nitrile derivatives due to a different geometry of the cysteine adduct in the enzyme active site. This study led to the identification of the primary amide 2g, which is an inhibitory substrate, with an IC(50) of 10 nM against cathepsin K and excellent selectivity versus the other cathepsins.     

Statistical inference for valued-edge networks: the generalized exponential random graph model

Across the sciences, the statistical analysis of networks is central to the production of knowledge on relational phenomena. Because of their ability to model the structural generation of networks based on both endogenous and exogenous factors, exponential random graph models are a ubiquitous means of analysis. However, they are limited by an inability to model networks with valued edges. We address this problem by introducing a class of generalized exponential random graph models capable of modeling networks whose edges have continuous values (bounded or unbounded), thus greatly expanding the scope of networks applied researchers can subject to statistical analysis.     

黑素皮质素受体-4的研究进展

黑素皮质素受体 4 (MC4R)是人类中枢神经系统中参与调节肥胖症发生的重要因素 ,可调节动物的体重和采食量。自MC4R基因克隆以来 ,学者们对MC4R的结构 ,生理功能 ,调控 ,作用机制及其基因突变与体重的关系等方面进行了大量的研究。     

用酵母双杂交系统筛选影响apo-AI和SR-BI相互作用的苦豆子活性成分

本文通过将苦豆子总提取物及其分离得到的10个组分加入含有AH109菌株(携带大鼠apo-AI及其受体SR-BI全基因)的培养基中,利用报告基因半乳糖苷酶活力有无变化来寻找能够促进大鼠载脂蛋白apo-AI及其受体SR-BI相互作用的激动剂.经测试,我们观察到苦豆子总提取物(K-1),在上述系统中能显著增强这两种蛋白的相互作用.继续用硅胶柱层析方法从k-1中分出10个组分后,利用酵母双杂交系统再次筛选,发现有五个组分能增强两种蛋白的相互作用,(与空白对照组相比其中有两个组分有极显著差异)另外三个组分显著地抑制上述两种蛋白的相互作用,剩下的两个组分则没有差异.该实验还提示该酵母双杂交系统可能成为一种跟踪具有调脂功能的先导化合物的有效方法.     

Evidence from population genetics that the ectomycorrhizal basidiomycete Laccaria amethystina is an actual multihost symbiont

It is commonly assumed that ectomycorrhizal (ECM) fungi associated with temperate forest tree roots are not host-specific. Because this assumption relies on species delineations based on fruitbodies morphology or ribosomal DNA sequences, host-specific, cryptic biological species cannot be ruled out. To demonstrate that Laccaria amethystina has true generalist abilities, we sampled 510 fruitbodies on three French sites situated 150–450 km away from each other. At each site, populations from monospecific stands ( Abies alba , Castanea europea and Fagus sylvatica ) or mixed stands ( F. sylvatica  +  Quercus robur or Q. robur  + Carpinus betulus ) were sampled. Three different sets of markers were used for genotyping: (i) five microsatellite loci plus the ribosomal DNA intergenic spacer, (ii) the mitochondrial large ribosomal DNA subunit, and (iii) direct amplification of length polymorphism (DALP), a new method for fungi providing dominant markers. Evidence for allogamous populations (with possible inbreeding at local scale) and possibly for biparental mitochondrial inheritance was found. All markers congruently demonstrated that L. amethystina populations show little structure at this geographical scale, indicating high gene flow (as many as 50% of founding spores in all populations being of external origin). Our results also showed that host species contributed even less to population differentiation, and there was no evidence for cryptic biological species. This first in situ demonstration of a true multihost ability in an ECM species is discussed in terms of ecology and evolutionary biology.     

A Periplasmic Polymer Curves Vibrio cholerae and Promotes Pathogenesis

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运用稳定同位素技术分析大宁河主要鱼类营养层级

运用氮稳定同位素技术分析了大宁河静水水域和流水河段主要鱼类的氮稳定同位素比值和营养层级,并对静水水域不同水文时期相同鱼类的营养层级进行了比较研究。结果表明, 颗粒有机物(POM)氮稳定性同位素变化幅度较大, 并存在季节差异。大宁河下游静水水域鱼类15N 值范围为4.5417.51, 营养级处于1.513.88, 平均营养层级为2.49;上游流水水域鱼类的15N 值范围为2.2510.81, 营养层级范围为1.494.01, 平均营养层级为2.87。大宁河上游鱼类的平均营养层级大于下游静水水域, 可能是由于上游底栖生物丰富, 鱼类倾向摄食适口性更高的动物性食物而导致。大宁河下游静水水域汛期的鱼类营养层级较非汛期的值显著降低, 可能是因为汛期的水文扰动影响鱼类摄食中间捕食者, 以及水位的降低导致鱼类食物竞争增加迫使其摄食低营养水平的食物。重复基准生物采样建立精确充足的基线值以及确定合适的富集度,是提高营养层级评估准确性的重要手段。       

利手、优势足及扣手的遗传方式初探

采用Slater区分单基因和多基因遗传的计算模式及Smith无偏分析方法对21个家系资料的分析表明：利手、优势足、扣手特征均为常染色体单基因显性遗传,R型为显性性状。虽然环境因素对这类特征的表现也有一定的影响,但遗传因素仍起主要作用。 Abstract:The data of 21 families were analyzed by the method of Slater's calculating model to differentiate between single-gene and multi-gene heredity and by the method of non-deviation analysis.The results showed that the hereditary mode of handedness or preferential foot or hand-clasping is the dominant heredity of single gene of autosome,and the right type of all of them is the dominant character.In a way,although environmental factors affected the phenotypes of these characters,hereditary factors were also the decisive ones.     

利手、优势足及扣手的遗传方式初探

采用Slater区分单基因和多基因遗传的计算模式及Smith无偏分析方法对21个家系资料的分析表明：利手、优势足、扣手特征均为常染色体单基因显性遗传,R型为显性性状。虽然环境因素对这类特征的表现也有一定的影响,但影响因素仍起主要作用。