Identification of anticancer agents based on the thieno[2,3-b]pyridine and 1H-pyrazole molecular scaffolds

Structural similarity search of commercially available analogues of thieno[2,3-b]pyridine and 1H-pyrazole derivatives, known anticancer agents, resulted in 717 hits. These were docked into the phosphoinositide specific-phospholipase C (PLC) binding pocket, the putative target of the compounds, to further focus the selection. Thirteen derivatives of the thieno[2,3-b]pyridines were identified and tested against the NCI60 panel of human tumour cell lines. The most active derivative 1 was most potent against the MDA-MB-435 melanoma cell line with GI₅₀ at 30 nM. Also, it was found that a piperidine moiety is tolerated on the thieno[2,3-b]pyridine scaffold with GI₅₀ = 296 nM (MDA-MB-435) for derivative 10 considerably expanding the structure activity relationship for the series. For the 1H-pyrazoles four derivatives were identified using the in silico approach and additionally ten were synthesised with various substituents on the phenyl moiety to extend the structural activity relationship but only modest anticancer activity was found.     

简论相似性测度的选择——以奥陶纪末大灭绝后全球腕足动物古地理为例

灭绝事件对古生物地理格局的影响已引起关注,近期研究表明奥陶纪末大灭绝事件后多样性显著高于传统认识,而全球该时期腕足动物的古生物地理分布情况尚未见报道。本文基于已发表的和最新的资料及所掌握新数据的整理,建立全球腕足动物志留纪初鲁丹(Rhuddanian)早期（残存期）13个产地72属137个出现信息(occurrence...     

河北省侧蒴藓类植物的地理成分及其与邻近地区的比较

通过对河北省侧蒴藓类植物较详尽的野外考察、标本采集、鉴定和系统研究,已知河北省侧蒴藓类植物17科,66属,196种(包括种下单位),其地理成分可划分为9种类型,北温带分布型占主导地位,东亚分布型次之,热带分布型不起主要作用。运用物种丰富度、优势科比较、属相似性系数等统计方法,对河北与邻近地区的区系地理成分进行了比较、分析和讨论。从河北省与我国东北、内蒙古、山东、秦岭、西藏和横断山等6个地区侧蒴藓类区系组成的比较分析得出,本省该类群物种丰富度位居第4,横断山居于第1位,河北与其它6个地区的共有优势科前3位为青藓科、柳叶藓科、灰藓科;河北与内蒙古、山东相似程度最高,与东北和秦岭相似程度次之,与西藏、横断山相差最大。同时对这7个地区的具体地理成分也作了比较。这些结果有力地说明了河北省侧蒴藓类植物区系具有明显的温带性质,同时兼有浓厚的东亚区系色彩,也表明了中国华北与日本、欧洲和北美东北部在苔藓植物区系物种起源上有深厚的历史渊源。     

新疆博格达山地面生苔藓植物物种多样性研究

采用相似性系数和物种多样性指数对新疆博格达山地面生苔藓植物的物种多样性进行了研究．结果表明,博格达山地区苔藓植物区系具有丰富性和复杂性的特点,共有地面生苔藓植物32科73属186种(含变种、变型);山地荒漠带和山地草原带苔藓植物物种相似性最高,为0．6809,山地森林带和高山垫状植被带相似性最低,仅为0．1342;山地森林带苔藓植物在整个博格达山地面生苔藓植物群落中占据优势地位;山地森林带苔藓植物物种多样性最为丰富,为该山地苔藓植物多样性的分布中心,是苔藓植物多样性保护的关键地区．     

Benzopyrazine derivatives: A novel class of growth factor receptor bound protein 7 antagonists

Growth factor receptor bound protein 7 (Grb7) is an adapter protein that functions as a downstream effector of growth factor mediated signal transduction. Over-expression of Grb7 has been implicated in a variety of cancers such as breast, blood, pancreatic, esophageal, and gastric carcinomas. Inhibition of Grb7 has been shown to reduce the migratory and proliferative potential of these cancers, making it an attractive therapeutic target. Starting with a known peptide antagonist, the present work reports the application of a succession of computational ligand design tools comprising a ligand shape based similarity search, molecular docking and a 2D-similarity search to identify small molecular antagonists of the Grb7-SH2 domain from the NCI chemical database. Binding to the Grb7-SH2 domain was then experimentally tested using melting point shift assays and isothermal titration calorimetry. Overall, a total of 11 benzopyrazine based small molecular antagonists were identified with affinity for the Grb7-SH2 domain. Representative compounds tested using ITC were revealed to possess moderate binding affinity in the low micromolar range. Finally, the lead compound (NSC642056) was found to reduce the growth of a Grb7-expressing breast cancer cell line with an IC₅₀ of 86 ??M. It is expected that the identified antagonists will be useful additions to further explore the function of Grb7 and for the development of inhibitors with therapeutic potential.     

Alternative partitioning of the genotype-by-environment interaction

Summary Alternative methods for partitioning the genotype-by-environment interaction, for an arbitrary number of genotypes or environments, were examined. Partitioning of the interaction is important in order to determine the nature of the interaction. Two methods of partitioning were examined; both separated the interaction into two types: (1) due to heterogeneous variances or (2) due to imperfect correlations. Method 1 was based on heterogeneity among environments in the scaling of differences among genotypes. Method 2 was based on heterogeneity among genotypes in the scaling of differences among environments. Any remaining interaction arises from deviations from the perfect positive correlation of genotypic rankings among environments (Method 1) or of environmental rankings among genotypes (Method 2). Method 1 is more appropriate for random genotypes that are to be tested in either fixed or random environments. With Method 1, the interactions that arise mainly from heterogeneity of genotypic scaling among environments are generally unimportant. However, if environments are fixed and interactions are mainly due to imperfect correlations of rankings, specialized lines may be indicated for each environment. Method 2 is more useful in evaluating fixed genotypes for sensitivity to random environments. A partitioning of the interaction into that due to the type of interaction within each genotype was shown to be useful in that situation.Journal Paper No. 123737 of the Purdue University Agricultural Experiment Station     

Heterogeneity ratio: a measure of beta-diversity and its use in community classification

Fifteen previously proposed similarity indices are examined for the effects of sample size and/or group size (the number of samples included in a cluster). The three indices ofCλ,NESS, andC′λ are free from effects, but the former two are unsuitable for arithmetic averaging unless all of the sample sizes are equal. Thus clustering usingC′λ is found to be superior to the combination of any other similarity index and the group-average strategy. Unfortunately none of these measures have the desirable property of measuring the difference in component species among samples independent of the alpha-diversity. A new index of similarity (HR) is developed based on the assumption that community from which samples are taken is described by a logseries distribution. This new index measures the beta-diversity among samples without the influence of sample size and group size, and has the advantage that the significance of fusing samples can statistically be tested. An example clustering withHR is shown and compared with those obtained by other clustering strategies.     

Local-scale spatial diversity patterns of ectomycorrhizal fungal communities in a subtropical pine-oak forest

This study aimed to analyze spatial patterns of soil ectomycorrhizal fungal (EMF) communities at the local scale in a subtropical pine-oak forest located in the Nearctic-Neotropical transition in central Mexico, to underpin biodiversity conservation strategies in forest fragments of this region. We used a spatially-explicit nested square sampling design with the same sampling representativeness at all scales and replicated three times. We detected 674 EMF OTUs within 19,200 m² and 65 OTUs on average per sample. Seventy percent of OTUs were detected in only 1–4 samples. Average community similarity was below 5%, showed minor change within 14 and 339 m distance and increased with the spatial grain used to compare the data. We found a high species-area relationship and beta diversity coefficients for soil fungi indicating that, at the local scale, increasing area by a constant factor of four represented an increase in OTU richness by a factor of two.     

Calculating phenotypic similarity between genes using hierarchical structure data based on semantic similarity

Phenotypic similarity is correlated with a number of measures of gene function, such as relatedness at the level of direct protein-protein interaction. The phenotypic effect of a deleted or mutated gene, which is one part of gene annotation, has caught broad attention. However, there have been few measures to study phenotypic similarity with the data from Human Phenotype Ontology (HPO) database, therefore more analogous measures should be developed and investigated. We used five semantic similarity-based measures (Jiang and Conrath, Lin, Schlicker, Yu and Wu) to calculate the human phenotypic similarity between genes (PSG) with data from HPO database, and evaluated their accuracy with information of protein-protein interaction, protein complex, protein family, gene function or DNA sequence. Compared with the gene pairs that were random selected, the results of these methods were statistically significant (all P<0.001). Furthermore, we assessed the performance of these five measures by receiver operating characteristic (ROC) curve analysis, and found that most of them performed better than the previous methods. This work had proved that these measures based on semantic similarity for calculation of PSG were effective for hierarchical structure data. Our study contributes to the development and optimization of novel algorithms of PSG calculation and provides more alternative methods to researchers as well as tools and directions for PSG study.