Building a tree of knowledge: analysis of bitter molecules

A phylogenetic-like tree of structural fragments has been constructed to extract useful insights from a structural database of bitter molecules. The tree of structural fragments summarizes the substructural groups present in the molecules from the bitter database. These structural fragments are compared with a large number of random molecules to highlight substructures specific to bitter molecules. This organization of the structures enabled the detection of structure-activity relationships for the bitter molecules through the construction of R-tables. Key structural groups, able to distinguish between bitter and random molecules, were identified through an analysis of the tree. This information can be used to further understand which structural components are involved in producing a bitter taste.     

Preparation of pure populations of covalently stabilized amyloid β-protein oligomers of specific sizes

Evidence suggests that amyloid β-protein (Aβ) oligomers may be seminal pathogenic agents in Alzheimer's disease (AD). If so, developing oligomer-targeted therapeutics requires an understanding of oligomer structure. This has been difficult due to the instability of these non-covalently associated Aβ assemblies. We previously used rapid, zero-length, in situ chemical cross-linking to stabilize oligomers of Aβ40. These enabled us to isolate pure, stable populations of dimers, trimers, and tetramers and to determine their structure-activity relationships. However, equivalent methods applied to Aβ42 did not produce stable oligomers. We report here that the use of an Aβ42 homologue, [F10, Y42]Aβ42, coupled with sequential denaturation/dissociation and gel electrophoresis procedures, provides the means to produce highly pure, stable populations of oligomers of sizes ranging from dimer through dodecamer that are suitable for structure-activity relationship determination.     

Mapping species diversity patterns in the Kansas shortgrass region by integrating remote sensing and vegetation analysis

Abstract. Field reconnaissance data are used in a supervised classification of a 1989 Landsat Thematic Mapper (TM) scene to create a digital database of high and low quality grasslands for northwestern Kansas. To test the classification of grassland quality, plot-based vegetation data collected from 32 sites are analyzed for differences in species composition, and evaluated for relationships between TM data and plant diversity. Significant differences between predicted high and low quality grassland sites are identified for the following variables: cover of the dominant and common species, overall species richness, number of forbs, number of grasses, and plant diversity using Shannon's index. Linear regression analysis reveals a significant relationship (r²= 0.61) between species diversity and the prediction of grassland quality from the supervised classification. The addition of spectral data to this model did not improve the prediction of species diversity, but spectral brightness is identified as a key feature in mapping shortgrass vegetation diversity patterns with TM data.     

基于多模态生态治理数据构建生态管理知识图谱技术

我国新时代十年是生态环境保护认识最深、力度最大、举措最实、推进最快、成效最显著的十年。生态环境治理取得成效的同时,管理措施也逐步成熟和规范化,相关生态管理知识成果的文本、视频、照片等多模态数据也日益丰厚。采用先进的知识图谱理念创新我国生态环境保护工作,对未来助力打赢污染防治攻坚战,构建现代环境治理体系具有重要意义。聚焦我国美丽中国和生态文明建设工程领域,将典型污染防治攻坚战、生态恢复工程多模态素材作为数据源,通过数据整合、知识抽取、知识融合后形成标准知识表述,构建生态管理知识图谱体系。具体包括(1)定量分析深圳市"散乱污"企业整治成功案例数据,抽取管理主体、管理对象等实体,挖掘其空间特征、污染特征、治理效果关系;(2)关联分析企业驻点、污染物热点和城市空间相互关系;(3)通过我国典型生态环境损害赔偿案件中的"实施行为-破坏对象-损害功能"特定关系分析,抽取"生态治理行为--受影响环境要素--生态服务提升程度"生态环境管理知识图谱;(4)最终形成了整合"散乱污"治理、生态环境治理行为的综合性生态管理知识图谱,构建了包含12类本体、82个实体,4类、201条关系的图数据库。研究表明,通过污染防治攻坚战成功案例、生态恢复工程成效的多模态数据构建我国生态管理知识图谱,能够形成贴近现实需求的知识体系,有助于依法治污、科学治污和精准治污全过程;也有助于生态环境损害鉴定评估工作中的"多因一果"和"一因多果"分析。建议未来加大生态管理知识图谱的应用,精准识别管理对象、实现科学分析与智能决策,促进公众参与生态管理和加快生态产品价值实现。     

SNPs3D: Candidate gene and SNP selection for association studies

Background  

The relationship between disease susceptibility and genetic variation is complex, and many different types of data are relevant. We describe a web resource and database that provides and integrates as much information as possible on disease/gene relationships at the molecular level.     

MicroPhenoDB Associates Metagenomic Datawith Pathogenic Microbes,Microbial Core Genes,and Human Disease Phenotypes

Microbes play important roles in human health and disease. The interaction between microbes and hosts is a reciprocal relationship, which remains largely under-explored. Current computational resources lack manually and consistently curated data to connect metagenomic data to pathogenic microbes, microbial core genes, and disease phenotypes. We developed the MicroPhenoDB database by manually curating and consistently integrating microbe-disease association data. MicroPhenoDB provides 5677 non-redundant associations between 1781 microbes and 542 human disease phenotypes across more than 22 human body sites. MicroPhenoDB also provides 696,934 relationships between 27,277 unique clade-specific core genes and 685 microbes. Disease phenotypes are classified and described using the Experimental Factor Ontology (EFO). A refined score model was developed to prioritize the associations based on evidential metrics. The sequence search option in MicroPhenoDB enables rapid identification of existing pathogenic microbes in samples without running the usual metagenomic data processing and assembly. MicroPhenoDB offers data browsing, searching, and visualization through user-friendly web interfaces and web service application programming interfaces. MicroPhenoDB is the first database platform to detail the relationships between pathogenic microbes, core genes, and disease phenotypes. It will accelerate metagenomic data analysis and assist studies in decoding microbes related to human diseases. MicroPhenoDB is available through http://www.liwzlab.cn/microphenodb and http://lilab2.sysu.edu.cn/microphenodb.     

Discovery of substituted phenyl urea derivatives as novel long-acting β2-adrenoreceptor agonists

The synthesis of diverse functionalized ureas in a semi-parallel fashion is described, as well as their β₁/β₂-adrenergic activities and the corresponding structure-activity relationship (SAR). We have focused on lipophilicity and duration of action, and we have discovered a strong correlation in this series of molecules. A quantitative structure-activity relationship (QSAR) analysis will be presented that quantifies this relationship.     

An automatic method involving cluster analysis of secondary structures for the identification of domains in proteins.

With a growing number of structures available in the Brookhaven Protein Data Bank, automatic methods for domain identification are required for the construction of databases. Domains are considered to be clusters of secondary structure elements. Thus, helices and strands are first clustered using intersecondary structural distances between C alpha positions, and dendrograms based on this distance measure are used to identify domains. Individual domains are recognized by a disjoint factor, which enables the automatic identification and classification into disjoint, interacting, and conjoint domains. Application to a database of 83 protein families and 18 unique structures shows that the approach provides an effective delineation of boundaries and identifies those proteins that can be considered as a single domain. A quantitative estimate of the interaction between domains has been proposed. The database of protein domains is a useful tool for understanding protein folding, for recognizing protein folds, and for understanding structure-activity relationships.     

QSAR and docking studies of anthraquinone derivatives by similarity cluster prediction

Forty anthraquinone derivatives have been downloaded from PubChem database and investigated in a quantitative structure-activity relationships (QSAR) study. The models describing log P and LD50 of this set were built up on the hypermolecule scheme that mimics the investigated receptor space; the models were validated by the leave-one-out procedure, in the external test set and in a new version of prediction by using similarity clusters. Molecular docking approach using Lamarckian Genetic Algorithm was made on this class of anthraquinones with respect to 3Q3B receptor. The best scored molecules in the docking assay were used as leaders in the similarity clustering procedure. It is demonstrated that the LD50 data of this set of anthraquinones are related to the binding energies of anthraquinone ligands to the 3Q3B receptor.     

New Approaches of PARP-1 Inhibitors in Human Lung Cancer Cells and Cancer Stem-Like Cells by Some Selected Anthraquinone-Derived Small Molecules

Poly (ADP-ribose) polymerase-1 (PARP-1) and telomerase, as well as DNA damage response pathways are targets for anticancer drug development, and specific inhibitors are currently under clinical investigation. The purpose of this work is to evaluate anticancer activities of anthraquinone-derived tricyclic and tetracyclic small molecules and their structure-activity relationships with PARP-1 inhibition in non-small cell lung cancer (NSCLC) and NSCLC-overexpressing Oct4 and Nanog clone, which show high-expression of PARP-1 and more resistance to anticancer drug. We applied our library selected compounds to NCI''s 60 human cancer cell-lines (NCI-60) in order to generate systematic profiling data. Based on our analysis, it is hypothesized that these drugs might be, directly and indirectly, target components to induce mitochondrial permeability transition and the release of pro-apoptotic factors as potential anti-NSCLC or PARP inhibitor candidates. Altogether, the most active NSC747854 showed its cytotoxicity and dose-dependent PARP inhibitory manner, thus it emerges as a promising structure for anti-cancer therapy with no significant negative influence on normal cells. Our studies present evidence that telomere maintenance should be taken into consideration in efforts not only to overcome drug resistance, but also to optimize the use of telomere-based therapeutics. These findings will be of great value to facilitate structure-based design of selective PARP inhibitors, in general, and telomerase inhibitors, in particular. Together, the data presented here expand our insight into the PARP inhibitors and support the resource-demanding lead optimization of structurally related small molecules for human cancer therapy.     

基因重组与基因合成实验设计软件系统的建立

本文报导了用于基因重组与基因合成实验设计的软件系统的建立.此系统由30个功能模块组成,为研究者提供了包括在DNA分子上寻找限制性内切酶位点、核酸分子片段之间同源性比较,基因化学合成的实验设计、特定顺序分析引物及核酸杂交探针的设计、阅读框的查找等功能.此外,本系统可以对外来数据库的资料进行援引和进一步分析,为分子生物学的研究提供有价值的信息.     

A Comparative Analysis of the Synergistic Interaction Between N'-Phenylsulfanilamides and Benzylpyrimidines Using Qsar Techniques

Abstract

Growth inhibition of E. coli cell culture has been determined for a series of 4-substituted-N'-phenylsulfonamides tested in the presence and absence of synergistic concentrations of trimethoprim. Quantitative structure-activity relationships, established by regression analysis, exhibit an identical dependence of bacterial growth inhibition on sulfonamide pK_a irrespective of the presence or absence of trimethoprim. Examination of a small series of benzylpyrimidines in the presence or absence of 4-dimethylamino-N¹-phenylsulfanilamide gave similar results. Since the presence of a synergistic agent affords no change in structure-activity relationships, it is concluded that no direct interaction between sulfonamides and benzylpyrimidines occurs and that the synergism observed is solely the result of the kinetic consequences of sequential blockade of the folate biosynthetic pathway.     

Relationship between fire,climate oscillations,and drought in British Columbia,Canada, 1920–2000

Climate oscillations such as El Niño–Southern Oscillation (ENSO) and Pacific Decadal Oscillation (PDO) are known to affect temperature and precipitation regimes and fire in different regions of the world. Understanding the relationships between climate oscillations, drought, and area burned in the past is required for anticipating potential impacts of regional climate change and for effective wildfire‐hazard management. These relationships have been investigated for British Columbia (BC), Canada, either as part of national studies with coarse spatial resolution or for single ecosystems. Because of BC's complex terrain and strong climatic gradients, an investigation with higher spatial resolution may allow for a spatially complete but differentiated picture. In this study, we analyzed the annual proportion burned–climate oscillation–drought relationships for the province's 16 Biogeoclimatic Ecosystem Classification (BEC) zones. Analyses are based on a digital, spatially explicit fire database, climate oscillation indices, and monthly precipitation and temperature data with a spatial resolution of 400 m for the period 1920–2000. Results show that (1) fire variability is better related to summer drought than to climate oscillations, and that (2) fire variability is most strongly related to both, climate oscillations and summer drought in southeastern BC. The relationship of area burned and summer drought is strong for lower elevations in western BC as well. The influence of climate oscillations on drought is strongest and most extensive in winter and spring, with higher indices being related to drier conditions. Winter and spring PDO and additive winter and spring PDO+ENSO indices show BC's most extensive significant relationship to fire variability. Western BC is too wet to show a moisture deficit in summer that would increase annual area burned due to teleconnections.     

Global variation in thermal tolerances and vulnerability of endotherms to climate change

The relationships among species'' physiological capacities and the geographical variation of ambient climate are of key importance to understanding the distribution of life on the Earth. Furthermore, predictions of how species will respond to climate change will profit from the explicit consideration of their physiological tolerances. The climatic variability hypothesis, which predicts that climatic tolerances are broader in more variable climates, provides an analytical framework for studying these relationships between physiology and biogeography. However, direct empirical support for the hypothesis is mostly lacking for endotherms, and few studies have tried to integrate physiological data into assessments of species'' climatic vulnerability at the global scale. Here, we test the climatic variability hypothesis for endotherms, with a comprehensive dataset on thermal tolerances derived from physiological experiments, and use these data to assess the vulnerability of species to projected climate change. We find the expected relationship between thermal tolerance and ambient climatic variability in birds, but not in mammals—a contrast possibly resulting from different adaptation strategies to ambient climate via behaviour, morphology or physiology. We show that currently most of the species are experiencing ambient temperatures well within their tolerance limits and that in the future many species may be able to tolerate projected temperature increases across significant proportions of their distributions. However, our findings also underline the high vulnerability of tropical regions to changes in temperature and other threats of anthropogenic global changes. Our study demonstrates that a better understanding of the interplay among species'' physiology and the geography of climate change will advance assessments of species'' vulnerability to climate change.     

Ecological scaling laws link individual body size variation to population abundance fluctuation

Scaling research has seen remarkable progress in the past several decades. Many scaling relationships were discovered within and across individual and population levels, such as species–abundance relationship, Taylor's law, and density mass allometry. However none of these established patterns incorporate individual variation in the formulation. Individual body size variation is a key evolutionary phenomenon and closely related to ecological diversity and species adaptation. Using a macroecological approach, I test 57 Long‐Term Ecological Research data sets and show that a power‐law and a generalized power‐law function describe well the mean‐variance scaling of individual body mass. This relationship connects Taylor's law and density mass allometry, and leads to a new scaling pattern between the individual body size variation and population abundance fluctuation, which is confirmed using freshwater fish and forest tree data. Underlying mechanisms and implications of the proposed scaling relationships are discussed. This synthesis shows that integration and extension of existing ecological laws can lead to the discovery of new scaling patterns and complete our understanding of the relation between individual trait and population abundance. Synthesis Scaling relationships are useful for community ecology as they reveal ubiquitous patterns across different levels of biological organizations. This work extends and integrates two existing scaling laws: Taylor's law and density‐mass allometry, and derives a new variance allometry between individual body mass and population abundance. The result shows that diverse individual body size is associated with stable population fluctuation, reflecting the effect of individual traits on population characteristics. Confirmed by several empirical data sets, these scaling relationships suggest new ways to study the underlying mechanisms of Taylor's law and have profound implications for fisheries and other applied sciences.     

The Pathway Tools software

MOTIVATION: Bioinformatics requires reusable software tools for creating model-organism databases (MODs). RESULTS: The Pathway Tools is a reusable, production-quality software environment for creating a type of MOD called a Pathway/Genome Database (PGDB). A PGDB such as EcoCyc (see http://ecocyc.org) integrates our evolving understanding of the genes, proteins, metabolic network, and genetic network of an organism. This paper provides an overview of the four main components of the Pathway Tools: The PathoLogic component supports creation of new PGDBs from the annotated genome of an organism. The Pathway/Genome Navigator provides query, visualization, and Web-publishing services for PGDBs. The Pathway/Genome Editors support interactive updating of PGDBs. The Pathway Tools ontology defines the schema of PGDBs. The Pathway Tools makes use of the Ocelot object database system for data management services for PGDBs. The Pathway Tools has been used to build PGDBs for 13 organisms within SRI and by external users.