EXS Pub Date : 2009-01-01 DOI: 10.1007/978-3-7643-8336-7_8

Roberto Sánchez-Olea, Mónica R Calera, Alexei Degterev

引用次数: 6

Toxicogenomics: transcription profiling for toxicology assessment. 毒物基因组学:毒理学评估的转录谱分析。

EXS Pub Date : 2009-01-01 DOI: 10.1007/978-3-7643-8336-7_12

Tong Zhou, Jeff Chou, Paul B Watkins, William K Kaufmann

引用次数: 15

High-throughput screening for analysis of in vitro toxicity. 体外毒性分析的高通量筛选。

EXS Pub Date : 2009-01-01 DOI: 10.1007/978-3-7643-8336-7_14

Willem G E J Schoonen, Walter M A Westerink, G Jean Horbach

{"title":"High-throughput screening for analysis of in vitro toxicity.","authors":"Willem G E J Schoonen, Walter M A Westerink, G Jean Horbach","doi":"10.1007/978-3-7643-8336-7_14","DOIUrl":"https://doi.org/10.1007/978-3-7643-8336-7_14","url":null,"abstract":"The influence of combinatorial chemistry and high-throughput screening (HTS) technologies in the pharmaceutical industry during the last 10 years has been enormous. However, the attrition rate of drugs in the clinic due to toxicity during this period still remained 40-50%. The need for reduced toxicity failure led to the development of early toxicity screening assays. This chapter describes the state of the art for assays in the area of genotoxicity, cytotoxicity, carcinogenicity, induction of specific enzymes from phase I and II metabolism, competition assays for enzymes of phase I and II metabolism, embryotoxicity as well as endocrine disruption and reprotoxicity. With respect to genotoxicity, the full Ames, Ames II, Vitotox, GreenScreen GC, RadarScreen, and non-genotoxic carcinogenicity assays are discussed. For cytotoxicity, cellular proliferation, calcein uptake, oxygen consumption, mitochondrial activity, radical formation, glutathione depletion as well as apoptosis are described. For high-content screening (HCS), the possibilities for analysis of cytotoxicity, micronuclei, centrosome formation and phospholipidosis are examined. For embryotoxicity, endocrine disruption and reprotoxicity alternative assays are reviewed for fast track analysis by means of nuclear receptors and membrane receptors. Moreover, solutions for analyzing enzyme induction by activation of nuclear receptors, like AhR, CAR, PXR, PPAR, FXR, LXR, TR and RAR are given.","PeriodicalId":77125,"journal":{"name":"EXS","volume":"99 ","pages":"401-52"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/978-3-7643-8336-7_14","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27934498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 62

Role of DNA repair in the protection against genotoxic stress. DNA修复在抗基因毒性应激中的作用。

EXS Pub Date : 2009-01-01 DOI: 10.1007/978-3-7643-8336-7_5

Ulrike Camenisch, Hanspeter Naegeli

{"title":"Role of DNA repair in the protection against genotoxic stress.","authors":"Ulrike Camenisch, Hanspeter Naegeli","doi":"10.1007/978-3-7643-8336-7_5","DOIUrl":"https://doi.org/10.1007/978-3-7643-8336-7_5","url":null,"abstract":"The genome of all organisms is constantly attacked by a variety of environmental and endogenous mutagens that cause cell death, apoptosis, senescence, genetic diseases and cancer. To mitigate these deleterious endpoints of genotoxic reactions, living organisms have evolved one or more mechanisms for repairing every type of naturally occurring DNA lesion. For example, double-strand breaks are rapidly religated by non-homologous end-joining. Homologous recombination is used for the high-fidelity repair of interstrand cross-links, double-strand breaks and other DNA injuries that disrupt the replication fork. Some genotoxic lesions inflicted by alkylating agents can be repaired by direct reversal of DNA damage. The base excision repair pathway takes advantage of multiple DNA glycosylases to remove modified or incorrect bases. Finally, the nucleotide excision repair machinery provides a versatile strategy to monitor DNA quality and eliminate all forms of helix-distorting DNA lesions, including a wide diversity of carcinogen adducts. The efficiency of DNA repair responses is enhanced by their coupling to transcription and coordination with the cell cycle circuit.","PeriodicalId":77125,"journal":{"name":"EXS","volume":"99 ","pages":"111-50"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/978-3-7643-8336-7_5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27936179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 22

Physiologically based toxicokinetic models and their application in human exposure and internal dose assessment. 基于生理学的毒物动力学模型及其在人体暴露和内剂量评估中的应用。

EXS Pub Date : 2009-01-01 DOI: 10.1007/978-3-7643-8336-7_2

David Kim, Leena A Nylander-French

{"title":"Physiologically based toxicokinetic models and their application in human exposure and internal dose assessment.","authors":"David Kim, Leena A Nylander-French","doi":"10.1007/978-3-7643-8336-7_2","DOIUrl":"https://doi.org/10.1007/978-3-7643-8336-7_2","url":null,"abstract":"Human populations may exhibit large interindividual variation in toxicokinetic response to chemical exposures. Rapid developments in dosimetry research have brought medicine and public health closer to understanding the biological basis of this heterogeneity. The toxicokinetic behavior of chemicals is, in part, controlled by the properties of the epithelium surrounding organs, some of which are effective barriers to penetration into the systemic circulation. Physiologically based toxicokinetic (PBTK) models have been developed and used to simulate the mechanism of uptake into the systemic circulation, to extrapolate between doses and exposure routes, and to estimate internal dosimetry and sources of heterogeneity in animals and humans. Recent improvements to PBTK models include descriptions of active transport across biological membranes, carrier-mediated clearance, and fractal kinetics. The expanding area of toxicogenetics has provided valuable insight for delineating toxicokinetic differences between individuals; genetic differences include inherited single nucleotide polymorphisms, copy number variants, and dynamic changes in the methylation pattern of imprinted genes. This chapter discusses the structure of PBTK models and how toxicogenetic information and newer biological descriptions have improved our understanding of variability in response to toxicant exposures.","PeriodicalId":77125,"journal":{"name":"EXS","volume":"99 ","pages":"37-55"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/978-3-7643-8336-7_2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27935672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

The aryl hydrocarbon receptor at the crossroads of multiple signaling pathways. 芳烃受体在多个信号通路的十字路口。

EXS Pub Date : 2009-01-01 DOI: 10.1007/978-3-7643-8336-7_9

Ci Ma, Jennifer L Marlowe, Alvaro Puga

引用次数: 49

Regulatory small RNAs in plants. 植物中的调节小rna。

EXS Pub Date : 2007-01-01 DOI: 10.1007/978-3-7643-7439-6_5

Cameron Johnson, Venkatesan Sundaresan

{"title":"Regulatory small RNAs in plants.","authors":"Cameron Johnson, Venkatesan Sundaresan","doi":"10.1007/978-3-7643-7439-6_5","DOIUrl":"https://doi.org/10.1007/978-3-7643-7439-6_5","url":null,"abstract":"The discovery of microRNAs in the last decade altered the paradigm that protein coding genes are the only significant components for the regulation of gene networks. Within a short period of time small RNA systems within regulatory networks of eukaryotic cells have been uncovered that will ultimately change the way we infer gene regulation networks from transcriptional profiling data. Small RNAs are involved in the regulation of global activities of genic regions via chromatin states, as inhibitors of 'selfish' sequences (transposons, retroviruses), in establishment or maintenance of tissue/organ identity, and as modulators of the activity of transcription factor as well as 'house keeping' genes. With this chapter we provide an overview of the central aspects of small RNA function in plants and the features that distinguish the different small RNAs. We furthermore highlight the use of computational prediction methods for identification of plant miRNAs/precursors and their targets and provide examples for the experimental validation of small RNA candidates that could represent trans-regulators of downstream genes. Lastly, the emerging concepts of small RNAs as modulators of gene expression constituting systems networks within different cells in a multicellular organism are discussed.","PeriodicalId":77125,"journal":{"name":"EXS","volume":"97 ","pages":"99-113"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26664721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 9

Methods, applications and concepts of metabolite profiling: primary metabolism. 代谢物谱分析的方法、应用和概念:初级代谢。

EXS Pub Date : 2007-01-01 DOI: 10.1007/978-3-7643-7439-6_8

Dirk Steinhauser, Joachim Kopka

{"title":"Methods, applications and concepts of metabolite profiling: primary metabolism.","authors":"Dirk Steinhauser, Joachim Kopka","doi":"10.1007/978-3-7643-7439-6_8","DOIUrl":"https://doi.org/10.1007/978-3-7643-7439-6_8","url":null,"abstract":"In the 1990s the concept of a comprehensive analysis of the metabolic complement in biological systems, termed metabolomics or alternately metabonomics, was established as the last of four cornerstones for phenotypic studies in the post-genomic era. With genomic, transcriptomic, and proteomic technologies in place and metabolomic phenotyping under rapid development all necessary tools appear to be available today for a fully functional assessment of biological phenomena at all major system levels of life. This chapter attempts to describe and discuss crucial steps of establishing and maintaining a gas chromatography/electron impact ionization/ mass spectrometry (GC-EI-MS)-based metabolite profiling platform. GC-EI-MS can be perceived as the first and exemplary profiling technology aimed at simultaneous and non-biased analysis of primary metabolites from biological samples. The potential and constraints of this profiling technology are among the best understood. Most problems are solved as well as pitfalls identified. Thus GC-EI-MS serves as an ideal example for students and scientists who intend to enter the field of metabolomics. This chapter will be biased towards GC-EI-MS analyses but aims at discussing general topics, such as experimental design, metabolite identification, quantification and data mining.","PeriodicalId":77125,"journal":{"name":"EXS","volume":"97 ","pages":"171-94"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/978-3-7643-7439-6_8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26664610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Introduction to systems biology. 系统生物学导论。

EXS Pub Date : 2007-01-01 DOI: 10.1007/978-3-7643-7439-6_1

Frank J Bruggeman, Jorrit J Hornberg, Fred C Boogerd, Hans V Westerhoff

{"title":"Introduction to systems biology.","authors":"Frank J Bruggeman, Jorrit J Hornberg, Fred C Boogerd, Hans V Westerhoff","doi":"10.1007/978-3-7643-7439-6_1","DOIUrl":"10.1007/978-3-7643-7439-6_1","url":null,"abstract":"The developments in the molecular biosciences have made possible a shift to combined molecular and system-level approaches to biological research under the name of Systems Biology. It integrates many types of molecular knowledge, which can best be achieved by the synergistic use of models and experimental data. Many different types of modeling approaches are useful depending on the amount and quality of the molecular data available and the purpose of the model. Analysis of such models and the structure of molecular networks have led to the discovery of principles of cell functioning overarching single species. Two main approaches of systems biology can be distinguished. Top-down systems biology is a method to characterize cells using system-wide data originating from the Omics in combination with modeling. Those models are often phenomenological but serve to discover new insights into the molecular network under study. Bottom-up systems biology does not start with data but with a detailed model of a molecular network on the basis of its molecular properties. In this approach, molecular networks can be quantitatively studied leading to predictive models that can be applied in drug design and optimization of product formation in bioengineering. In this chapter we introduce analysis of molecular network by use of models, the two approaches to systems biology, and we shall discuss a number of examples of recent successes in systems biology.","PeriodicalId":77125,"journal":{"name":"EXS","volume":"97 ","pages":"1-19"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26664717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Differential display and protein quantification. 差异显示和蛋白质定量。

EXS Pub Date : 2007-01-01 DOI: 10.1007/978-3-7643-7439-6_6

Erich Brunner, Bertran Gerrits, Mike Scott, Bernd Roschitzki

引用次数: 2

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