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Role of Apoptosis in Neurotoxicology

The role of apoptosis in development and neurodegeneration has become increasingly apparent in the past 10 yr. Normal apoptosis occurs in the central nervous system (CNS) from the embryonic stage through senescence, with different cells in each region of the nervous system having charac ...

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Cell-Type Specific Responses of the Nervous System to Lead

Cells that make up the nervous system interact in complex, dynamic structural and biochemical contexts to generate organ function. A neurotoxicant that alters the activities of a particular cell type also induces secondary changes in the interactions between this cell and other cells. A ...

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Effects of Toxicants on Neural Differentiation

Differentiation is a complex process by which a terminal cell phenotype is determined. During neural development, in vivo cells of the nervous system reach this terminal phenotype through both preprogrammed genetic signaling and epigenetic signaling. This genetic program can set up ...

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Impairment of Synaptic Function by Exposure to Lead

Of all known neurotoxicants, lead (Pb) has received by far the most research attention. Because of increasing awareness of its untoward effects, investigation of the metal’s central nervous system (CNS) actions has extended over several decades and across multiple experimental speci ...

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The Use of Two-Dimensional Gel Electrophoresis for Plasma Biomarker Discovery

Two-dimensional polyacrylamide gel electrophoresis (2-DE) is one of the most widely used and versatile methods of protein expression profiling among a rapidly growing arsenal of proteomics technologies. 2-DE combines two orthogonal and independent electrophoretic steps: is ...

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Difference In-Gel Electrophoresis: A High-Resolution Protein Biomarker Research Tool

Difference in-gel electrophoresis (DIGE) is a recent adaptation of conventional two-dimensional gel electrophoresis (2-DE) that incorporates novel fluorescent labels, has multiplex attributes, and boasts software-assisted image analysis. Combined, these character ...

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Label-Free Mass Spectrometry-Based Protein Quantification Technologies in Protein Biomarker Discovery

Major technological advances have made proteomics an extremely active field for biomarker discovery in recent years due primarily to the development of newer mass spectrometric technologies and the explosion in genomic and protein bioinformatics. This leads to an increased emph ...

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Top-Down Quantitative Proteomic Analysis Using a Highly Multiplexed Isobaric Mass Tagging Strategy

Proteomic analysis has proved to be key to determining drug mechanisms and assessing toxicologic potential during preclinical screening studies. A major goal in proteomics is to accurately measure changes in the relative abundance of large sets of proteins in complex biological sys ...

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SELDI Technology for Identification of Protein Biomarkers

The ProteinChip SELDI System and chip arrays provide a sensitive, high-throughput methodology for protein biomarker discovery. The combination of retentate chromatography and time-of-flight mass spectrometry allows for the detection of increased peak numbers even when pro ...

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LC-MS Metabonomics Methodology in Biomarker Discovery

Metabonomics as an important component of functional genomics and system biology has gained increasing interest in drug development and biomarker discovery. Comprehensive metabonomics investigations are primarily a challenge for analytical chemistry. The main advanta ...

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Sandwich ELISA Microarrays: Generating Reliable and Reproducible Assays for High-Throughput Screens

The sandwich ELISA microarray is a powerful screening tool in biomarker discovery and validation because of its ability to simultaneously probe for multiple proteins in a miniaturized assay. The technical challenges of generating and processing the arrays are numerous. However, ca ...

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NMR-Based Metabolomics for Biomarker Discovery

Metabolomics provides a powerful set of tools for pharmaceutical and clinical research in a number of important areas that include drug development, early disease detection, patient stratification for treatment, and information on disease processes. With its ability to discover n ...

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GC-MS-Based Metabolomics

Gas chromatography–mass spectrometry (GC/MS)-based metabolomics profiling methods have been developed and used for plant metabolite profiling since the 1980s. Only during the past few years has the technology been more widely used for metabolomics studies in animals and humans wi ...

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Unraveling Glycerophospholipidomes by Lipidomics

In recent years, proteomics has driven developments of mass spectrometric approaches. Simultaneously, the research community has regained a major interest in lipids, with mass spectrometry unambiguously facilitating the development of lipidomics. Quantitative determ ...

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Biomarker Sample Collection and Handling in the Clinical Setting to Support Early-Phase Drug Development

The era of increased application of pharmacodynamic biomarker measures for early-phase drug development is upon us in response to the introduction to the clinic of targeted therapeutics. This unprecedented opportunity to perform measures of human physiology responding to pharm ...

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Gene Expression-Based Biomarkers of Drug Safety

Large-scale gene expression profiling with microarray platforms represents a new approach to identify much needed, novel mechanism-based biomarkers of toxicity for use in preclinical and clinical studies. These biomarkers may have diagnostic and/or predictive values and may c ...

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Real-Time Polymerase Chain Reaction Gene Expression Assays in Biomarker Discovery and Validation

Biomarkers have shown great potential in molecular classification and targeted treatment of human diseases. Biomarkers are also expected to play an increasingly important role in all phases of drug development as well as regulatory decision making. However, translating biomark ...

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Profiling Gene Expression Signatures Using Fluorescent Microspheres

One of the primary goals of genome-wide expression profiling is to identify subsets of gene transcripts that can be associated with specific biological conditions. Once these gene expression “signatures” have been elucidated, they can be used in screening assays to identify compounds t ...

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Single Nucleotide Polymorphisms and DNA Methylation Analysis Using Pyrosequencing Methods

The data generated from the Human Genome Project has led to an explosion of technology for low-, medium-, and high-throughput genotyping methods. Pyrosequencing is a genotyping assay based on sequencing by synthesis. Short runs of sequence around each polymorphism are generated, allowi ...

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SAGE Analysis in Identifying Phenotype Single Nucleotide Polymorphisms

Serial analysis of gene expression (SAGE) has been extensively used to evaluate gene expression in a variety of biological contexts. In this review, we provide a general overview of the SAGE methodology and its major applications. Furthermore, we provide a detailed, day-by-day based protoc ...

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