bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toxicogenomics: An Overview with Special Reference to Genetic and Genomic Approaches to the Identification of Toxic Effects
Authors: Banerjee Mayukh , Giri Ashok K. 
Published: March 2013

AbstractToxicology, the study of poisons, has been explored widely since ages immemorial. However, only recently, workers have begun to apply the state‐of‐the‐art “omics” technologies to study toxicological problems. This has led to exciting possibilities in the field of toxicology and holds promise to revolutionize the study of poisons and their effects in ways more than one. However, with all these advantages, this new technique also has the disadvantage of being exorbitantly costly as well as low in reproducibility. Hence, the results obtained from toxicogenomic techniques need to be vindicated by classical cytogenetic and molecular biology methods before reaching any tangible conclusion. This article gives a glimpse of the genomic and genetic components used extensively in contemporary toxicological studies and elucidates how an appropriate interaction between the two approaches can help workers to generate high‐quality data and reach proper conclusions by avoiding possible pitfalls.
Toxicogenomics — Applications in Systems Toxicology
Authors: Joseph Pius 
Published: March 2013

AbstractHuman exposure to toxic chemicals is almost unavoidable. The toxicity owing to human exposure to chemicals may result in adverse health effects such as illnesses and even death. It is therefore important to determine whether human exposure to chemicals may result in toxicity and, if so, to obtain a full understanding of the mechanism(s) underlying the toxicity. Recent developments in genomics and their application in toxicology (toxicogenomics) have facilitated a better understanding of chemical toxicity. Unlike traditional toxicity studies, toxicogenomics studies have the potential to detect toxicity pre‐clinically (before the onset of clinical manifestations of toxicity) and this may have implications even in predicting the toxicity of chemicals. Recent studies have demonstrated the potential application of genomics‐based toxicity determination in surrogate tissues such as blood, for monitoring human exposure to toxic chemicals. The potential of toxicogenomics in determining the toxicity of chemicals is best illustrated in the case of hepatotoxic chemicals. It is anticipated that toxicogenomics studies, in conjunction with the traditional toxicity determination approaches, may be useful to determine the systems toxicity of chemicals.
A Community‐Based Participatory Research/Translational Biomedical Research Strategy for Personalizing Nutrition, Medicine, and Healthcare
Authors: Williams Anna , Wise Carolyn , Lovera Dalia , McCabe‐Sellers Beverly , Bogle Margaret , Kaput Jim 
Published: March 2013

AbstractPersonal and public health information is usually derived from studies of large population groups. Although reported as population attributable risk (PAR), these estimates are often applied to individuals. PARs for intake of nutrients, exposure to toxins, responses to drug, having certain genetic variants, and, more recently, nutrient{‐‐}gene interactions are statistical estimates of the percentage reduction in disease in the population if the risk were to be avoided or the gene variant were not present. Individuals differ in genetic makeup, life‐style, and dietary patterns and may not be represented by individuals in the study population. Although these risk factors are valuable guidelines, they may not apply to individuals. Intervention studies are likewise limited by small sample sizes, short time frames to assess physiological changes, and variable experimental designs that often preclude comparative or consensus analyses. A fundamental challenge for personalizing nutritional recommendations to optimize health and medicine for getting the right drug to the right person at the right time will be to develop a means to sort individuals into groups and, eventually, develop risk factors for individuals. The classic case{‐‐}control prospective design may need to be revised in order to develop individual risk factors. A promising approach for more complete analyses of the interaction of genetic makeups and environment relies on translational research strategies where the study participant is physiologically monitored over time. Community‐based participatory research (CBPR) methodology is a form of translational research whose central focus is developing a partnership among researchers and individuals in a community that allows for more in‐depth life‐style analyses but simultaneously helps improve the health of individuals and communities through application of research outcomes.
Integration of Systems Toxicology into Drug Discovery
Authors: Fielden Mark 
Published: March 2013

Abstract

Success in the pharmaceutical industry is plagued by high rates of late‐stage attrition because of unanticipated pre‐clinical and clinical toxicity. In order to improve success rates, it is necessary to consider potential on‐ and off‐target‐mediated toxicity at an earlier stage in product development to shift attrition upstream in the process. This will help to avoid resource‐intensive development activities, such as pre‐clinical toxicology and human clinical studies, on compounds that are ultimately destined to fail. Large‐scale gene expression profiling technologies, such as toxicogenomics, have the potential to diagnose and predict certain safety liabilities using
in vitro
and
in vivo
models. When used appropriately in the early stages of lead optimization and pre‐clinical drug testing, it has the potential to improve compound selection at an earlier stage of drug discovery and thus decrease the probability of late‐stage attrition. A more thorough understanding of a drug's mechanism of action and toxicity is also expected to improve human risk assessment and help define appropriate screening strategies to avoid toxicophores in subsequent iterations of drug discovery. This chapter will focus on the application of systems toxicology using toxicogenomics in drug discovery for the early safety assessment of small molecule therapeutics.
Applications of Proteomic Technologies to Toxicology
Authors: Ge Yue , Bruno Maribel , Foth Heidi 
Published: March 2013

AbstractProteomics is the large‐scale study of gene expression at the protein level. This cutting edge technology has been extensively applied to toxicology research recently. The up‐to‐date development of proteomics has presented the toxicology community with an unprecedented opportunity to reexamine conventional toxicological principles, methods and practices, and to transform this traditional subject into more informative and comprehensive science for a better understanding of the potential toxic mechanisms and/or modes of action, toxicity pathways, environmental biomarkers, and assessment of adverse human health risks. The application of proteomics and other OMICS technologies to toxicology has given rise to the new field of toxicology, systems toxicology. This book chapter provides an introduction to modern proteomic technologies and approaches, with particular reference to their applications to toxicology. Key proteomic technologies such as two‐dimensional gel electrophoresis based and mass spectrometry‐based proteomic methods and approaches are described. Examples of recent applications of these technologies and methodologies to mechanistic toxicology and applied toxicology such as chemical toxicity testing and screening, clinical toxicology, drug discovery, environmental toxicity, and toxicity biomarker are presented. The discussion includes a focus on challenges and future directions of toxicoproteomics and systems toxicology.
Application of Quantitative Proteomic Approaches to Toxicology
Authors: Prasad T.S. Keshava , Chaerkady Raghothama 
Published: March 2013

AbstractEpidemiological and genetic studies have significantly contributed to our understanding of hazardous effects of various environmental pollutants on biological systems at a molecular level. However, only limited reports exist those describe proteomic alterations associated with toxicity of such pollutants. Proteomic signatures can be employed as biomarkers for exposure as well as toxicity. Improved protein/peptide labeling technologies have led to the development of a variety of methodologies for quantitative proteomics that can be used to obtain differential protein profiles. This review highlights various quantitative proteomic technologies, which can be applied to unravel proteomic changes in response to toxicants.
Biomarkers for the Assessment of Acetaminophen Induced Liver Injury
Authors: Pathmasiri Wimal , Snyder Rodney W. , Burgess Jason P. , Popp James A. , Fennell Timothy R. , Sumner Susan J. 
Published: March 2013

Abstract
This chapter summarizes a selection of literature regarding the development of biomarkers of acetaminophen (APAP)–induced liver injury (AILI), and provides new data related to the use of metabolomics for the development of a noninvasive marker profile for AILI. Our research investigation used male rats dosed daily with APAP at 0, 10, or 1500 per kg per day for up to 9 days. Urine, blood, and liver were obtained following a day and nine. Metabolomics of urine and extracts of liver showed separation of groups based on dose and duration of dose. Serum transaminases were evaluated. Histopathological analysis revealed complex pathological incidences for three lobes of the liver (left, right, and median), where centrilobular hypertrophy, centrilobular necrosis, and centrilobular inflammation were prominent in all lobes. Subsets of metabolites were identified that correlated with presence of AILI, even in cases were clinically relevant serum enzymes were not consistently correlated with pathology findings. Metabolite changes consistent with the presence of liver damage correlated with interruptions in amino acid, histidine, purine and pyrimidine, and glutamate metabolism. This study reveals markers that could find pre‐clinical and clinical use, and provides insights into mechanisms involved in AILI.
Immunotoxicogenomics: A Systems Approach
Authors: Vandebriel Rob J. , van Loveren Henk , Baken Kirsten A. , Pennings Jeroen L.A. 
Published: March 2013

AbstractImmunotoxicity can be defined as the adverse effects of toxicants on the immune system. Low‐molecular‐weight chemicals that are able to induce allergy can be divided into contact and respiratory sensitizers. These sensitizers differ not only in their relevant exposure routes and the clinical effects they can induce, but also in risk assessment. Various types of data suggest that the oxidative stress response pathway is the most significant one affected by contact sensitizer exposure. Less abundant, primarily toxicogenomics, data suggest that the PTEN pathway is the most significant pathway affected by respiratory sensitizer exposure. The chemical characteristics that determine whether a sensitizer is a contact or respiratory sensitizer are beginning to be understood. We hypothesize how the oxidative stress and PTEN pathways may result in thein vivoobservations of preferential Th1 and Th2 responses by contact and respiratory sensitizers, respectively. While for contact sensitization risk assessment seems to be feasible, this prospect is still remote for respiratory sensitization, partly because a validatedin vivomodel and quantitative data are lacking. To be able to identify respiratory sensitizers, we propose to develop non‐animal assays on the basis of human data. This proposition also holds for risk assessment of respiratory sensitization. We anticipate that development of non‐animal assays as well as risk assessment will depend on a systems toxicology framework.
In SilicoToxicology Prediction Using Toxicogenomics Data
Authors: Okuno Yasushi , Minowa Yohsuke , Yamada Hiroshi , Ohno Yasuo , Urushidani Tetsuro 
Published: March 2013

AbstractToxicogenomics holds the promise of unprecedented advances in two broad, overlapping fields: mechanistic or investigative toxicology, and predictive toxicology. The progress of toxicogenomics has been supported by DNA microarray technology, a powerful tool for directly monitoring patterns of cellular perturbations through the identification and quantification of global shifts in gene expression resulting from pathological alterations within cells and tissues. Microarrays provide a large amount of transcriptional expression data for thousands of individual genes under various experimental conditions. Bioinformatics technologies can determine which genes are meaningful, facilitating the analysis of huge pools of toxicogenomics data in mechanistic and predictive toxicology. This chapter is devoted to computational approaches for the data mining of biomarker genes from toxicogenomics data, leading to toxicity prediction. Many algorithms have been developed for feature gene selection. Most studies on feature selection have found that wrapper methods are superior to filter methods, but many of these studies have over‐emphasized prediction accuracy and over‐looked the robustness of the selected genes. In fact, this study illustrates that intensity‐based moderatedt‐statistics–support vector machine (SVM) produces more stable gene lists than recursive feature elimination–SVM. Therefore, we have to carefully gauge not only prediction performance but also the robustness of gene sets in feature gene selection.
Multifunctional Nanomaterials for Biomedical Applications: The Onset of Nanomedicine
Authors: Xu Yang , Mahmood Meena , Biris Alexandru S. 
Published: March 2013

AbstractGiven their unique properties, the nanostructural materials have found a large number of applications in medicine and biology. Some of these applications range from cell visualization, specific targeting and destruction of cancer cells, drug and gene delivery, or scaffolds for tissue regeneration. Novel multifunctional nanomaterials with magnetic properties and graphitic shells were synthesized and were found to act as strong thermal agents for cellular thermal ablation under radio frequency excitation. Also carbon‐based nanomaterials were found to synergistically enhance the activity of anti ‐cancer drugs, opening the possibility of complex approaches for cancer treatment.
In VivoToxicity Studies of Metal and Metal Oxide Nanoparticles
Authors: Adamcakova‐Dodd Andrea , Thorne Peter S. , Grassian Vicki H. 
Published: March 2013

AbstractManufactured nanomaterials are in more than 1000 consumer products that contain some nanotechnology‐based material on the market today. In the last five years there has been much effort put toward understanding the health effects associated with nanoparticle exposure. Toxicity assessment plays a significant role in this effort since human exposure can occur during production processes, handling, as well as their use and application. Although, though there is a large body of literature on “ultrafine particles” from a pulmonary exposure assessment, one should proceed with caution to expand this information to nanomaterials as we are still just at the beginning stages of their toxicity assessment. In this chapter, we consider the respiratory system as the main route of exposure to nanoparticles and we focus our attention mainly on metal‐based nanomaterials andin vivomodels used to evaluate them. We also discuss available data for other materials, since similar material properties whether size, shape, or chemical composition could lead to comparable toxicities and this will help in the development of screening strategies for nanomaterials that are very much warranted at this time.
Health Effects of Nanoparticles
Authors: Baeza‐Squiban Armelle , Boland Sonja , Hussain Salik , Marano Francelyne 
Published: March 2013

Abstract
Increasing utilizations of nanomaterials in the industrial as well as consumer products augment the possibilities of environmental and occupational human exposures. Because of this fact, nanoparticles (NPs) have become potential candidates for the risk assessment. Among the possible exposure routes, inhalation represents the most important route of non‐intentional exposure to NPs. There are increasing evidences that NPs exhibit ability to cross biological barriers getting access to the bloodstream and secondary target organs where they could accumulate and induce pathological consequences. The surface area and reactivity of particles increase many fold relative to particle mass as particle size is reduced. Together with chemical composition, they constitute important determinants of NPs toxicity. They contribute in the production of reactive oxygen species (ROS) leading to the toxicological outcomes induced by NPs. In this study, we present a systemic overview of the current knowledge on the exposure, secondary organ translocation and potential health effects of the NPs. Moreover, potential mechanisms of NP‐induced cellular effects and role of physico‐chemical characteristics are elaborated. The potentially deleterious effects of NPs require further studies in order to build on our mechanistic understanding of the toxicological events in which they can be implicated.
Systems Toxicological Approach to the Risk Assessment of Nanomaterials
Authors: Jeong Sang‐Hee , Cho Wan‐Seob , Kim Ji‐Eun , Cho Myung‐Haing 
Published: March 2013

AbstractNowadays, nanomaterials have come into the spotlight as new materials that have lots of prominent benefits in various fields of human life. Risk assessment of the nanomaterials requires a multidisciplinary understanding of the differences from their large particles in surface physicochemistry and dosimetry. The size, biological effective dose, surface chemistry, interactions with biological membrane and dispersion media are important factors that make unique characteristics of nanomaterials in their toxicity potency. Conventional methods for the toxicological assessment may have limitations in proper understanding of the dose‐response relationships of the diversity of structures and compositions of nanomaterials. Challenges to toxicological testing of nanomaterials will be covered with the strategy of systems toxicology including toxico‐genomics, toxico‐proteomics and toxico‐metabolomics. The data driven from systems toxicology are valuable in the identification and characterization of the mode of action of nanomaterials. Many of toxicogenomic and toxicoproteomic studies have released that the production of reactive oxygen species and inflammation caused by oxidative stress are the key mechanism of toxicity of nanomaterials. However, there is still limited information for the assessment of toxicity thresholds based on dose‐response relationships and for the estimation of exposure in risk assessment of nanomaterials. More integrated and systemic studies are required for the risk assessment of human health impact considering various but unique properties of nanomaterials.
Technical Note: Reliability of suchey‐brooks and buckberry‐chamberlain methods on 3D visualizations from CT and laser scans
Authors: Villa Chiara , Buckberry Jo , Cattaneo Cristina , Lynnerup Niels 
Published: March 2013

ABSTRACTPrevious studies have reported that the ageing method of Suchey‐Brooks (pubic bone) and some of the features applied by Lovejoy et al. and Buckberry‐Chamberlain (auricular surface) can be confidently performed on 3D visualizations from CT‐scans. In this study, seven observers applied the Suchey‐Brooks and the Buckberry‐Chamberlain methods on 3D visualizations based on CT‐scans and, for the first time, on 3D visualizations from laser scans. We examined how the bone features can be evaluated on 3D visualizations and whether the different modalities (direct observations of bones, 3D visualization from CT‐scan and from laser scans) are alike to different observers. We found the best inter‐observer agreement for the bones versus 3D visualizations, with the highest values for the auricular surface. Between the 3D modalities, less variability was obtained for the 3D laser visualizations. Fair inter‐observer agreement was obtained in the evaluation of the pubic bone in all modalities. In 3D visualizations of the auricular surfaces, transverse organization and apical changes could be evaluated, although with high inter‐observer variability; micro‐, macroporosity and surface texture were very difficult to score. In conclusion, these methods were developed for dry bones, where they perform best. The Suchey‐Brooks method can be applied on 3D visualizations from CT or laser, but with less accuracy than on dry bone. The Buckberry‐Chamberlain method should be modified before application on 3D visualizations. Future investigation should focus on a different approach and different features: 3D laser scans could be analyzed with mathematical approaches and sub‐surface features should be explored on CT‐scans. Am J Phys Anthropol 151:158–163, 2013. © 2013 Wiley Periodicals, Inc.
Maternal immune activation promotes hippocampal kindling epileptogenesis in mice
Authors: Pineda Eduardo , Shin Don , You Su Jeong , Auvin Stéphane , Sankar Raman , Mazarati Andréy 
Published: March 2013

ObjectiveMaternal immune activation (MIA) triggered by infections has been identified as a cause of autism in offspring. Considering the involvement of perturbations in innate immunity in epilepsy, we examined whether MIA represents a risk factor for epilepsy as well. The role of specific MIA components interleukin (IL)‐6 and IL‐1β was also addressed.MethodsMIA was induced in C57BL/6 mice by polyinosinic–polycytidylic acid (PIC) injected during embryonic days 12 to 16. Beginning from postnatal day 40, the propensity of the offspring to epilepsy was examined using hippocampal kindling; autismlike behavior was studied using the sociability test. The involvement of IL‐6 and IL‐1β in PIC‐induced effects was studied by the coadministration of the cytokine antibodies with PIC, and by delivering recombinant cytokines in lieu of PIC.ResultsThe offspring of PIC‐exposed mice exhibited increased hippocampal excitability, accelerated kindling rate, prolonged increase of seizure susceptibility after kindling, and diminished sociability. Epileptic impairments were abolished by antibodies to IL‐6 or IL‐1β. Neither of the recombinant cytokines alone increased the propensity to seizures; however, when combined, they produced effects similar to those induced by PIC. PIC‐induced behavioral deficits were abolished by IL‐6 antibodies and were mimicked by recombinant IL‐6; IL‐1β was not involved.InterpretationIn addition to confirming the previously established critical role of IL‐6 in the development of autismlike behavior following MIA, the present study shows that concurrent involvement of IL‐6 and IL‐1β is required for priming the offspring for epilepsy. These data shed light on mechanisms of comorbidity between autism and epilepsy. Ann Neurol 2013;74:11–19