519 research outputs found
Inverted Expression Profiles of Sex-Biased Genes in Response to Toxicant Perturbations and Diseases
10.1371/journal.pone.0056668PLoS ONE82
A fatal case of oral intoxication by mustard gas
Opisan je slučaj peroralne intosikacije iperitom u namjeri samoubojstva i iznesen obdukcioni nalaz. Ukratko su izneseni neki toksikološki pogledi na otrovanje iperifom, te klinički simptomi i patomorfološke promjene kod intoksikacije ovim otrovom.A case is presented of a man aged 27 who swallowed 50 g of mustard gas (dichlor-diethylsulphide) in order to commit suicide. Although immediately treated at the Internal Clinic of the Medical Faculty, he died 8 hours and 20 minutes after taking the poison. A postmortem examination carried out 19 hours after death, as well as histological findings showed congestion and oedema of the brain, fragmentation of cardiac muscle, oedema of mucous membranes of the upper part of gastrointestinal tract, oedema of larynx and epiglotis, oedema of the liver, and congestion of the spleen, adrenal glands, and kidneys. A microscopic examination of the lung tissue revealed hemorrhages probably due to the irritative effect of the poison
Toxicogenomic Analysis Suggests Chemical-Induced Sexual Dimorphism in the Expression of Metabolic Genes in Zebrafish Liver
10.1371/journal.pone.0051971PLoS ONE712
Selection of reliable biomarkers from PCR array analyses using relative distance computational model: Methodology and proof-of-concept study
10.1371/journal.pone.0083954PLoS ONE812-POLN
Toxicogenomic and Phenotypic Analyses of Bisphenol-A Early-Life Exposure Toxicity in Zebrafish
Bisphenol-A is an important environmental contaminant due to the increased early-life exposure that may pose significant health-risks to various organisms including humans. This study aimed to use zebrafish as a toxicogenomic model to capture transcriptomic and phenotypic changes for inference of signaling pathways, biological processes, physiological systems and identify potential biomarker genes that are affected by early-life exposure to bisphenol-A. Phenotypic analysis using wild-type zebrafish larvae revealed BPA early-life exposure toxicity caused cardiac edema, cranio-facial abnormality, failure of swimbladder inflation and poor tactile response. Fluorescent imaging analysis using three transgenic lines revealed suppressed neuron branching from the spinal cord, abnormal development of neuromast cells, and suppressed vascularization in the abdominal region. Using knowledge-based data mining algorithms, transcriptome analysis suggests that several signaling pathways involving ephrin receptor, clathrin-mediated endocytosis, synaptic long-term potentiation, axonal guidance, vascular endothelial growth factor, integrin and tight junction were deregulated. Physiological systems with related disorders associated with the nervous, cardiovascular, skeletal-muscular, blood and reproductive systems were implicated, hence corroborated with the phenotypic analysis. Further analysis identified a common set of BPA-targeted genes and revealed a plausible mechanism involving disruption of endocrine-regulated genes and processes in known susceptible tissue-organs. The expression of 28 genes were validated in a separate experiment using quantitative real-time PCR and 6 genes, ncl1, apoeb, mdm1, mycl1b, sp4, U1SNRNPBP homolog, were found to be sensitive and robust biomarkers for BPA early-life exposure toxicity. The susceptibility of sp4 to BPA perturbation suggests its role in altering brain development, function and subsequently behavior observed in laboratory animals exposed to BPA during early life, which is a health-risk concern of early life exposure in humans. The present study further established zebrafish as a model for toxicogenomic inference of early-life chemical exposure toxicity
Expression of key ion transporters in the gill and esophageal- gastrointestinal tract of euryhaline mozambique tilapia oreochromis mossambicus acclimated to fresh water, seawater and hypersaline water
10.1371/journal.pone.0087591PLoS ONE91-POLN
Transcriptomic Analyses of Sexual Dimorphism of the Zebrafish Liver and the Effect of Sex Hormones
10.1371/journal.pone.0053562PLoS ONE81
Zebrafish Whole-Adult-Organism Chemogenomics for Large-Scale Predictive and Discovery Chemical Biology
The ability to perform large-scale, expression-based chemogenomics on whole adult organisms, as in invertebrate models (worm and fly), is highly desirable for a vertebrate model but its feasibility and potential has not been demonstrated. We performed expression-based chemogenomics on the whole adult organism of a vertebrate model, the zebrafish, and demonstrated its potential for large-scale predictive and discovery chemical biology. Focusing on two classes of compounds with wide implications to human health, polycyclic (halogenated) aromatic hydrocarbons [P(H)AHs] and estrogenic compounds (ECs), we generated robust prediction models that can discriminate compounds of the same class from those of different classes in two large independent experiments. The robust expression signatures led to the identification of biomarkers for potent aryl hydrocarbon receptor (AHR) and estrogen receptor (ER) agonists, respectively, and were validated in multiple targeted tissues. Knowledge-based data mining of human homologs of zebrafish genes revealed highly conserved chemical-induced biological responses/effects, health risks, and novel biological insights associated with AHR and ER that could be inferred to humans. Thus, our study presents an effective, high-throughput strategy of capturing molecular snapshots of chemical-induced biological states of a whole adult vertebrate that provides information on biomarkers of effects, deregulated signaling pathways, and possible affected biological functions, perturbed physiological systems, and increased health risks. These findings place zebrafish in a strategic position to bridge the wide gap between cell-based and rodent models in chemogenomics research and applications, especially in preclinical drug discovery and toxicology
Super Resolution Microscopy Reveals that Caveolin-1 Is Required for Spatial Organization of CRFB1 and Subsequent Antiviral Signaling in Zebrafish
10.1371/journal.pone.0068759PLoS ONE87-POLN
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