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In conclusion, this study proves that DAS-induced HETs formation plays an immune toxicity role in chicken liver injury and these results provide a new therapeutic target for DAS-induced liver injury in chickens.Effective inducing of ovarian maturation in female shrimp broodstock is important for successful breeding programs. Vitellogenesis is a biochemical process during which a yolk protein precursor vitellogenin (Vg) is synthesized and thus, can be used to indicate ovarian maturation stage. In this study, transcriptional regulation of Vg synthesis in the black tiger shrimp, Penaeus monodon was investigated. Genome walking on 5' upstream sequence of Vg gene revealed several putative binding sites of lipophilic retinoic acid response elements (RARE), and nuclear hormone responsive elements. Deletion of RARE significantly reduced the promoter activity to drive the expression of luciferase reporter gene in Sf-9 cells. To validate the trans-factor that potentially controls Vg expression through RARE, a cDNA encoding retinoid X receptor (PmRXR), one of the RARE-bound transcription factors was cloned from P. monodon's ovary. PmRXR expression was detected in various shrimp tissues, and was up-regulated during ovary development in a similar way to Vg expression. The DNA-binding domain of PmRXR protein showed specific binding to RARE-containing region on Vg 5' upstream sequence as determined by Electrophoretic Mobility Shift Assay (EMSA). Furthermore, dsRNA-mediated PmRXR silencing in previtellogenic and vitellogenic shrimp revealed that suppression of PmRXR could reduce Vg transcript in both stages. Taken together, the results presented in this study indicate that RXR is possibly an activator protein that modulates Vg expression in shrimp ovary through the binding to RARE.Hydropower plants (HPPs) are a source of "green" energy but also a threat to migrating fish such as the European eel (Anguilla anguilla) owing to the disruption of river connectivity and the obstruction of downstream migration. The impact of HPP are well-documented in terms of fish survival and damages but there is no available information concerning the condition of surviving and unharmed fish. The aim of this study is to assess the impact of the passage through HPP on the survival, the physiological and health status of adult eels. Two trials were carried with variants of the Kaplan turbine - one of the most common types in Europe. After a deliberate passage through the turbines, we studied direct mortality, external and internal damages, stress and immune biomarkers such as plasma cortisol and glucose levels, alternative complement (ACH50), lysozyme and peroxidase activities, and total immunoglobulin (Ig) content. Our results showed a lower survival and a higher external and internal damages rates in the HPP groups. Glucose levels, ACH50, lysozyme and peroxidase activities and TIgc were also affected by the passage depending on HPP characteristics. Those findings suggest a greater energy expenditure and a disruption in innate immunity due to this passage. HPPs can not only have an impact in terms of direct mortality and injuries but also affect the physiological and health condition of the surviving eels. This impact may explain the delayed mortality observed in telemetric studies and the passage through many HPPs may compromise the ability of adult eels to migrate successfully to the ocean.The testing and classification of chemicals to determine adverse ocular effects are routinely conducted to ensure that materials are appropriately classified, labeled, and meet regulatory and safety guidelines. We have performed a same-chemical analysis using publicly available validation study results and compared the performance between tests for the same chemicals. Selleck GSK484 To normalize for chemical selection, we matched chemicals tested by pairs of tests so that each matched set compared performance for the exact same chemicals. Same-chemical accuracy comparisons demonstrate a chemical selection effect that results in a wide range of overlapping false-positive (FP) rates and accuracies for all test methods. In addition, the analysis suggests that a tiered-testing strategy with specific combinations of tests can reduce the FP rate for some combinations. However, reductions in the FP rates were typically accompanied by an increase in the false-negative rates, resulting in minimal advantage in terms of accuracy. In addition, actual improvements in the FP rate after retesting positives with a second test are not as good as the theoretical improvements because some chemicals and functional groups appear to be broadly misclassified by all test methods, which, to the extent the tests make the same-chemical misclassifications, reduces the advantage of using tiered-testing strategies.The iodide recycling enzyme, iodotyrosine deiodinase (IYD), is a largely unstudied molecular mechanism through which environmental chemicals can potentially cause thyroid disruption. This highly conserved enzyme plays an essential role in maintaining adequate levels of free iodide for thyroid hormone synthesis. Thyroid disruption following in vivo IYD inhibition has been documented in mammalian and amphibian models; however, few chemicals have been tested for IYD inhibition in either in vivo or in vitro assays. Presented here are the development and application of a screening assay to assess susceptibility of IYD to chemical inhibition. With recombinant human IYD enzyme, a 96-well plate in vitro assay was developed and then used to screen over 1800 unique substances from the U.S. EPA ToxCast screening library. Through a tiered screening approach, 194 IYD inhibitors were identified (inhibited IYD enzyme activity by 20% or greater at target concentration of 200 μM). 154 chemicals were further tested in concentration-response (0.032-200 μM) to determine IC50 and rank-order potency. This work broadens the coverage of thyroid-relevant molecular targets for chemical screening, provides the largest set of chemicals tested for IYD inhibition, and aids in prioritizing chemicals for targeted in vivo testing to evaluate thyroid-related adverse outcomes.
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