Application of a nonradioactive assay for high throughput screening for inhibition of thyroid hormone uptake via the transmembrane transporter MCT8
Why this work is in the frame
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Bibliographic record
Abstract
Thyroid hormones (THs) play important roles in almost all physiological processes. High-throughput screening (HTS) assays are needed to screen the vast numbers of chemicals for their potential to disrupt TH signalling. The current work has confirmed the ability of a rapid assay to identify substances inhibiting TH uptake through monocarboxylate transporter (MCT) 8. Perturbation of MCT8 function results in significant developmental impairments, suggesting substances inhibiting MCT8 may be important developmental toxicants. We examined the accuracy and consistency of a recently described method to identify TH inhibitors via MCT8, using MDCK cells overexpressing human MCT8 gene. We confirmed the method detected T3 uptake in a concentration/time-dependent manner, and this effect was blocked by substances previous reported to block TH uptake via MCT8. Assay performance was assessed extensively and the system was found to have high signal dynamic range and Z' factor. The assay was also validated with a diverse set of training chemicals. This assay was then used to screen chemicals suspected to disrupt TH signalling. Other than bisphenol A (BPA), all substances tested were negative. Our results suggest that this assay could be part of a battery of screening assays to predict the potential thyroid disrupting activity of chemicals.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it