A novel approach using C. elegans DNA damage-induced apoptosis to characterize the dynamics of uptake transporters for therapeutic drug discoveries
Bibliographic record
Abstract
Organic cation transporter (OCT) function is critical for cellular homeostasis. C. elegans lacking OCT-1 displays a shortened lifespan and increased susceptibility to oxidative stress. We show that these phenotypes can be rescued by downregulating the OCT-1 paralogue, OCT-2. Herein, we delineate a biochemical pathway in C. elegans where uptake of genotoxic chemotherapeutics such as doxorubicin and cisplatin, and subsequent DNA damage-induced apoptosis of germ cells, are dependent exclusively upon OCT-2. We characterized OCT-2 as the main uptake transporter for doxorubicin, as well as a number of other therapeutic agents and chemical compounds, some identified through ligand-protein docking analyses. We provide insights into the conserved features of the structure and function and gene regulation of oct-1 and oct-2 in distinct tissues of C. elegans. Importantly, our innovative approach of exploiting C. elegans uptake transporters in combination with defective DNA repair pathways will have broad applications in medicinal chemistry.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".