Uncovering Novel Anthelmintics: Targeting Caenorhabditis elegans Hyperosmotic Stress Recovery with Small Molecules
Bibliographic record
Abstract
Around a quarter of the world’s population is infected with soil-transmitted helminths (STHs). Anthelmintics are the primary treatment for STH infections. However, due to prolonged and intensive use, anthelmintic resistance is emerging, and new drugs need to be developed. From literature, I found that osmoregulation is essential for STHs to establish infections within hosts. Using Caenorhabditis elegans as a model, I screened a RIKEN drug library and identified 12 hits that inhibited hyperosmotic recovery in worms. Interestingly, 4/12 hits targeted mitochondria, so I shifted my focus onto mitochondrial inhibitors. By testing them, I found that Complex II is especially important during hyperosmotic recovery. However, my experiments showed that the recovery defect due to Complex II inhibition was not directly caused by reduced ATP levels or a disrupted TCA cycle. Further studies are needed to clarify Complex II’s role during hyperosmotic recovery, which could reveal new targets for anthelmintic development.
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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) | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".