Mutation of the Glc-2 Gene May Confer Dominant Ivermectin Resistance
Bibliographic record
Abstract
Background: Ivermectin is a widely used anti-parasitic drug that binds to and activates glutamate-gated chloride channels (GluCls), giving it its nematocidal (nematode-killing) properties. Due to excessive use of ivermectin, frequent cases of resistance to this nematicide are being reported, suggesting that ivermectin is beginning to lose its efficacy. This project seeks to study whether a mutation of the glc-2 gene, which encodes for a β subunit of the GluCl channel, confers ivermectin resistance. We hypothesize that a glc-2 mutation achieves nematicide resistance by creating a defective GluCl channel that cannot bind to ivermectin. Methods: We used classical genetics to obtain the desired mutants from stock worms. We then tested the worms for resistance profile using ivermectin sensitivity assays. Finally, we examined in vivo interactions by expressing relevant RNA in a heterologous system and performed electrophysiological recordings. Results: We were able to demonstrate that presence of the defective glc-2 leads to increased resistance profiles when given the chance to associate with select GluClα subunits (e.g. AVR-15). We also demonstrated that co-injection of glc-2 and glc-3 compromises GluCl response to L-glutamate, a critical indicator of channel functionality. Conclusion: Our results lend strong support to our hypothesis that glc-2 is able to interact with certain α subunits of GluCl to confer ivermectin resistance. This finding provides a framework for future dominant ivermectin resistance studies.
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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 | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 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".