The <i>Dirofilaria immitis unc-49</i> gene encodes a pharmacologically unique cys-loop GABA receptor
Bibliographic record
Abstract
Abstract Nematode cys-loop GABA receptors play important roles in movement and locomotion. GABA receptors encoded by unc-49 appear to be widespread in nematode genomes including parasitic nematodes but are poorly characterized in filarial parasites. Dirofilaria immitis is a filarial parasite responsible for heartworm disease in dogs. Macrocyclic lactones are widely used to prevent heartworm infection. However, like many anthelmintics, resistance has emerged and new solutions are needed including the discovery of new anthelmintic drug targets. In this study, we report the isolation of two unc-49 subunit mRNAs ( unc-49b and unc-49c ) from the canine parasitic nematode D. immitis . When expressed in Xenopus oocytes, Dim-UNC-49B formed a functional homomeric GABA-gated channel, whereas Dim-UNC-49C did not. We further demonstrated that Dim-UNC-49B and Dim-UNC-49C gave rise to a functional heteromeric channel. Pharmacological characterization of these receptors and cross-species co-expression with UNC-49 subunits from the parasitic nematode Haemonchus contortus showed some unique properties compared to the same receptors characterized from other nematodes. These results revealed new properties of UNC-49 receptors in filarial worms.
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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 | 0.000 | 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) | 0.001 | 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".