Characterization of an Epilepsy‐associated variant of the AE3 Cl <sup>‐</sup> /HCO3 <sup>‐</sup> exchanger
Bibliographic record
Abstract
Anion exchanger 3 (AE3), expressed in brain, heart and retina, extrudes intracellular HCO 3 ‐ in exchange for extracellular Cl ‐ . There are two isoforms of AE3, brain or full length AE3 (AE3fl) and cardiac AE3 (cAE3). Epilepsy is a heterogeneous group of disorders characterized by recurrent unprovoked seizures that affect about 50 million people worldwide. Idiopathic generalized epilepsy (IGE) accounts for approximately 30% of all epilepsies. Interestingly, the occurrence of the A867D AE3 allele in humans has been reported to be associated with the development of IGE. Moreover, AE3 knockout mice are reported to display a reduced threshold for chemically induced seizures. We evaluated wild type (WT) and A867D AE3fl functional and physiological parameters in transfected HEK cells. Although both proteins are processed similarly to the plasma membrane (32 ± 2 % vs 37 ± 5 %, respectively), A867D AE3fl displays a significantly reduced transport activity (47 ± 13 %, p < 0.05) when compared to the WT. Protein Kinase A (PKA) regulates the transport activity of both proteins since stimulation with 8‐Br cAMP increases transport and pre‐incubation with the PKA‐specific inhibitor H89 abolished this increase. Together this suggests that the decreased activity of A867D AE3 may cause changes in cell volume and abnormal intracellular pH. In the brain, these alterations may promote neuron hyperexitability and the generation of seizures. This research is supported by Canadian Institutes of Health Research.
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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 | 0.001 |
| 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 | 0.001 | 0.001 |
| 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".