Bibliographic record
Abstract
Long QT syndrome (LQTS) is a debilitating cardiac arrhythmia, and mutations or malfunctions in the human ether-a-go-go–related gene (hERG) are the most common cause of LQTS. hERG is responsible for the cardiac potassium current (IKr), which is important for cardiac repolarization. It has 6 transmembrane domains, ranging from S1 to S6, and a complex N-linked oligosaccharide chain resides on the extracellular S5 pore linker region. The role of this glycosylation chain in hERG function has not yet been well distinguished and in the current study we aim to investigate the relationship between hERG protease susceptibility and the presence of the glycosylation chain. Using molecular techniques, we demonstrate that de-glycosylated hERG channels are degraded by the serine protease Proteinase K at a much faster rate than their glycosylated counter parts. Additionally, through removal of the end-chain sialic acid residues using the enzyme neuraminidase, we conclude that it is likely the physical blockade of susceptible protease sites that grants wild type hERG this glycosylation-dependent protection as opposed to charge repulsion facilitated by specific sugars in the carbohydrate chain. Our data show that the glycosylation chain found on hERG plays a role in protecting the channel from protease degradation, and could provide valuable insight into the development of the cardiac arrhythmia Long QT Syndrome.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| 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 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".