Cardiac troponin T mutations promote life-threatening arrhythmias
Bibliographic record
Abstract
Mutations in contractile proteins in heart muscle can cause anatomical changes that result in cardiac arrhythmias and sudden cardiac death. However, a conundrum has existed because mutations in one such contractile protein, a so-called Ca2+ sensor troponin T (TnT), can promote ventricular rhythm disturbances even in the absence of hypertrophy or fibrosis. Thus, these mutations must enhance abnormal electrophysiological events via alternative means. In this issue of the JCI, Baudenbacher et al. report a novel mechanism to explain this puzzle (see the related article beginning on page 3893). They show that a selected TnT mutation in the adult mouse heart can markedly increase the sensitivity of cardiac muscle myofilaments to Ca2+ and enhance the susceptibility to arrhythmia, even in the absence of anatomical deformities. As these same mutations can cause some forms of arrhythmias in humans, these findings are of both basic and translational significance.
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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 | 0.001 | 0.008 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.010 | 0.005 |
| Insufficient payload (model declined to judge) | 0.005 | 0.004 |
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".