Abstract 321: Deletion Of The Translational Repressors Eukaryotic Translation Initiation Factor 4e Binding Proteins 1 And 2 Protects Against Pressure Overload Induced Heart Failure
Bibliographic record
Abstract
Assembly of the translation initiation machinery is negatively regulated by the eukaryotic translation initiation factor 4E binding proteins, which sequester the mRNA cap-binding protein eIF4E, thus preventing assembly of an intact initiation complex. However, the role of translational control on the development of congestive heart failure (CHF) has not been systematically examined. Here we perturbed translational control in mice by knockout of both 4E binding protein 1 (Eif4ebp1) and 2 (Eif4ebp2) (designated as Eif4ebp1/2 double knockout) to study its impact on left ventricular hypertrophy and CHF resulting from transverse aortic constriction. Eif4ebp1/2 double knockout caused a modest increase in left ventricular mass under basal conditions. However, following transverse aortic constriction, Eif4ebp1/2 double knockout profoundly attenuated the development of CHF and its attendant mortality. Examination of candidate genes involved in the mechanism revealed increased expression of transcription factors for genes governing energy metabolism and mitochondrial biogenesis with corresponding increases in the expression of their target genes. Our data indicate that removing physiological restraints on translation initiation exerts a profound cardiac protective effect against pressure overload induced CHF, suggesting that method(s) to disrupt the function of the 4E binding proteins may be a novel therapeutic approach for preventing or treating CHF.
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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) | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".