Abstract 205: Mlip is a New Integrator of Physiological Stress Required For Proper Cardiac Adaptation
Bibliographic record
Abstract
Aging and diseases are generally a result of the inability of tissues to properly adapt to stress. The heart is particularly vulnerable to disequilibrium in homeostasis as its regenerative capacities are limited. Many molecular players have been identified as cardiac gate-keepers and integrators of stress, all essential to preserve cardiac function. However, the molecular basis of the relationship between aging and the pathogenesis of cardiac dysfunction remains poorly understood. Muscle enriched A-type lamin interacting protein (MLIP) is a unique mammalian protein of unknown function that was recently identified through its interaction with A-type lamins in the heart and as a modulator of cardiac hypertrophy in vitro. Here we report that young Mlip deficient mice develop dilated cardiomyopathy, manifested by an increase in heart mass with reduced cardiac function. Through global gene expression profiling of the Mlip deficient hearts, we identified a deregulation in mTOR signalling, a key stress sensing canonical pathway. Analysis of mTOR regulatory proteins (AMPK and AKT) revealed hyperactivation of the mTOR pathway and a deregulated integration of these two stress/nutrient sensors. These data support the notion that Mlip deficient hearts have impaired cardiac adaptation due to deregulated mTOR activity resulting in maladaptive remodeling, and the development of dilated cardiomyopathy. These results are further supported by a genetic association between Mlip and early response to pro-hypertrophic stimulus. Collectively, these results demonstrate that Mlip is required for normal integration of physiological stress (postnatal cardiac growth, isoproterenol-induced hypertrophy) through the regulation of the AMPK/Akt/mTOR pathway to maintain cardiac homeostasis in the adult heart.
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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 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.002 |
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".