G protein-coupled receptor-mediated transcriptional regulation in pathological cardiac remodelling
Bibliographic record
Abstract
Pathological cardiac remodelling is an adaptive response to various stressors placed on the heart, such as sustained hypertension or following myocardial infarction.The remodelling attempts to preserve cardiac function and contractility through increased left ventricular wall thickness via a hypertrophic response in cardiomyocytes.At the same time, cardiac fibroblasts are activated and mediate a fibrotic response in damaged areas to maintain structural integrity and aid in wound healing.While initially adaptative, chronic activation of these processes can lead to left ventricle dilation and heart failure, where the heart is no longer able to maintain the necessary cardiac output.This remodelling is predominantly mediated through neurohormonal activation of multiple G protein-coupled receptors (GPCRs), as well as their Gα and Gβγ partner proteins, to elicit intracellular signalling cascades in the different cell types.Currently, the primary therapies are aimed at blocking these receptors.Despite modest clinical success of these therapies, heart failure remains a leading cause of mortality in Canada.Therefore, development of new approaches are required to understand and impact disease progression and improve patient prognosis.GPCR signalling pathways converge on the transcriptional machinery to regulate gene expression changes critical for the development of pathological cardiac remodelling.Due to the integration of multiple pathological signals by the transcriptional machinery, therapies targeting To the members of my advisory committee (Dr.
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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) | 0.000 | 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) | 0.015 | 0.005 |
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".