Cardiac-specific transgenic overexpression of α<sub>1B</sub>-adrenergic receptors induce chronic activation of ERK MAPK signalling
Bibliographic record
Abstract
Cardiomyocyte-specific overexpression of the wild-type alpha(1B)-adrenergic receptor (alpha(1B)-AR) produces a slowly progressing cardiomyopathy associated with clinical signs of heart failure and premature death around middle age (Lemire et al. 2001). In the heart, alpha(1)-AR activate the extracellular signal-regulated kinase (ERK) MAPK cascade. The aim of this project was to determine if cardiac-specific overexpression of the wild-type alpha(1B)-AR results in sustained activation of the ERK pathway. At 3 and 9 months, ERK activity was increased in alpha(1B)-AR overexpressing hearts relative to non-transgenic animals. Similarly, phosphorylation of MEK and p90(rsk) were also elevated. MAP kinase phosphatases (MKPs), which inactivate MAP kinases, are transcriptionally regulated. MKP2 mRNA levels were reduced at 3 months in alpha(1B)-AR overexpressing hearts. Interestingly, there was a general trend for reduced expression of MKP-1, -2, and -3 with increased age. In addition, expression of the modulatory calcineurin-interacting protein (MCIP) 1, an indicator of calcineurin activity, was elevated 3-fold in alpha(1B)-AR overexpressing hearts at both 3 and 9 months. These results indicate that the overexpression of the wild-type alpha(1B)-AR leads to chronic changes in the activation of signalling pathways previously shown to be associated with the hypertrophic response.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".