Phospholamban is localized in autophagosome in dilated cardiomyopathy mouse model, TgPLN <sup>R9C</sup> mice
Bibliographic record
Abstract
An Arg 9 to Cys point mutation in phospholamban (PLN) is the leading cause of dilated cardiomyopathy (DCM) in both humans and in transgenic mice (TgPLN R9C mice). Our earlier study of PLN showed that impaired autophagic flux in HECT domain and Ankyrin repeat‐containing E3 ubiquitin protein ligase 1 (HACE1)‐null mouse hearts was associated with increased PLN protein levels. Here, we show that HACE1 expression was decreased in 8‐, 16‐weeks old TgPLN R9C mouse hearts, and PLN was co‐immunoprecipitated with the autophagic adapter protein, p62, and confocal immunofluorescent microscopy revealed intracellular co‐localization of PLN with p62. At the same time, electron microscopy showed increased autophagosome in TgPLN R9C mouse hearts. These results suggest that PLN is degraded by autophagy, and an impairment of the autophagy pathway promotes PLN accumulation in TgPLN R9C mouse hearts. Furthermore, we also observed decreased expression of the von Hippel‐Lindau (VHL), another E3 ubiquitin ligase in TgPLN R9C mouse hearts. Taken together, we propose that diminished expression of E3 ubiquitin ligases, such as HACE1 and VHL could be related to the progression to DCM in TgPLN R9C mice.
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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 | 0.001 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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".