Immune-mediated hemolytic anemia in a 6 year-old Golden Retriever
Bibliographic record
Abstract
PDZRN3 (also known as LNX3) is a member of the PDZ domain-containing RING finger protein family. We previously showed that PDZRN3 is essential for differentiation of myoblasts into myotubes and that depletion of PDZRN3 inhibits such differentiation downstream of the upregulation of myogenin, a basic helix-loop-helix (bHLH) transcription factor required for completion of the differentiation process. However, the mechanism by which PDZRN3 controls this process has remained unclear. Myogenin is rendered active during the late stage of myogenic differentiation by the downregulation of Id2, a negative regulator of bHLH transcription factors. We now show that depletion of PDZRN3 inhibits the differentiation of C2C12 cells by inducing the upregulation of Id2 and thereby delaying its downregulation. Knockdown of Id2 by RNA interference restores the differentiation of PDZRN3-depleted cells. Luciferase reporter assays revealed that a putative binding site for STAT5b in the Id2 gene promoter is required for the upregulation of Id2 expression by PDZRN3 depletion. In addition, the amount of phosphorylated Id2 was reduced and that of the nonphosphorylated protein concomitantly increased in PDZRN3-depleted cells, with the inhibitory effect of Id2 on bHLH transcription factors having previously been shown to be attenuated by phosphorylation of Id2 catalyzed by the complex of Cdk2 with cyclin A2 or E1. Indeed, the expression of cyclin A2, but not that of cyclin E1, was reduced in PDZRN3-depleted cells. Our results thus indicate that PDZRN3 plays a key role in the differentiation of myoblasts into myotubes by regulating Id2 at both transcriptional and posttranslational levels.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 0.000 |
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 teacher head, 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".