c-Myc Signalling in the Genetic Mechanism of Polycystic Kidney Disease
Bibliographic record
Abstract
The Myc family of transcription factors regulates major biological processes such as proliferation, stem/progenitor cell pluripotency, metabolism, apoptosis, cell growth and differentiation. The most-studied member c-Myc is essential in embryonic development and cellular homeostasis. Dysregulation of c-Myc protein function is not only associated with malignant transformation and human tumors but is also implicated in autosomal dominant polycystic kidney disease (ADPKD), a human genetic disorder, considered a neoplasia in disguise. Studies from human ADPKD kidneys, caused by mutation in the PKD1 or PKD2 genes, revealed high expression of c-Myc with strong signal detected over cystic tubular epithelium. Consistent with human ADPKD pathogenesis, mouse models produced by dysregulation of Pkd1 and Pkd2 gene dosage show stimulation of renal c-Myc expression. Induced renal c-Myc expression is also observed in several non-orthologous animal models of PKD. Significantly, c-Myc overexpression specifically targeted to renal epithelial cells in transgenic mice closely reproduces human ADPKD. The specific causal effect of c-Myc in PKD was demonstrated by targeting different oncogenes which could not mimic the PKD phenotype. In fact, c-Myc was shown to be a major mediator of renal cystogenesis through various mechanisms and signalling pathways. Most importantly, inhibition of c-Myc in vivo, directly by repressing translation or indirectly with a small-molecule inhibitor, significantly delayed cystogenesis in the mouse. In summary, c-Myc is a central node in the pathogenesis of Pkd1/Pkd2 mouse models and of human ADPKD development and progression.
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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 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".