The Invulnerability of Adult Neurons: A Critical Role for p73
Bibliographic record
Abstract
Here, we investigated the intracellular mechanisms that underlie the relative invulnerability of adult versus developing dorsal root ganglion (DRG) sensory neurons. In culture, adult neurons were resistant to stimuli that caused apoptosis of their neonatal counterparts. In both adult and neonatal neurons, death stimuli induced the apoptotic c-Jun N-terminal protein kinase (JNK) pathway, but JNK activation only caused death of neonatal neurons, indicating that adult neurons have a downstream block to apoptosis. Expression of the dominant-inhibitory p53 family member, DeltaNp73, rescued JNK-induced apoptosis of neonatal neurons, suggesting that it might participate in the downstream apoptotic block in adult neurons. To test this possibility, we examined adult DRG neurons cultured from p73+/- mice. Adult p73+/- DRG neurons were more vulnerable to apoptotic stimuli than their p73+/+ counterparts, and invulnerability could be restored to the p73+/- neurons by increased expression of DeltaNp73. Moreover, although DRG neuron development was normal in p73+/- animals in vivo, axotomy caused death of adult p73+/- but not p73+/+ DRG neurons. Thus, one way adult neurons become invulnerable is to enhance endogenous survival pathways, and one critical component of these survival pathways is p73.
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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 | 0.010 |
| 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 | 0.000 |
| 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".