Neuropathogenesis of Noonan syndrome is mediated by inflammatory microglia
Bibliographic record
Abstract
Abstract Microglia are resident hematopoietic cells that play important roles in the damaged or degenerating adult nervous system. Microglia are involved in neuropathogenesis of various diseases. Microglia are also essential for neuroprotection and comprise an essential component of the neural stem cell niche. The activation of microglia is an important phenomenon associated with several neurological disorders that arise from infections to developmental abnormalities and behavioral pathologies. Noonan syndrome (NS) is associated with mutations in the PTPN11 gene and also accounts for mental retardation in children. Interestingly, in mouse models of NS, mutations in the PTPN11 gene resulted in dysregulation of neural progenitors. The present study describes the activation of microglia in the NS mouse model, which results in an inflammatory phenotype with expression of IL-1b and defective phagocytosis. To test whether microglia from NS mice are important for neural precursor maintenance or self-renewal, embryonic neural precursors from the cortex of WT mice were cultured. Microglia from NS and WT mice were then added to cortical precursor cells which showed that microglia from NS mice inhibited astrogenesis. Together, these results demonstrate that microglia can dysregulate neural precursor development in NS, and suggest that alterations in microglial number as a consequence of genetic or pathological events may perturb neural development by directly affecting embryonic neural precursors.
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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 | 0.000 |
| 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".