Neuropilin-1 is a molecular target of the transcription factor E2F1 and is involved in cerebral ischemia–induced neuronal death
Bibliographic record
Abstract
After cerebral ischemia, neurons must integrate a multitude of both inhibitory and stimulatory molecular cues, generated as a result of cortical damage, into a functional response. More often than not the response is one of growth cone collapse, axonal retraction and cell death. The mechanisms through which a repelled axon may transduce a death signal to the soma and through which the soma may signal axonal retraction/collapse remain largely unknown, however the neuropilin family of receptors for the repellant semaphorins has been implicated in such responses. Our previous studies have shown that the nuclear transcription factor E2F1 pathway plays an important role in modulating neuronal death in response to a wide range of insults such as glutamate toxicity and cerebral ischemia. Using a high density DNA microarray, we identified that the expression of an axonal guidance molecule, neuropilin-1, is regulated by the transcription factor E2F1. Bioinformatics analysis allowed the identification of a putative E2F1 binding site in the promoter region of neuropilin-1. Subsequent electrophoretic mobility gel shift analysis provided evidence to demonstrate that E2F1 protein is indeed physically capable of binding with specificity to the NRP-1 promoter sequence. Moreover, such binding by E2F1 to the promoter sequence increased in mouse brains subjected to focal cerebral ischemia (Fig 1). The increased occupation of E2F1 at the neuropilin-1 promoter sequence correlated with the temporal induction profile of the mRNA level of neuropilin-1, suggesting that E2F1 transcriptionally up-regulated neuropilin-1 during neuronal death following cerebral ischemia. Taken together, these findings support a model in that nuclear death factors contribute to processes which determine the fate of the damaged distal axons by increasing the amounts of receptors expression to axonal repellent guidance cues that may ultimately lead to cell death and failure to regenerate. Blocking this detrimental signal transduction pathway may have potential therapeutic values.
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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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".