Tubedown regulation of retinal endothelial permeability signaling pathways
Why this work is in the frame
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Bibliographic record
Abstract
Tubedown (Tbdn; Naa15), a subunit of the N-terminal acetyltransferase NatA, complexes with the c-Src substrate Cortactin and supports adult retinal homeostasis through regulation of vascular permeability. Here we investigate the role of Tbdn expression on signaling components of retinal endothelial permeability to understand how Tbdn regulates the vasculature and supports retinal homeostasis. Tbdn knockdown-induced hyperpermeability to Albumin in retinal endothelial cells was associated with an increase in the levels of activation of the Src family kinases (SFK) c-Src, Fyn and Lyn and phospho-Cortactin (Tyr421). The knockdown of Cortactin expression reduced Tbdn knockdown-induced permeability to Albumin and the levels of activated SFK. Inhibition of SFK in retinal endothelial cells decreased Tbdn knockdown-induced permeability to Albumin and phospho-Cortactin (Tyr421) levels. Retinal lesions of endothelial-specific Tbdn knockdown mice, with tissue thickening, fibrovascular growth, and hyperpermeable vessels displayed an increase in the levels of activated c-Src. Moreover, the retinal lesions of patients with proliferative diabetic retinopathy (PDR) associated with a loss of Tbdn expression and hyperpermeability to Albumin displayed increased levels of activated SFK in retinal blood vessels. Taken together, these results implicate Tbdn as an important regulator of retinal endothelial permeability and homeostasis by modulating a signaling pathway involving c-Src and Cortactin.
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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 | 0.001 | 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 it