Cross-brain Notch1 Concentrations In Response To Hypocapnia And Hypercapnia
Bibliographic record
Abstract
Notch1 has been recognized as an essential regulator of peripheral vascular endothelial function, particularly in response to increased vascular wall shear stress, such as during exercise. However, there is limited data on activity of Notch1 in the brain, and whether it is an important regulator of cerebral vascular endothelial function. PURPOSE: To determine if changes in pH mediated shear stress in the cerebral vasculature impacts Notch1 activity. METHODS: 12 (7 male) young (27 ± 3 yrs) healthy (BMI: 23 ± 2 kg/m2) participants performed a single laboratory visit. Cerebral blood flow (CBF) and shear was manipulated by steady state (5 min) hypercapnia (+9 PaCO2) and hypocapnia (-10 PaCO2) using dynamic end-tidal forcing, with a minimum of 10 min rest between conditions. At baseline (BL), hypercapnia, and hypocapnia, simultaneous blood samples were drawn from the radial artery and internal jugular vein, to determine cross brain concentrations of Notch1, measured by an ELISA. CBF was determined by simultaneous duplex ultrasound of the left vertebral and right internal carotid arteries. Cerebral exchange of Notch1 was calculated from the arterial-venous Notch1 difference multiplied by the CBF. RESULTS: All values are mean ± SD. Statistical analysis was performed by Bonferroni corrected two-tailed T-Tests. At BL there was an average net release of Notch1 from the brain by -38 ± 70 ng/min, corresponding with a higher (non-significant, P = 0.058) concentration of Notch1 in the venous (188 ± 185 pg/mL) vs. arterial (138 ± 131 pg/mL) circulation. Compared to BL, there was no change in the cerebral exchange of Notch1 in hypercapnia (-11 ± 73 ng/min, P = 0.453), however, hypocapnia caused a significant flip of cerebral Notch1 uptake (30 ± 64 ng/min, P = 0.035). The net uptake of Notch1 in the brain during hypocapnia was attributable to an elevated arterial (214 ± 185 pg/mL, P = 0.014) and not venous (166 ± 170 pg/mL, P = 0.659) Notch1. CONCLUSION: Notch1 appears to be more responsive in the peripheral vasculature than the brain, as the relatively localized increase in cerebral shear with hypercapnia had no impact. The physiologic relevance of Notch1 (extracellular domain) uptake in the brain remains to be determined but may play an important role for cerebral vascular homeostasis in response to systemic increases in vascular wall shear stress.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".