Bibliographic record
Abstract
The vasculature is essential for the delivery of oxygen and nutrients and the removal of metabolic wastes from tissues of the body. The embryonic vasculature is developed through the processes of vasculogenesis, angiogenesis, and arteriogenesis. Once the vasculature is fully developed and stabilized, the adult vasculature shows very little proliferation or cell death. Nevertheless, the endothelium, which lines the lumen of the blood vessels, is actively involved in the control of vascular tone, permeability, blood flow, coagulation, inflammation and tissue repair. An injury to the endothelium is important for progression of diseases such as atherosclerosis and the sepsis syndrome. The Notch signaling pathway has emerged in the recent decade as an important player in multiple vascular processes and endothelial behaviors. This thesis examines the role of the Notch signaling pathway in embryonic arteriogenesis and endothelial survival signaling. The first part of this thesis investigates the developmental source of vascular smooth muscle cells. This study presents the first in situ observation of an immediate smooth muscle precursor cell present in all embryonic arteries. This Tie1⁺/CD31⁺/VE-cadherin⁻ precursor requires Notch signaling to differentiate into vascular smooth muscle cells and to ensure vascular stability of newly formed arteries. However, Notch activation is not required in the precursor cells to maintain the medial layer of the arteries once the vessel is invested with vascular smooth muscle cells. In the second part of this thesis, the mechanism of Notch-induced endothelial survival signaling is examined. In endothelial cells, Notch signaling activates phosphotidylinositol-3 kinase (PI3K) through up-regulation of a secreted factor. Activity of PI3K is required to offset the parallel apoptotic signaling induced by Notch activation and to maintain endothelial survival through the up-regulation of Slug, a direct Notch target with anti-apoptotic activity. Upon treatment with apoptotic stimuli, Notch activation shows context-dependent effects on endothelial survival. Inhibition of PI3K activity and Slug expression by a stimulus abolishes Notch-induced endothelial survival and increases apoptotic death. The work presented in this thesis shows that the Notch signaling pathway is essential for the stability of the vasculature through regulation of vascular smooth muscle cell differentiation and endothelial cell survival.
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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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".