Effect of covalent antithrombin-heparin complex on developmental mechanisms in the lung
Bibliographic record
Abstract
We have developed a potent antithrombin (AT)-heparin conjugate (ATH) that is retained in the lung to prevent pulmonary thrombosis associated with respiratory distress in premature newborns. During continuing maturation, pulmonary angiogenesis in premature infants would be a crucial process in lung development. A naturally occurring latent form of antithrombin (L-AT) has antiangiogenic effects on lung vascularization. However, impact of latent ATH (L-ATH) on developing lung vascularization is unknown. Thus, effects of L-AT and L-ATH on fetal murine lung development were compared. Lung buds from embryonic day 11.5 (E11.5) Tie2-LacZ mouse embryos were incubated in DMEM plus FBS supplemented with PBS, AT, L-AT, heparin, ATH, or L-ATH. Vasculature of cultured explants was quantified by X-galactosidase staining. RNA was analyzed with murine gene probes for angiopoietin (Ang)-1, Ang-2, fibroblast growth factor 2 (FGF2), platelet endothelial cell adhesion molecule (PECAM), and vascular endothelial growth factor (VEGF). FGF2-supplemented medium was used to test contribution to effects of L-AT and L-ATH on angiogenesis. Epithelial branching morphogenesis was inhibited by L-AT (P = 0.003) and heparin (P < 0.001). L-AT and heparin decreased relative vascular area compared with PBS, ATH, and L-ATH. Expressions of all genes studied were downregulated by L-AT. However, L-AT and L-ATH inhibited branching morphogenesis and vasculature with added FGF2. These findings indicate that covalent linkage of AT to heparin negates disruptive effects of these moieties on lung morphology, vascularization, and growth factor gene expression. ATH may have enhanced safety as an anticoagulant during vascular development.
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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) | 0.001 | 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".