Conditional deletion of FoxO1/3/4 improves recovery from hindlimb ischemia
Bibliographic record
Abstract
FoxO proteins have anti-proliferative and angiostatic functions. We recently reported increased FoxO1 protein in rat skeletal muscle capillaries following hindlimb ischemia induced by iliac artery ligation. We hypothesized that reduction of FoxO protein would improve capillary growth post-ligation. We utilized a mouse model of conditional deletion of FoxO1/3/4 genes. MxCre−:FoxO1/3/4f/f (Cre−) or MxCre+:FoxO1/3/4f/f(Cre+) mice were injected with poly inosine:cytosine (pIC) to activate Cre expression, or phosphate-buffered saline (PBS), 1 week prior to femoral artery ligation or sham surgery (n=4–6/group). After 10 days, Laser Doppler flow measurements were recorded and hindlimb muscles were removed to analyze capillary to fiber ratio (C:F). FoxO deletion, assessed by PCR analysis of genomic DNA, was observed in Cre+, but not Cre-, mice injected with pIC. At day 10 post-ligation, blood flow ratio (ischemic:contralateral leg) was 0.5 +/−0.09 and 0.8 +/−0.09 in Cre− and Cre+ mice, respectively (p<0.05). 10 days post-ligation, C:F was 0.91+/−0.08 and 1.32+/−0.03 in Cre- and Cre+ mice respectively (p<0.05), compared with 1.04+/−0.04 and 1.16+/−0.08 in respective sham mice. These data support a signifcant role for FoxO proteins in regulating capillary growth and blood flow recovery to the ischemic mouse hindlimb. Funded by CIHR.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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".