Alterations of plasma lipids in mice via adenoviral-mediated hepatic overexpression of human ABCA1
Bibliographic record
Abstract
ATP binding cassette transporter A1 (ABCA1) is a widely expressed lipid transporter essential for the generation of HDL. ABCA1 is particularly abundant in the liver, suggesting that the liver may play a major role in HDL homeostasis. To determine how hepatic ABCA1 affects plasma HDL cholesterol levels, we treated mice with an adenovirus (Ad)-expressing human ABCA1 under the control of the cytomegalovirus promoter. Treated mice showed a dose-dependent increase in hepatic ABCA1 protein, ranging from 1.2-fold to 8.3-fold using doses from 5 x 108 to 1.5 x 109 pfu, with maximal expression observed on Day 3 posttreatment. A selective increase in HDL cholesterol occurred at Day 3 in mice treated with 5 x 108 pfu Ad-ABCA1, but higher doses did not further elevate HDL cholesterol levels. In contrast, total cholesterol, triglycerides, phospholipids, non-HDL cholesterol, and apolipoprotein B levels all increased in a dose-dependent manner, suggesting that excessive overexpression of hepatic ABCA1 in the absence of its normal regulatory sequences altered total lipid homeostasis. At comparable expression levels, bacterial artificial chromosome transgenic mice, which express ABCA1 under the control of its endogenous regulatory sequences, showed a greater and more specific increase in HDL cholesterol than Ad-ABCA1-treated mice. Our results suggest that appropriate regulation of ABCA1 is critical for a selective increase in HDL cholesterol levels.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".