Adenovirus mediated alteration of phosphatidylethanolamine N‐methyltransferase expression <i>in vivo</i>
Bibliographic record
Abstract
Hepatic phosphatidylcholine (PC) is required for normal secretion of VLDL. In all nucleated mammalian cells, PC is synthesized from choline via the Kennedy (CDP‐choline) pathway, and the flux through this pathway is regulated by the activity of CTP: phosphocholine cytidylyltransferase (CT). Liver cells are uniquein that they can also synthesize PC via the sequential methylation of phosphatidylethanolamine, catalyzed by phosphatidylethanolamine N ‐methyltransferase (PEMT). We have previously reported that Pemt −/− mice have impaired VLDL secretion that leads to mild steatosis. To further investigate regulation of lipid metabolism by PEMT, we produced adenoviruses (Ad) that expressed either the PEMT cDNA (Ad.PEMT) or a PEMT siRNA (Ad.siPEMT). In the first set of experiments, we observed that in vivo administration of Ad.PEMT to Pemt −/− mice normalized hepatic PEMT activity within 7 days. The restoration of PEMT activity in Pemt −/− mice returned hepatic TG to wildtype levels. Adenoviral overexpression of CTα also normalized hepatic TG in Pemt −/− mice. Although both Ad.PEMT and Ad.CT were successful in reversing steatosis in Pemt −/− mice, only CT overexpression increased plasma TG levels. In the second study, Ad.siPEMT was administered, by i.v. injection, to wildtype mice. After 7 days, the levels of PEMT mRNA, protein, and activity were reduced by 20 to 40% as compared to control mice. Although the suppression of PEMT was minor, a lowering of plasma TG was observed, suggesting that an acute decrease in PEMT was sufficient to alter lipid metabolism. The creation of these adenoviruses provides us with a valuable tool to investigate the influence of acute changes in hepatic PC biosynthesis on lipid and lipoprotein metabolism. Supported by Canadian Institutes of Health Research .
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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 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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".