Bibliographic record
Abstract
Golgi beta1,6N-acetylglucosaminyltransferase V (Mgat5) produces beta1,6GIcNAc-branched N-glycans on glycoproteins, which increases their affinity for galectins and opposes loss from cell surface to constitutive endocytosis. Oncogenic transformation increases Mgat5 expression, and enhances sensitivities to growth factors, cell motility and tumour metastasis. Therefore, I explored growth and tissue renewal of Mgat5-/- mice, and found that they are hypoglycaemic, resistant to weight-gain, hypersensitive to fasting, display increased oxidative respiration, reduced fecundity and decreased serum leptin. These phenotypes are similar to that of calorie restricted (CR) rodents; however, unlike CR animals, Mgat5-/- mice have accelerated loss of muscle and bone mass and reduced lifespan. CR-induced longevity involve downregulation of the PI3K/Akt/TOR pathway, downstream of many growth factor receptors including EGF, PDGF and IR. In this regard, Mgat5-/- primary MEFs and macrophages are suppressed in MAPK activation in response to EGF, PDGF, IGF, and FCS. However, muscle satellite cells and bone marrow osteoblasts revealed a FCS-induced signalling imbalance, favouring Smad2/3 activation over Erk, which may contribute to reduced growth, self-renewal and longevity of the Mgat5-/- animals. Pten opposes PI3K/Akt signalling and is a potent tumour suppressor. Mgat5 +/- Pten+/- and Mgat5-/- Pten +/- mutant mice showed a small increase in lifespan compared with Pten+/- mice, due to an apparent delay in tumour progression. Primary Pten+/-Mgat5-/- MEFs are normalised for Akt activation and cell spreading, and Pten+/- MEFs have enhanced L-PHA staining, suggesting that Mgat5 structures are regulated by P13K signalling. Aged CR rodents exhibit decreased oxidative damage, implicating either decreased ROS production or elevated antioxidant activity. I demonstrated that Mgat5-/- primary MEFs have decreased glucose uptake and mitochondrial ROS. Unlike WT control, PyMT Mgat5-/- cells fail to down regulate glucose transport, protein synthesis, ROS and activation of Erk and Akt following serum withdrawal. PyMT transformation reveals that Mgat5-deficiency not only impairs positive growth signalling, but also suppresses negative growth regulation, allowing for proliferation and tumourigenicity. Mgat5 participates upstream of PyMT signalling through N-glycan modification of growth factor receptors, but also downstream of Akt signalling through its dependence on glucose uptake for supply of UDP-GlcNAc. Therefore, Mgat5 enhances cellular signalling and growth, and metabolism and longevity in the animal.
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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 | 0.001 |
| Meta-epidemiology (broad) | 0.000 | 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 | 0.002 |
| Insufficient payload (model declined to judge) | 0.007 | 0.002 |
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".