<i>Drosophila</i> egg-derived tyrosine phosphatase (EDTP): a novel target for improved survivorship to prolonged anoxia and cellular protein aggregates
Bibliographic record
Abstract
Abstract Drosophila egg-derived tyrosine phosphatase (EDTP), a lipid phosphatase that removes 3-position phosphate at the inositol ring, has dual functions in the oogenesis and the muscle performance during adult stages. A mammalian homologous gene MTMR14 , which encodes the myotubularin-related protein 14, negatively regulates autophagy. Mutation of EDTP/MTMR14 , however, causes at least three deleterious consequences: (1) lethality in the early embryogenesis in Drosophila ; (2) “jumpy” phenotype with apparently impaired motor functions; and (3) association with a rare genetic disorder called centronuclear myopathy. Here we show that flies carrying a heterozygous EDTP mutation had increased survivorship to prolonged anoxia; tissue-specific downregulation of EDTP in non-muscle tissues, particularly motoneurons, extended the lifespan; and tissue-specific downregulation of EDTP in motoneurons improved the survivorship to beta-amyloid peptides (Aβ42) and polyglutamine (polyQ) protein aggregates. MTMR14 expression was evident in the hippocampus and cortex in C57BL/6J and APP/PS1 mice. Compared with C57BL/6J mice, APP/PS1 mice had reduced MTMR14 in the cortex but not in the hippocampus. Hippocampal expression of MTMR14 was increased and plateaued at 9-17 months compared with 2-6 months in C57BL/6J mice. Aβ42 treatment increased the expression of MTMR14 in the primarily cultured hippocampal neurons of Sprague/Dawley rats and mouse Neuro2a neuroblasts. We demonstrated a novel approach of tissue-specific manipulation of the disease-associated gene EDTP/MTMR14 for lifespan extension and the improvement of survivorship to cellular protein aggregates.
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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".