TER94 , the Drosophila Homologue of the ALS-related VCP gene, Influences Lifespan and Leads to a Decline in Motor Function
Bibliographic record
Abstract
Abstract Background: Valosin-Containing Protein (VCP) is an essential AAA+ ATPase with diverse functions within the cell. Mutations in the VCP gene have been detected in patients with familial amyotrophic lateral sclerosis (ALS). The aim of this study is to create a novel model of human neurodegenerative disease in Drosophila melanogaster by altering the expression of TER94, the Drosophila orthologue of the human VCP gene. TER94 expression was altered in all neurons, the dopaminergic neurons and in the motor neurons, with longevity and locomotor function assessed over time. Altered TER94 expression in combination with the altered expression of known Parkinson Disease (PD) genes was examined to investigate potential interactions.Results: Inhibition of TER94 altered median lifespan in a manner dependent upon the transgene selected for use and the tissue-specific expression directed by the Gal4 transgene selected. Locomotor ability was significantly reduced in all cases of TER94 inhibition tested. The inhibition of TER94 by two TER94-RNAi inhibitory transgenes, in the motor neurons via D42-Gal4 lead to increases in median lifespan, with one inhibitory transgene generating a slightly reduced lifespan. Inhibition of TER94 in the dopaminergic neurons resulted in a severe reduction in lifespan. The co-inhibition of TER94 and parkin in the neurons resulted in a major decline in lifespan by approximately 30%. While the inhibition of TER94 and the co-expression of alpha-synuclein in the neurons resulted in an increase in lifespan by approximately 28%. Conclusions: The inhibition of TER94 in the motor neurons is an interesting model of ALS, due to the small, but reduced lifespan coupled with a strong decline in locomotor function. The inhibition of TER94 in the dopaminergic neurons is a potential model of ALS, due to the reduction of both lifespan and locomotor function over time. The co-inhibition of TER94 and parkin in the neurons provides a promising novel model of neurodegenerative disease, displaying a great reduction in lifespan and in locomotor ability over time.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 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".