Mimicking of tau hyperphosphorylation in GABAergic motoneurons of <i>C. elegans</i> induces severe peripheral and neuronal alterations
Bibliographic record
Abstract
Abstract In several neurodegenerative diseases including Alzheimer’s disease (AD), tau, a microtubule-associated protein (MAP) enriched in the axon, becomes hyperphosphorylated, detaches from microtubules, redistributes to the somato-dendritic compartment and self-aggregates. The mechanisms leading to neuronal dysfunction and death by tau pathology remain to be fully elucidated. C. elegans has been successfully used by several groups including ours to identify mechanisms involved in neurodegeneration. We generated three strains, one overexpressing wild-type human tau (WT Tau), one a tau mutant mimicking hyperphosphorylation (hyperP Tau) and one preventing phosphorylation (hypoP Tau) in GABA motor neurons. A significant reduction of body size and egg laying was noted in these tau strains. Starting at day 1, we found that the worms overexpressing hyperP Tau were smaller than the N2 control strain and the worms either overexpressing WT Tau or hypoP Tau. Starting at day 5, the worms overexpressing WT Tau were smaller than control and the worms overexpressing hypoP Tau. Egg laying was reduced in both hyperP Tau and WT Tau worms. Survival was only decreased in WT Tau worms. Motility deficits were also observed. For age-dependent paralysis, a difference was noted between control and hyperP Tau. Swimming activity and speed were increased in hypoP Tau and decreased in hyperP Tau strains. Axonal integrity was altered in all tau strains. In the case of synaptic activity, at day 1, it was increased in the hypoP Tau strain and decreased in the hyperP Tau one. Collectively, our data revealed that overexpression of tau exerted neuronal and peripheral defects indicating that tau dysfunction could affect cell-cell communication.
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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 | 0.000 |
| 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) | 0.001 | 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".