Microbial Composition, Disease Trajectory and Genetic Background in a Slow Onset Model of Frontotemporal Lobar Degeneration
Bibliographic record
Abstract
Slow-onset neurodegenerative disease in a low-expresser 2N4R P301L transgenic (Tg) mouse model is marked by neuroinflammation and by differing patterns of CNS deposition and accumulation of tau conformers, with such heterogeneities present even within inbred backgrounds. Gut microbial genotypes were notably divergent within C57BL6/Tac or 129SvEv/Tac congenic (Cg) sublines of TgTauP301L mice, and these sublines differed when challenged with antibiotic treatment and fecal microbial transplantation. Whereas aged, transplanted Cg 129SvEv/Tac TgTauP301L mice had neuroanatomical deposition of tau resembling controls, transplanted Cg C57BL6/Tac TgTauP301L mice had different proportions of rostral versus caudal tau accumulation (p = 0.0001). These data indicate the potential for environmental influences on tau neuropathology in this model. Furthermore, Cg C57BL6/Tac TgTauP301L cohorts differed from 129SvEv/Tac counterparts by showing 28% versus 9% net intercurrent loss (p = 0.0027). While the origin of this phenomenon is not established, it offers a parallel to differing patterns of frailty observed in C57BL6 versus 129 SvEv Tg mice expressing the 695 amino acid isoform of human amyloid precursor protein. We infer that generalized responses to protein aggregation might account for similar reductions in viability even when expressing different human proteins in the same inbred strain background.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 teacher head, 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".