microRNA-146a as a biomarker for transmissible spongiform encephalopathy
Bibliographic record
Abstract
The pro-inflammatory, innate-immune system ribonucleic acid mediator microRNA-146a, constitutively expressed in the brain and central nervous system (CNS) of both the mouse and the human, is pathologically up-regulated in multiple transmissible spongiform encephalopathies (TSEs) to several times its basal level. miRNA-146a: (i) exists as a ~22-ribonucleotide (nt) single-stranded non-coding RNA (sncRNA) whose sequence is unique and highly selected over evolution; (ii) is brain-, CNS- and lymphoid-tissue enriched and exhibits a 100% RNA sequence homology between the mouse and the human; (iii) has been repeatedly shown to play critical immunological and pro-inflammatory roles in the onset and propagation of several human CNS disorders including progressive, incapacitating, and lethal neurological syndromes that include prion disease (PrD) and Alzheimer's disease (AD); (iv) is a fascinating molecular entity because it is representative of the smallest class of soluble, information-carrying, amphipathic sncRNA yet described; (v) has capability to be induced by cellular stressors and the pro-inflammatory transcription factor NF-kB (p50/p65); (vi) has capability to post-transcriptionally regulate multiple mRNAs and cellular processes in neurological health and disease; (vii) is upregulated in human host cells after viral invasion by single-stranded RNA (ssRNA) or double-stranded DNA (dsDNA) neurotropic viruses; and (viii) has an immense potential in neuro-degenerative disease therapeutics via anti-NF-kB and/or anti-miRNA-146a treatment strategies. In this short communication we provide for the first time evidence that miRNA-146a is a prominent sncRNA species in experimental murine prion disease, progressively increasing in the pre-symptomatic stages in C57BL/6J, SJL/J or Swiss Albino murine scrapie prion models. The highest miRNA-146a levels were quantified in these three different murine scrapie models exhibiting full symptomology of prion infection. The results suggest that miRNA-146a levels in the brain may be useful as an accessory diagnostic, prognostic or response-to-treatment biomarker to monitor the onset and development of PrD in experimental murine models that may also be extrapolated to be a relevant adjunct biomarker in human TSEs.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".