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Record W2991070411 · doi:10.1002/jnr.24554

Dysfunctional RNA‐binding protein biology and neurodegeneration in experimental autoimmune encephalomyelitis in female mice

2019· article· en· W2991070411 on OpenAlexafffund
Hannah E. Salapa, Cole D. Libner, Michael C. Levin

Bibliographic record

VenueJournal of Neuroscience Research · 2019
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA Research and Splicing
Canadian institutionsSaskatchewan Health AuthorityUniversity of Saskatchewan
FundersSaskatchewan Health Research FoundationSaskatoon City Hospital Foundation
KeywordsNeurodegenerationExperimental autoimmune encephalomyelitisDysfunctional familyRNA-binding proteinRNANeuroscienceImmunologyBiologyMedicineMultiple sclerosisGeneticsInternal medicineDiseaseGenePsychiatry

Abstract

fetched live from OpenAlex

Abstract Altered stress granule (SG) and RNA‐binding protein (RBP) biology have been shown to contribute to the pathogenesis of several neurodegenerative diseases, yet little is known about their role in multiple sclerosis (MS). Pathological features associated with dysfunctional RBPs include RBP mislocalization from its normal nuclear location to the cytoplasm and the formation of chronic SGs. We tested the hypothesis that altered SG and RBP biology might contribute to the neurodegeneration in experimental autoimmune encephalomyelitis (EAE). C57BL/6 female mice were actively immunized with MOG 35‐55 to induce EAE. Spinal cords were examined for mislocalization of the RBPs, heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) and TAR‐DNA binding protein‐43 (TDP‐43), SGs, neurodegeneration (SMI‐32), T cells (CD3), and macrophages (CD68). In contrast to naive mice, mice with EAE showed SG formation ( p < 0.0001) and mislocalization of hnRNP A1 ( p < 0.05) in neurons of the ventral spinal cord gray matter, which correlated with clinical score ( R = 0.8104, p = 0.0253). In these same areas, there was a neuronal loss ( p < 0.0001) and increased SMI‐32 immunoreactivity (both markers of neurodegeneration) and increased staining for CD3 + T cells and IFN‐gamma. These findings recapitulate the SG and RBP biology and markers of neurodegeneration in MS tissues and suggest that altered SG and RBP biology contribute to the neurodegeneration in EAE, which might also apply to the pathogenesis of MS.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.002
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.137
Threshold uncertainty score0.260

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0020.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.044
GPT teacher head0.369
Teacher spread0.325 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

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".

Quick stats

Citations31
Published2019
Admission routes2
Has abstractyes

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