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Record W2167386605 · doi:10.1186/s40478-015-0202-6

FUS/TLS deficiency causes behavioral and pathological abnormalities distinct from amyotrophic lateral sclerosis

2015· article· en· W2167386605 on OpenAlexaff
Yoshihiro Kino, Chika Washizu, Masaru Kurosawa, Mizuki Yamada, Haruko Miyazaki, Takumi Akagi, Tsutomu Hashikawa, Hiroshi Doi, Toru Takumi, Geoffrey G. Hicks, Nobutaka Hattori, Tomomi Shimogori, Nobuyuki Nukina

Bibliographic record

VenueActa Neuropathologica Communications · 2015
Typearticle
Languageen
FieldMedicine
TopicAmyotrophic Lateral Sclerosis Research
Canadian institutionsUniversity of Manitoba
FundersCore Research for Evolutional Science and TechnologyRIKEN Brain Science InstituteRIKENJapan Society for the Promotion of ScienceMinistry of Education, Culture, Sports, Science and Technology
KeywordsAmyotrophic lateral sclerosisPhenotypeFrontotemporal lobar degenerationKnockout mousePathologicalC9orf72BiologyPathogenesisDownregulation and upregulationNeurosciencePathologyConditional gene knockoutNeurodegenerationMedicineFrontotemporal dementiaGeneGeneticsTrinucleotide repeat expansionDiseaseAllele

Abstract

fetched live from OpenAlex

INTRODUCTION: FUS/TLS is an RNA-binding protein whose genetic mutations or pathological inclusions are associated with neurological diseases including amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration, and essential tremor (ET). It is unclear whether their pathogenesis is mediated by gain or loss of function of FUS/TLS. RESULTS: Here, we established outbred FUS/TLS knockout mice to clarify the effects of FUS/TLS dysfunction in vivo. We obtained homozygous knockout mice that grew into adulthood. Importantly, they did not manifest ALS- or ET-like phenotypes until nearly two years. Instead, they showed distinct histological and behavioral alterations including vacuolation in hippocampus, hyperactivity, and reduction in anxiety-like behavior. Knockout mice showed transcriptome alterations including upregulation of Taf15 and Hnrnpa1, while they have normal morphology of RNA-related granules such as Gems. CONCLUSIONS: Collectively, FUS/TLS depletion causes phenotypes possibly related to neuropsychiatric and neurodegenerative conditions, but distinct from ALS and ET, together with specific alterations in RNA metabolisms.

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 machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.002
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.000
Insufficient payload (model declined to judge)0.0020.000

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 head0.220
GPT teacher head0.351
Teacher spread0.131 · 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 source (direct Gemma or distilled Codex), 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

Citations112
Published2015
Admission routes1
Has abstractyes

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Same venueActa Neuropathologica CommunicationsSame topicAmyotrophic Lateral Sclerosis ResearchFrench-language works237,207