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Record W4404126970 · doi:10.1093/hmg/ddae162

SMN depletion impairs skeletal muscle formation and maturation in a mouse model of SMA

2024· article· en· W4404126970 on OpenAlexafffund
Hong Liu, Lucia Chehadé, Marc‐Olivier Deguise, Yves De Repentigny, Rashmi Kothary

Bibliographic record

VenueHuman Molecular Genetics · 2024
Typearticle
Languageen
FieldMedicine
TopicNeurogenetic and Muscular Disorders Research
Canadian institutionsUniversity of OttawaChildren's Hospital of Eastern OntarioOttawa Hospital
FundersMuscular Dystrophy CanadaCanadian Institutes of Health ResearchUniversity of OttawaCure SMAMuscular Dystrophy Association
KeywordsBiologySMA*Skeletal muscleCell biologyAnatomyGenetics

Abstract

fetched live from OpenAlex

Spinal muscular atrophy (SMA) is characterized by low levels of the ubiquitously expressed Survival Motor Neuron (SMN) protein, leading to progressive muscle weakness and atrophy. Skeletal muscle satellite cells play a crucial role in muscle fiber maintenance, repair, and remodelling. While the effects of SMN depletion in muscle are well documented, its precise role in satellite cell function remains largely unclear. Using the Smn2B/- mouse model, we investigated SMN-depleted satellite cell biology through single fiber culture studies. Myofibers from Smn2B/- mice were smaller in size, shorter in length, had reduced myonuclear domain size, and reduced sub-synaptic myonuclear clusters-all suggesting impaired muscle function and integrity. These changes were accompanied by a reduction in the number of myonuclei in myofibers from Smn2B/- mice across all disease stages examined. Although the number of satellite cells in myofibers was significantly reduced, those remaining retained their capacity for myogenic activation and proliferation. These findings support the idea that a dysregulated myogenic process could be occurring as early in muscle stem cells during muscle formation and maturation in SMA. Targeting those pathways could offer additional options for combinatorial therapies for SMA.

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 score0.003
Threshold uncertainty score0.009

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0020.000
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0030.001

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.

Opus teacher head0.024
GPT teacher head0.299
Teacher spread0.275 · 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

Citations2
Published2024
Admission routes2
Has abstractyes

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