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Record W3203574791 · doi:10.1101/2021.09.27.462048

Characterizing SERCA function in murine skeletal muscles after 35-37 days of spaceflight

2021· preprint· en· W3203574791 on OpenAlexafffund
Jessica L. Braun, Mia S. Geromella, Sophie I. Hamstra, Holt N. Messner, Val A. Fajardo

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2021
Typepreprint
Languageen
FieldMedicine
TopicSpaceflight effects on biology
Canadian institutionsBrock University
FundersNatural Sciences and Engineering Research Council of CanadaCanadian Institutes of Health ResearchBrock University
KeywordsSERCASpaceflightPhospholambanMuscle atrophySkeletal muscleInternal medicineChemistryEndocrinologyMyosinSoleus muscleAtrophyEndoplasmic reticulumATPaseBiologyBiochemistryMedicine

Abstract

fetched live from OpenAlex

Abstract It is well established that microgravity exposure causes significant muscle weakness and atrophy via muscle unloading. On Earth, muscle unloading leads to a disproportionate loss in muscle force and size with the loss in muscle force occurring at a faster rate. Though the exact mechanisms are unknown, a role for Ca 2+ dysregulation has been suggested. The sarco(endo)plasmic reticulum Ca 2+ ATPase (SERCA) pump actively brings cytosolic Ca 2+ into the SR, eliciting muscle relaxation and maintaining low intracellular Ca 2+ ([Ca 2+ ] i ). SERCA dysfunction contributes to elevations in [Ca 2+ ] i , leading to cellular damage and thus may contribute to the muscle weakness and atrophy observed with spaceflight. Here, we investigated SERCA function, SERCA regulatory protein content (sarcolipin, phospholamban, and neuronatin), and reactive oxygen/nitrogen species (RONS) protein adduction in murine skeletal muscle after 35-37 days of spaceflight. In male and female soleus muscles, spaceflight led to drastic impairments in Ca 2+ uptake despite significant increases in SERCA1a protein content. We attribute this impairment to an increase in RONS production and elevated total protein tyrosine (T) nitration and cysteine (S) nitrosylation. Contrarily, in the tibialis anterior (TA) we observed an enhancement in Ca 2+ uptake, which we attribute to a shift towards a faster muscle fiber type (i.e., increased myosin heavy chain IIb and SERCA1a) without elevated total protein T-nitration and S-nitrosylation. Thus, spaceflight affects SERCA function differently between the soleus and TA. As the soleus is severely affected by spaceflight, future studies should determine whether improving SERCA function in this muscle can mitigate muscle atrophy and weakness.

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: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

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

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 head0.010
GPT teacher head0.222
Teacher spread0.213 · 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 designObservational
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

Citations7
Published2021
Admission routes2
Has abstractyes

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