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Record W4399535090 · doi:10.1038/s41467-023-42013-y

Single-cell analysis identifies conserved features of immune dysfunction in simulated microgravity and spaceflight

2024· article· en· W4399535090 on OpenAlexaff
Fei Wu, Huixun Du, Eliah Overbey, JangKeun Kim, Priya Makhijani, Nicholas G. Martin, Chad A. Lerner, Khiem Nguyen, Jordan J. Baechle, Taylor R. Valentino, Matías Fuentealba, Juliet M. Bartleson, Heather Halaweh, Shawn Winer, Cem Meydan, Francine E. Garrett-Bakelman, Nazish Sayed, Simon Melov, Masafumi Muratani, Akos A. Gerencser, Herbert G. Kasler, Afshin Beheshti, Christopher E. Mason, David Furman, Daniel A. Winer

Bibliographic record

VenueNature Communications · 2024
Typearticle
Languageen
FieldMedicine
TopicSpaceflight effects on biology
Canadian institutionsUniversity Health NetworkMount Sinai HospitalUniversity of Toronto
FundersNational Institute of Mental HealthJapan Aerospace Exploration AgencyNational Institutes of HealthNational Institute on AgingNuclear Safety and Security CommissionWorldQuant FoundationBuck Institute for Research on AgingArizona State UniversityNational Aeronautics and Space Administration
KeywordsCell biologyInnate immune systemBiologyImmune systemPyroptosisCellInflammationSignal transductionImmunologyInflammasomeGenetics

Abstract

fetched live from OpenAlex

Microgravity is associated with immunological dysfunction, though the mechanisms are poorly understood. Here, using single-cell analysis of human peripheral blood mononuclear cells (PBMCs) exposed to short term (25 hours) simulated microgravity, we characterize altered genes and pathways at basal and stimulated states with a Toll-like Receptor-7/8 agonist. We validate single-cell analysis by RNA sequencing and super-resolution microscopy, and against data from the Inspiration-4 (I4) mission, JAXA (Cell-Free Epigenome) mission, Twins study, and spleens from mice on the International Space Station. Overall, microgravity alters specific pathways for optimal immunity, including the cytoskeleton, interferon signaling, pyroptosis, temperature-shock, innate inflammation (e.g., Coronavirus pathogenesis pathway and IL-6 signaling), nuclear receptors, and sirtuin signaling. Microgravity directs monocyte inflammatory parameters, and impairs T cell and NK cell functionality. Using machine learning, we identify numerous compounds linking microgravity to immune cell transcription, and demonstrate that the flavonol, quercetin, can reverse most abnormal pathways. These results define immune cell alterations in microgravity, and provide opportunities for countermeasures to maintain normal immunity in space.

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)0.000
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: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.728
Threshold uncertainty score0.523

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.002
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
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 head0.015
GPT teacher head0.306
Teacher spread0.291 · 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

Citations44
Published2024
Admission routes1
Has abstractyes

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