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Record W4404497328 · doi:10.1038/s41598-024-79724-1

Milk derived extracellular vesicle uptake in human microglia regulates the DNA methylation machinery

2024· article· en· W4404497328 on OpenAlexafffund
Sanoji Wijenayake, Shafinaz Eisha, Megha K. Purohit, Patrick O. McGowan

Bibliographic record

VenueScientific Reports · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicExtracellular vesicles in disease
Canadian institutionsUniversity of TorontoUniversity of WinnipegSt. Michael's Hospital
FundersNatural Sciences and Engineering Research Council of Canada
KeywordsMicrogliaDNMT1EpigeneticsDNA methylationCell biologyGene expressionExtracellularBiologyMethylationRegulation of gene expressionmicroRNADownregulation and upregulationDNA methyltransferaseInflammationChemistryGeneImmunologyBiochemistry

Abstract

fetched live from OpenAlex

Mammalian milk contains milk-derived extracellular vesicles (MEVs), a group of biological nanovesicles that transport macromolecules. Their ability to cross the blood brain barrier and the presence of cargo capable of modifying gene function have led to the hypothesis that MEVs may play a role in brain function and development. Here, we investigated the uptake of MEVs by human microglia cells in vitro and explored the functional outcomes of MEV uptake. We examined the expression of the miR-148/152 family, highly abundant MEV microRNAs, that directly suppress the translation of DNA methyltransferase (DNMT) enzymes crucial for catalyzing DNA methylation modifications. We also measured phenotypic and inflammatory gene expression in baseline homeostatic and IFN-γ primed microglia to determine if MEVs induce anti-inflammatory effects. We found that MEVs are taken up and localize in baseline and primed microglia. In baseline microglia, MEV supplementation reduced miR-148a-5P levels, increased DNMT1 transcript, protein abundance, and enzymatic activity, compared to cells that did not receive MEVs. In primed microglia, MEV supplementation decreased miR-148a-5P levels and increased DNMT1 protein abundance, but DNMT1 transcript and enzymatic levels remained unchanged. Contrary to predictions, MEV supplementation failed to attenuate pro-inflammatory IL1β expression in primed microglia. This study provides the first evidence of MEV uptake by a brain macrophage, suggesting a potential role in regulating epigenetic machinery and neuroimmune modulation.

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
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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 head0.257
Teacher spread0.247 · 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

Citations14
Published2024
Admission routes2
Has abstractyes

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