MétaCan
Menu
← Back to cohort
Record W3081316705 · doi:10.1371/journal.pone.0237773

Lack of a site-specific phosphorylation of Presenilin 1 disrupts microglial gene networks and progenitors during development

2020· article· en· W3081316705 on OpenAlexfundno aff
José Henrique Ledo, Ran Zhang, Luka Mesin, Diego Mourão‐Sá, Estefania P. Azevedo, Olga G. Troyanskaya, Victor Bustos, Paul Greengard

Bibliographic record

VenuePLoS ONE · 2020
Typearticle
Languageen
FieldNeuroscience
TopicNeuroinflammation and Neurodegeneration Mechanisms
Canadian institutionsnot available
FundersPew Charitable TrustsNational Institutes of HealthNational Institute of General Medical SciencesCanadian Institute for Advanced ResearchCure Alzheimer's FundNational Institute on AgingFisher Center for Alzheimer's Research Foundation
KeywordsMicrogliaBiologyIRF8PresenilinPhosphorylationProgenitor cellTranscription factorCell biologyEmbryonic stem cellTranscriptomeNeuroscienceGeneGene expressionStem cellGeneticsImmunologyInflammationMedicinePathologyAlzheimer's disease

Abstract

fetched live from OpenAlex

Microglial cells play a key role in brain homeostasis from development to adulthood. Here we show the involvement of a site-specific phosphorylation of Presenilin 1 (PS1) in microglial development. Profiles of microglia-specific transcripts in different temporal stages of development, combined with multiple systematic transcriptomic analysis and quantitative determination of microglia progenitors, indicate that the phosphorylation of PS1 at serine 367 is involved in the temporal dynamics of microglial development, specifically in the developing brain rudiment during embryonic microgliogenesis. We constructed a developing brain-specific microglial network to identify transcription factors linked to PS1 during development. Our data showed that PS1 functional connections appear through interaction hubs at Pu.1, Irf8 and Rela-p65 transcription factors. Finally, we showed that the total number of microglia progenitors was markedly reduced in the developing brain rudiment of embryos lacking PS1 phosphorylation compared to WT. Our work identifies a novel role for PS1 in microglial development.

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 score0.001
Threshold uncertainty score0.005

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 integrity0.0000.001
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 head0.117
GPT teacher head0.244
Teacher spread0.127 · 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

Citations11
Published2020
Admission routes1
Has abstractyes

Explore more

Same venuePLoS ONE→Same topicNeuroinflammation and Neurodegeneration Mechanisms→French-language works237,207→