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Record W4414162116 · doi:10.1371/journal.pbio.3002659

Microglial deficiency in the ATRX chromatin remodeler elicits a viral mimicry immune response that impacts neuronal function and behavior

2025· article· en· W4414162116 on OpenAlexafffund
Sarfraz Shafiq, Alireza Ghahramani, Miguel A. Pena‐Ortiz, Julia K. Sunstrum, Milica Pavlović, Yan Jiang, Megan E. Rowland, Wataru Inoue, Nathalie G. Bérubé

Bibliographic record

VenuePLoS Biology · 2025
Typearticle
Languageen
FieldNeuroscience
TopicNeuroinflammation and Neurodegeneration Mechanisms
Canadian institutionsChildren’s Health Research InstituteWestern University
FundersCanadian Institutes of Health Research
KeywordsATRXChromatinMicrogliaHippocampal formationNeuroinflammationChromatin remodelingDeath-associated protein 6Immune system

Abstract

fetched live from OpenAlex

The importance of chromatin-mediated processes in neurodevelopmental and intellectual disability disorders is well recognized. However, how chromatin dysregulation in glial cells impacts cognitive abilities is less well understood. Here, we demonstrate that targeted loss of the ATRX chromatin remodeler targeted to microglia leads to altered cell morphology, increased chromatin accessibility profiles, and de-repression of endogenous retroelements, triggering viral mimicry. In mice that lack ATRX in microglia, CA1 hippocampal neuron morphology and electrophysiological properties are affected, and the mice display specific behavioral deficits. These findings demonstrate that ATRX is required in microglia to preserve chromatin structure and maintain microglial homeostasis. Disruption of these functions elicits neuroinflammation and may contribute to the pathology of human neurological disorders caused by ATRX mutations.

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: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.049
Threshold uncertainty score0.536

Codex and Gemma teacher scores by category

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)0.0000.000

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 head0.035
GPT teacher head0.274
Teacher spread0.239 · 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

Citations2
Published2025
Admission routes2
Has abstractyes

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