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Record W2568063219 · doi:10.1111/imm.12710

A role for the histone H2A deubiquitinase <scp>MYSM</scp>1 in maintenance of <scp>CD</scp>8<sup>+</sup> T cells

2017· article· en· W2568063219 on OpenAlex
Michael Förster, Rupinder K. Boora, Jessica C. Petrov, Nassima Fodil, Isabella Albanese, Jamie Kim, Philippe Gros, Anastasia Nijnik

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueImmunology · 2017
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicUbiquitin and proteasome pathways
Canadian institutionsMcGill University
FundersCanadian Institutes of Health ResearchDeutsche ForschungsgemeinschaftCanada Foundation for InnovationFaculty of Medicine, McGill University
KeywordsCytotoxic T cellBiologyCD8Cell biologyLymphopoiesisHaematopoiesisImmunosurveillanceT cellStem cellImmune systemCancer researchImmunologyGeneticsIn vitro

Abstract

fetched live from OpenAlex

Summary Several previous studies outlined the importance of the histone H2A deubiquitinase MYSM 1 in the regulation of stem cell quiescence and haematopoiesis. In this study we investigated the role of MYSM 1 in T‐cell development. Using mouse models that allow conditional Mysm1 ablation at late stages of thymic development, we found that MYSM 1 is intricately involved in the maintenance, activation and survival of CD 8 + T cells. Mysm1 ablation resulted in a twofold reduction in CD 8 + T‐cell numbers, and also led to a hyperactivated CD 8 + T‐cell state accompanied by impaired proliferation and increased pro‐inflammatory cytokine production after ex vivo stimulation. These phenotypes coincided with an increased apoptosis and preferential up‐regulation of p53 tumour suppressor protein in CD 8 + T cells. Lastly, we examined a model of experimental cerebral malaria, in which pathology is critically dependent on CD 8 + T cells. In the mice conditionally deleted for Mysm1 in the T‐cell compartment, CD 8 + T‐cell numbers remained reduced following infection, both in the periphery and in the brain, and the mice displayed improved survival after parasite challenge. Collectively, our data identify MYSM 1 as a novel factor for CD 8 + T cells in the immune system, increasing our understanding of the role of histone H2A deubiquitinases in cytotoxic T‐cell biology.

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.

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)0.001
metaresearch head score (Gemma)0.002
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
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 score0.244
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0010.000
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 head0.012
GPT teacher head0.254
Teacher spread0.242 · 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