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Psmb11 molds the transcriptome of cortical TECs and CD8 thymocytes

2017· article· en· W4313382090 on OpenAlexaff
Anca Apavaloaei, Alexandre Rouette, Sylvie Brochu, Claude Perreault

Bibliographic record

VenueThe Journal of Immunology · 2017
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicUbiquitin and proteasome pathways
Canadian institutionsUniversité de MontréalInstitute for Research in Immunology and Cancer
Fundersnot available
KeywordsTranscriptomeCD8Flow cytometryCell biologyProtein subunitBiologyMolecular biologyGeneChemistryAntigenGene expressionImmunologyBiochemistry

Abstract

fetched live from OpenAlex

Abstract Psmb11 is a catalytic subunit of the thymoproteasome, expressed exclusively in cTECs (cortical thymic epithelial cells). It has been shown that Psmb11-mediated positive selection is pivotal for the generation of an immunocompetent T-cell repertoire. We found that lack of Psmb11 results in a suite of gene expression changes in cTECs and not in mTECs, about 200 genes with enrichment in cell-cell interaction and antigen processing and presentation. One yet unsolved question is why the cellularity of CD8+ single-positive (SP8) but not SP4 thymocytes decreases strongly as a consequence of Psmb11-deficiency. Our transcriptomic analyses of pure SM, M1 and M2 subsets of developing SP4 and SP8 T cells show that the maturation of SP4 cells is essentially independent of Psmb11. However SP8 thymocytes present a dysregulated development with impaired migration, survival and lineage commitment in Psmb11 knock-out mice, also detected at the protein level by flow-cytometry. Thymocytes present decreased surface levels of CD127 on SP8 and slightly increased CD5 on all subsets. This indicates a stronger activation of the developing T cells, which alone cannot explain the impact on the SP8 cellularity. We have identified a novel role of Psmb11 in modulating, directly or indirectly, the expression of genes in cTECs, which is necessary to guide and complete the positive selection of SP8 thymocytes.

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 score0.004

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 head0.016
GPT teacher head0.258
Teacher spread0.241 · 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

Citations1
Published2017
Admission routes1
Has abstractyes

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