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Record W3030172446 · doi:10.1101/2020.05.28.120501

Severe dysregulation of TNF expression leads to multiple inflammatory diseases and embryonic death

2020· preprint· en· W3030172446 on OpenAlexfundno aff
Elise Clayer, Destiny Dalseno, Andrew J. Kueh, Derek Lacey, Minhsuang Tsai, Elysa Carr, Verena C. Wimmer, Philippe Bouillet

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2020
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA Research and Splicing
Canadian institutionsnot available
FundersStanford Institute for Research in the Social SciencesAustralian GovernmentCampbell Family Institute for Breast Cancer ResearchNational Health and Medical Research CouncilArthritis AustraliaLeukemia and Lymphoma Society
KeywordsPost-transcriptional regulationUntranslated regionMessenger RNATumor necrosis factor alphaBiologyTranscriptional regulationThree prime untranslated regionCell biologyInflammationTranslational regulationTranslation (biology)Translational efficiencyCytokineGene expressionImmunologyGeneGenetics

Abstract

fetched live from OpenAlex

Abstract Post-transcriptional regulation mechanisms regulate mRNA stability or translational efficiency via ribosomes and recent evidence indicates that it is a major determinant of the accurate levels of cytokine mRNAs. While transcriptional regulation of Tnf has been well studied and found to be important for the rapid induction of Tnf mRNA and regulation of the acute phase of inflammation, study of its post-transcriptional regulation has been largely limited to the role of the AU-rich element (ARE), and to a lesser extent, that of the constitutive decay element (CDE). We have identified a new regulatory element (NRE) in the 3’ untranslated region (3’UTR) of Tnf , and demonstrate that ARE, CDE and NRE cooperate to efficiently down regulate Tnf expression and prevent autoimmune inflammatory diseases. We also show for the first time that excessive TNF may lead to embryonic death.

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)0.0010.001

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 head0.013
GPT teacher head0.236
Teacher spread0.223 · 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

Citations0
Published2020
Admission routes1
Has abstractyes

Explore more

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