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Record W2767888279 · doi:10.1371/journal.pgen.1007072

A mutation in the viral sensor 2’-5’-oligoadenylate synthetase 2 causes failure of lactation

2017· article· en· W2767888279 on OpenAlexfundno aff
Samantha R. Oakes, David Gallego‐Ortega, Prudence M. Stanford, Simon Junankar, Wendy W.Y. Au, Zoya Kikhtyak, Anita von Korff, C. Marcelo Sergio, Andrew M. K. Law, Lesley Castillo, Stephanie L. Allerdice, Adelaide I.J. Young, Catherine Piggin, Belinda Whittle, Edward M. Bertram, Matthew J. Naylor, Daniel Roden, Jesse Donovan, Alexei Korennykh, Christopher C. Goodnow, Moira K. O’Bryan, Christopher J. Ormandy

Bibliographic record

VenuePLoS Genetics · 2017
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicVirus-based gene therapy research
Canadian institutionsnot available
FundersNational Institute of General Medical SciencesInstitute of Medical Science, University of TokyoNational Health and Medical Research CouncilR.T. Hall TrustMonash UniversityCure Cancer Australia FoundationNational Institutes of HealthCancer AustraliaSidney Kimmel Foundation for Cancer ResearchCongressionally Directed Medical Research ProgramsPrinceton UniversityAustralian Research CouncilNational Breast Cancer FoundationOntario Ministry of Natural Resources and ForestryBurroughs Wellcome Fund
KeywordsBiologyLactationMutationMutagenesisGeneMutantRNase PPhenotypeInterferonMolecular biologyCell biologyGeneticsRNA

Abstract

fetched live from OpenAlex

We identified a non-synonymous mutation in Oas2 (I405N), a sensor of viral double-stranded RNA, from an ENU-mutagenesis screen designed to discover new genes involved in mammary development. The mutation caused post-partum failure of lactation in healthy mice with otherwise normally developed mammary glands, characterized by greatly reduced milk protein synthesis coupled with epithelial cell death, inhibition of proliferation and a robust interferon response. Expression of mutant but not wild type Oas2 in cultured HC-11 or T47D mammary cells recapitulated the phenotypic and transcriptional effects observed in the mouse. The mutation activates the OAS2 pathway, demonstrated by a 34-fold increase in RNase L activity, and its effects were dependent on expression of RNase L and IRF7, proximal and distal pathway members. This is the first report of a viral recognition pathway regulating lactation.

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 score0.001
Threshold uncertainty score0.373

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 head0.028
GPT teacher head0.313
Teacher spread0.286 · 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

Citations31
Published2017
Admission routes1
Has abstractyes

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