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Record W4405175789 · doi:10.1016/j.isci.2024.111518

Roles for the long non-coding RNA Pax6os1/PAX6-AS1 in pancreatic beta cell function

2024· article· en· W4405175789 on OpenAlexafffund
Livia López–Noriega, Rebecca Callingham, Aida Martínez-Sánchez, Sameena Nawaz, Grazia Pizza, Nejc Haberman, Nevena Cvetešić, Marie‐Sophie Nguyen‐Tu, Boris Lenhard, Piero Marchetti, Lorenzo Piemonti, Eelco J.P. de Koning, A. M. James Shapiro, Paul Johnson, Isabelle Leclerc, Benoît Hastoy, Benoit R. Gauthier, Timothy J. Pullen, Guy A. Rutter

Bibliographic record

VenueiScience · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer-related molecular mechanisms research
Canadian institutionsUniversité de MontréalMcGill University Health CentreUniversity of Alberta
FundersBreakthrough T1D CanadaDivision of Diabetes, Endocrinology, and Metabolic DiseasesNational Institute of Diabetes and Digestive and Kidney DiseasesHorizon 2020Spanish National Plan for Scientific and Technical Research and InnovationWellcome TrustBiotechnology and Biological Sciences Research CouncilMedical Research CouncilFaculty of Science and Engineering, University of ManchesterHorizon 2020 Framework ProgrammeNational Institutes of HealthJuvenile Diabetes Research Foundation United KingdomJuvenile Diabetes Research Foundation InternationalDiabetes UKCanadian Institutes of Health ResearchInnovative Medicines InitiativeEuropean Regional Development FundMinisterio de Ciencia e InnovaciónUniversity of AlbertaEuropean CommissionUniversity of the EastDiabetes Research and Wellness FoundationStichting Diabetes Onderzoek NederlandDiabetes FondsAgencia Estatal de InvestigaciónBontius Stichting
KeywordsPAX6Function (biology)Coding (social sciences)RNAComputational biologyChemistryBiologyCell biologyBiochemistryGeneTranscription factorSociology

Abstract

fetched live from OpenAlex

Long non-coding RNAs (lncRNAs) are emerging as crucial regulators of beta cell function. Here, we show that an lncRNA-transcribed antisense to Pax6, annotated as Pax6os1/PAX6-AS1, was upregulated by high glucose concentrations in human as well as murine beta cell lines and islets. Elevated expression was also observed in islets from mice on a high-fat diet and patients with type 2 diabetes. Silencing Pax6os1 / PAX6-AS1 in MIN6 or EndoC-βH1 cells increased several beta cell signature genes' expression. Pax6os1/PAX6-AS1 was shown to bind to EIF3D, indicating a role in translation of specific mRNAs, as well as histones H3 and H4, suggesting a role in histone modifications. Important interspecies differences were found, with a stronger phenotype in humans. Only female Pax6os1 null mice fed a high-fat diet showed slightly enhanced glucose clearance. In contrast, silencing PAX6-AS1 in human islets enhanced glucose-stimulated insulin secretion and increased calcium dynamics, whereas overexpression of the lncRNA resulted in the opposite phenotype.

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)0.001
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: none
Teacher disagreement score0.844
Threshold uncertainty score0.338

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
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 head0.012
GPT teacher head0.276
Teacher spread0.264 · 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

Citations3
Published2024
Admission routes2
Has abstractyes

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