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Record W3008860275 · doi:10.1038/s41467-019-14143-9

REEP5 depletion causes sarco-endoplasmic reticulum vacuolization and cardiac functional defects

2020· article· en· W3008860275 on OpenAlexafffund
Shin‐Haw Lee, Sina Hadipour‐Lakmehsari, Harsha Murthy, Natalie Gibb, Tetsuaki Miyake, Allen C. T. Teng, Jake Cosme, Jessica Yu, Mark Moon, Sang-Hyun Lim, Victoria Wong, Peter Liu, Filio Billia, Rodrigo Fernández‐González, Igor Štagljar, Parveen Sharma, Thomas Kislinger, Ian C. Scott, Anthony O. Gramolini

Bibliographic record

VenueNature Communications · 2020
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCellular transport and secretion
Canadian institutionsYork UniversityHospital for Sick ChildrenPrincess Margaret Cancer CentreOttawa Heart InstituteTed Rogers Centre for Heart ResearchUniversity Health NetworkUniversity of Toronto
FundersCIHR Skin Research Training CentreCanadian Institutes of Health ResearchCanadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of CanadaNatural Sciences and Engineering Research Council of CanadaGovernment of CanadaYale University
KeywordsEndoplasmic reticulumVacuolizationZebrafishCell biologyMyocyteCardiac myocyteUnfolded protein responseBiologyContractilityIn vivoRyanodine receptor 2Cardiac function curveInternal medicineEndocrinologyHeart failureMedicineRyanodine receptorBiochemistryGeneticsGene

Abstract

fetched live from OpenAlex

Abstract The sarco-endoplasmic reticulum (SR/ER) plays an important role in the development and progression of many heart diseases. However, many aspects of its structural organization remain largely unknown, particularly in cells with a highly differentiated SR/ER network. Here, we report a cardiac enriched, SR/ER membrane protein, REEP5 that is centrally involved in regulating SR/ER organization and cellular stress responses in cardiac myocytes. In vitro REEP5 depletion in mouse cardiac myocytes results in SR/ER membrane destabilization and luminal vacuolization along with decreased myocyte contractility and disrupted Ca2+ cycling. Further, in vivo CRISPR/Cas9-mediated REEP5 loss-of-function zebrafish mutants show sensitized cardiac dysfunction upon short-term verapamil treatment. Additionally, in vivo adeno-associated viral (AAV9)-induced REEP5 depletion in the mouse demonstrates cardiac dysfunction. These results demonstrate the critical role of REEP5 in SR/ER organization and function as well as normal heart function and development.

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 score0.002
Threshold uncertainty score0.007

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 integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.001

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 head0.015
GPT teacher head0.237
Teacher spread0.221 · 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

Citations44
Published2020
Admission routes2
Has abstractyes

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Same venueNature CommunicationsSame topicCellular transport and secretionFrench-language works237,207