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Record W2169029824 · doi:10.1073/pnas.1106911108

<i>Iroquois homeobox gene 3</i> establishes fast conduction in the cardiac His–Purkinje network

2011· article· en· W2169029824 on OpenAlexafffund
Shanshan Zhang, Kyoung-Han Kim, Anna Rosén, James W. Smyth, Rui Sakuma, Paul Delgado-Olguı́n, Mark M. Davis, Vijitha Puviindran, Nathalie Gaborit, Tatyana Sukonnik, John N. Wylie, Koroboshka Brand‐Arzamendi, Gerrie P. Farman, Ji‐Eun Kim, Robert A. Rose, Phillip A. Marsden, Yonghong Zhu, Yuqing Zhou, Lucile Miquerol, R. Mark Henkelman, Didier Y. R. Stainier, Robin M. Shaw, Chi‐chung Hui, Benoit G. Bruneau, Peter H. Backx

Bibliographic record

VenueProceedings of the National Academy of Sciences · 2011
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCongenital heart defects research
Canadian institutionsUniversity of TorontoUniversity Health NetworkHospital for Sick Children
FundersU.S. Public Health ServiceNational Institutes of HealthNational Heart, Lung, and Blood InstituteGladstone InstitutesHeart and Stroke Foundation of CanadaNational Center for Research ResourcesNational Institute of Neurological Disorders and StrokeAmerican Heart AssociationLawrence J. and Florence A. DeGeorge Charitable TrustCanadian Institutes of Health ResearchAmerican Federation for Aging Research
KeywordsHomeoboxHomeobox A1Homeobox protein Nkx-2.5Purkinje fibersGeneGeneticsBiologyNeuroscienceGene expressionElectrophysiology

Abstract

fetched live from OpenAlex

Rapid electrical conduction in the His-Purkinje system tightly controls spatiotemporal activation of the ventricles. Although recent work has shed much light on the regulation of early specification and morphogenesis of the His-Purkinje system, less is known about how transcriptional regulation establishes impulse conduction properties of the constituent cells. Here we show that Iroquois homeobox gene 3 (Irx3) is critical for efficient conduction in this specialized tissue by antithetically regulating two gap junction-forming connexins (Cxs). Loss of Irx3 resulted in disruption of the rapid coordinated spread of ventricular excitation, reduced levels of Cx40, and ectopic Cx43 expression in the proximal bundle branches. Irx3 directly represses Cx43 transcription and indirectly activates Cx40 transcription. Our results reveal a critical role for Irx3 in the precise regulation of intercellular gap junction coupling and impulse propagation in the heart.

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)0.002
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 score0.110
Threshold uncertainty score0.242

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0020.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0010.000
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 head0.054
GPT teacher head0.300
Teacher spread0.246 · 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

Citations133
Published2011
Admission routes2
Has abstractyes

Explore more

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