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Record W2889695061 · doi:10.1111/jcmm.13810

P‐Glycoprotein (P‐gp)/<scp>ABCB</scp>1 plays a functional role in extravillous trophoblast (<scp>EVT</scp>) invasion and is decreased in the pre‐eclamptic placenta

2018· article· en· W2889695061 on OpenAlexafffund
Caroline Dunk, Jane J. Pappas, Phetcharawan Lye, Mark Kibschull, Mohsen Javam, Enrrico Bloise, Stephen J. Lye, Moshe Szyf, Stephen G. Matthews

Bibliographic record

VenueJournal of Cellular and Molecular Medicine · 2018
Typearticle
Languageen
FieldMedicine
TopicPregnancy and preeclampsia studies
Canadian institutionsMcGill UniversityUniversity of TorontoSinai Health SystemLunenfeld-Tanenbaum Research Institute
FundersInstitute of Human Development, Child and Youth HealthCanadian Institutes of Health ResearchYork UniversityMcGill University
KeywordsSyncytiotrophoblastCytotrophoblastTrophoblastBiologyPlacentaCell biologyGene silencingAndrologyGeneticsGeneFetusPregnancyMedicine

Abstract

fetched live from OpenAlex

Abstract Dysregulation of trophoblast differentiation is implicated in the placental pathologies of intrauterine growth restriction and pre‐eclampsia. P‐glycoprotein (P‐gp encoded by ABCB 1 ) is an ATP ‐binding cassette transporter present in the syncytiotrophoblast layer of the placenta where it acts as a molecular sieve. In this study, we show that P‐gp is also expressed in the proliferating cytotrophoblast ( CT ), the syncytiotrophoblast ( ST ) and the extravillous trophoblast ( EVT ), suggesting our hypothesis of a functional role for P‐gp in placental development. Silencing of ABCB 1, via si RNA duplex, results in dramatically reduced invasion and migration, and increased tube formation and fusion in the EVT ‐like HTR 8/ SV neo cell line. In both EVT and CT explant differentiation experiments, silencing of ABCB 1 leads to induction of the fusion markers human hCG, ERVW‐1 and GJA1 and terminal differentiation of both trophoblast subtypes. Moreover, P‐gp protein levels are decreased in both the villous and the EVT of severe early‐onset pre‐eclamptic placentas. We conclude that, in addition to its role as a syncytial transporter, P‐gp is a key factor in the maintenance of both CT and EVT lineages and that its decrease in severe pre‐eclampsia may contribute to the syncytial and EVT placental pathologies associated with this disease.

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)0.001
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: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.612
Threshold uncertainty score0.910

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
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)0.0000.000

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 head0.013
GPT teacher head0.234
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 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

Citations53
Published2018
Admission routes2
Has abstractyes

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