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Human MRP2 polymorphisms and their impact on substrate transport

2008· article· en· W7707487 on OpenAlexaff
Vandana Megaraj, Philip M. Gerk, Richard Kim, Mary Vore

Bibliographic record

VenueThe FASEB Journal · 2008
Typearticle
Languageen
FieldMedicine
TopicDrug Transport and Resistance Mechanisms
Canadian institutionsWestern University
Fundersnot available
KeywordsMultidrug resistance-associated protein 2Single-nucleotide polymorphismOrganic anion-transporting polypeptideChemistryBiologySNPInternal medicineEndocrinologyTransporterATP-binding cassette transporterBiochemistryGeneGenotypeMedicine

Abstract

fetched live from OpenAlex

Multidrug resistance protein 2 (MRP2/ABCC2) mediates the biliary excretion of endo‐ and xenobiotic organic anion conjugates. Single nucleotide polymorphisms (SNPs) in the MRP2 gene contribute to variability in drug response and adverse effects between individuals and different ethnic populations. We characterized the transport of wild type MRP2 (WT) and two MRP2 SNP variants, M4 (A1450T) and M5 (V417I) for the substrates LTC 4 (leukotrieneC4), E 2 3G (estradiol‐3‐glucuronide), TUDC (tauroursodeoxycholic acid) and E 2 17G (estradiol‐17β‐lucuronide) Methods : WT, M4 and M5 were expressed in Sf9 insect cells and kinetic parameters (K m , μM; V max , pmol/mg −1 .min −1 ; Hill coefficient [HC]) of ATP dependant transport of 3 H‐LTC 4 , 3 H‐E 2 3G, 3 H‐TUDC and 3 H‐E 2 17G determined in Sf9 plasma membrane vesicles. Transport activity of M4 and M5 was normalized to WT protein expression. Results Conclusion The SNP in the nucleotide‐binding domain of M4 decreased the V max by 50% for LTC 4 , E 2 3G and TUDC and decreased the HC for TUDC and E 2 17G. The SNP in the transmembrane domain 2 of M5 minimally influenced the V max , but increased the K m 2–3 fold, increased the HC for TUDC and decreased the HC for E 2 17G. (HD 58299)

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: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.004
Threshold uncertainty score0.013

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 integrity0.0010.000
Insufficient payload (model declined to judge)0.0040.001

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 head0.023
GPT teacher head0.254
Teacher spread0.231 · 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 designObservational
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

Citations0
Published2008
Admission routes1
Has abstractyes

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