Substrate Dependent Regulation of the Human Equilibrative Nucleoside Transporter 1 (hENT1) in HEK293 Cells
Bibliographic record
Abstract
Nucleosides and nucleoside analog drugs enter cells through nucleoside transporters, such as the human equilibrative nucleoside transporter 1 (hENT1). The regulation of nucleoside transporters is poorly understood. In this study, through fluorescence-activated cell sorting (FACS) analyses, confocal microscopy and radio-ligand binding assays, I show a decrease in hENT1 abundance at the plasma membrane (PM) in HEK cells treated in the presence of a bolus amount of cytidine (40μM) for 6 hours. Kinetic and transport assays indicate that the remaining hENT1 population at the PM has a higher Vmax and Km but there is no change in overall substrate uptake compared to untreated cells. I also show that cytidine pre-treatment leads to an increased cytotoxicity from gemcitabine (a nucleoside analog drug). These are the first data that show direct substrate dependent regulation of a nucleoside transporter by a mechanism that may involve increased recycling/internalization of the transporter.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".