Characterizing Lithium-Mediated Nucleoside Transport by Human Concentrative Nucleoside Transporters 1 and 3 (hCNT1 and hCNT3)
Bibliographic record
Abstract
The human concentrative nucleoside transporters (hCNTs) utilize coupling and movement of cations down their electrochemical gradient to mediate inward transport of nucleosides against their concentration gradient. Of the three hCNT family members, hCNT3 exhibits the broadest nucleoside selectivity and cation specificity, utilizing Na+, Li+, and H+ to drive nucleoside transport. Xenopus laevis oocytes were injected with hCNT1 and hCNT3 RNA transcripts and incubated for 48 hours to allow protein expression and localization to the plasma membrane. The two-electrode voltage clamp (TEVC) method was used to perform electrophysiological studies. Oocytes were voltage-clamped, and currents were measured in response to various cation conditions, addition of different nucleosides and changes in membrane potential. Voltage-dependence of hCNT1- and hCNT3-mediated uridine uptake and hCNT3-mediated nucleoside uptake-induced currents was determined using NaCl, ChCl and LiCl transport media. Li+ addition resulted in decreases in uptake of uridine both by hCNT1 and hCNT3. hCNT1 and hCNT3 exhibited similar trends in voltage-dependence of uridine transport; currents generated increased as potentials became more negative. It was shown that whereas Na+-coupled hCNT3 has broad nucleoside selectivity, Li+-coupled transport varied widely and was greatest for uridine, and least for thymidine (uridine > cytidine > guanosine > adenosine > inosine > thymidine). Our results indicate a possible role of the nucleoside nitrogenous base ring structure in the differential uptake of various nucleosides. Despite no significant role of Li+ in vivo, further understanding of hCNT3 interactions with this cation may lead to a better understanding it’s transport mechanism and assist in the future design and delivery of effective anti-cancer drugs and anti-viral nucleoside drugs. Keywords: electrophysiology, nucleoside transport, Xenopus laevis, two-electrode voltage clamp, secondary active transporters, influx rates
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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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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.
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".