THE PRODUCTION OF THE SMALL COPPER CARRIER AND INVESTIGATION INTO ITS STRUCTURE, AND UPTAKE BY CULTURED CELLS
Bibliographic record
Abstract
Wilson disease results in excess copper (Cu) build up in the liver stopping secretion into the bile for excretion. Instead, some of the excess Cu is removed in the urine where a small Cu carrier (SCC) was identified. The goals of our research were to produce and purify SCC in cultured cells, to determine its structure, and to investigate if SCC-Cu was taken up by cells and if so how. SCC was produced by hepatic and intestinal cells, which (in the case of rat hepatoma cells) was enhanced by preloading them with Cu. It was partially purified by 3 kDa ultrafiltration, dialysis, and small pore size exclusion chromatography (SEC). NMR data of the purified sample showed that there was at least one Cu containing component among contaminants. SCC-Cu was found to be taken up by all cells tested, as shown by a linear rate of uptake from SCC-67Cu over 5 h. Since it was readily taken up by cells we investigated methods potentially involved in the uptake. There was reduced uptake of 67Cu-labeled SCC when the high affinity Cu uptake protein 1 (CTR1) was inhibited by excess silver (Ag) ions, which competes with Cu(I) for uptake by CTR1. Excess Cu(I) competed with uptake of SCC-67Cu and when CTR1 was knocked out there was a markedly reduced rate of uptake. However, there was still uptake of SCC-67Cu by cells where CTR1 had been knocked out implying CTR1 is not the only transporter involved. High concentrations of Cu(I) completely inhibited uptake of Cu from SCC-67Cu in CTR1 knockout cells suggesting another form of uptake also involves Cu(I). Cu(II) almost completely abolished uptake and was toxic to the cells, suggesting there is an alternate Cu(II) uptake transporter. Inhibition of divalent metal transporter-1 (DMT1) did not reduce uptake of SCC-67Cu indicating it is not involved. Inhibition of endocytosis also had no effect. Based on this evidence SCC’s function is the transport of Cu for the purpose of Cu homeostasis.
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 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".