Luminescent insulin–Au(<scp>iii</scp>) conjugate retains insulin biological properties in human microglia
Bibliographic record
Abstract
The aims of this study were to establish if insulin conjugated with auric gold Au(III) can be visualized in living cells expressing insulin receptors, and if key steps in insulin signaling are undisturbed. Au(III) is coordinated with three tyrosines of insulin and is strongly stabilized by coordination with these tyrosines into a metal-ion coordinated insulin template. We combined theoretical and experimental approaches, including computational analyses, immunocytochemistry and functional assays to analyze the cellular effects of this construct. Results in this study show that the insulin-Au(III) conjugate does not impair several steps in insulin signaling and downstream metabolic functions in lysosomes and lipid droplets. Namely, the signaling kinases protein kinase B (Akt1) and mitogen-activated protein kinases (ERK1/2) are phosphorylated to a comparable extent as with unmodified insulin. Immunocytochemistry also shows a comparable decrease in nuclear transcription factor EB (TFEB), an essential regulator of lysosomal biogenesis. Fluorescence co-labelling of lysosomes with LysoTracker and lipid droplets with BODIPY 493/503 shows normal organellar morphology and slightly enhanced lipid droplet content. The luminescent properties of insulin-Au(III) could serve to combine biochemical and imaging studies in human cells beyond microglia.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| 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 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".