Recombinant Transthyretin Purification and Competitive Binding with Organohalogen Compounds in Two Gull Species (Larus argentatus and Larus hyperboreus)
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Glaucous gulls (Larus hyperboreus) from Svalbard, Norway (marine), and herring gulls (Larus argentatus) from the Laurentian Great Lakes (freshwater) of North America are differentially exposed to persistent and bioaccumulative anthropogenic contaminants, such as polychlorinated biphenyls (PCBs) and polybrominated diphenyl ether (PBDE) flame retardants and metabolic products. Such compounds can potentially perturb hormone transport via binding interactions with proteins such as transthyretin (TTR, prealbumin). In this present study, we isolated, cloned and sequenced TTR cDNA from the brain and liver of two species (herring and glaucous gull), which, to our knowledge, is the first report describing the TTR nucleic acid and amino acid sequences from any gull species. Identical TTR nucleotide and amino acid sequences were obtained from both gull species (liver and brain). Recombinant TTR (rTTR) was expressed and purified, and determined as a monomer of 18 kDa and homodimer of 36 kDa that putatively is comprised of the two protein monomers. Concentration dependent, competitive TTR-binding curves with each of the natural TTR ligands 3,5,3'-triiodothyronine (T(3)) and thyroxine (T(4)) were generated as well as by treatment with a range of concentrations (10(-3)-10(5)nM) of 2,2',3,4',5,5',6-heptaCB (CB187), 2,2',4,4'-tetrabromoDE (BDE47), and hydroxyl- (OH) and methoxyl (MeO)-containing analogs (i.e., 4-OH-CB187, 6-OH-BDE47, 4'-OH-BDE49, 4-MeO-CB187, and 6-MeO-BDE47). Relative to the nonsubstituted BDE47 and CB187 and their MeO-substituted analogs, the OH-substituted analogs all had lower K(i) and K(d) values, indicating greater affinity and more potent competitive binding to both T(3) and T(4). The OH-substitution position and/or the diphenyl ether substitution of the four bromine atoms resulted in more potent, greater affinity, and greater relative potency for 4'-OH-BDE49 relative to 6-OH-BDE47. CB187 was more comparable in binding potency and affinity to 4-OH-CB187, then was 6-OH-BDE47 and 4'-OH-BDE49 relative to BDE47 where the binding potency and affinity was several orders of magnitude greater for 6-OH-BDE47 and 4'-OH-BDE49. This indicated that the combination of the more thyroid hormone-like brominated diphenyl ether backbone (relative to the chlorinated biphenyl backbone), and in combination of having an OH-group, results in a more effective competitive ligand on gull TTR relative to both T(3) and T(4). Known circulating levels of 4-OH-CB187, 6-OH-BDE47, and 4'-OH-BDE49 in the plasma of free-ranging Svalbard glaucous gulls were comparable to the concentration of in vitro competitive potency of T(3) and T(4) with gull TTR. These results suggest that environmentally relevant and selected OH-containing PCB, and to a lesser extent PBDE congeners have the potential to be physiologically effective in these gull species via perturbation of T(4) and T(3) transport.
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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 | 0.001 | 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 | 0.001 | 0.005 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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 it