Using piglets as an animal model: Dose-response study on the impact of short-term marginal zinc supply on oxidative stress dependent and cell fate associated gene expression in the heart muscle
Bibliographic record
Abstract
During the last decade, zinc was shown to be involved in oxidative stress reactions demonstrating the pathological significance of zinc deficiency. However, those investigations mainly focused on situations of massive zinc depletion compared to sufficiently fed and oversupplied animals [1]. Though, the more common zinc deficiency phenotype in men and animals is marginal alimentary undersupply, due to plant based diets rich in antinutritive factors like phytate and fibre [2]. In order to mimic this situation, a dose-response study of gradually increasing zinc addition to a zinc deficient diet (corn soybean based diet; 28 mg native zinc content/kg diet; +0, +5, +10, +15, +20, +30, +40, +60 mg zinc/kg as ZnSO4) with 48 weaning piglets (n = 6 animals per group) was conducted. The diet with +60 mg zinc/kg served as baseline and was fed to all animals for two weeks prior to the study. Treatment lasted for eight days in order to stay within margin of physiological capacity of zinc mobilization and to avoid clinical symptoms of zinc deficiency. Analysis included blood plasma zinc levels and mRNA expression patterns of genes associated with antioxidative defense and cell fate in the heart muscle. The plasma zinc content of the groups increased linearly (R2 = 0.93) from 0.21 to 0.63 mg zinc/L in group +0 mg zinc/kg to +60 mg zinc/kg respectively, proving the efficacy of the model to produce a fine-graded undersupply in dietary zinc. A statistically significant upregulation of proapoptotic factors was monitored in the +0 mg zinc/kg group compared to all other groups (Bax, Fas, Casp9), in concordance to an up-regulation of the transcription factor p53. This might be due to increasing abundance of reactive oxygen species as zinc supply declines marked by an increased transcription of glutathione reductase and catalase. Simultaneously, p21 and Gadd45a (regulating cell cycle arrest in a p53 dependent manner) were lower expressed with reduced dietary zinc supply. In summary, undersupply of zinc proved to increase the transcription of genes associated with oxidative stress and apoptosis in the heart muscle, even under condition of short term exposure.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| 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 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".