TRPV6 and Cav1.3 Mediate Distal Small Intestine Calcium Absorption Before Weaning
Bibliographic record
Abstract
Background & Aims Intestinal Ca 2+ absorption early in life is vital to achieving optimal bone mineralization. The molecular details of intestinal Ca 2+ absorption have been defined in adults after peak bone mass is obtained, but they are largely unexplored during development. We sought to delineate the molecular details of transcellular Ca 2+ absorption during this critical period. Methods Expression of small intestinal and renal calcium transport genes was assessed by using quantitative polymerase chain reaction. Net calcium flux across small intestinal segments was measured in Ussing chambers, including after pharmacologic inhibition or genetic manipulation of TRPV6 or Ca v 1.3 calcium channels. Femurs were analyzed by using micro–computed tomography and histology. Results Net TRPV6-mediated Ca 2+ flux across the duodenum was absent in pre-weaned (P14) mice but present after weaning. In contrast, we found significant transcellular Ca 2+ absorption in the jejunum at 2 weeks but not 2 months of age. Net jejunal Ca 2+ absorption observed at P14 was not present in either Trpv6 mutant (D541A) mice or Ca v 1.3 knockout mice. We observed significant nifedipine-sensitive transcellular absorption across the ileum at P14 but not 2 months. Ca v 1.3 knockout pups exhibited delayed bone mineral accrual, compensatory nifedipine-insensitive Ca 2+ absorption in the ileum, and increased expression of renal Ca 2+ reabsorption mediators at P14. Moreover, weaning pups at 2 weeks reduced jejunal and ileal Ca v 1.3 expression. Conclusions We have detailed novel pathways contributing to transcellular Ca 2+ transport across the distal small intestine of mice during development, highlighting the complexity of the multiple mechanisms involved in achieving a positive Ca 2+ balance early in life.
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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 | 0.001 |
| 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 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".