Modelling Sex Differences in Circadian Regulation of Kidney Function of the Mouse
Bibliographic record
Abstract
Abstract Kidney function is regulated by the circadian clock. Not only do glomerular filtration rate (GFR) and urinary excretion oscillate during the day, the expressions of several renal transporter proteins also exhibit circadian rhythms. Interestingly, the circadian regulation of these transporters may be sexually dimorphic. Thus, the goal of this study is to investigate the mechanisms by which kidney function of the mouse is modulated by sex and time of day. To accomplish this, we have developed the first computational models of epithelial water and solute transport along the mouse nephrons that represent the effects of sex and circadian clock on renal hemodynamics and transporter activity. We conduct simulations to study how the circadian control of renal transport genes affects overall kidney function, and how that process differs between male and female mice. Simulation results predict that tubular transport differs substantially among segments, with relative variations in water and Na + reabsorption along the proximal tubules and thick ascending limb tracking that of GFR. In contrast, relative variations in distal segment transport are much larger, with Na + reabsorption almost doubling during the active phase. Oscillations in Na + transport drive K + transport variations in the opposite direction. Model simulations of BMAL1 knockout mice predict a significant reduction in net Na + reabsorption along the distal segments in both sexes, but more so in males than females. This can be attributed to the reduction of mean ENaC activity in males only, a sex-specific effect that may lead to a reduction in blood pressure in males.
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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 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".