Acid sphingomyelinase is a gatekeeper of placental labyrinthine architecture and function
Bibliographic record
Abstract
Sphingolipids are a class of bioactive signaling lipids that regulate an array of fundamental cellular processes, including cell survival, proliferation and differentiation. Deficiency of acid sphingomyelinase - an enzyme of the sphingolipid metabolic pathway - has been previously implicated in human placental pathologies. We demonstrate that acid sphingomyelinase (Smpd1) is required for normal placental development in the mouse, and its deficiency results in an intrauterine growth restriction phenotype. Smpd1-deficient placentas display several anatomical abnormalities, including a reduced labyrinth compartment and increased fetal-maternal interhaemal distance. Finally, we observed several hallmarks of defective autophagy and lysosomal impairment in Smpd1-/- placentas, which could explain the inability of Smpd1-/- trophoblast to respond to nutrient starvation. Fetal growth restriction could not be rescued by transfer of Smpd1-deficient embryos into a wild-type uterine environment; however, restoration of transcription factor EB phosphorylation was detected. Thus, we conclude that, due to a smaller labyrinthine area, Smpd1 deficiency leads to a decrease in exchange between maternal and fetal blood space, limiting the supply of nutrients to the fetus and resulting in growth restriction.
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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 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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".