Abstract 15006: Imaging the Mitochondrial Nucleoid Body in Pulmonary Arterial Hypertension Reveals Changes in Nucleoid Body Distribution and Composition in Human Pulmonary Artery Smooth Muscle Cells
Bibliographic record
Abstract
Introduction: Pulmonary arterial hypertension (PAH) exhibits excessive proliferation of pulmonary artery smooth muscle cells (PASMC). This is related to mitochondrial abnormalities, including a metabolic shift to aerobic glycolysis, and increased mitochondrial fragmentation. Mitochondrial DNA (mtDNA) encodes 13 proteins critical to mitochondrial function and is supported by multi-protein complexes called nucleoid bodies (NB) comprised of key mtDNA maintenance proteins. Previous data shows increased mtDNA damage and increased NB protein levels in PAH vs control PASMC. This seems to suggest an attempted compensatory response to mtDNA damage in PAH. We aim to identify NB composition and distribution changes in PAH. We hypothesize that NB structure and distribution throughout the mitochondrial network are dysregulated in PAH. Methods: NBs were visualized in control and PAH PASMC (n=15 per group). Cells were loaded with MitoTracker Deep Red (mitochondrial matrix dye) and visualized using stimulated emission depletion (STED) microscopy. We simultaneously imaged mtDNA and NB proteins TFAM, POLG and SSBP. NB protein distribution was quantified by comparing the rates of mtDNA-protein interactions per mitochondrial area. Results: On visualization of PASMC, mitochondrial fragmentation was evident in PAH vs control. Qualitative findings in PAH PASMC included increased heterogeneity of NB size (diameter) and spatial distribution in PAH compared to control. IF quantitation showed decreased mtDNA/cell (193±20 vs 326±28 mtDNA/cell, p<0.05) and increased SSBP (0.91±0.07 vs 0.59±0.37 SSBP/mtDNA, p<0.05) in PAH cells. These results are consistent with previous findings. Conclusion: These findings suggest a compensatory remodeling of NB in PASMC and is an important step in characterizing the NB shape, distribution, and composition in PAH. These findings will direct experiments analyzing gene and protein expression to further elucidate the role of NB in PAH.
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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 | 0.000 |
| 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 | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.007 | 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".