Abstract P150: Genes of a Brown Norway Chromosome 2 Fragment Introgressed Into Hypertensive Dahl Salt-Sensitive Background Exert Pro-Inflammatory Effects When Stimulated by a High-Salt Diet
Bibliographic record
Abstract
Background: Chromosome 2 (Chr2) introgression from normotensive Brown Norway (BN) rats into hypertensive Dahl salt-sensitive (SS) background (consomic S B 2) reduced blood pressure (BP) and vascular inflammation under normal-salt diet (NSD). We hypothesized that BN Chr2 contains anti-inflammatory genes that could reduce BP elevation and vascular inflammation in rats fed NSD and high-salt diet (HSD). Method: Four- to 6-week old male SS and congenic rats containing the BN Chr2 distal portion (S B 2a) and middle segment (S B 2b) were fed NSD or HSD (4% NaCl) for 8 weeks. We determined systolic BP (SBP) by telemetry, reactive oxygen species (ROS) generation using dihydroethidium staining, and vascular cell adhesion molecule 1 (VCAM-1), monocyte chemoattractant protein-1 (MCP-1) expression and monocyte/macrophage (MoMϕ) infiltration by immunofluorescence in aorta or perivascular fat (PVAT). RNA was extracted from aorta and used for small and total RNA sequencing and data were analyzed using a systems biology approach. Differentially expressed genes (DEGs) were identified with fold change >1.3 and fold discovery rate <0.05 and some of them were validated with RT-qPCR. Results: SS SBP was 145±2 mm Hg under NSD and 168±1 mm Hg under HSD, which was lower in S B 2a and S B 2b SBP (125±3 and 127±6, P <0.05) under NSD but similar under HSD. Examination of ROS generation, VCAM-1 and MCP-1 expression and MoMϕ infiltration revealed that S B 2a present less and more inflammation under NSD and HSD, respectively, compared to SS. DEGs were identified in S B 2a vs SS uniquely under NSD (15↑ and 8↓) and HSD (318↑ and 221↓) and under both diet (3↑ and 3↓), and in S B 2b vs SS uniquely under NSD (43↑ and 65↓) and HSD (4↑ and 7 ↓) and under both diet (3↑ and 4 ↓). DEGs encoded within BN Chr2a were uniquely identified under NSD (1↑ and 1↓) and HSD (6↑ and 1↓), and in both diets (1↑ and 1↓). Gene enrichment analysis revealed that under NSD, 2 BN Chr2a DEGs are involved in regulation of BP, and under HSD, 7 BN Chr2a DEGs in cell proliferation, cell differentiation, signal transduction and the immune system. RT-qPCR validated DEGs encoded within BN Chr2a under NSD (2) and HSD (4). Conclusions: DEGs encoded within BN Chr2a fragment are associated with anti- and pro-inflammatory effects under NSD and HSD, respectively.
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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) | 0.001 | 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 | 0.001 |
| 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".