A78 INHIBITION OF DAPK-1 PROMOTES INTESTINAL BACTERIA TRANSLOCATION AND INCREASES SEVERITY OF DSS-INDUCED COLITIS
Bibliographic record
Abstract
Epithelial intestinal barrier is a first-line of defense often compromised in inflammatory bowel disease (IBD). Lumen-derived commensal bacteria enter the mucosa and are likely important in etiology and pathophysiology of the disease. Genome wide association studies have identified that mutation is autophagy genes (e.g. ATG16L1 and IRG1) is a susceptibility trait for IBD. Death-associated protein kinase (DAPK)-1 is a regulator of autophagy and a polymorphism in the DAPK-1 gene was reported in some patients with IBD. The aim of this study was to analyze if the inhibition of DAPK-1 would increase the severity of colitis. Balb/c mice received 2.5% (wt./vol.) DSS or normal water and were treated daily i.p. with the DAPK-1 pharmacologic inhibitor DAPK6 or vehicle for 5 days. Colitis was assessed by standard indices: disease activity score (DAS), colon length and weight loss and histopathology. Intestinal barrier function was assessed by the number of aerobic bacteria within the mesenteric lymph nodes (MLN), spleen and colonic mucosal. With this low dose of DSS, as expected, mice experience a mild or negligible inflammation and there were not obvious increases in DAS or intestinal barrier function in Balb/c mice. However, animals treated with DSS and DAPK6 presented with a significant increase in the severity of colitis, showing higher DAS, shorter colon length, and greater weight loss in comparison with naïve control, DAPK6/water- and DSS/vehicle-treated mice groups. Also, DSS+DAPK6 treatment resulted in increased translocation of aerobic bacteria into the colonic mucosal, MLN and the spleen. Finally, the inhibition of DAPK-1 alone (i.e. DAPK6/water treatment) resulted in shortening of the colon and loss of body weight. DAPK-1, a component of the autophagy cascade, is important for normal gut homeostatic activity and for limiting the severity of colitis, likely via inactivation of bacteria via xenophagy. CAG, CIHRAlberta Innovates, Allergan
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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) | 0.001 | 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 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".