INCREASED EPITHELIAL PERMEABILITY DUE TO ENTEROPATHOGENIC E. COLI IS RHO KINASE‐DEPENDENT AND CASPASE‐INDEPENDENT
Bibliographic record
Abstract
AIM: The attaching and effacing (A/E) organism enteropathogenic E. coli (EPEC) is an important cause of diarrhea in developing countries. Our aim was to evaluate the mechanisms whereby EPEC and Citrobacter rodentium (murine EPEC) might disrupt tight junctions and induce epithelial apoptosis. METHODS: Mouse colorectal carcinoma CMT‐93 cells and human T84 cells were exposed to C. rodentium and EPEC, respectively. Permeability was measured via the paracellular translocation of a FITC‐conjugated dextran probe. Immunofluorescence was performed to assess tight junctional disruption. For assessment of apoptosis, cells were processed via a Cell Death ELISA or immunoblotted for cleaved PARP. Caspase activity was determined using proteolytic activity kits. Rho kinase activity was determined by ELISA. RESULTS: CMT‐93 and T84 cells demonstrated increased Rho kinase activity and apoptosis upon exposure to C. rodentium or EPEC, respectively. Infected cells also displayed increased paracellular permeability that was independent of caspase‐3 activity, but was dependent on Rho kinase. Interestingly, C. rodentium‐induced CMT‐93 cell apoptosis was caspase‐independent, while EPEC‐induced T84 cell apoptosis was caspase‐dependent. Further analysis revealed that EPEC‐induced T84 cell apoptosis was dependent on caspases‐8 and ‐9. Immunofluorescence confirmed the caspase‐3‐independent disruption of claudins‐4 and‐5 by the A/E pathogens. CONCLUSION: A/E pathogens may induce host epithelial malfunction characterized by apoptosis and increased permeability. The host and pathogen signals involved in these responses are diverse, and may be species‐specific.
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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 | 0.002 | 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 | 0.001 | 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) | 0.000 | 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".