<i>Plasmodium falciparum</i> histidine-rich protein 2 exhibits cell penetration and cytotoxicity with autophagy dysfunction
Bibliographic record
Abstract
Plasmodium falciparum is a major cause of severe malaria. This protozoan infects human red blood cells and secretes large quantities of histidine-rich protein 2 (PfHRP2) into the bloodstream, making it a well-known diagnostic marker. Here, however, we identified PfHRP2 as a pathogenic factor produced by P. falciparum. PfHRP2 showed cell penetration and cytotoxicity against various human cells. PfHRP2 also exhibited significant cytotoxicity at concentrations found in P. falciparum-infected patients' blood (90-100 n m). We also showed that PfHRP2 binds to Ca2+ ions, localizes to intracellular lysosomes, increases lysosomal Ca2+ levels, and inhibits the basal level of autophagy by preventing autolysosome formation. Furthermore, the Ca2+-dependent cytotoxicity of PfHRP2 was suppressed by the metal ion chelator ethylenediaminetetraacetic acid. In summary, our findings suggest PfHRP2 as a crucial pathogenic factor produced by P. falciparum and its mode of action. Overall, this study provides preliminary insights into P. falciparum malaria pathogenesis.
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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 | 0.001 |
| 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".