How malaria merozoites reduce the deformability of infected RBC
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Bibliographic record
Abstract
The pathogenesis of malaria is largely due to stiffening of the infected red blood cells (RBCs). The current understanding ascribes the loss of RBC deformability to a 10-fold increase in membrane stiffness caused by extra cross-linking in the spectrin network. Local measurements by micropipette aspiration, however, have reported only an increase of about 3-fold in the shear modulus. We believe the discrepancy stems from the rigid parasite particles inside infected cells, and have carried out numerical simulations to demonstrate this mechanism. The cell membrane is represented by a set of discrete particles connected by linearly elastic springs. The cytosol is modeled as a homogeneous Newtonian fluid, and discretized by particles as in standard smoothed particle hydrodynamics. The malaria parasite is modeled as an aggregate of particles constrained to rigid-body motion. We simulate RBC stretching tests by optical tweezers in three dimensions. The results demonstrate that the presence of a sizeable parasite greatly reduces the ability of RBCs to deform under stretching. With the solid inclusion, the observed loss of deformability can be predicted quantitatively using the local membrane elasticity measured by micropipettes. Malaria is caused by mosquito-borne parasites of the genus Plasmodium, of which Plas- modium falciparum is a commonly studied species. The infective cycle consists of the ring, trophozoite and schizont stages, with progressive changes in the shape, size and structure of the infected red blood cell (iRBC) as well as those of the parasite itself. Mechanically, the iRBC gradually loses its deformability and becomes more easily adhered to the vascular walls and to other cells. When stretched by optical tweezers, the overall deformation of the iRBC decreases by several folds (1). The prevailing thinking in the literature is that the higher rigidity of the iRBC is due to remodeling of the RBC cytoskeleton by parasite-derived proteins. Recent numerical simulations of cell stretching have expressed this rigidification in terms of an elevated shear modulus Gs for the cell membrane. In the late stages of infection, Gs is estimated to be as high as 60 �N/m (1-3), up from roughly 6 �N/m for
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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 | 0.000 |
| 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 it