Disruption of the AKT/MTOR pathway by Leishmania major promastigotes
Bibliographic record
Abstract
Signaling through the Akt/mammalian target of rapamycin (mTOR) pathway plays a pivotal role in the regulation of multiple cellular processes, including proliferation, apoptosis, protein synthesis and autophagy.It is therefore a major target of microbial infections and tumors.Protozoa of the Leishmania genus cause a wide spectrum of diseases in humans, termed leishmaniases, with clinical manifestations ranging from self-healing skin ulcers to life-threatening visceral disease.These parasites primarily infect macrophages and are renowned for their ability to sabotage host-cell signal transduction pathways.Here, we report that infection of Balb/c bone marrow-derived macrophages with the promastigote stage of Leishmania major results in rapid, time-dependent degradation of key components of the Akt/mTOR axis, including Akt, mTOR and the tuberous sclerosis complex-2 (TSC-2).Disruption of the Akt/mTOR pathway by L. major is dependent on the surface metalloprotease gp63, an important virulence factor of the parasite, and appears to be strain-and species-specific.The consequences of the degradation of key intermediates in the Akt/mTOR pathway on downstream responses are currently being investigated.These studies highlight a novel mechanism by which L. major interferes with macrophage functions and responses and will provide a better understanding of Leishmania pathogenesis.
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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) | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".