Investigation of Stage-Specific Distinction in the Leishmania mexicana Translational Machinery
Bibliographic record
Abstract
Leishmaniasis is a parasitic infection found in tropical, subtropical and southern European regions. The Leishmania life cycle is digenic and transitions between the sandfly and human hosts, which have distinct environmental conditions. Near-constitutive transcription in kinetoplasts renders gene regulation overwhelmingly post-transcriptional, placing heightened regulatory emphasis on RNA binding protein function. Modulation of translation plays a major role in parasite survival and adaptation. Our knowledge of the molecular mechanisms of translation in Leishmania remains limited, and it is unknown to what extent the composition of the translational machinery varies throughout the parasite life cycle Therefore, to expand this knowledge, enrichment strategies for Leishmania ribosomes were evaluated in order to generate samples suitable for mass spectrometry analysis of stage-specific ribosome-associated proteins. Immunoprecipitation was employed using antibodies against ribosomal protein P0 (also known as uL10) to capture the ribosomes on beads, which were subsequently analysed by mass spectrometry. Polysome profiling was also performed to identify the ideal conditions for RNA digestion to ensure the enrichment of ribosomes, to isolate both translating and non-translating ribosomes from L. mexicana promastigote stages and specifically exclude any RNA binding proteins (RBPs) interacting with an mRNA mid-translation. Further optimisation is required to realise this strategy. Bioinformatic analyses of mass spectrometry data have enabled comparisons of the translational machinery between the procyclic (PCF) and the metacyclic promastigotes (META). This has highlighted differentially abundant proteins involved in specific processes, which are key to cell regulation, translation and differentiation. It also illustrates how post-translational modifications (PTM) promote parasitic adaptation; specifically, protein kinase activity and phosphoregulation in META differentiation and metacyclogenesis. Key findings from our mass spectrometry include the enrichment of CRK9, RDK2 kinases and serine/threonine phosphatases in META.
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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 | 0.000 |
| 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".