The molecular mechanism for the pain caused by Pterois volitans venom
Why this work is in the frame
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Bibliographic record
Abstract
The wealth of biodiversity in the world's library of venoms and their toxins represents an enormous untapped resource that could contain the scaffolds for novel therapeutic drugs.The red lionfish (Pterois volitans) is a venomous species of fish originating from the Indo-Pacific but now invasive in many regions, where it poses a significant stress on marine ecosystems and produces one of the most painful stings in the ocean.In a study I completed prior to this thesis, we demonstrated the qualities of the pain elicited by the venom (in mice) as well as its high specificity for its cellular target -nonpeptidergic nociceptors.These cells are responsible for detecting pain in the peripheral nervous system and the venom somehow specifically activates them over other sensory neurons responsible for touch or proprioception.How can the venom target these cells specifically?This was the broad question that led to this doctoral project.The objective of this thesis was to gain insights into the human pain experience of lionfish stings, the proteinaceous toxin components of the venom and its molecular mechanism of action.In chapter 2, I used a detailed pain questionnaire, completed by over 500 lionfish sting victims, to understand the pain they experienced and its impact on their daily lives.This was the first broadscale study of lionfish stings ever performed and provided key insights into the average duration of pain caused by lionfish stings, causes of stings, locations of stings and other important variables.In chapter 3, I examined the toxin composition of the venom using a combinatorial transcriptomic and proteomic approach.We performed de novo RNA sequencing of the lionfish's venomous spines and assembled a transcriptome which we used in mass spectrometry experiments to identify the proteins expressed in the lionfish venom.From there, I characterized the most abundant proteins and transcripts, screened venom fractions for their ability to activate nociceptors,
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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 | 0.004 | 0.004 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.007 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.002 | 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 it