Studies on the immunosuppressive effects and detection of naturally-occuring toxins
Bibliographic record
Abstract
Episodes of toxin-producing phytoplankton occur worldwide, causing both animal and\nhuman fatalities. Toxicity occurs through consumption of phycotoxins, including\nazaspiracid, which accumulate in filter-feeding shellfish. Microcystins are hepatotoxins,\nproduced mainly by freshwater cyanobacteria. Aflatoxins are potent, fungal\nhepatocarcinogens, which occur mainly in food and feed products. The purpose of this\nresearch was to examine the cytotoxic and immunosuppressive effects of aflatoxins (B1,\nB2 and G1), azaspiracid-1 and microcystin-LR in vitro, using the murine macrophage\ncell line, J774A.1. The results clearly demonstrated that azaspiracid and microcystin had\na significant effect on host defence functions, through deregulation of IL-6, IL-10, IL12p40 and TNF-α cytokine expression. Microcystin exposure significantly decreased\nIL-1β expression. ‘Toll-like’ receptor (TLR2 and CD14) expression was altered\nfollowing aflatoxin exposure, while apoptotic marker (caspase-1) expression was\naffected following microcystin exposure. This knowledge should be taken into\nconsideration in the implementation of detection limits, aimed at minimising risks to\nhuman health through toxin exposure.\nIncreased awareness of the hazards presented by toxins led to the requirement for\nrecombinant antibodies for these targets, for incorporation into sensitive detection\nimmunoassays. This thesis describes the production of leprine and avian immune\nlibraries for azaspiracid and microcystin, respectively. Attempts were made to isolate\nazaspiracid-specific antibodies with little success. Phage display was utilised to\nsuccessfully isolate two single chain antibody fragments (scFvs) to microcystin from the\navian library. Error-prone PCR resulted in the isolation of a mutant clone which\ndisplayed a 2.3-fold improvement in sensitivity by ELISA, with an LOD of 1.4 ng/mL.\nThe mutant scFv displayed an altered cross-reactivity profile to the microcystin variants\ntested using Biacore™ inhibition analysis. The recombinant antibodies were\nsuccessfully applied to the development of fluorescence-based immunoassay formats.\nThe biotinylated mutant scFv was incorporated into a slide-based assay format on a\nfunctionalised glass substrate (IC50 ~ 1 µg/L). This assay had the potential to accurately\ndetect microcystin and its variants, below the regulatory limit of 1 µg/L. The application\nof these highly-sensitive recombinant antibodies into rapid and inexpensive\nfluorescence detection systems could aid in the development of an early warning system\nfor toxin outbreaks.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 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 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".