Bibliographic record
Abstract
Nosema disease of the Western honey bee (Apis mellifera L.), is caused by two distinct microsporidian fungal species, Nosema ceranae Fries et al. and Nosema apis Zander. N. apis infection of A. mellifera was first documented in 1909, while N. ceranae infection of A. mellifera was described in 1996. N. ceranae infection has been implicated in colony collapse disorder (CCD) and decreased survival of overwintered colonies. There is currently only one registered chemical treatment available to control Nosema disease in apiculture in Canada, namely Fumagilin-B®, a potent fungal metabolite first isolated from Aspergillus fumigatus Fres. Fumagilin-B® (and the equivalent Fumidil-B®) has been extensively used against N. apis since its discovery in the early 1950’s, and has more recently been used to control N. ceranae infections. The toxicity of fumagillin, which has limited its use in human medicine, is also of concern for beekeeping, since any residues of fumagillin remaining in hive products pose a direct risk to the consumer. All analytical methods published to date measure only fumagillin and its decomposition products in honey, but overlook the fact that fumagillin is present in a 1:1 stoichiometric ratio with its dicyclohexylamine (DCH) counter ion in the commercial salt formulations (Fumagilin-B® and Fumidil-B®). DCH is almost five times more toxic than fumagillin to rats, and also exhibits genotoxic and tumorigenic properties. A reversed phase (RP) liquid chromatography tandem mass spectrometric (LC-MS/MS) method was developed to confirm and quantitate trace levels of fumagillin and DCH residues in honey. A labelled d10-DCH internal standard was also synthesized and used to compensate for observed matrix affects when quantitating DCH in honey from different floral origins. While analyzing domestically produced honey samples fumagillin was seldom detected at levels above 10 ng g-1 (method limit of quantitation), while DCH was detected in almost all of the samples at concentrations above 10 ng g-1. The frequency and concentrations of DCH detected, even in the absence of any detectable amounts of fumagillin or its known degradation products, led to the design of an experiment to evaluate the relative stability of fumagillin and DCH in honey under a range of time-temperature exposures. During this experiment it was observed that DCH was significantly more stable in honey than fumagillin highlighting DCH as an important potential contaminant of honey. This further emphasizes the importance of evaluating all of the potentially active ingredients that may be present in a pharmaceutical formulation, since the latter may be more important than immediately apparent. Finding alternative chemical treatments to fumagillin is necessary, as the sustained usage of this drug in apiculture for six decades may lead to the development of resistance in Nosema spp. In human medicine fumagillin has been tested against a variety of diseases, including cancer. Fumagillin inhibits angiogenesis (the formation of new blood vessels around a cancerous tumor) through covalently bonding to the methionine aminopeptidase 2 (MetAP-2) enzyme. This enzyme occurs ubiquitously in humans, honey bees and in both N. apis and N. ceranae. I hypothesized that the MetAP-2 structure-activity relationships discovered in human medicine could be extrapolated to apiculture. Several semi-synthetic and purely synthetic compounds were designed and synthesized to mimic this mode of action, and were subsequently tested on N. ceranae-infected bees in cage trial assays. Fumagillol, the basic hydrolysis product of fumagillin, as well as two semisynthetic fumagillin analogues and four other synthetic compounds exhibited activity against N. ceranae-infected caged bees. None of these compounds were, however, as effective as Fumagilin-B®. Commercially available thymol and enilconazole also exhibited activity against N. ceranae, with thymol being the most promising chemical treatment other than Fumagilin-B®. In addition, high bee mortality was observed while evaluating Fumagilin-B®, and a series of cage trial experiments were thus conducted to evaluate the effect of fumagillin, Fumagilin-B® (fumagillin and DCH) and DCH on N. ceranae-infected bees. From these experiments it was observed that orally ingested DCH caused a statistically significant risk of increased bee mortality in N. ceranae-infected bees.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 |
| 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 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".