Heterocyclic Amine-Induced Feeding Deterrence and Antennal Response of Honey Bees.

The productivity and survival of managed honey bee colonies is negatively impacted by a diverse array of interacting factors, including exposure to agrochemicals, such as pesticides. This study investigated the use of volatile heterocyclic amine (HCA) compounds as potential short-term repellents that could be employed as feeding deterrents to reduce the exposure of bees to pesticide-treated plants. Parent and substituted HCAs were screened for efficacy relative to the repellent ,-diethyl-meta-toluamide (DEET) in laboratory and field experiments.

Terpenoid-Induced Feeding Deterrence and Antennal Response of Honey Bees.

Multiple interacting stressors negatively affect the survival and productivity of managed honey bee colonies. Pesticides remain a primary concern for beekeepers, as even sublethal exposures can reduce bee immunocompetence, impair navigation, and reduce social communication. Pollinator protection focuses on pesticide application guidelines; however, a more active protection strategy is needed.

Age- and sex-related ABC transporter expression in pyrethroid-susceptible and -resistant Aedes aegypti.

Resistance mechanisms to synthetic insecticides often include point mutations and increased expression of genes encoding detoxification enzymes. Since pyrethroids are the main adulticides used against Aedes aegypti, which vectors pathogens such as Zika virus, understanding resistance to this insecticide class is of significant relevance. We focused on adenosine triphosphate (ATP)-binding cassette (ABC) transporters in the pyrethroid-resistant Puerto Rico (PR) strain of Ae.

Bacteria-mediated modification of insecticide toxicity in the yellow fever mosquito, Aedes aegypti.

The incidence of mosquito-borne disease poses a significant threat to human and animal health throughout the world, with effective chemical control interventions limited by widespread insecticide resistance. Recent evidence suggests that gut bacteria of mosquitoes, known to be essential in nutritional homeostasis and pathogen defense, may also play a significant role in facilitating insecticide resistance. This study investigated the extent to which bacteria contribute to the general esterase and cytochrome P450 monooxygenase (P450)-mediated detoxification of the insecticides propoxur and naled, as well as the insecticidal activity of these chemistries to the yellow fever mosquito, Aedes aegypti.

Vapor delivery of plant essential oils alters pyrethroid efficacy and detoxification enzyme activity in mosquitoes.

The use of synthetic insecticides to limit the spread of mosquito-borne disease faces a number of significant challenges, including insecticide resistance, concerns related to the environmental impact of widespread insecticide use, as well as slowed development of new insecticide chemistries. One important alternative to broadcast insecticides is the use of personal protection strategies to limit contact with vector species, including the use of spatial repellents that can employ synthetic pyrethroids or botanical products to effect control. A currently underexplored area of research involves the investigation of botanical products for their potential to serve as insecticide synergists when delivered as a vapor.

Chlorothalonil Exposure Alters Virus Susceptibility and Markers of Immunity, Nutrition, and Development in Honey Bees.

Chlorothalonil is a broad spectrum chloronitrile fungicide that has been identified as one of the most common pesticide contaminants found in managed honey bees (Hymenoptera: Apidae: Apis mellifera L.), their food stores, and the hive environment. While not acutely toxic to honey bees, several studies have identified potential sublethal effects, especially in larvae, but comprehensive information regarding the impact of chlorothalonil on adults is lacking.

Association of age, sex, and pyrethroid resistance status on survival and cytochrome P450 gene expression in Aedes aegypti (L.).

Aedes aegypti is a vector of viruses that negatively impact human health. Insecticide resistance complicates mosquito control efforts, but understanding the mechanisms of resistance can help to improve management practices. This study examined different factors that could influence the interpretation of toxicity bioassays and gene expression studies in A.

In-Hive Acaricides Alter Biochemical and Morphological Indicators of Honey Bee Nutrition, Immunity, and Development.

The honey bee is a widely managed crop pollinator that provides the agricultural industry with the sustainability and economic viability needed to satisfy the food and fiber needs of our society. Excessive exposure to apicultural pesticides is one of many factors that has been implicated in the reduced number of managed bee colonies available for crop pollination services. The goal of this study was to assess the impact of exposure to commonly used, beekeeper-applied apicultural acaricides on established biochemical indicators of bee nutrition and immunity, as well as morphological indicators of growth and development.

Interactions between pesticides and pathogen susceptibility in honey bees.

There exist a variety of factors that negatively impact the health and survival of managed honey bee colonies, including the spread of parasites and pathogens, loss of habitat, reduced availability or quality of food resources, climate change, poor queen quality, changing cultural and commercial beekeeping practices, as well as exposure to agricultural and apicultural pesticides both in the field and in the hive. These factors are often closely intertwined, and it is unlikely that a single stressor is driving colony losses. There is a growing consensus, however, that increasing prevalence of parasites and pathogens are among the most significant threats to managed bee colonies.

ATP-sensitive inwardly rectifying potassium channel regulation of viral infections in honey bees.

Honey bees are economically important pollinators of a wide variety of crops that have attracted the attention of both researchers and the public alike due to unusual declines in the numbers of managed colonies in some parts of the world. Viral infections are thought to be a significant factor contributing to these declines, but viruses have proven a challenging pathogen to study in a bee model and interactions between viruses and the bee antiviral immune response remain poorly understood. In the work described here, we have demonstrated the use of flock house virus (FHV) as a model system for virus infection in bees and revealed an important role for the regulation of the bee antiviral immune response by ATP-sensitive inwardly rectifying potassium (K) channels.

Amitraz and its metabolite modulate honey bee cardiac function and tolerance to viral infection.

The health and survival of managed honey bee (Apis mellifera) colonies are affected by multiple factors, one of the most important being the interaction between viral pathogens and infestations of the ectoparasitic mite Varroa destructor. Currently, the only effective strategy available for mitigating the impact of viral infections is the chemical control of mite populations. Unfortunately, the use of in-hive acaricides comes at a price, as they can produce sublethal effects that are difficult to quantify, but may ultimately be as damaging as the mites they are used to treat.

ATP-sensitive inwardly rectifying potassium channel modulators alter cardiac function in honey bees.

ATP-sensitive inwardly rectifying potassium (K) channels couple cellular metabolism to the membrane potential of the cell and play an important role in a variety of tissue types, including the insect dorsal vessel, making them a subject of interest not only for understanding invertebrate physiology, but also as a potential target for novel insecticides. Most of what is known about these ion channels is the result of work performed in mammalian systems, with insect studies being limited to only a few species and physiological systems. The goal of this study was to investigate the role that K channels play in regulating cardiac function in a model social insect, the honey bee (Apis mellifera), by examining the effects that modulators of these ion channels have on heart rate.

Dissection and Observation of Honey Bee Dorsal Vessel for Studies of Cardiac Function.

The European honey bee, Apis mellifera L., is a valuable agricultural and commercial resource noted for producing honey and providing crop pollination services, as well as an important model social insect used to study memory and learning, aging, and more. Here we describe a detailed protocol for the dissection of the dorsal abdominal wall of a bee in order to visualize its dorsal vessel, which serves the role of the heart in the insect.

Mosquito-borne viruses and suppressors of invertebrate antiviral RNA silencing.

The natural maintenance cycles of many mosquito-borne viruses require establishment of persistent non-lethal infections in the invertebrate host. While the mechanisms by which this occurs are not well understood, antiviral responses directed by small RNAs are important in modulating the pathogenesis of viral infections in disease vector mosquitoes. In yet another example of an evolutionary arms race between host and pathogen, some plant and insect viruses have evolved to encode suppressors of RNA silencing (VSRs).

Rational design of fatty acid amide hydrolase inhibitors that act by covalently bonding to two active site residues.

The design and characterization of α-ketoheterocycle fatty acid amide hydrolase (FAAH) inhibitors are disclosed that additionally and irreversibly target a cysteine (Cys269) found in the enzyme cytosolic port while maintaining the reversible covalent Ser241 attachment responsible for their rapid and initially reversible enzyme inhibition. Two α-ketooxazoles (3 and 4) containing strategically placed electrophiles at the C5 position of the pyridyl substituent of 2 (OL-135) were prepared and examined as inhibitors of FAAH. Consistent with the observed time-dependent noncompetitive inhibition, the cocrystal X-ray structure of 3 bound to a humanized variant of rat FAAH revealed that 3 was not only covalently bound to the active site catalytic nucleophile Ser241 as a deprotonated hemiketal, but also to Cys269 through the pyridyl C5-substituent, thus providing an inhibitor with dual covalent attachment in the enzyme active site.

Inhibition of monoacylglycerol lipase attenuates nonsteroidal anti-inflammatory drug-induced gastric hemorrhages in mice.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used analgesics, but can cause gastric and esophageal hemorrhages, erosion, and ulceration. The endogenous cannabinoid (endocannabinoid; eCB) system possesses several potential targets to reduce gastric inflammatory states, including cannabinoid receptor type 1 (CB(1)), cannabinoid receptor type 2 (CB(2)), and enzymes that regulate the eCB ligands 2-arachidonoylglycerol (2-AG) and N-arachidonoyl ethanolamine (anandamide; AEA). In the presented study, we tested whether 4-nitrophenyl 4-(dibenzo[d][1,3]dioxol-5-yl(hydroxy)methyl)piperidine-1-carboxylate (JZL184), a selective inhibitor of the primary catabolic enzyme of 2-AG, monoacylglycerol lipase (MAGL), would protect against NSAID-induced gastric damage.

CB1 receptors mediate rimonabant-induced pruritic responses in mice: investigation of locus of action.

Rationale: Cannabinoids have recently been identified as potential neuronal modulators of pruritic response, representing a potential target in the treatment of itch associated with a variety of pathophysiologic conditions. While the selective CB(1) receptor antagonist rimonabant is an established pruritic agent in both animal and clinical testing, its receptor mechanism of action and anatomical loci remain unclear.

Objective: The purpose of this study was to determine whether CB(1) receptor blockade is critical to rimonabant-induced scratching and to identify differences in scratching response based on different routes of administration.

Inhibition of endocannabinoid catabolic enzymes elicits anxiolytic-like effects in the marble burying assay.

Cannabinoids have long been shown to have a range of potential therapeutic effects, including antiemetic actions, analgesia, and anxiolysis. However, psychomimetic and memory disruptive side effects, as well as the potential for abuse and dependence, have restricted their clinical development. Endogenous cannabinoids (i.