Repellent activity of essential oils to the Lone Star tick, Amblyomma americanum.

Background: The Lone Star tick, Amblyomma americanum is important to human health because of a variety of pathogenic organisms transmitted to humans during feeding events, which underscores the need to identify novel approaches to prevent tick bites. Thus, the goal of this study was to test natural and synthetic molecules for repellent activity against ticks in spatial, contact and human fingertip bioassays.

Methods: The efficacy of essential oils and naturally derived compounds as repellents to Am.

Cross resistance to brevetoxin-3 by kdr and super-kdr mutations in house flies.

The dinoflagellate Karenia brevis is a causative agent of red tides in the Gulf of Mexico and generates a potent family of structurally related brevetoxins that act via the voltage-sensitive Na channel. This project was undertaken to better understand the neurotoxicology and kdr cross-resistance to brevetoxins in house flies by comparing the susceptible aabys strain to ALkdr (kdr) and JPskdr (super-kdr). When injected directly into the hemocoel, larvae exhibited rigid, non-convulsive paralysis consistent with prolongation of sodium channel currents, the known mechanism of action of brevetoxins.

nymph saliva protein blocks host inflammation and complement-mediated killing of Lyme disease agent, .

Tick serine protease inhibitors (serpins) play crucial roles in tick feeding and pathogen transmission. We demonstrate that Ixodes scapularis (Ixs) nymph tick saliva serpin (S) 41 (IxsS41), secreted by Borrelia burgdorferi (Bb)-infected ticks at high abundance, is involved in regulating tick evasion of host innate immunity and promoting host colonization by Bb. Recombinant (r) proteins were expressed in Pichia pastoris, and substrate hydrolysis assays were used to determine.

ATP-sensitive inward rectifier potassium channels regulate secretion of pro-feeding salivary proteins in the lone star tick (Amblyomma americanum).

Understanding the physiological and molecular regulation of tick feeding is necessary for developing intervention strategies to curb disease transmission by ticks. Pharmacological activation of ATP-gated inward rectifier potassium (K) channels reduced fluid secretion from isolated salivary gland and blood feeding in the lone star tick, Amblyomma americanum, yet the temporal expression pattern of K channel proteins remained unknown. K channels were highly expressed in type II and III acini in off-host stage and early feeding phase ticks, yet expression was reduced in later stages of feeding.

Defining the toxicological profile of 4-hydroxyphenylpyruvate dioxygenase-directed herbicides to Aedes aegypti and Amblyomma americanum.

Inhibitors targeting the 4-hydroxyphenyl pyruvate dioxygenase (HPPD) enzyme are well established herbicides and HPPD is also a primary enzyme within the tyrosine metabolism pathway in hematophagous arthropods, which is an essential metaboilic pathway post-blood feeding to prevent tyrosine-mediated toxicity. The objective of this study was to characterize the toxicity of triketone, pyrazole, pyrazolone, isoxazole, and triazole herbicides that inhibit HPPD to blood-fed mosquitoes and ticks. Topical exposure of nitisinone to blood-fed Aedes aegypti yielded high toxicity with an LD of 3.

Potassium ion channels as a molecular target to reduce virus infection and mortality of honey bee colonies.

Declines in managed honey bee populations are multifactorial but closely associated with reduced virus immunocompetence and thus, mechanisms to enhance immune function are likely to reduce viral infection rates and increase colony viability. However, gaps in knowledge regarding physiological mechanisms or 'druggable' target sites to enhance bee immunocompetence has prevented therapeutics development to reduce virus infection. Our data bridge this knowledge gap by identifying ATP-sensitive inward rectifier potassium (K) channels as a pharmacologically tractable target for reducing virus-mediated mortality and viral replication in bees, as well as increasing an aspect of colony-level immunity.

Bioinsecticidal activity of cajeput oil to pyrethroid-susceptible and -resistant mosquitoes.

Mosquito-borne diseases are a significant threat to human health. The frequent and repetitive application of insecticides can result in the selection of resistant mosquito populations leading to product failures for reducing community disease transmission. It is important that new interventions are discovered and developed for reducing mosquito populations and, in turn, protecting human health.

Functional interactions between potassium-chloride cotransporter (KCC) and inward rectifier potassium (Kir) channels in the insect central nervous system.

The K/Cl cotransporter (KCC) is the primary mechanism by which mature neurons maintain low intracellular chloride (Cl) concentration and has been shown to be functionally coupled to the GABA-gated chloride channels (GGCC) in Drosophila central neurons. Further, pharmacological inhibition of KCC has been shown to lead to acute toxicity of mosquitoes that highlights the toxicological relevance of insect KCC. Yet, gaps in knowledge remain regarding physiological drivers of KCC function and interactions of ion flux mechanisms upstream of GGCC in insects.

Molecular targets of insecticides and herbicides - Are there useful overlaps?

New insecticide modes of action are needed for insecticide resistance management strategies. The number of molecular targets of commercial herbicides and insecticides are fewer than 35 for both. Few commercial insecticide targets are found in plants, but ten targets of commercial herbicides are found in insects.

Acute toxicity of atrazine, alachlor, and chlorpyrifos mixtures to honey bees.

The acute toxicity of chlorpyrifos and chlorpyrifos-oxon (organophosphorothioate insecticides) was examined alone and in combination with atrazine (triazine herbicide) and alachlor (chloroacetanilide herbicide) to honey bees (Apis mellifera). Atrazine and alachlor were observed to not be acutely toxic to bees at doses up to 10 and 4 μg per bee, respectively. However, atrazine significantly increased chlorpyrifos toxicity by 3-fold while reducing chlorpyrifos-oxon toxicity by 1.

Catalyzing systemic movement of inward rectifier potassium channel inhibitors for antifeedant activity against the cotton aphid, Aphis gossypii (Glover).

Background: The cotton aphid, Aphis gossypii Glover (Hemiptera: Aphididae), is a destructive agricultural pest, capable of photosynthate removal and plant virus transmission. Therefore, we aimed to test the antifeedant properties of small-molecule inhibitors of inward rectifier potassium (Kir) channels expressed in insect salivary glands and develop an approach for enabling systemic movement of lipophilic Kir inhibitors.

Results: Two Kir channel inhibitors, VU041 and VU730, reduced the secretory activity of the aphid salivary glands by 3.

Profile of commercialized aphicides on the survivorship and feeding behavior of the cotton aphid, Aphis gossypii.

The cotton aphid, Aphis gossypii Glover (Hemiptera: Aphididae), is one of the most destructive agricultural pests due to photosynthate removal and horizontal transmission of plant viruses. Horizontal transmission of plant viruses by aphids occurs during distinct feeding behavioral events, such as probing for non-persistent viruses or phloem feeding for persistent viruses. We employed toxicity bioassays and electrical penetration graph (EPG) methodology to compare toxicity and quantify changes to feeding behavior and toxicity of A.

Mode of action and toxicological effects of the sesquiterpenoid, nootkatone, in insects.

Nootkatone, a sesquiterpenoid isolated from Alaskan yellow cedar (Cupressus nootkatensis), is known to possess insect repellent and acaricidal properties and has recently been registered for commercial use by the Environmental Protection Agency. Previous studies failed to elucidate the mechanism of action of nootkatone, but we found a molecular overlay of picrotoxinin and nootkatone indicated a high degree of structural and electrostatic similarity. We therefore tested the hypothesis that nootkatone was a GABA-gated chloride channel antagonist, similar to picrotoxinin.

ATP-sensitive inward rectifier potassium channels reveal functional linkage between salivary gland function and blood feeding in the mosquito, Aedes aegypti.

Reducing saliva secretions into the vertebrate host reduces feeding efficacy by most hematophagous arthropods. However, seminal studies suggested saliva is not a prerequisite for blood feeding in Aedes aegypti. To test this paradigm, we manually transected the salivary duct of female A.

Toxicological analysis of stilbenes against the fall armyworm, Spodoptera frugiperda.

The fall armyworm (FAW), Spodoptera frugiperda, is a global pest of multiple economically important row crops and the development of resistance to commercially available insecticidal classes has inhibited FAW control. Thus, there is a need to identify chemical scaffolds that can provide inspiration for the development of novel insecticides for FAW management. This study aimed to assess the sensitivity of central neurons and susceptibility of FAW to chloride channel modulators to establish a platform for repurposing existing insecticides or designing new chemicals capable of controlling FAW.

The Molecular Physiology and Toxicology of Inward Rectifier Potassium Channels in Insects.

Inward rectifier K (Kir) channels have been studied extensively in mammals, where they play critical roles in health and disease. In insects, Kir channels have recently been found to be key regulators of diverse physiological processes in several tissues. The importance of Kir channels in insects has positioned them to serve as emerging targets for the development of insecticides with novel modes of action.

Characterization of Toxicological and Neurophysiological Effects of Natural Product Based Chromenes to Fall Armyworm, Spodoptera frugiperda.

We previously extracted and purified a chromene amide from Amyris texana and found this scaffold is moderately insecticidal and thus, this study aimed to test the insecticidal properties of 13 synthetically derived chromene analogs to the fall armyworm (FAW, Spodoptera frugiperda). Microinjection of chromenes with alcohol or aldehydes substitutions at the meta position on the benzopyran moiety led to moderate toxicity that was approximately 2- to 3-fold less toxic when compared to permethrin, yet microinjection of differently substituted chromenes exhibited little to no toxicity. Similarly, chromenes with alcohol or aldehydes substitutions at the meta position on the benzopyran moiety were among the most toxic chromenes studied through ingested exposure.

Neurochemical regulation of Aedes aegypti salivary gland function.

The salivary gland of hematophagous arthropods is critical for blood meal acquisition, blood vessel localization, and secretion of digestive enzymes. Thus, there is significant interest in the regulation of salivary gland function and mechanisms driving the secretion of saliva and digestive proteins. We aimed to gain a broader understanding of the regulatory role of aminergic, cholinergic, and octopaminergic neuromodulators to saliva and protein secretion from the female A.

Reduced neuronal sensitivity and susceptibility of the fall armyworm, Spodoptera frugiperda, to pyrethroids in the absence of known knockdown mutations.

Neurophysiological recordings were employed to quantify neuronal sensitivity to neurotoxic insecticides and assessed toxicity across field and laboratory fall armyworm (FAW) populations. Topical toxicity resistance ratios (RR) in field-collected FAW was 767-fold compared to laboratory strains and, importantly, a 1750-fold reduction in potency was observed for λ-cyhalothrin in neurophysiological assays. Field collected FAW were found to have a RR of 12 to chlorpyrifos when compared to the susceptible strain and was 8-fold less sensitive in neurophysiological assays.

Comparative effects of technical-grade and formulated chlorantraniliprole to the survivorship and locomotor activity of the honey bee, Apis mellifera (L.).

Background: The loss of honey bee colonies is a nationally recognized problem that demands attention from both the scientific community and the beekeeping industry. One outstanding threat is the unintended exposure of these pollinators to agricultural pesticides. Anthranilic diamides, such as chlorantraniliprole, are registered for use in stone and pome fruits, vegetables, turf, and grains.

Small-Molecule Inhibitors of Inward Rectifier Potassium (Kir) Channels Reduce Bloodmeal Feeding and Have Insecticidal Activity Against the Horn Fly (Diptera: Muscidae).

Bloodmeal feeding by the horn fly, Haematobia irritans (L.), is associated with reduced milk production and blood loss that ultimately prevents weight gain of calves and yearlings. Thus, blood feeding by H.

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.

Perspectives on new strategies for the identification and development of insecticide targets.

The discovery and development of new active ingredients to control arthropod populations and circumvent the inevitable evolution of insecticide resistance has been of consistent interest to the field of insecticide science. This interest has resulted in a slow, but steady increase in the diversity of chemical scaffolds and biochemical target sites within the insecticide arsenal over the past 70 years with growth from three biochemical target sites in the 1950s to 22 distinct biochemical targets in 2018. Despite this growth, the number of biochemical target sites for insecticides remains relatively limited when compared to human pharmaceuticals, which has approximately 700 distinct biochemical targets that are targeted by FDA approved drugs.

Is DEET a dangerous neurotoxicant?

Controversies surrounding the safety of N,N-diethyl-meta-toluamide (DEET) when used as an insect repellent are centered around conflicting findings in the scientific literature and inaccurate reporting in the public media. Lethal cases of DEET poisoning are few, and usually due to deliberate or other overdoses that ignore product label instructions. Deleterious effects of DEET typically involve skin reactions and even when encephalopathies, such as seizures, occur they often abate without sequelae.

Functional Coupling of K-Cl Cotransporter (KCC) to GABA-Gated Cl Channels in the Central Nervous System of Drosophila melanogaster Leads to Altered Drug Sensitivities.

GABAergic signaling is the cornerstone for fast synaptic inhibition of neural signaling in arthropods and mammals and is the molecular target for insecticides and pharmaceuticals, respectively. The K-Cl cotransporter (KCC) is the primary mechanism by which mature neurons maintain low intracellular Cl concentration, yet the fundamental physiology, comparative physiology, and toxicological relevance of insect KCC is understudied. Considering this, we employed electrophysiological, genetic, and pharmacological methods to characterize the physiological underpinnings of KCC function to the Drosophila CNS.