RNAi: Applications in Vertebrate Pest Management

Sequence-directed inhibition of protein synthesis by RNAi has potential as a means to control pest wildlife. Species specific by design, RNAi reduces impacts on nontarget species and the environment. Additional research advancing the field of RNAi-based management of vertebrate pest wildlife is timely. Despite the potential diverse applications of RNAi technology in vertebrates (fertility control, invasive species eradication, and pest species control to protect human health and agriculture), little progress has been made in applying RNAi to these classes of animals. A single proof-of-concept study using RNAi to control sea lampreys combined with recent advances in RNAi delivery have opened the door to numerous innovative applications of this technology in vertebrate management [12]. One of the hurdles to further development of RNAi in vertebrates will be delivery. To facilitate widespread use of RNAi-based products, oral baits will likely be necessary. Delivering RNAi orally will face many challenges, including protection from the hostile conditions in the gastrointestinal tract (GI), uptake into the systemic circulation, and shuttling the RNAi to the site of action. Research in nanotechnology has led to the development of numerous different nanoparticles that have been shown to facilitate effective oral delivery and GI uptake [13]. Other scientists are making progress tackling cellular delivery and internalization using cell-penetrating peptides [14]. Continued research in delivery, in vivo shuttling, and cell penetration will be imperative for the success of RNAi technology in vertebrate pest management applications. Because they are species-specific by design, RNAi-based products reduce risks to nontarget organisms, enabling them to be used broadly across landscapes, even in ecosystems that historically have been avoided because of environmental concerns. However, the small segments of nucleotides that make up RNAi molecules may still be recognized as foreign by both target and nontarget animals, thereby eliciting an immune response. These possible immune adverse effects of RNAi will need to be considered during RNAi development. Advances have been made toward reducing immune activation but continued research is important to ensure low risks to nontarget species [15]. Another benefit of interfering RNA is that it does not involve modification of the genome and consequently is not heritable; therefore, it is free from the controversy surrounding gene drives. Continued research in RNAi will provide breakthrough advancements in tools to control animal species protecting human health, agriculture, and infrastructure. Their use on the landscape level will require careful development of baits that retain activity through exposure to the conditions of the GI tract and are stable in harsh environmental conditions of varying temperature, humidity, and UV exposure

Macrophage migration inhibitory factor: controller of systemic inflammation

Macrophage migration inhibitory factor (MIF) is a cytokine that is secreted by the anterior pituitary and immune cells in response to surgical stress, injury, and sepsis. This cytokine appears to be a critical regulator of the inflammatory pathways, leading to systemic inflammatory response syndrome and subsequent multiple organ dysfunction syndrome. This report provides an integrated scheme describing the manner by which MIF controls the neurohormonal response and the adaptive immune system, namely the T-helper (Th)1 and Th2 lymphocytes, which results in the release of pro-inflammatory cytokines and the anti-inflammatory cytokine interleukin-10. The development of systemic inflammatory response syndrome and subsequent development of multiple organ dysfunction syndrome appear to be related to MIF levels and the balance of Th1 and Th2 function

Assessment of zinc phosphide bait shyness and tools for reducing flavor aversions

Prairie voles (Microtus ochrogaster Wagner) cause extensive damage in agricultural, suburban, and urban environments. Control of these animals has historically relied on the use of anticoagulant rodenticides and zinc phosphide. However, shyness to zinc phosphide baits has reduced its efficacy. The aim of this study was to evaluate the factors involved in zinc phosphide bait shyness through preference testing. Baits were made using a rolled oat base and contained various combinations of the components of zinc phosphide baits such as lecithin, magnesium carbonate and known flavor modulators sodium cyclamate and zinc sulfate. Encapsulation of zinc phosphide was also tested as a potential means to mask undesirable flavor qualities of the compound. Consumption of test baits was measured in four day laboratory feeding trials. Results demonstrated that numerous components of current bait formulations serve as salient cues during conditioned aversions and therefore may contribute to bait shyness. Vole avoidance of zinc sulfate and sodium cyclamate revealed that these potential additives would not decrease bait shyness. Encapsulation of zinc phosphide may have masked some of the negative flavor cues and therefore should be considered in future bait development. This study suggests that, since voles are able to distinguish components of current bait formulations, varying composition of zinc phosphide baits between applications may serve to reduce bait shyness

Pharmacokinetics of Anticoagulant Rodenticides in Target and Non-target Organisms

The concentration of a compound at the site of action is a determinant of its toxicity. This principle is affected by a variety of factors including the chemical properties of the compound (pKa, lipophilicity, molecular size), receptor binding affinity, route of exposure, and physiological properties of the organism. Many compounds have to undergo chemical changes, biotransformation, into more toxic or less toxic forms. Because of all of these variables, predicting toxic effects and performing risk assessments of compounds based solely on dose are less accurate than those that include data on absorption, distribution, metabolism (biotransformation), and excretion of the compound. These factors are commonly referred to as ADME. The quantitative study of these properties is called pharmacokinetics and often encompasses the determination of compound concentrations in tissues of interest including blood and the time course of absorption, metabolism, and excretion. A goal of pharmacokinetics is an understanding of the relationship between dose and the concentration of the active compound at the target site. Toxicokinetics is a “unique expansion of pharmacokinetics”, with doses being much greater than those in pharmacokinetic studies (Welling 1995). This is a complicated task, especially for anticoagulant rodenticides (ARs), as exposure (dose) frequently occurs over multiple days and can result from consumption of poisoned animals containing varying concentration of ARs and their metabolites, not simply a toxic bait

Environmental Contaminant Concentrations in Canada Goose (\u3ci\u3eBranta canadensis\u3c/i\u3e) Muscle: Probabilistic Risk Assessment for Human Consumers

The issue of food insecurity affects millions of people in the United States every year. Often these people rely on soup kitchens, food banks, and shelters for proper meals, and these organizations often depend on donations to meet needs. One of the most limited food resources is meat. To help alleviate this problem, the U.S. Department of Agriculture Wildlife Services donates more than 60 tons of wild game (deer, moose, feral hogs, goats, geese, and ducks) to a variety of charitable organizations each year. Although commercially produced meat routinely undergoes screening for contaminants, potential exposure to environmental contaminants from eating wild game is not well characterized. In this study, the concentration of 17 contaminants of concern in the breast meat of wild geese was examined. These concentrations were then used in a probabilistic model to estimate potential risk associated with consumption of this meat. Based on model predictions, more than 99% of all adults were below exposure limits for all of the compounds tested. For all consumer age classes modeled, consumption of wild goose meat may expose a small fraction of these populations to levels of lead higher than the recommended exposure limits. Similarly, mercury exposure was predicted to be higher than the recommended limits when the meat was served as steaks. This information about concentrations of contaminants of concern in goose meat and potential exposures associated with meat consumption based on probabilistic models will enable others to make informed decisions about the risks associated with the consumption of wild meat

Environmental Contaminant Concentrations in Canada Goose (\u3ci\u3eBranta canadensis\u3c/i\u3e) Muscle: Probabilistic Risk Assessment for Human Consumers

The issue of food insecurity affects millions of people in the United States every year. Often these people rely on soup kitchens, food banks, and shelters for proper meals, and these organizations often depend on donations to meet needs. One of the most limited food resources is meat. To help alleviate this problem, the U.S. Department of Agriculture Wildlife Services donates more than 60 tons of wild game (deer, moose, feral hogs, goats, geese, and ducks) to a variety of charitable organizations each year. Although commercially produced meat routinely undergoes screening for contaminants, potential exposure to environmental contaminants from eating wild game is not well characterized. In this study, the concentration of 17 contaminants of concern in the breast meat of wild geese was examined. These concentrations were then used in a probabilistic model to estimate potential risk associated with consumption of this meat. Based on model predictions, more than 99% of all adults were below exposure limits for all of the compounds tested. For all consumer age classes modeled, consumption of wild goose meat may expose a small fraction of these populations to levels of lead higher than the recommended exposure limits. Similarly, mercury exposure was predicted to be higher than the recommended limits when the meat was served as steaks. This information about concentrations of contaminants of concern in goose meat and potential exposures associated with meat consumption based on probabilistic models will enable others to make informed decisions about the risks associated with the consumption of wild meat

A probabilistic approach to detect structural problems in flexible pavement sections at network level assessment

Presently, most of the road agencies use Non-Destructive (NDT) tools to help them prioritise pavement maintenance and rehabilitation (M&R) activities at the network level, thus optimising the limited budgetary resources. One of the most widely used NDT techniques for pavement structural evaluations, at the network level assessment, is the Falling Weight Deflectometer (FWD). Using a database comprising of a wide array of typical layer moduli and thicknesses of traditional flexible pavements, that were generated based on multiple Monte Carlo numerical simulations, as a reference datum, this study successfully developed probabilistic models that allow for analysing the condition of a flexible pavement, at the network level, from FWD surface deflection data, namely the Deflection Bowl Parameters (DBPs), to identify which layers of the pavement structure present a probability of structural failure or damage

Effects of Repeated Sublethal External Exposure to Deep Water Horizon Oil on the Avian Metabolome

We assessed adverse effects of external sublethal exposure of Deepwater Horizon, Mississippi Canyon 252 oil on plasma and liver metabolome profiles of the double-crested cormorant (Phalacrocorax auritus), a large (1.5 to 3.0 kg) diving waterbird common in the Gulf of Mexico. Metabolomics analysis of avian plasma showed significant negative effects on avian metabolic profiles, in some cases after only two external exposures (26 g cumulative) to oil. We observed significant (p \u3c 0.05) changes in intermediate metabolites of energy metabolism and fatty acid and amino acid metabolic pathways in cormorants after repeated exposure to oil. Exposure to oil increased several metabolites (glycine, betaine, serine and methionine) that are essential to the one-carbon metabolism pathway. Lipid metabolism was affected, causing an increase in production of ketone bodies, suggesting lipids were used as an alternative energy source for energy production in oil exposed birds. In addition, metabolites associated with hepatic bile acid metabolism were affected by oil exposure which was correlated with changes observed in bile acids in exposed birds. These changes at the most basic level of phenotypic expression caused by sublethal exposure to oil can have effects that would be detrimental to reproduction, migration, and survival in avian species

Comparative Toxicity of Diphacinone to Northern Bobwhite (\u3ci\u3eColinus virginianus\u3c/i\u3e) and American Kestrels (\u3ci\u3eFalco sparverius\u3c/i\u3e)

The acute oral toxicity of the anticoagulant rodenticide diphacinone was found to be about 20 times greater to American kestrels (LD50=97 mg/kg) than to northern bobwhite (LD50=2,014 mg/kg). Several precise and sensitive clotting assays (prothrombin time, Russell’s Viper venom time, thrombin clotting time) were adapted for use in these species, and this combination of assays is recommended to detect effects of diphacinone and other rodenticides on coagulation. Oral administration of diphacinone over a range of doses (sublethal to the extrapolated LD15) prolonged prothrombin time and Russell’s Viper venom time within 24 to 48 hrs post-exposure. Prolongation of in vitro clotting time reflects impaired coagulation complex activity and was detected before or at the onset of overt signs of toxicity and lethality. These data will assist in the development of a pharmacodynamic model to assess and predict rodenticide toxicity to non-target avian species