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Research Project: Understanding and Mitigating the Adverse Effects of Poisonous Plants on Livestock Production Systems

Location: Poisonous Plant Research

2014 Annual Report


Objectives
Objective 1: Develop and implement novel management protocols for establishing improved forage species on sites infested with known poisonous plants to reduce the risk of livestock mortality and morbidity, improve livestock performance, and improve rangeland resiliency and diversity. Specifically, develop science-based guidelines for grazing livestock on rangelands infested with Lupinus, Senecio, Delphinium and swainsonine and selenium-containing plants. Objective 2: Reduce the risks of livestock losses due to variations in quantitative and qualitative differences in toxin accumulation over time and plant species by quantifying the influence of endophytes, climate changes, and genotype on plant toxin accumulation (particularly swainsonine-containing plants and Delphinium and Lupinus species). Objective 3: Enhance feed and food safety by improving risk assessment and diagnosis of plant-induced poisoning to livestock by improving analytical methods for analyzing plant and animal tissues for toxins; measuring toxicokinetics, assessing carcinogenic and genotoxic potential, and identifying toxin metabolites and biomarkers of toxicoses. Objective 4: Develop improved procedures with guidelines for diagnostic and prognostic evaluation to reduce negative impacts of poisonous plants on livestock reproduction and embryo/fetal growth by improving early identification of poisoned animals, predicting poisoning outcomes, and management and treatment options through improved understanding of clinical, morphological and molecular alterations of plant-induced toxicosis. Objective 5: Develop guidelines to aid producers and land managers in making genetic-based herd management decisions to improve livestock performance and safety on grazed rangelands infested with poisonous plants through the use of identified animal genes, physiological pathways, and molecular mechanisms of action that underlie Conium, Cicuta, Delphinium, Lupinus, and Nicotiana, and other neurotoxic plant effects.


Approach
Livestock poisoning by plants results in over $503,000,000 lost to the livestock industry annually in the 17 western United States from death losses and abortions alone (Holechek, 2002). Plant poisonings extend worldwide to include 333 million poisonous plant-infested hectares in China and 60 million hectares in the central western region of Brazil, to name a few. There are over 6,000 species of pyrrolizidine alkaloid (PA)-containing plants, and over 350 individual PAs causing diseases in animals and humans have been identified. Economic losses are much larger as significant amounts of nutritious forage are wasted and management costs are increased due to the threat of toxic plant-related livestock losses. The Poisonous Plant Research Laboratory (PPRL) has provided worldwide leadership in poisonous plant research to the livestock industry and consumers including numerous solutions to toxic plant problems using an integrated, interdisciplinary approach (see Figure below). The research team investigates plant poisonings in a systematic matter by identifying the plant, describing the effects in animals, determining the toxin(s) and evaluating the mechanisms of action. The ultimate goal is to develop research-based solutions to reduce livestock losses from toxic plants. There are five coordinated objectives in this project plan providing guidelines for potential genetic-based management. This research will reduce livestock losses from plants and enhance the economic well-being of rural communities, improve rangeland health by combating invasive plant species, and help to provide safe animal products free from potential plant toxins for consumers.


Progress Report
Poisonous plants continue to cause large economic losses to the livestock industry from death losses, birth defects, reduced reproductive performance and lost forage value. Natural toxins may also contaminate human food supplies. ARS researchers at the Poisonous Plant Research Lab (PPRL) in Logan, UT continue to mitigate poisonous plant losses through a concerted interdisciplinary team approach. Five objectives have been defined in the project plan to develop research-based solutions to reduce livestock losses from poisonous plants. Research progress over the last year includes the continued evaluation of improved rangeland grass species and forage Kochia varieties seeded into research, demonstration and ranch scale plots on the channeled scablands of central Washington State. Two improved and one native grass species and one forage Kochia variety successfully established. Current data suggest that annual grass and poisonous plant reinvasion is suppressed where these improved varieties have established. Vavilov II, Hycrest wheat grasses, Sherman Big Blue grass and Immigrant forage Kochia were the most successful species and show promise to establish and provide improved forage quality while successfully competing with cheat grass, medusa head rye and poisonous plants in this harsh environment of the Washington scablands. Analytical methods developed by ARS scientists at PPRL were used to detect pyrrolizidine alkaloids (PAs) in contaminated food and feed supplies. Examples include the continued monitoring of subsistence grain supplies from the Tigray region of Ethiopia, honey and pollen samples from the islands of Hawaii and contaminated chicken feed from Colombia. In addition, the analytical method for detection of pyrrolizidine alkaloid metabolites in liver and blood diagnostic samples was significantly improved and used in the investigation of the relative toxicity of the various alkaloids as tested in a small animal assay model. Significant progress has been made on the NIH funded PA research over the last five years including large scale isolation and purification of epimeric lycopsamine and intermedine and synthesis and purification of their N-oxides. Analytical methods to screen herbal products including comfrey for PAs have been completed. Echimidine was isolated from Echium vulgare and purified and the N-oxide synthesized. Three separate commercial samples of butterbur root powder (Petasites spp.), an herbal remedy, were screened for PAs and one contained two dehydropyrrolizidine alkaloids. Histologic evaluation of PA carcinogenicity studies in P53 heterozygous mice were concluded. Both acute exposures and chronic low dose exposure to riddelliine caused increased incidence of PA-induced neoplasms. The neoplasm type differed by exposure, i.e. chronic low dose exposures produced hepatic vascular neoplasms while acute high dose exposures produced neoplasms outside the hepatic vasculature. This work suggests that any PA exposure can increase the incidence of PA-related carcinogenesis. Studies of the carcinogenic potential of other PAs are currently being evaluated. Additional work using in vitro cell cultures and in vivo models to better document PA toxicity and correlate that toxicity to their carcinogenicity has been extended, and specific PAs have been ranked according to their toxicity to cells. Four PAs—lasiocarpine, seneciophylline, senecionine and heliotridine—are more toxic than riddelliine and will be evaluated for their potential carcinogenicity. A sensitive small animal model for in vivo PA toxicity has been developed. This model has been used to directly compare the toxicity of 20 purified PAs from different plant sources. Initial findings support the cellular toxicity results, indicating that lasiocarpine, seneciophylline, senecionine, heliotridine and monocrotaline are more toxic than riddelliine. This model is important because with relatively small amounts of pure alkaloid and/or their metabolites, comparative toxicity can be evaluated. These methodologies are important to aid in the diagnosis of PA exposure in animals and to determine how metabolite concentrations correlate with disease progression and PA exposure. Research to aid producers and land managers in making genetic-based herd management decisions to improve livestock performance and safety on grazed rangelands infested with poisonous plants has progressed. Animal genes, physiological pathways, and molecular mechanisms of action that underlie the effects of neurotoxic plants such as lupine, larkspurs, and poison hemlock have been identified. Of the cattle breeds tested to date, differences have been identified and Brahman cattle are most sensitive and dairy breeds most resistant. Cell-based assays have been completed to determine the molecular mechanism of the plant neuro toxins and the neuro toxin lamprolobine from lupine was evaluated. A plant extract-based assay to study the action of Cicuta (water hemlock) toxins at the GABAA receptors in the brain was developed. Since the 1900’s tremetone was reported to be the toxin in rayless goldenrod in the Southwest and white snakeroot in the Midwest. Recent chemical studies have isolated and identified many benzofuran ketones including tremetone from these plants. Subsequent animal studies suggest that tremetone is not the primary toxin. Recent studies indicate that other benzofuran ketones act together with tremetone to cause toxicity. Different plant populations with variable benzofuan ketone concentrations are being evaluated to determine why poisoning in animals occurs in some locations while the same or similar plant species in another location may not cause poisoning. Seleniferous forages are toxic to livestock and are suspected to cause decreased reproductive rates in some livestock species. Studies were conducted to determine the effects of high selenium in the diet on reproductive performance. Additional studies were completed to determine the effects of high selenium in the diet on feed preferences of sheep, cattle and elk and to study the rate and processes of elimination of the selenium compounds. Larkspur specific primers have been developed and validated for all the larkspur species in the Intermountain West that have resulted in cattle losses. They have been used to detect larkspur that has been incubated in rumen cultures and in cannulated cows as a potential PCR-based diagnostic tool. A new group of locoweed seedlings has been started to evaluate fungicide applications as a treatment to reduce swainsonine (produced by the endophyte in locoweed plants) and render the plants less toxic. Data analysis has been completed on the effects of elevated CO2 levels on locoweed growth and swainsonine concentrations. In collaboration with researchers at the University of Kentucky and New Mexico State University, research to elucidate the swainsonine biosynthetic pathway in swainsonine-producing endophyte is progressing. Genome sequencing of two swainsonine producing fungal endophytes is underway. In collaboration with researchers at Indiana University, we have screened several Convolvulaceae taxa for swainsonine using herbarium specimens and identified several species that contain swainsonine. Locoweed poisoning was studied in various animal models and we found that huge differences in susceptibility, disease progression, lesions, and lesion distribution exist between animal species. Initial work indicated this is largely due to swainsonine affinity to a species’ mannosidase enzymes. Additional comparisons of mannosidase expression in tissues and correlation of that expression with lesion development are ongoing. Goats and horses are highly susceptible to locoweed poisoning, developing severe neurologic disease. Early reproductive studies in goats determined that the goat fetus is very sensitive to the effects of locoweed, resulting in fetal loss. Comparative studies of species specific locoweed-induced ophthalmic lesions have been completed and we found that locoweed blindness was due to neurological lesions and not lesions in the eye. Studies were conducted to determine if co-exposure of cattle to death camas will exacerbate low larkspur toxicity. Samples of bark and needles were collected from young and mature juniper trees to determine if there is a difference in the concentration of the abortifacient compounds between and young and mature trees. Additionally, samples of bark and needles have been collected bi-monthly for two years to evaluate seasonal variations in the abortifacient compounds in western juniper trees.


Accomplishments
1. Reduction in annual grass and poisonous plant invasion. Annual grasses have extensively invaded the rangelands of the channeled scablands of central Washington State which are already infested with lupines. When the grasses dry out in early summer, lupines become the preferred forage, exacerbating lupine-induced “crooked calf syndrome”. ARS scientists from Logan, Utah established small plots on the channeled scablands of central Washington State to determine which grass species is best adapted for this harsh environment and if forage Kochia would grow in this area. Data suggest that Vavilov II, Hycrest and Sherman Big Blue are the grasses most likely to germinate and establish, and demonstration and range scale plots were planted. Immigrant Kochia germinated and established over a three year period on the demonstration and range scale plots. Preliminary information suggests that these improved perennial grasses and forage Kochia will germinate, persist in the short term (three years to date) and reduce the re-invasion of the annual grasses and poisonous plants to provide an improved forage base for livestock and wildlife.

2. Pyrrolizidine alkaloids (PAs) found in honey and eggs. Pyrrolizidine alkaloid (PAs) exposure in humans is most often via contamination of a primary food source such as in grains. The potential for long term, low level exposure in foods, including pollen and honey as well as eggs, milk and perhaps meat, is unknown. ARS scientists in Logan, Utah provided analytical support for two studies. Significant concentrations of PAs were detected in experimental hives near fields infested with fireweed. No PAs were detected in honey and pollen from hives physically isolated from fireweed-contaminated fields. Secondly, ARS scientists in cooperation with the National University of Colombia investigated the effect of dietary supplementation of chicken feed with Crotalaria seeds during a 35 day feeding of commercial laying hens. Eggs collected during the 35 days of the treatment feedings were found to contain significant concentrations of PAs with decreased concentrations within seven days after removal of the contaminated feed. Information from this research is being used to direct the agriculture industries to avoid PA contamination of food supplies.

3. Discovery of pyrrolizidine alkaloids (PAs) in herbal products (NIH funded project). ARS scientists at Logan, Utah completed large scale isolation of two important PAs (lycopsamine and intermedine) found in animal feeds and herbal products. Echimidine, a PA found in Symphytum uplandicum (comfrey), was isolated from Echium vulgare (Paterson's curse). Samples of three commercial herbal products of butterbur root powder (Petasites spp.) have been analyzed for dehydropyrrolizidine alkaloids and one showed the presence of two PAs, senecionine and integerrimine. The screening and analytical methods developed will be standardized and provided for reference labs around the world to monitor safety of herbal products and food sources.

4. Pyrrolizidine alkaloid (PA) may cause an increased risk of cancer. PAs often contaminate feed, food, and medicinal or herbal products, poisoning livestock, wildlife and humans. Several PAs have been linked with cancer but only one, riddelliine, has been officially classified as a potential human carcinogen. ARS scientists at Logan, UT showed that both high-dose, short exposure and chronic, low-dose exposure increased the incidence of PA-induced tumors. The type of tumor differed by exposure. Acute high dose exposures produced many tumors in the liver and chronic low dose exposures produce tumors in the blood vessels of the liver. This work is important as it indicates that any PA exposure can increase the incidence of PA-related cancers.

5. Toxicity of pyrrolizidine alkaloids (PAs) in liver cell cultures. ARS scientists at Logan, Utah developed cell cultures and animal models to better document PA toxicity and correlate toxicity with cancer formation. Specific PAs were ranked according to their toxicity to cells. Four PAs—lasiocarpine, seneciophylline, senecionine and heliotridine—are more toxic than riddelliine. As the mechanisms of toxicity and cancer induction are probably similar, these four PAs are likely to cause liver cancer, similar to riddelliine, and they should be further evaluated to determine their potential to cause cancer. This information is critical for making science based decisions about the safety of herbal products and certain food sources.

6. Effects of plant toxins on the nervous system and muscle function. Plants containing toxins that affect the nervous system are commonly found on open rangelands where livestock can be poisoned when they consume too much of these plants. A significant clinical sign observed in livestock poisoned by these plants is the disruption of coordinated muscle function. ARS scientists at Logan, Utah characterized the muscle function and coordination deficiencies that occur upon exposure to a non-lethal dose of several plant toxins. Experiments using rodent models provided valuable information regarding the acute toxicity of these plants and identifying their toxins. ARS scientists found that animals which survive poisoning episodes from neurotoxic plant alkaloids will fully recover without lasting muscular dysfunction or coordination deficits. The results obtained from these studies provide a basic understanding of acute toxicity and adverse effects, including motor function and coordination, of specific toxins. This information is used to better design experiments using livestock species to help in providing management recommendations to livestock producers, extension agents, and government regulatory agencies.

7. Blood profiles of several plant toxins. The metabolism, rate of absorption, and elimination (toxicokinetics) of plant toxins in livestock is often unknown. ARS scientists at Logan, Utah characterized the blood profiles of numerous toxins from several plants that cause significant livestock losses. The blood profiles were shown to correlate directly with physiologic changes in livestock. The blood profile of the larkspur alkaloids was compared between susceptible and resistant breeds of cattle, which may be a factor in the differences in susceptibility to larkspur poisoning. This research provides important data regarding feed safety for animals as well as food safety for humans. Knowledge of the absorption and elimination of plant toxins in animals provides the necessary information for ARS scientists to develop safe grazing practices and pasture rotations to ensure that animal losses are minimized as they better understand how long these toxins remain in the animals. This information helps to ensure that livestock exposed to poisonous plants are safe for human consumption. It also provides livestock owners, extension agents, and veterinarians with valuable information regarding management and treatment of intoxicated animals (for example, how soon they can safely move an intoxicated animal to safe pastures).

8. The genetic association of resistance to plant toxins in cattle. The selection of genetically superior cattle for grazing on rangelands is important because losses from toxic plants such as larkspur and lupine cost ranchers millions of dollars each year. ARS scientists at Logan, Utah have identified both breed-associated and individual differences in resistance to intoxication. ARS researchers are currently identifying resistant Angus and susceptible Hereford steers with the Illumina BovineHD Genotyping platform to identify genetic markers for resistance to plant toxins. This research will ultimately result in genetic markers that can be used to make genetic-based herd management decisions.

9. Identification of cattle gene markers for resistance to lupine-induced birth defects. There are differences in the rates of lupine toxin elimination between individuals and breeds of cattle. ARS scientists at Logan, Utah have shown that selected dairy breeds eliminate larkspur toxins faster than selected beef breeds and there is individual animal to animal variation within each breed as well as breed differences. This research determined the elimination rates of four lupine toxins from velvet lupine orally dosed to four Holstein steers as an initial step to identify why certain animals are resistant to lupine poisoning. ARS scientists determined that dairy breeds are inherently more resistant to plant toxins that affect the nervous system than beef breeds. This research will be important in selection of cattle for replacements and bulls for herd sires.

10. Individual animal variation in the susceptibility to larkspur toxins. Research by ARS scientists at Logan, Utah demonstrated that there is variation in the susceptibility to larkspur toxins between different strains of mice. Using mice as a model system for cattle, several potential susceptibility factors were identified that could explain the differences in susceptibility of the different strains of mice to larkspur poisoning. Studies determined that genetically engineered mice lacking a specific gene receptor are not more resistant to larkspur poisoning, indicating that this receptor (alpha 7) does not play an integral role in the acute toxic effect of larkspur. However, several other potential genetic markers have been identified which will provide the basis for future experiments to identify genetic factors that correlate with sensitivity to larkspur poisoning in cattle. Once this research is validated in cattle, this knowledge will provide livestock producers with specific information that will be useful in breeding, culling, and grazing management programs to reduce or prevent larkspur poisoning on rangelands.

11. Characterization of pine needle-induced late term abortions in cattle. ARS scientists at Logan, Utah discovered that cattle pre-conditioned to ponderosa pine needles metabolize the abortifacient toxins in the needles more quickly than naïve cattle. Additionally, they demonstrated that western juniper trees can also cause late term abortions in cattle. Research into the effects of western juniper exposure on reproduction demonstrated that western juniper does not affect the reproductive cycle of cattle nor their ability to become pregnant. The results from this work provide an increased knowledge and understanding regarding the ability of pine and juniper trees to cause late-term abortions as well as differences between naïve and conditioned cattle in their susceptibility to the adverse outcomes, e.g., abortions. This information is useful in further developing livestock management recommendations for ranchers. Government action agencies, extension agents, veterinarians, and livestock owners can use this information in formulating management recommendations and procedures regarding the grazing of cattle on rangelands with pine and juniper trees to limit reproductive losses.

12. Evaluation of co-exposure of multiple poisonous plants in animals. In most cases where livestock are poisoned by plants on rangelands, they are grazing on multiple species of poisonous plants. Two poisonous plants often found growing simultaneously in the same area are death camas and low larkspur. ARS scientists at Logan, Utah demonstrated that the co-administration of toxins from death camas and low larkspur have an additive effect (they both contribute to the toxicity), resulting in enhanced toxicity in a rodent model. However, similar experiments performed in sheep support previous findings that sheep are resistant to larkspur poisoning. Thus co-exposure of low larkspur does not enhance toxicity of death camas in sheep. These results provide an increased knowledge and understanding regarding the acute toxicity of death camas and risk of co-exposure of multiple plant toxins. This information is useful in developing livestock management recommendations for ranchers. Government action agencies, extension agents, veterinarians, and livestock owners can use this information in formulating management recommendations and procedures regarding the grazing of cattle in larkspur and death camas-infested rangelands.

13. Survey of Palicourea plants in South America for the toxin monofluoroacetate (MFA). The genus Palicourea represents one of the most important poisonous plants in Brazil. Two species of Palicourea cause sudden death and contain MFA. ARS scientists at Logan, Utah developed a rapid method to analyze MFA and used it to screen herbarium specimens of 46 Palicourea species from South America. Ten species of Palicourea were identified that contained MFA, two previously reported and eight newly reported. This research impacts livestock production systems in South America as it provides a representative list of Palicourea species that contain MFA and thus pose a risk to grazing livestock.

14. Chemistry of plant toxins with unique structures. ARS scientists at Logan, Utah developed cell-based assays for the evaluation of toxins that occur in plants as right and left handed pairs. There is a difference in activity depending on which of the pairs is dominant in the plant. The results from this research suggest that it is the concentration of each toxin present in the plant that determines toxicity, not just total toxin concentration. Prior to this work, livestock management decisions were based on total toxin concentrations and ignored the presence and impact of these pairs of toxins which vary from plant population to plant population. This information will enhance current risk assessment by scientists and land managers to reduce livestock losses from these plants. If land managers do not consider the ratio of each toxin when developing management plans, then the toxicity of a plant population may be underestimated.

15. Determination of the toxins in rayless goldenrod and white snakeroot. ARS scientists at Logan, Utah demonstrated that the toxic component in rayless goldenrod and white snakeroot is a mixture of toxins and not a single toxin as historically thought. These plants continue to poison animals and pose a risk of contaminating milk in the Southwest and Midwest. This information is important when assessing the risk of plant populations and diagnosing cases of livestock poisoning.

16. Excess selenium decreases reproductive rates in sheep. ARS scientists at Logan, Utah completed pen studies that determined a 20 to 40% decrease in pregnancy rates in ewes fed high selenium forages for three weeks before being exposed to rams. This information is beneficial to manage sheep grazing on selenium contaminated ranges so that producers can maximize the reproductive efficiency of their flocks.

17. Locoweed poisoning in goats and other species. Locoweed poisoning costs the livestock industry millions of dollars each year. ARS scientists at Logan, Utah determined there are substantial animal differences in locoweed-induced disease, lesions and subsequent costs. An early indicator of poisoning in pregnant animals is fetal toxicity and fetal loss. This research demonstrates that all livestock species are at risk; however, horses and goats are extremely sensitive and should not be allowed to graze in pastures where any level of locoweed is found.

18. Locoweed-induced eye pathology. Locoweed poisoning in cattle and other livestock has historically been associated with dull, glassy appearing eyes, and there are some reports of blindness. ARS scientists at Logan, Utah found that in horses, cows, sheep and goats; locoweed poisoning does not cause true blindness. Eye examinations of these animals are normal including normal reflexes. However the tear ducts showed abnormal changes in all four species and the tear production in poisoned horses was about 50% below normal. Visible mucous strands were often observed. This indicates that the dull appearing eyes of poisoned animals is due to changes in tear duct secretion and the tear film. Poisoned animals are not truly blind but the reported “blindness” behavior is most likely due to the effects of locoweed poisoning on the brain.

19. Wild parsnip causes sunburn and inflammation to the skin. Wild parsnip (Pastinaca sativa) is a biennial introduced weed that is often associated with sunburn of livestock and humans. ARS scientists at Logan, Utah found that parsnip toxins are quickly excreted in the urine by cattle, sheep and goats. Generally, sunburn is due to repeated exposures to the photo-active toxins on the skin such as what happens in walking through or grazing in patches of wild parsnip. Reports of skin inflammation in horses fed parsnip contaminated hay suggests its metabolism in horses may be different than in cattle. This research is only preliminary and more work is needed to better define these differences.


Review Publications
Adrien, M.L., Riet-Correa, G., Oliveira, C.A., Pfister, J.A., Cook, D., Souza, E.G., Riet-Correa, F., Schild, A.L. 2013. Conditioned food aversion to Ipomoea carnea var. fistulosa induced by Baccharis coridifolia in goats. Pesquisa Veterinaria Brasileira. 33(8):999-1003.
Albuquerque, S.S., Rocha, B.P., Almeida, V.M., Oliveira, J.S., Riet-Correa, F., Lee, S.T., Neto, J.E., Mendoca, F.S. 2014. Cardiac fibrosis associated to the poisoning of Amorimia septentrionalis in cattle. Pesquisa Veterinaria Brasileira. 34(5):433-437.
Almeida, M.B., Schild, A.L., Pfister, J.A., Assis-Brasil, N.D., Pimental, M., Forster, K.M., Riet-Correa, F. 2013. Methods of inducing conditioned food aversion to Baccharis coridifolia (mio-mio) in cattle. Electronic Publication. 43(10):1866-1871.
Beck, J.J., Mahoney, N.E., Cook, D., Gee, W.S., Baig, N. 2014. Comparison of the volatile emission profiles of ground almond and pistachio mummies: part 1 – addressing a gap in knowledge of current attractants of navel orangeworm. Phytochemistry Letters. 9:102-106. DOI.10.1016/j.phytol.2014.04.010.
Becker, M., Caldeira, F.H., Carneiro, F.M., Oliveira, L.P., Tokarnia, C.H., Riet-Correa, F., Lee, S.T., Colodel, E.M. 2013. Epidemiological aspects of field intoxication by Amorimia pubiflora (Malpighiaceae) in cattle in Mato Grosso and experimental reproduction of intoxication in cattle and sheep. Pesquisa Veterinaria Brasileira. 33(9):1049-1056.
Colegate, S.M., Welsh, S.L., Gardner, D.R., Betz, J.M., Panter, K.E. 2014. Profiling of dehydropyrrolizidine alkaloids and their N-oxides in herbarium-preserved specimens of Amsinckia species using HPLC-esi(+)MS. Journal of Agricultural and Food Chemistry. 62(30):7382-7392.
Cook, D., Gardner, D.R., Pfister, J.A. 2014. Swainsonine-containing plants and their relationship to endophytic fungi. Journal of Agricultural and Food Chemistry. 62(30):7326-7334.
Cook, D., Lee, S.T., Taylor, C.M., Bassuner, B., Riet-Correa, F., Pfister, J.A., Gardner, D.R. 2014. Detection of toxic monofluoroacetate in Palicourea species. Toxicon. 80:9-16.
Dale, L.M., Thewis, A., Boudry, C., Rotar, I., Pacurar, F.S., Abbas, O., Dardenne, P., Baeten, V., Pfister, J.A., Fernandez Pierna, J.A. 2013. Discrimination of grassland species and their classification in botanical families by laboratory scale hyperspectral imaging NIR: preliminary results. Talanta. 116:149-154.
Davis, T.Z., Green, B.T., Stegelmeier, B.L., Lee, S.T., Welch, K.D., Pfister, J.A. 2013. Physiological and serum biochemical changes associated with rayless goldenrod (Isocoma pluriflora) poisoning in goats. Toxicon. 76:247-254.
Davis, T.Z., Stegelmeier, B.L., Green, B.T., Welch, K.D., Hall, J.O. 2013. Evaluation of the respiratory elimination kinetics of selenate and Se-methylselenocysteine after oral administration in lambs. Research in Veterinary Science. 95(3):1163-1168.
Davis, T.Z., Stegelmeier, B.L., Hall, J.O. 2014. Analysis in horse hair as a means of evaluating selenium toxicoses and long-term exposures. Journal of Agricultural and Food Chemistry. 62(30):7393-7397.
Davis, T.Z., Stegelmeier, B.L., Lee, S.T., Green, B.T., Hall, J.O. 2013. Experimental rayless goldenrod (Isocoma pluriflora) toxicosis in horses. Toxicon. 73:88-95.
Davis, T.Z., Stegelmeier, B.L., Welch, K.D., Pfister, J.A., Panter, K.E., Hall, J.O. 2013. Comparative oral dose toxicokinetics of selenium compounds commonly found in selenium accumulator plants. Journal of Animal Science. 91(9):4501-4509.
Duarte, A.L., Medeiros, R.M., Carvalho, F.K., Lee, S.T., Cook, D., Pfister, J.A., Costa, V.M., Riet-Correa, F. 2014. Induction and transfer of resistance to poisoning by Amorimia (Macagnia) septentrionalis in goats. Journal of Applied Toxicology. 34(2):220-223.
Gardner, D.R., Riet-Correa, F., Lemos, D., Welch, K.D., Pfister, J.A., Panter, K.E. 2014. Teratogenic effects of Mimosa tenuiflora in a rat model and possible role of N-methyl and N,N-dimethyltryptamine. Journal of Agricultural and Food Chemistry. 62(30):7398-7401.
Green, B.T., Lee, S.T., Welch, K.D., Panter, K.E. 2013. Plant alkaloids that cause developmental defects through the disruption of cholinergic neurotransmission. Birth Defects Research Part C: Embryo Today: Reviews. 99:235-246.
Green, B.T., Welch, K.D., Gardner, D.R., Stegelmeier, B.L., Lee, S.T. 2013. A toxicokinetic comparison of two species of low larkspur (Delphinium spp.) in cattle. Research in Veterinary Science. 95(2):612-615.
Green, B.T., Welch, K.D., Panter, K.E., Lee, S.T. 2013. Plant toxins that affect nicotinic acetylcholine receptors: A review. Chemical Research in Toxicology. 26(8):1129-1138.
Green, B.T., Welch, K.D., Pfister, J.A., Chitko-Mckown, C.G., Gardner, D.R., Panter, K.E. 2014. Mitigation of larkspur poisoning on rangelands through the selection of cattle. Rangelands. 36(1):10-15.
Grum, D.S., Cook, D., Baucom, D., Mott, I.W., Gardner, D.R., Creamer, R., Allen, J.G. 2013. Production of the alkaloid swainsonine by a fungal endophyte in the host Swainsona canescens. Journal of Natural Products. 76(10):1984-1988.
Irwin, R.E., Cook, D., Richardson, L.L., Manson, J.S., Gardner, D.R. 2014. Secondary compounds in floral rewards of toxic rangeland plants: Impacts on pollinators. Journal of Agricultural and Food Chemistry. 62(30):7335-7344.
Porto, M.R., Saturnino, K.C., Lima, E.M., Lee, S.T., Lemos, R.A., Marcolongo-Pereira, C., Riet-Correa, F., Castro, M.B. 2013. Evaluation of solar exposure on the experimental intoxication by Brachiaria decumbens in sheep. Pesquisa Veterinaria Brasileira. 33(8):1009-1015.
Latorre, A.O., Caniceiro, B.D., Fukumasu, H., Gardner, D.R., Lopes, F.M., Wyospchi Jr, H.L., Da Silva, T.C., Haraguchi, M., Bressan, F.F., Gorniak, S.L. 2013. Ptaquiloside reduces NK cell activities by enhancing metallothionein expression, which is prevented by selenium. Toxicology. 304:100-108.
Lee, S.T., Cook, D., Molyneux, R.J. 2014. Identification of the quinolizidine alkaloids in Sophora leachiana. Biochemical Systematics and Ecology. 54:1-4.
Lee, S.T., Cook, D., Pfister, J.A., Allen, J.G., Colegate, S.M., Riet-Correa, F., Taylor, C.M. 2014. Monofluoroacetate-containing plants that are potentially toxic to livestock. Journal of Agricultural and Food Chemistry. 62(30):7345-7354.
Lee, S.T., Welch, K.D., Panter, K.E., Gardner, D.R., Garrossian, M., Chang, C.T. 2014. Cyclopamine: From cyclops lambs to cancer treatment. Journal of Agricultural and Food Chemistry. 62(30):7355-7362.
Lima, F.G., Haraguchi, M., Pfister, J.A., Guimaraes, V.Y., Andrade, D.D., Ribeiro, C.S., Costa, G.L., Araujo, A.L., Fioravanti, M.C. 2013. Weather and plant age affect the levels of steroidal saponin and Pithomyces chartarum spores in Brachiaria grass. International Journal of Poisonous Plant Research. 2:45-53.
Maia, L.A., De Lucena, R.B., Da T Nobre, V.M., Dantas, A.F., Colegate, S.M., Riet-Correa, F. 2013. Natural and experimental poisoning of goats with the pyrrolizidine alkaloid-producing plant Crotalaria retusa L. Journal of Veterinary Diagnostic Investigation. 25(5):592-595.
Manson, J.S., Cook, D., Gardner, D.R., Irwin, R.E. 2013. Dose-dependent effects of nectar alkaloids in a montane plant-pollinator community. Journal of Ecology. 1001:1604-1612.
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