Proceedings for the 10th International Symposium on Poisonous Plants (ISOPP).

The 10th International Symposium on Poisonous Plants (ISOPP) was held on September 16-20, 2018 at the Red Lion Conference Center in St. George, Utah, USA. The meeting was truly international with 55 attendees from across the globe. The attendees were a diverse mix of research scientists, academicians, students, veterinarians, private industry representatives, extension agents and government regulators. Dr. Joseph Betz, Acting Director of the Office of Dietary Supplements at the National Institutes of Health, was the plenary speaker for the symposium, wherein he spoke regarding the safety of botanical supplements. There were six sessions of oral presentations including sessions on Global Perspectives on Poisonous Plants, Natural Toxins and the Systems They Affect, Emerging Poisonous Plant Problems, Diagnostics, and Advances in Research. Two posters sessions provided a great opportunity for interaction and discussion. The highlight of the meeting was an evening banquet whereupon Drs. Anthony Knight, Kip Panter, Steven Colegate, and Franklin Riet-Correa were honored with the ISOPP Lifetime Achievement Award. These four individuals dedicated their scientific careers to studying poisonous plants. They were also key players in many of the previous ISOPPs. There was also time for networking and socializing during a bus tour of Southern Utah / Northern Arizona to observe the natural plant communities in these areas as well as during a Dutch oven dessert social one evening. We are already looking forward to the next ISOPP, which is going to be held at the veterinary school campus in Lyon, France in July of 2021 or 2022. Stay tuned for further developments. We hope to see you all there

Herbicide Control of Broom Snakeweed (Gutierrezia sarothrae)

Broom snakeweed (Gutierrezia sarothrae [Pursh] Britton & Rusby) is a native invasive species that is widely distributed across western North America. It is very competitive with other vegetation and can reduce or displace desirable grasses and forbs. Removal of snakeweed from rangelands can result in increased forage production of desirable plant species. The evaluation of new herbicides to determine their efficacy in controlling broom snakeweed assists in providing land managers with alternatives to control broom snakeweed. The objective of this study was to evaluate herbicides applied in the spring to determine efficacy of control of broom snakeweed. 2,4-D + triclopyr had the greatest reduction in snakeweed density at 97 ± 14.6 % (P \u3c 0.0001). Aminopyralid and 2,4-D were also effective at reducing snakeweed density at 73 ± 14.6 % control. Our results demonstrate that 2,4-D + triclopyr, a new herbicide, can be used in controlling broom snakeweed in the spring

Broom Snakeweed Extracts Dosed to Late-Term Pregnant Cattle Do Not Cause Premature Parturition

Broom snakeweed [Gutierrezia sarothrae (Pursh) Britton and Rusby] and threadleaf snakeweed [G. microcephala (DC.) A. Gray] are found on many rangelands in western North America. Snakeweeds are generally unpalatable; however, animals will graze them when other forage is not available and there are field reports that pregnant cows that graze snakeweeds may abort calves. Subsequent feeding studies using fresh cut snakeweed, ground and gavaged into pregnant cattle have failed to reproduce abortions, though it was evident that at high doses snakeweed quickly damaged the rumen microflora resulting in severe rumen atony, bloating and acidosis. We report here an attempt to solvent extract the snakeweeds, mix the extracts with ground alfalfa hay, and test the extracts for abortifacient activity in late-term pregnant cattle. The dosed extracts again appear to be unable to reproduce snakeweed induced abortions in cattle. Extracts from snakeweed chemotype 1 plant appear to be quite toxic to the rumen and caused complete rumen stasis after 2-3 days. In contrast, cattle receiving chemotype 2 extracts were able to tolerate over twice the dosage as that given for chemotype 1 extracts. We conclude that broom snakeweed plants are unlikely to be directly responsible for cattle abortions observed in cattle grazing snakeweed infested rangelands. It is more likely that cattle may be affected by rumen toxicity and/or might suffer from poor nutritional factors given the lack of quality forage that might be available on rangelands with high snakeweed infestation

Evasion of autophagy mediated by Rickettsia surface protein OmpB is critical for virulence.

Rickettsia are obligate intracellular bacteria that evade antimicrobial autophagy in the host cell cytosol by unknown mechanisms. Other cytosolic pathogens block different steps of autophagy targeting, including the initial step of polyubiquitin-coat formation. One mechanism of evasion is to mobilize actin to the bacterial surface. Here, we show that actin mobilization is insufficient to block autophagy recognition of the pathogen Rickettsia parkeri. Instead, R. parkeri employs outer membrane protein B (OmpB) to block ubiquitylation of the bacterial surface proteins, including OmpA, and subsequent recognition by autophagy receptors. OmpB is also required for the formation of a capsule-like layer. Although OmpB is dispensable for bacterial growth in endothelial cells, it is essential for R. parkeri to block autophagy in macrophages and to colonize mice because of its ability to promote autophagy evasion in immune cells. Our results indicate that OmpB acts as a protective shield to obstruct autophagy recognition, thereby revealing a distinctive bacterial mechanism to evade antimicrobial autophagy

Embryotoxic Effects of Three Natural Occurring \u3cem\u3eVeratrum\u3c/em\u3e Alkaloids and One Synthetic Analog using In Vitro Produced Bovine Embryos

Three natural occurring plant toxins from Veratrum californicum and one related synthetic analog were screened for embryotoxicity using in vitro bovine embryo production techniques. Bovine oocytes were aspirated from ovaries collected from a local abattoir and embryos were generated through in vitro maturation (IVM) and in vitro culture (IVC) procedures. The three natural steroidal alkaloids, cyclopamine, jervine and veratramine and the synthetic steroidal derivative of cyclopamine, cyclopamine-4-en-3-one, were added to IVM and IVC media at 12 μM. Oocytes were exposed to the toxins during maturation (IVM) and pre-implantation embryo during culture (IVC). Cleavage rates and embryo growth (morula and blastocyst production) and development through the hatched blastocyst stage were evaluated. Cyclopamine and cyclopamine-4-en-3-one inhibited cleavage rates and embryo growth and development of morulae and blastocysts in culture. Oocytes that were exposed to cyclopamine and cyclopamine-4-en-3-one during IVM only showed reduced cleavage rates and resulted in lower numbers of embryos that developed to the morula, blastocyst, and hatched blastocyst stages. The effects of these steroidal alkaloids on the oocyte during IVM and on the embryo during all stages of development up to and including the hatched blastocyst stage, demonstrates a dramatic cytotoxic effect on oocytes maturation and early pre-implantation embryos. This research also suggests that the Hedgehog signaling pathway may play a role in the maturing oocyte as well as the pre-implantation embryo. These in vitro fertilization techniques provide an economical, rapid through put and effective method to screen natural toxins, especially suspected reproductive toxins for cytotoxicity

An Evaluation of the Susceptibility of Goats to Larkspur Toxicosis

Larkspurs (Delphinium spp.) are a major cause of cattle losses in western North America, whereas sheep have been shown to be resistant to larkspur toxicosis. Goats are often used as a small ruminant model to study poisonous plants, even though they can be more resistant to some poisonous plants. It is not known how susceptible goats are to the adverse effects of larkspurs. In this study, we evaluated the susceptibility of goats to larkspur toxicosis by performing a dose-response study. We dosed goats with D. barbeyi collected near Cedar City, Utah at 3.3, 4.4, 6.6, 8.8 and 10.0 g plant material per kg body weight. None of the goats, at any of the doses, exhibited clinical signs typical of larkspur poisoning, including no observable muscle weakness. We conclude that goats are resistant to larkspur toxicosis, and thus it is very unlikely that goats would be poisoned by larkspur

Comparison of Sheep and Goats to the Acute Toxic Effects of Foothill Death Camas

Death camas (Zigadenus spp) is a perennial forb found throughout the western United States, which is known to kill both sheep and cattle. In a previous study, goats appeared to be somewhat resistant to the adverse effects of death camas. Therefore, the objective of this study was to directly compare the susceptibility of goats and sheep to the acute toxic effects of death camas. Sheep and goats were dosed at 0.5, 1.0, 2.0, 4.0, and 6.0 g death camas per kg BW. The data presented in this manuscript suggest that goats are more susceptible to death camas than sheep. There were no differences in the serum concentrations of zygadenine in sheep versus goats. There was a difference between goats and sheep in the severity of observed clinical signs of poisoning. This is highlighted by the fact that five goats from the two highest doses died, whereas none of the sheep died. Consequently, when grazing goats in death camas infested pastures as much caution, if not more, should be taken than one would with sheep. Additionally, the data presented in the study suggests that goats can be used as a small ruminant model to study the toxic effects of death camas

Neurobehavioral Evaluation of Mice Dosed With Water Hemlock Green Seeds and Tubers

Water hemlock are plants of the genus Cicuta and are toxic to animals and humans. The primary toxin is cicutoxin, which is abundant in the tubers, but less abundant in other parts of the plant. Other cicutoxin-like compounds, such as cicutols, which may also contribute to the toxicity of water hemlock, are more abundant in non-tuber plant parts. The objective of this study was to determine the toxicity of different parts of water hemlock and characterize their effects on motor function/coordination in mice. An aqueous extract of green seeds, dry seeds, tubers, flowers and stems of water hemlock was dosed orally to mice to determine their acute toxicity. The results indicated that only the green seeds and tubers were sufficiently toxic to animals to induce seizures and death. The LD50 for tubers and green seeds was 17 mg/kg and 1320 mg/kg, respectively. Several tests were used to evaluate motor function and behavior in treated mice including rotarod, tremor monitor, and open field. The animals were evaluated before dosing and 30, 90, 120, 150, 180, 240, and 300 min after dosing. Water hemlock affected muscle function of mice, including their balance and motility on a rotarod, motor activity, and exploratory and anxiety-related (i.e., thigmotaxis) behaviors in an open field. Seizures interspersed with central nervous system (CNS) motor depression were observed in animals poisoned by water hemlock. Extracts from tubers were especially potent in causing a decrease in motor activity and resultant depression, while periodically provoking seizures. Further research is needed to identify, quantitate, and purify cicutoxin and the other polyacetylene compounds from the various water hemlock plant parts to evaluate their toxicity and effects on motor function

Functional Glycosylation of Dystroglycan Is Crucial for Thymocyte Development in the Mouse

BACKGROUND: Alpha-dystroglycan (alpha-DG) is a cell surface receptor providing a molecular link between the extracellular matrix (ECM) and the actin-based cytoskeleton. During its biosynthesis, alpha-DG undergoes specific and unusual O-glycosylation crucial for its function as a high-affinity cellular receptor for ECM proteins. METHODOLOGY/PRINCIPAL FINDINGS: We report that expression of functionally glycosylated alpha-DG during thymic development is tightly regulated in developing T cells and largely confined to CD4(-)CD8(-) double negative (DN) thymocytes. Ablation of DG in T cells had no effect on proliferation, migration or effector function but did reduce the size of the thymus due to a significant loss in absolute numbers of thymocytes. While numbers of DN thymocytes appeared normal, a marked reduction in CD4(+)CD8(+) double positive (DP) thymocytes occurred. In the periphery mature naïve T cells deficient in DG showed both normal proliferation in response to allogeneic cells and normal migration, effector and memory T cell function when tested in acute infection of mice with either lymphocytic choriomeningitis virus (LCMV) or influenza virus. CONCLUSIONS/SIGNIFICANCE: Our study demonstrates that DG function is modulated by glycosylation during T cell development in vivo and that DG is essential for normal development and differentiation of T cells

Mechanisms of breast cancer metastasis

Invasive breast cancer tends to metastasize to lymph nodes and systemic sites. The management of metastasis has evolved by focusing on controlling the growth of the disease in the breast/chest wall, and at metastatic sites, initially by surgery alone, then by a combination of surgery with radiation, and later by adding systemic treatments in the form of chemotherapy, hormone manipulation, targeted therapy, immunotherapy and other treatments aimed at inhibiting the proliferation of cancer cells. It would be valuable for us to know how breast cancer metastasizes; such knowledge would likely encourage the development of therapies that focus on mechanisms of metastasis and might even allow us to avoid toxic therapies that are currently used for this disease. For example, if we had a drug that targeted a gene that is critical for metastasis, we might even be able to cure a vast majority of patients with breast cancer. By bringing together scientists with expertise in molecular aspects of breast cancer metastasis, and those with expertise in the mechanical aspects of metastasis, this paper probes interesting aspects of the metastasis cascade, further enlightening us in our efforts to improve the outcome from breast cancer treatments