Differentiation among the North American Triatominae Species (Vectors of the Chagas Disease Parasite) and Their Commonly Misidentified Doppelgängers

Chagas disease is increasingly recognized as a major public health concern in the United States. The disease is caused by infection with the protozoan parasite Trypanosoma cruzi, which is spread by blood-sucking insects commonly referred to as kissing bugs (Reduviidae: Triatominae). Limited outreach and educational resources are available regarding Chagas disease for the public and medical or veterinary practitioners that may encounter infected patients. A key challenge, especially in outreach and public health awareness, is differentiating the kissing bug vectors from common look-alike insects that do not feed on blood and do not pose a risk of T. cruzi transmission. The presence of these look-alikes, or Doppelgängers, is associated with both psychological and economic consequences, as they cause needless worry among the public and encounters with these insects have led to unwarranted human and canine blood testing for Chagas disease. In my thesis, I developed outreach materials suitable for use by the lay public as well as veterinarians, medical doctors, pest control operators, public health officials, and others to facilitate the identification of kissing bugs. First, I created identification and pictorial guides to North American Triatominae species and their common look-alikes, including a step-by-step dichotomous key to differentiate key anatomical features useful in discriminating species. Next, I developed a process for manufacturing resin-embedded kissing bugs and look-alike species resulting in high quality products that are safe to handle; these specimens will be long-lasting and valuable in outreach programs to show differences in size, shape, and color that photos alone cannot detai

INDIVIDUAL VARIATION IN WINTER BROOK TROUT (SALVELINUS FONTINALIS) MOVEMENT IN A SMALL NORTHERN MICHIGAN STREAM

Winter is a time of year of low temperatures and limited food availability. Brook trout (Salvelinus fontinalis) survival in winter is dependent on several factors including their condition after spawning in the fall and possibly their behavior in winter. Ice that forms during winter can potentially aid in survival by decreasing predation risk, decreasing stress, and acting as a thermal refuge. The emphasis of this project was to evaluate the relationship between movement patterns of brook trout and winter ice distribution. In the fall of 2017 and again in the fall of 2018, brook trout in a northern Michigan stream were collected by electroshocking. All fish had their length and weight measured, and fish over 100 mm were tagged with a Passive Integrated Transponder (PIT). Following tagging, fish were tracked and their locations within the field site were recorded as well as if they were in open water or under ice cover. In the spring of 2018 and 2019, electroshocking surveys were performed again, and tagged fish were measured for length and weight. Tracking surveys occurred biweekly and showed that brook trout used ice covered areas. Two movement groups were present, a sedentary group consisting of 90% of fish and a mobile group consisting of 10%. Surface covering ice was used by fish throughout all stages of winter. Recaptured brook trout did not demonstrate any statistically significant change in their Fulton’s condition factor. These results highlight the importance of specific surface cover during winter to brook trout behavior and their movement during winter

No. 1 - Legal Systems in Transition

A January 24-28, 2000 visit by Justice Ivana Janu, Dean Josef Bejcek, and some of the Czech colleagues to the Dean Rusk Center and the University of Georgia provided an occasion for the exchange of ideas concerning transition in the legal structure and content in the former Socialist states of central and eastern Europe. Justice Janu and Dean Bejcek prepared papers and agreed to their publication. The availability of these two important papers, one on constitutional courts and the other on transitions in commercial law, rendered to the Rusk Center the necessary impetus for the creation of the Occasional Papers Series

Mechanistic and Synthetic Studies of Oxidopyrylium Cycloaddition Reactions

Cycloaddition chemistry has historically served as a robust route to stereo-rich and highly functionalized cyclic and heterocyclic compounds. Herein we describe our examination of 3-hydroxy-4-pyrone-derived oxidopyrylium cycloadditions in both mechanistic considerations as well as the unique synthetic advancements of their corresponding cycloadducts. Chapter 1 is a literature review where we specifically outline the use of oxidopyrylium cycloadditions in the synthesis of natural products. This includes the mention of previous syntheses prior to 2008, and a more thorough examination of the natural products synthesized from 2008 to present. The work exploits this chemistry as a facile route to highly complex 7-membered natural products, among other unique structures. In Chapter 2, we look closer into the dimerization of the reactive intermediate in these cycloadditions, the oxidopyrylium ylide, and factors to which it is influenced by. Previously our lab found that 3-hydroxy-4-pyrone-derived dimers can be used as ylide surrogates in cycloaddition reactions. We found through kinetic and computational work that this was occurring via full reversibility of the dimer to the reactive ylide. In addition, the studies show that the methyl placement on isomers, maltol and allo maltol-derived ylides, substantially influences reactivity’s observed in both their dimerization and cycloaddition pathways. Due to steric factors, maltol-derived ylides were shown to have a higher energy barriers to dimerization, making it possible to trap out the ylide rapidly with electrophilic dipolarophiles. Allo maltol-derived ylides have lower energy barriers to dimerization, making trapping capabilities less efficient. We then showed that maltol-derived cycloadducts, to whose synthetic utility is not well known, undergoes rapid regiodivergent acid-mediated ring contraction cascades to guaiacol derivatives. These studies expanded upon the current known utility of 3-hydroxy-4-pyrone derived oxidopyrylium cycloadditions. In Chapter 3 we continued to expand upon the synthetic utility of 3-hydroxy-4-pyrone derived cycloadducts by developing a route to 2-methoxytropones via a samarium iodide- mediated reductive ring opening approach. Previously, our lab had primarily explored acid-mediated approaches to biologically active highly oxygenated tropolones. However, the reductive ring opening provided a facile route to a novel A-C colchicine analog. Additionally, the A-C analog synthesized was shown to be highly atropisomerically stable, with computed energy barriers to rotation of greater than 35 kcal/mol, that was also supported experimentally. Biological assay data showed one atropisomer to be biologically active with a GI50 value of 0.4 micromolar, and was approximately 10 fold more potent than its enantiomer. This methodology is currently being applied to the synthesis of alternative analogs as well as in the total synthesis of colchicine

Autocrine PDGF stimulation in malignancies

Platelet-derived growth factor (PDGF) isoforms are important mitogens for different types of mesenchymal cells, which have important functions during the embryonal development and in the adult during wound healing and tissue homeostasis. In tumors, PDGF isoforms are often over-expressed and contribute to the growth of both normal and malignant cells. This review focuses on tumors expressing PDGF isoforms together with their tyrosine kinase receptors, thus resulting in autocrine stimulation of growth and survival. Patients with such tumors could benefit from treatment with inhibitors of either PDGF or PDGF receptors

Differentiation among the North American Triatominae Species (Vectors of the Chagas Disease Parasite) and Their Commonly Misidentified Doppelgängers

Chagas disease is increasingly recognized as a major public health concern in the United States. The disease is caused by infection with the protozoan parasite Trypanosoma cruzi, which is spread by blood-sucking insects commonly referred to as kissing bugs (Reduviidae: Triatominae). Limited outreach and educational resources are available regarding Chagas disease for the public and medical or veterinary practitioners that may encounter infected patients. A key challenge, especially in outreach and public health awareness, is differentiating the kissing bug vectors from common look-alike insects that do not feed on blood and do not pose a risk of T. cruzi transmission. The presence of these look-alikes, or Doppelgängers, is associated with both psychological and economic consequences, as they cause needless worry among the public and encounters with these insects have led to unwarranted human and canine blood testing for Chagas disease. In my thesis, I developed outreach materials suitable for use by the lay public as well as veterinarians, medical doctors, pest control operators, public health officials, and others to facilitate the identification of kissing bugs. First, I created identification and pictorial guides to North American Triatominae species and their common look-alikes, including a step-by-step dichotomous key to differentiate key anatomical features useful in discriminating species. Next, I developed a process for manufacturing resin-embedded kissing bugs and look-alike species resulting in high quality products that are safe to handle; these specimens will be long-lasting and valuable in outreach programs to show differences in size, shape, and color that photos alone cannot detai