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Towards A Better Understanding Of The Effects Of Praziquantel On The Interaction Between The Helminth Parasite Schistosoma Mansoni And Its Murine Host, Melissa C. Sanchez
Towards A Better Understanding Of The Effects Of Praziquantel On The Interaction Between The Helminth Parasite Schistosoma Mansoni And Its Murine Host, Melissa C. Sanchez
Biology ETDs
Schistosomiasis is a neglected tropical disease (NTD) that infects 206 million individuals worldwide. This disease is caused by dioecious trematodes of the genus Schistosoma, and its pathology is associated with the large number of eggs that are released by the female. Entrapped eggs lead to host immune and inflammatory responses resulting in disease progression. Chemotherapy provides the main means of control and praziquantel (PZQ) is the only widely available drug that is used in all mass drug administration (MDA) programs. As the number of individuals receiving PZQ continues to grow, the development of PZQ resistance is a concern and …
Structure-Activity Profiling Of Alkaloid Natural Product Pharmacophores Against A Schistosoma Serotonin Receptor, Jonathan S. Marchant, Wayne W. Harding, John D. Chan
Structure-Activity Profiling Of Alkaloid Natural Product Pharmacophores Against A Schistosoma Serotonin Receptor, Jonathan S. Marchant, Wayne W. Harding, John D. Chan
Publications and Research
Serotonin (5-HT) is an important regulator of numerous aspects of flatworm biology, ranging from neuromuscularfunctionto sexualmaturationandegglaying. Intheparasiticblood flukeSchistosomamansoni,5-HTtargets several G-protein coupled receptors (GPCRs), one of which has been demonstrated to couple to cAMP and regulate parasite movement. This receptor, Sm.5HTRL, has been successfully co-expressed in mammalian cells alongside a luminescent cAMP-biosensor, enabling pharmacological profiling for candidate anti-schistosomal drugs. Here, we have utilized this assay to perform structure-activity investigations of 143 compounds containing previously identified alkaloid natural product pharmacophores (tryptamines, aporphines and protoberberines) shown to regulate Sm.5HTRL. These experiments mapped regions of the tryptamine pharmacophore amenable and intolerant to substitution, highlighting …
Hemocyanin-Like 1 Protein, Unique To Planorbid Snails, Supports Reproductive Output Of Biomphalaria Glabrata, Vector Of Schistosomiasis, Janeth Pena
Biology ETDs
The Neotropical freshwater snail, Biomphalaria glabrata is a major intermediate host of the parasite Schistosoma mansoni, causative agent of human intestinal schistosomiasis. Disease control efforts consist mainly of mass drug treatment but it is recognized that targeting of the snail vector is essential to prevent parasite transmission that leads to rapid (re)infections. This dissertation combines the knowledge of basic snail biology with modern molecular techniques including protein analysis, next-generation sequencing, proteomics, qRT-PCR and RNA interference to: (1) characterize hemocyanin-like genes in B. glabrata, in particular with further description of the egg mass fluid (EMF) protein hemocyanin-like 1 (Hcl-1), (2) …
Revealing Biotic Diversity: How Do Complex Environments Influence Human Schistosomiasis In A Hyperendemic Area, Martina R. Laidemitt
Revealing Biotic Diversity: How Do Complex Environments Influence Human Schistosomiasis In A Hyperendemic Area, Martina R. Laidemitt
Biology ETDs
Human schistosomiasis is one of the great neglected tropical diseases (NTDs) of our time with more than 206 million individuals infected and more than 90% of those infected reside in Sub-Saharan Africa (WHO 2017). Chemotherapy based control programs play an essential role in contributing to the elimination of human schistosomiasis; however, there is an increasing consensus that chemotherapy needs to be supplemented by other means if interruption of transmission and elimination are to be achieved. Given this situation, the focus of this dissertation was to better understand transmission dynamics in a hyperendemic setting in western Kenya and to find alternative …
Global Health And Societal Impacts Of Schistosomiasis, William Ryan
Global Health And Societal Impacts Of Schistosomiasis, William Ryan
Theses and Graduate Projects
Schistosomiasis, a parasitic infection, is classified as a Neglected Tropical Disease (NTD). While there are many NTDs that impact poor people across the world, schistosomiasis is one of the most prevalent. Currently 200 million people worldwide are infected with schistosomiasis and 800 million more are at risk for infection. Like other NTDs, this infection is preventable and treatable. Mass drug administration of the anti-parasitic drug praziquantel (the only drug available to treat schistosomiasis) is currently the main method of control. Although, China has recently demonstrated success by employing strategies that involve controlling the infection in the livestock population. Epidemiological surveys …