Establishing Influence and Authority in Ancient Civilizations and Modern Politics: The Rhetoric of Oracles and the Oracular Maneuvers of Political Action Committees

While most animals communicate in order to convey environmental information such as danger or where food is located, humans have evolved and developed an articulated language for a myriad of uses, and our language is the basis for how we shape and maintain reality. Language can be used to teach, express an attitude or affiliation to a group, and give us a sense of our state of being, but it can also be used to manipulate a narrative in order to gain power over others. This project argues that Political Action Committees (PACs), and the language that they use in advertising for or against a candidate or legislation, function as modern-day oracles in that they use language to obtain authority and power. In many ancient and archaic societies oracles were considered authoritative and trusted voices, and, therefore, were able to have a substantial influence on the culture in which they operated; oracles were instrumental in providing information on the best course of action to take in one’s life, where a government should send a colony, and they had the ability to keep widespread empires working toward the same objectives. Like oracles, PACs can influence what course of action a voter might take, or influence how the government operates, and even influence how groups of like-minded people, separated by distance and time, work toward the same objectives. PACs, therefore, can be seen to have similar functions in our modern culture as oracles had in their own cultures

Characterization of the sporozoite and eythrocytic stages (SES) protein

The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file.Vita."December 2007"Thesis (Ph. D.) University of Missouri-Columbia 2007.The Plasmodium sporozoite is infective for mosquito salivary glands and vertebrate host tissues. Although it is a key developmental stage of the malaria parasite, relatively few sporozoite surface or secreted proteins have been identified and characterized. A novel surface molecule, designated the Sporozoite and Erythrocytic Stage (SES) protein, is preferentially-expressed in salivary gland sporozoites versus oocyst and hemolymph sporozoites of Plasmodium gallinaceum. PgSES exhibits a spiral surface labeling pattern that overlays a known sporozoite surface antigen, the circumsporozoite protein, with only minor co-localization. It consists of 551 amino acids encoding a putative 63.2 kDa protein that has been shown to be expressed not only on particular sporozoite stages, but also during the erythrocytic stages. This novel protein has three conserved regions of unknown function that are present in eight Plasmodium spp. representing human, avian, non-human primate, and rodent malarias. Antibody blocking studies assessing the role of PgSES in sporozoite invasion of mosquito salivary glands show that anti-PgSES antibodies block invasion by 49-87%. The Plasmodium falciparum homolog, PfSES, also appears to have expression during the sporozoite and erythrocytic stages. Additional studies assessing the function of both PgSES and PfSES in the sporozoite and erythrocytic stages are being conducted. Ultimately, if the SES protein is found to be critical to parasite development and/or invasion of host tissues, it could be a target for novel malaria intervention efforts.Includes bibliographical reference

Effects of Artesunate on Parasite Recrudescence and Dormancy in the Rodent Malaria Model Plasmodium vinckei

Artemisinin (ART) is the recommended first line therapy for treating uncomplicated and drug-resistant Plasmodium falciparum, the most pathogenic form of malaria. However, treatment failure following ART monotherapy is not uncommon and resistance to this rapidly acting drug has been reported in the Thai-Cambodian border. Recent in vitro studies have shown that following treatment with dihydroartemisinin (DHA), the development of ring-stage parasites is arrested for up to 20 days. These arrested (i.e. dormant) rings could be responsible for the recrudescence of infection that is observed following ART monotherapy. To develop a better understanding of the stage-specific effects of ART and determine if dormancy occurs in vivo, the ART derivative artesunate (AS) was used to treat mice infected with the synchronous rodent malaria parasites P. vinckei petteri (non-lethal) and P. v. vinckei (lethal). Results show that in both the non-lethal and lethal strains, ring-stage parasites are the least susceptible to treatment with AS and that the day of treatment has more of an impact on recrudescence than the total dose administered. Additionally, 24 hrs post-treatment with AS, dormant forms similar in morphology to those seen in vitro were observed. Finally, rate of recrudescence studies suggest that there is a positive correlation between the number of dormant parasites present and when recrudescence occurs in the vertebrate host. Collectively, these data suggest that dormancy occurs in vivo and contributes to recrudescence that is observed following AS treatment. It is possible that this may represent a novel mechanism of parasite survival following treatment with AS

Transcript and protein expression profile of PF11_0394, a Plasmodium falciparum protein expressed in salivary gland sporozoites

<p>Abstract</p> <p>Background</p> <p><it>Plasmodium falciparum </it>malaria is a significant problem around the world today, thus there is still a need for new control methods to be developed. Because the sporozoite displays dual infectivity for both the mosquito salivary glands and vertebrate host tissue, it is a good target for vaccine development.</p> <p>Methods</p> <p>The <it>P. falciparum </it>gene, <it>PF11_0394</it>, was chosen as a candidate for study due to its potential role in the invasion of host tissues. This gene, which was selected using a data mining approach from PlasmoDB, is expressed both at the transcriptional and protein levels in sporozoites and likely encodes a putative surface protein. Using reverse transcription-polymerase chain reaction (RT-PCR) and green fluorescent protein (GFP)-trafficking studies, a transcript and protein expression profile of PF11_0394 was determined.</p> <p>Results</p> <p>The PF11_0394 protein has orthologs in other <it>Plasmodium </it>species and Apicomplexans, but none outside of the group Apicomplexa. <it>PF11_0394 </it>transcript was found to be present during both the sporozoite and erythrocytic stages of the parasite life cycle, but no transcript was detected during axenic exoerythrocytic stages. Despite the presence of transcript throughout several life cycle stages, the PF11_0394 protein was only detected in salivary gland sporozoites.</p> <p>Conclusions</p> <p>PF11_0394 appears to be a protein uniquely detected in salivary gland sporozoites. Even though a specific function of PF11_0394 has not been determined in <it>P. falciparum </it>biology, it could be another candidate for a new vaccine.</p

Pharmacokinetic modelling of the anti-malarial drug artesunate and its active metabolite dihydroartemisinin

A four compartment mechanistic mathematical model is developed for the pharmacokinetics of the commonly used anti-malarial drug artesunate and its principle metabolite dihydroartemisinin following oral administration of artesunate. The model is structurally unidentifiable unless additional constraints are imposed. Combinations of mechanistically derived constraints are considered to assess their effects on structural identifiability and on model fits. Certain combinations of the constraints give rise to locally or globally identifiable model structures. Initial validation of the model under various combinations of the constraints leading to identifiable model structures was performed against a dataset of artesunate and dihydroartemisinin concentration–time profiles of 19 malaria patients. When all the discussed constraints were imposed on the model, the resulting globally identifiable model structure was found to fit reasonably well to those patients with normal drug absorption profiles. However, there is wide variability in the fitted parameters and further investigation is warranted

Dengue Outbreak Response During COVID-19 Pandemic, Key Largo, Florida, USA, 2020

We report a dengue outbreak in Key Largo, Florida, USA, from February through August 2020, during the COVID-19 pandemic. Successful community engagement resulted in 61% of case-patients self-reporting. We also describe COVID-19 pandemic effects on the dengue outbreak investigation and the need to increase clinician awareness of dengue testing recommendations

The Cinderella syndrome:why do malaria-infected cells burst at midnight?

An interesting quirk of many malaria infections is that all parasites within a host-millions of them-progress through their cell cycle synchronously. This surprising coordination has long been recognized, yet there is little understanding of what controls it or why it has evolved. Interestingly, the conventional explanation for coordinated development in other parasite species does not seem to apply here. We argue that for malaria parasites, a critical question has yet to be answered: is the coordination due to parasites bursting at the same time or at a particular time? We explicitly delineate these fundamentally different scenarios, possible underlying mechanistic explanations and evolutionary drivers, and discuss the existing corroborating data and key evidence needed to solve this evolutionary mystery. © 2012 Elsevier Ltd

Exoerythrocytic Plasmodium Parasites Secrete a Cysteine Protease Inhibitor Involved in Sporozoite Invasion and Capable of Blocking Cell Death of Host Hepatocytes

Plasmodium parasites must control cysteine protease activity that is critical for hepatocyte invasion by sporozoites, liver stage development, host cell survival and merozoite liberation. Here we show that exoerythrocytic P. berghei parasites express a potent cysteine protease inhibitor (PbICP, P. berghei inhibitor of cysteine proteases). We provide evidence that it has an important function in sporozoite invasion and is capable of blocking hepatocyte cell death. Pre-incubation with specific anti-PbICP antiserum significantly decreased the ability of sporozoites to infect hepatocytes and expression of PbICP in mammalian cells protects them against peroxide- and camptothecin-induced cell death. PbICP is secreted by sporozoites prior to and after hepatocyte invasion, localizes to the parasitophorous vacuole as well as to the parasite cytoplasm in the schizont stage and is released into the host cell cytoplasm at the end of the liver stage. Like its homolog falstatin/PfICP in P. falciparum, PbICP consists of a classical N-terminal signal peptide, a long N-terminal extension region and a chagasin-like C-terminal domain. In exoerythrocytic parasites, PbICP is posttranslationally processed, leading to liberation of the C-terminal chagasin-like domain. Biochemical analysis has revealed that both full-length PbICP and the truncated C-terminal domain are very potent inhibitors of cathepsin L-like host and parasite cysteine proteases. The results presented in this study suggest that the inhibitor plays an important role in sporozoite invasion of host cells and in parasite survival during liver stage development by inhibiting host cell proteases involved in programmed cell death