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Item Hepatic and intestinal responses to antibiotic-arsenic driven sepsis(Undergraduate Scholars Program, 2024-04) Rodini, Andreina L.; Wolfe, Trenton M.; Walk, Seth T.Arsenic is a potent group 1 carcinogen and immunosuppressant. Globally, it is estimated that 200 million people are exposed to unsafe levels in their drinking water. Previous work in the Walk lab has established that in murine models the microbiome is required for full protection against arsenicosis as antibiotic perturbation disrupts this protective mechanism. In epidemiological studies of humans, similarly exposed individuals exhibit high interindividual variability in arsenicosis outcome which is not explained by host genetics alone. We have developed a murine model co-exposed to the third-generation cephalosporin antibiotic cefoperazone and inorganic arsenic which recapitulates this interindividual variability. To the best our of knowledge, this is the only whole-organism arsenicosis model that does so. Currently, the reasons behind the interindividual variability in arsenicosis susceptibility remain unclear. However, recent work in our lab has demonstrated that co-exposed mice that succumb to arsenicosis exhibit altered blood chemistry indicative of liver and kidney dysfunction and decreased white blood cell counts indicative of immune dysfunction. Additionally, these sick mice have ceca with gross anatomical features suggestive of infection. In contrast, co-exposed mice that remain healthy exhibit normal blood chemistry and cecal anatomy. These observations suggest that co-exposed mice are succumbing to sepsis, which is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. Current work in our lab is aimed at identifying septic infection through culture-dependent and culture-independent methods, and determining which immune cells are involved.Item Maternal and Pediatric Oral Health: Impact of Social Determinants(Undergraduate Scholars Prorgam, 2024-04) Ludwig, Margaret; Moyce, SallyPrevious research has determined a definitive relationship between maternal oral health and hygiene and pediatric health. This has especially been investigated in the context of pediatric oral health; it has been found that maternal oral health can serve as a direct predictor of whether a child will develop early childhood caries due to colonization of maternal cariogenic bacteria. It has also been shown that maternal oral health can predict whether children will struggle with caries in adulthood. This finding demands the question of how directly maternal oral health predicts pediatric outcomes. How much of an influence does maternal oral health have upon pediatric health and wellbeing, and how influential are social determinants of health upon these outcomes? This project consisted of a comprehensive literature review examining the impact of a mother’s oral health on the overall health of her children. Studies were chosen for review on the basis of their focus upon mothers in the United States, and upon their discussion of social determinants of health which could impact maternal oral health. The findings of this literature review revealed that social determinants of health such as medical inequality, social status, discrimination, income, and education level have the potential to impact maternal oral health and therefore pediatric health. The implications of these findings are broad and could catalyze improvements within healthcare, education, and policy in Montana and across the United States.Item Sulfide oxidation by members of the Sulfolobales(Oxford University Press, 2024-05) Fernandes-Martins, Maria C.; Colman, Daniel R.; Boyd, Eric S.The oxidation of sulfur compounds drives the acidification of geothermal waters. At high temperatures (>80°C) and in acidic conditions (pH <6.0), oxidation of sulfide has historically been considered an abiotic process that generates elemental sulfur (S0) that, in turn, is oxidized by thermoacidophiles of the model archaeal order Sulfolobales to generate sulfuric acid (i.e. sulfate and protons). Here, we describe five new aerobic and autotrophic strains of Sulfolobales comprising two species that were isolated from acidic hot springs in Yellowstone National Park (YNP) and that can use sulfide as an electron donor. These strains significantly accelerated the rate and extent of sulfide oxidation to sulfate relative to abiotic controls, concomitant with production of cells. Yields of sulfide-grown cultures were ∼2-fold greater than those of S0-grown cultures, consistent with thermodynamic calculations indicating more available energy in the former condition than the latter. Homologs of sulfide:quinone oxidoreductase (Sqr) were identified in nearly all Sulfolobales genomes from YNP metagenomes as well as those from other reference Sulfolobales, suggesting a widespread ability to accelerate sulfide oxidation. These observations expand the role of Sulfolobales in the oxidative sulfur cycle, the geobiological feedbacks that drive the formation of acidic hot springs, and landscape evolution.Item Naegleria fowleri Detected in Grand Teton National Park Hot Springs(American Chemical Society, 2024-01) Barnhart, Elliot P.; Kinsey, Stacey M.; Wright, Peter R.; Caldwell, Sara L.; Hill, Vince; Kahler, Amy; Mattioli, Mia; Cornman, Robert S.; Iwanowicz, Deborah; Eddy, Zachary; Halonen, Sandra; Mueller, Rebecca; Peyton, Brent M.; Puzon, Geoffrey J.The free-living thermophilic amoeba Naegleria fowleri (N. fowleri) causes the highly fatal disease primary amoebic meningoencephalitis. The environmental conditions that are favorable to the growth and proliferation of N. fowleri are not well-defined, especially in northern regions of the United States. In this study, we used culture-based methods and multiple molecular approaches to detect and analyzeN. fowleri and other Naegleria spp. in water, sediment, and biofilm samples from five hot spring sites in Grand Teton National Park, Wyoming, U.S.A. These results provide the first detections of N. fowleri in Grand Teton National Park and provide new insights into the distribution of pathogenic N. fowleri and other nonpathogenic Naegleria spp. in natural thermal water systems in northern latitudes.Item Hydrophobic residues in S1 modulate enzymatic function and voltage sensing in voltage-sensing phosphatase(Rockefeller University Press, 2024-05) Rayaprolu, Vamseedhar; Miettinen, Heini M.; Baker, William D.; Young, Victoria C.; Fisher, Matthew; Mueller, Gwendolyn; Rankin, William O.; Kelley, John T.; Ratzan, William J.; Leong, Lee Min; Davisson, Joshua A.; Baker, Bradley J.; Kohout, Susy C.The voltage-sensing domain (VSD) is a four-helix modular protein domain that converts electrical signals into conformational changes, leading to open pores and active enzymes. In most voltage-sensing proteins, the VSDs do not interact with one another, and the S1–S3 helices are considered mainly scaffolding, except in the voltage-sensing phosphatase (VSP) and the proton channel (Hv). To investigate its contribution to VSP function, we mutated four hydrophobic amino acids in S1 to alanine (F127, I131, I134, and L137), individually or in combination. Most of these mutations shifted the voltage dependence of activity to higher voltages; however, not all substrate reactions were the same. The kinetics of enzymatic activity were also altered, with some mutations significantly slowing down dephosphorylation. The voltage dependence of VSD motions was consistently shifted to lower voltages and indicated a second voltage-dependent motion. Additionally, none of the mutations broke the VSP dimer, indicating that the S1 impact could stem from intra- and/or intersubunit interactions. Lastly, when the same mutations were introduced into a genetically encoded voltage indicator, they dramatically altered the optical readings, making some of the kinetics faster and shifting the voltage dependence. These results indicate that the S1 helix in VSP plays a critical role in tuning the enzyme’s conformational response to membrane potential transients and influencing the function of the VSD.