Physical Sciences and Mathematics Commons^™

Biomolecular Function From Structural Snapshots, Roshanak Etemadpour

Theses and Dissertations

Biological molecules can assume a continuous range of conformations during function. Near equilibrium, the Boltzmann relation connects a particular conformation's free energy to the conformation's occupation probability, thus giving rise to one or more energy landscapes. Biomolecular function proceeds along minimum-energy pathways on such landscapes. Consequently, a comprehensive understanding of biomolecular function often involves the determination of the free-energy landscapes and the identification of functionally relevant minimum-energy conformational paths on these landscapes. Specific techniques are necessary to determine continuous conformational spectra and identify functionally relevant conformational trajectories from a collection of raw single-particle snapshots from, e.g. cryogenic electron microscopy (cryo-EM) …

Nutrient Dynamics Of Freshwater Estuarine Sediments Disturbed By Dredging, Ryan Allan John Roekle

Theses and Dissertations

This study examined the nutrient environment of sediments in the Milwaukee River estuary and the dynamics of those nutrients during simulated disturbance experiments within the context of large-scale dredging remediation. Surface sediments were collected from throughout the Milwaukee estuary (including river, harbor, and nearshore stations) by PONAR, centrifuged to separate porewater (interstitial water) from solid material, and filtered to further isolate and stabilize dissolved material. Porewaters were analyzed for dissolved nutrients including ammoniacal nitrogen (AN), nitrate, nitrite, and soluble reactive phosphorus (SRP). Surface sediment porewaters within the estuary were often highly enriched in AN and SRP, which were often 10-2000x …

Impact Of The Pre-A Motif On Truncated Hemoglobin N Activity, Alexander Shayne Drena

Theses and Dissertations

Tuberculosis (TB) remains the leading cause of death by an infectious agent and therefore a global health crisis, according to the most recent report by the World Health Organization. This is due, in part, to Mycobacterium tuberculosis’ impressive defensive mechanisms against immune response, as well as the rise of Multi-Drug Resistant strains that have recently developed. Towards the turn of the century, a small heme protein called truncated hemoglobin N (trHbN) was discovered to protect the bacteria against reactive nitrogen species by converting nitric oxide (NO) to nitrate at rates far exceeding those of myoglobin and closer to those of …

Estimating Energy Cost Of Physical Activities From Video Using 3d-Cnn Networks, Pragya Shrestha Chansi

Theses and Dissertations

This research proposes a machine learning model that can estimate the energy cost of physical activities from video input. Currently, wearable sensors are commonly used for this purpose, but they have limitations in terms of practicality and accuracy. A deep learning model using three dimensional convolutional neural network (3D-CNN) architecture was used to process the video data and predict the energy cost in terms of metabolic equivalents (METs). The proposed model was evaluated on a dataset of physical activity videos and achieved an average accuracy of 71% on energy category prediction task and an root mean squared error (RMSE) of …

Influence Of Nutrients And The Native On E. Coli Survival In The Beach Environment, Brigid Meyers

Theses and Dissertations

E. coli is used as an indicator for water quality to determine if water poses a health risk for pathogens. Past research has shown that E. coli is present in high numbers in freshwater beach sands distinct from fecal pollution events, yet the precise mechanism for their persistence in not well understood. Persistent E. coli populations in sand can resuspend into adjacent water and lead to increased beach closures when no threat is present. This work identifies factors that influence the survival of E. coli in sand using laboratory microcosms to replicate beach conditions. Microcosms were deployed to examine the …

Spline Modeling And Localized Mutual Information Monitoring Of Pairwise Associations In Animal Movement, Andrew Benjamin Whetten

Theses and Dissertations

to a new era of remote sensing and geospatial analysis. In environmental science and conservation ecology, biotelemetric data recorded is often high-dimensional, spatially and/or temporally, and functional in nature, meaning that there is an underlying continuity to the biological process of interest. GPS-tracking of animal movement is commonly characterized by irregular time-recording of animal position, and the movement relationships between animals are prone to sudden change. In this dissertation, I propose a spline modeling approach for exploring interactions and time-dependent correlation between the movement of apex predators exhibiting territorial and territory-sharing behavior. A measure of localized mutual information (LMI) is …

The Effects Of An R103q Mutation On The Chemical And Physical Properties Of The Enzyme Cytochrome C Nitrite Reductase (Ccnir), Shahama Alam

Theses and Dissertations

Cytochrome c Nitrite Reductase (ccNiR) is a periplasmic homodimeric decaheme enzyme that catalyzes the reduction of nitrite to ammonium in a process that involves six electrons and eight protons. The project described herein explored the properties of the Shewanella oneidensis R103Q ccNiR variant and compared them to the properties of the wild type enzyme. Under standard assay conditions, which use the strong reducing agent methyl viologen monocation radical (MVred) as an electron source, the R103Q variant still catalyzes reduction of nitrite to ammonium, albeit with an MVred turnover rate that is 20% of the wild type’s (780 ± 50 s-1 …

The Effects Of Hybridization On Skeletal Morphology In Two Closely Related Populations Of Rhesus Macaques (Macaca Mulatta): A Geometric Morphometric Approach, Cody Zachery Schumacher

Theses and Dissertations

Precise identification and classification techniques are vital for the field of paleoanthropology to ensure that hominin fossilized remains are labeled accurately. The morphology of extinct hominin specimens will typically be compared to extant nonhuman primate species because of how closely related they are phylogenetically. Observable similarities in their morphological variation can be examined to infer which traits may be a result of evolution and this can update our understanding of their evolutionary relationships. The genus Macaca displays a level of morphological variation that is similar to that seen in the genus Homo, therefore macaques can be used as an analogous …

Transport And Fate Of Phosphorus In The Nearshore Zone Of Lake Michigan, Nathan Van Ee

Theses and Dissertations

Bioavailable phosphorus loads exported to Lake Michigan from the Milwaukee and Sheboygan River Watersheds appear to have increased in the last 40 years despite meeting total phosphorus (TP) loading goals set by the Great Lakes Water Quality Agreement (GLWQA).Overall, bioavailability of P delivered from the Milwaukee and Sheboygan Rivers was highest during the warmer months, which coincides with the nearshore nuisance algae growth season. However, first order loss rates of SRP calculated during baseflow recession were also greatest during the summer, suggesting that increased river residence time during the summer could reduce export of bioavailable P. Observations of phosphorus partitioning …

Evaluating The Biological Activities Of Novel Histone Deacetylase Inhibitors (Hdaci) In Adherent And Nonadherent Tumor Cell Lines, Samer Alanani

Theses and Dissertations

Epigenetic dysregulations are linked to many human diseases including neurodegenerative disorders, immunodeficiencies, cardiac disease, and most notably cancer. Changes in the mechanisms of histone modifications have been recognized as hallmarks of carcinogenesis. One of these modifications is histone acetylation which is regulated by the activities of histone acetyltransferases (HATs) and histone deacetylases (HDACs). The reversible actions of these enzymes govern the acetylome and maintain its balance allowing for activation and repression of gene transcription. However, aberrant overexpression of HDACs in certain tumors is associated with decreased levels of transcription leading to tumor progression and survival. Hence, small-molecule histone deacetylase inhibitors …

Transcriptomics And Toxcast Data Identify Bioeffects In Zebrafish Embryos Exposed To Chemical Mixtures In An Effluent-Dominated Stream, Emma Meade

Theses and Dissertations

Wastewater treatment plant (WWTP) effluent-dominated streams provide critical habitat for aquatic organisms but also continually expose them to complex mixtures of pharmaceuticals and other contaminants of emerging concern (CECs) that can potentially impair growth, behavior, and reproduction. Limited toxicity data on the adverse biological impacts of in vivo exposure to these mixtures make it difficult to assess risk for aquatic organisms, particularly with respect to pharmaceuticals whose designed bioactivity often extends beyond conventionally monitored biological pathways. To address this knowledge gap, the goal of this thesis was to identify biomarkers of exposure to complex CEC mixtures relevant to specific chemicals …

Selection And Demography Drive Range-Wide Patterns Of Mhc Variation In Mule Deer (Odocoileus Hemionus), Rachel M. Cook

Theses and Dissertations

Variation at functional genes involved in immune response is of increasing concern as wildlife diseases continue to emerge and threaten populations. The amount of standing genetic variation in a population is directly associated with its potential for rapid adaptation to novel environments. For genes in the major histocompatibility complex (MHC), which are crucial in activating the immune response and which have extremely high levels of polymorphism, the genetic variation has been shown to be influenced by both parasite-mediated selection and historical population demography. To better understand the relative roles of parasite-mediated selection and demography on MHC evolution in large populations, …

Molecular Weight Distributions And Size-Dependent Composition Of Dissolved Organic Matter In The Aquatic Continuum, Hui Lin

Theses and Dissertations

Dissolved organic matter (DOM) in aquatic environments is one of the most important carbon reservoirs in global carbon cycling. The molecular weight of DOM is strongly related to a great number of biogeochemical reactions, influencing ecological functions and the fate of bioactive elements in aquatic ecosystems. A new technique coupling flow field-flow fractionation with fluorescence excitation-emission matrix (EEM) and parallel factor (PARAFAC) analysis was developed to elucidate the variations in DOM composition and optical properties with molecular weight in the individual samples and their changes along the aquatic continuum. Based on the novel coupling technique, variations in DOM characteristics were …

Health Goals For Perfluorinated Alkyl Substances (Pfas): A Review Of Branched Isomers, The Role Of Industrial Sources, And The Implications Of Pfas In Biosolids On End-Of-Life Disposal Methods, Katarina Schulz

Theses and Dissertations

Per- and polyfluorinated alkyl substances, or PFAS, have been used for over half a century, but have become an emerging contaminant of significant concern due to their newly found widespread occurrence and recalcitrance in the environment, their tendency to bioaccumulate, and the health effects now associated with a very low level of exposure. Many gaps in knowledge remain about the fate of these chemicals in the environment and the extent of their impacts on biota. This thesis aims to fill some of the recognized gaps in knowledge: differences between linear and branched isomers of PFAS, predicting the presence of PFAS …

Structure & Function Of Enzymes In Two Uncharacterized Gene Clusters From Pseudomonas Brassicacearum & Streptomyces Griseofuscus, Lamia Tabassum Badhon

Theses and Dissertations

Pyridoxal 5’-phosphate (PLP)-dependent enzymes harness this versatile cofactor to catalyze a variety of reactions including transamination, decarboxylation, racemization and various elemination/subsitution reactions. Several years ago, a new class of PLP-dependent enzymes was discovered that uses PLP and molecular oxygen to catalyze the 4-electron oxidation of L-arginine to 4-hydroxy-2-ketoarginine. Work with the prototypical enzyme of this class, MppP from Streptomyces wadayamensis (SwMppP), showed that the dioxygen consumed during the reaction is reduced to hydrogen peroxide, and that the hydroxyl group installed in the product derives from water. Thus, SwMppP is an L-arginine oxidase, and not an oxygenase. This was surprising given …

Predicting Factors Of Re-Hospitalization After Medically Managed Intensive Inpatient Services In Opioid Use Disorder, Brian Kay

Theses and Dissertations

IntroductionOpioid use disorder has continued to rise in prevalence across the United States, with an estimated 2.5 million Americans ailing from the condition (NIDA, 2020). Medically managed detoxification incurs substantial costs and, when used independently, may not be effective in preventing relapse (Kosten & Baxter, 2019). While numerous studies have focused on predicting the factors of developing opioid use disorder, few have identified predictors of readmission to medically managed withdrawal at an inpatient level of care. Utilizing a high-fidelity dataset from a large multi-site behavioral health hospital, these predictors are explored.

MethodsPatients diagnosed with Opioid Use Disorder and hospitalized in …

Part I: Development Of Small-Molecule-Based Probes For The Vitamin D Receptor; Part Ii: Development Of A Scalable Manufacturing Process For Orcein Dye, Tania Roseann Mutchie

Theses and Dissertations

PART I:The vitamin D receptor (VDR) is a ligand-dependent transcription factor and member of the nuclear hormone receptor superfamily. VDR is expressed in the epithelia of endocrine organs, digestive system, bronchi, kidneys, and thymus, as well as being present in leukocytes and bone cells. Cell proliferation, cell differentiation, and immunomodulation, along with calcium and phosphate homeostasis, are all processes regulated by the receptor. Within the cell, VDR can be membrane-bound or located in the nucleus. Nuclear localization of VDR transpires following the binding of vitamin D metabolites, the most active of which is 1α,25-dihydroxyvitamin D3 (calcitriol). Within the nucleus, interactions …

Investigation Of G Protein-Coupled Receptor Quaternary Structure Through Fluorescence Micro-Spectroscopy And Theoretical Modeling: Interdependence Between Receptor-Receptor And Receptor-Ligand Interactions, Joel David Paprocki

Theses and Dissertations

Proteins are of high interest in biophysics research due to the important roles they play within cells, such as sensing of chemical (ions and small molecules) and physical (e.g., light) stimuli, providing structure, transporting ions/molecules, signaling, and intercellular communication. The studies described in this dissertation focus on a particular type of membrane proteins known as G protein-coupled receptors (GPCR), which play a key role in cellular response to external stimuli. We used the sterile 2 α-factor mating pheromone receptor (Ste2), a prototypical class D GPCR present within Saccharomyces cerevisiae (baker’s yeast). Ste2 is responsible for initiating the second messenger signal …

Autumn Tree Phenology In Northern Wisconsin: Humans Versus Photographs, Trevor Iglinski

Theses and Dissertations

Ecosystem primary productivity halts when plants go dormant, and so the timing of dormancy as it relates to autumn phenology has been a focus of much interdisciplinary research. While monitoring plant phenology has its roots in directly observing specimens, digital sensors along with modern methods have also become a mainstay in phenology. Results from different methods often vary, so there is still a need to better understand how digital cameras record autumn phenology, especially in comparison with ground-based observations (Keenan et al. 2014). This study compared autumn phenology derived from direct ground observations with upward-facing fisheye photography, in the context …

Modeling The Bidirectional Glutamine/ Ammonium Conversion Between Cancer Cells And Cancer-Associated Fibroblasts, Peter Hinow, Gabriella Pinter, Wei Yan, Shizhen Emily Wang

Mathematical Sciences Faculty Articles

Like in an ecosystem, cancer and other cells residing in the tumor microenvironment engage in various modes of interactions to buffer the negative effects of environmental changes. One such change is the consumption of common nutrients (such as glutamine/Gln) and the consequent accumulation of toxic metabolic byproducts (such as ammonium/NH⁴⁾. Ammonium is a waste product of cellular metabolism whose accumulation causes cell stress. In tumors, it is known that it can be recycled into nutrients by cancer associated fibroblasts (CAFs). Here we present monoculture and coculture growth of cancer cells and CAFs on different substrates: glutamine and ammonium. …

A Mechanistic Investigation Of Cytochrome C Nitrite Reductase Catalyzed Reduction Of Nitrite To Ammonia: The Search For Catalytic Intermediates, Shahid Shahid

Theses and Dissertations

Cytochrome c Nitrite Reductase (ccNiR) is a periplasmic homodimeric decaheme enzyme that catalyzes the reduction of nitrite to ammonium in a process that involves six electrons and eight protons. Under standard assay conditions, which use a strong reducing agent as an electron source, catalysis takes place rapidly without producing detectable intermediates. However, intermediates do accumulate when weaker reducing agents are employed, allowing the ccNiR mechanism to be studied. Herein, the early stages of Shewanella oneidensis ccNiR-catalyzed nitrite reduction were investigated in isolation by using the weak reducing agents N,N,N’,N’-tetramethyl-p-phenylenediamine (TMPD) and the 2-electron reduced form of indigo trisulfonate. Experiments were …

Macromolecular Structure Determination At X-Ray Free Electron Lasers From Single-Particle Imaging To Time-Resolved X-Ray Crystallography, Ishwor Poudyal

Theses and Dissertations

X-ray free-electron lasers (XFELs) open the possibility of obtaining diffraction information from a single biological macromolecule. This is because XFELs can generate extremely intense X-ray pulses which are so short that diffraction data can be collected before the sample is destroyed. By collecting a sufficient number of single-particle diffraction patterns from many tilts of a molecule relative to the X-ray beam, the three-dimensional electron density can be reconstructed ab-initio. The resolution and therefore the information content of the data will ultimately depend largely on the number of patterns collected at the experiment. We estimate the number of diffraction patterns required …

Analysis Of Plant Biomass Production Comparing Decoupled Aquaponics Against Equivalent Single-Loop Aquaponic And Hydroponic Systems Growing Lactuca Sativa, Haley Luise Lucas

Theses and Dissertations

Aquaponics is an emerging method of agriculture in which fish and plants are grown in an enclosed and recirculating environment. The method mimics a relationship found in nature where fish waste provides nutrients for plants and plants cleanse the water for the benefit of the fish. This symbiotic relationship has proven to be a sustainable method of agriculture in which there is less water use, no need for pesticides or herbicides, recycling of nutrient waste and a smaller spatial footprint. However, the production of both plants and fish in a recirculating aquaponics system has produced less yield and profit when …

An Investigation Into The Trophic Magnification Of Polychlorinated Biphenyls In The Lake Michigan Food Web, Philip Hurst

Theses and Dissertations

Polychlorinated biphenyls (PCBs) are a group of persistent organic pollutants known to contribute to several adverse health conditions in humans including cancers and a suite of liver diseases. While there exist 209 unique PCB congeners, the World Health Organization has identified 12 that pose the greatest health risk to humans due to these congeners’ functional similarity to dioxins, another notoriously toxic class of contaminants. Along with methylmercury, PCBs are the primary drivers behind fish consumption advisories in the Great Lakes. These guidelines are informed primarily by surveys of contaminants in freshwater biota. However, the proliferation of invasive species, such as …

Zinc Proteomics: Interactions Of Zn2+, Cd2+, And Metal-Binding Ligands With Zn-Binding Sites In The Proteome, Eric Daniel Lund

Theses and Dissertations

Cadmium ion causes toxicity in humans, most prominently in the kidney. This thesis focuses on mechanisms by which Cd2+ harms kidney proximal tubule cells. Previous experiments have shown the time-dependent distribution of Cd2+ and Zn2+ within supernatant of pig kidney, LLC-PK1 cells after exposure to Cd2+ plus the ionophore pyrithione1. The first part of this research describes the trafficking of cadmium within LLC-PK1 proximal tubule cells, including the time dependent distribution, speciation, and quantification of Cd2+ and Zn2+ in cells exposed to Cd2+ and Cd2+ plus pyrithione. The latter treatment introduces Cd2+ into cells at time zero and permits the …

Two Fields, One Pellet: Combining Demographics And Population Genetics Through Non-Invasive Sampling Of Snowshoe Hare Fecal Pellets In Michigan., Genelle Nicole Uhrig

Theses and Dissertations

As climate continues to change at a rapid rate, species are increasingly vulnerable to the resulting environmental changes. This is especially true for species whose fitness is closely linked to climate-associated environmental conditions. One of these vulnerable species is snowshoe hare, Lepus americanus, who depends on the timing and duration of snowfall to provide camouflage when they go through seasonal pelage changes from brown in the summer to white in the winter. Whereas snowshoe hare are stable across the core of their range, populations along the southern range edge are experiencing declines due to climate driven environmental changes that cause …

Quantifying The Variability In Heavy Metal Concentrations In Produce Grown In Metals-Rich Soil, Harris Lowell Byers

Theses and Dissertations

Childhood Pb exposure is associated with a multitude of poor health outcomes. In food-insecure areas, growing fresh produce in residential backyard gardens is one option for parents; however, commonly grown crops are known to accumulate Pb in consumable tissues when grown in metals-rich soils. A variety of produce representing a continuum of consumable tissues were grown in soils collected from two residential vegetable gardens, a former metal foundry, and commercial topsoil purchased from a local hardware store. The concentrations of heavy metals in crop tissues were measured with custom wavelength dispersive X-ray Fluorescence (WD-XRF) spectroscopy and portable energy dispersive X-ray …

Seasonal Offshore/Inshore Migration Of Round Gobies, Erik Carlson

Theses and Dissertations

Since the invasion of round gobies (Neogobius melanostomus) in Lake Michigan, they have become integrated into both the nearshore and offshore food webs. Round gobies can be found in shallower water (<20 m) during the summer, but they disappear from these depths in early fall. They have been collected, occasionally, offshore in depths greater than 70 m during fall and early spring. These observations and other anecdotal evidence indicate that round goby migrate offshore during the fall and return in the spring. To study this, a large remotely operated vehicle (ROV) was used to conduct video transects offshore at various depths. The offshore sampling showed that round gobies migrated away from nearshore habitat in early October and were almost exclusively found deeper than 20 m by November. The round gobies remained offshore (>30 m) until mid-May, when they began the return to nearshore habitat. The cues to start the offshore and return migrations were not the focus of this project, but the fall offshore migrations coincided with decreasing temperatures nearshore in the fall, and in spring, the offshore movement of the thermal bar. The offshore migration in fall provide an increase in forage opportunity for deep, cold-water predators such as …

The Curious Case Of Nad-Cleaving Nudix Hydrolases, Atreyei Ray

Theses and Dissertations

Nudix proteins are members of a large family of homologous enzymes that hydrolyze nucleoside diphosphates linked to other compounds (x). These enzymes have catalytic activity on a wide range of substrates such as dNTPs (both canonical and their oxidized forms), nucleotide sugars, alcohols, dinucleoside polyphosphates, dinucleotide cofactors, and nucleoside diphosphates linked to RNA. The bacterial genome encodes around 13, while the human genome encodes for 22 such nudix proteins.

The E. coli genome encodes for a mutT mutator gene, the progenitor of the family expressing the MutT pyrophosphohydrolase (NudA) protein (Treffers et al., 1954; Bhatnagar et al., 1988). The enzyme …

Development Of Indicators For Human Fecal Pollution Using Deep-Sequencing Of Microbial Communities, Shuchen Feng

Theses and Dissertations

The gut microbiome is shaped by both host physiology and environmental factors, which results in unique communities that contain certain members specific to a host. Microbial source tracking (MST) methods that rely on host-specific fecal microorganisms have been applied to detect human fecal pollution over the past two decades. The most common approach uses quantitative polymerase chain reaction (qPCR) to amplify certain sequences of these microorganisms, or human fecal markers. To date, most bacterial human fecal markers have focused on the HF183 cluster within the genus Bacteroides. However, cross-reactions with animals or variable Bacteroides abundance in humans have been found. …