Life Sciences Commons^™

Multi-Omic Understanding Of The Evolution Of Xenobiotic Tolerance In Bacterial Isolates And Communities, Tayte Paul Campbell

Arts & Sciences Electronic Theses and Dissertations

Xenobiotic compounds are any chemicals that are released into an environment by human action and that occur at concentrations higher than found naturally. Xenobiotics, including aromatic compounds and antibiotics, are recalcitrant to degradation because they are often toxic or mutagenic. Despite this toxicity, bacteria account for a large portion of xenobiotic degradation in the environment. Bacteria are able to adapt to these foreign chemicals, gaining increased levels of tolerance and increased rates of xenobiotic degradation. On the strain level, increased tolerance can be caused by mutations in individual cells or through the acquisition of genes from other cells. At the …

Mechanisms Of Nestmate Recognition Cue Production In The European Honey Bee, Apis Mellifera., Cassondra Leigh Vernier

Arts & Sciences Electronic Theses and Dissertations

Social insects are some of the world’s most ecologically successful animal groups, and their complex societies are considered one of the pinnacles of animal evolution. Since these organisms live in colonies composed of many individuals and stored resources, they are a target for intruders, such as parasites, predators and conspecific robbers. Therefore, many social insect species have evolved mechanisms for nest defense, including nestmate recognition, where guarding individuals at the entrance of the colony use cues on incoming individuals to determine whether they are nestmates or intruders. Although nestmate recognition is incredibly important for maintaining colony integrity and fitness, the …

Expression And Function Of Snornas In Acute Myeloid Leukemia, Wayne Alsworth Warner

Arts & Sciences Electronic Theses and Dissertations

Small nucleolar RNAs (snoRNAs) are non-coding RNAs that contribute to ribosome biogenesis and RNA splicing by modifying ribosomal RNA and spliceosome RNAs, respectively. These modifications are critical for a variety of cellular processes, including ribosomal biogenesis and splicing of RNAs. Recent studies have suggested an expanded role for snoRNAs beyond ribosomal biogenesis and splicing, including, regulation of chromatin structure, metabolism, and neoplastic transformation. The contribution of snoRNAs to the regulation of normal and malignant hematopoiesis is largely unknown. The lack of a method to accurately and comprehensively assess snoRNA expression has limited research in this area. In particular, array-based methods …

Diverse Far-Red Light Utilization Strategies In Cyanobacteria And Algae, Benjamin Martin Wolf

Arts & Sciences Electronic Theses and Dissertations

In their natural environments, photosynthetic organisms are often exposed to widely varied light environments. Species adapted to shade light, often found growing in lower layers of photosynthetic biofilms, must survive on filtered light alone. Filtered light is highly enriched in far-red wavelengths, which are normally unavailable for photosynthetic energy production in most oxygenic phototrophs. To overcome light limitations in filtered light environments, some species of algae and cyanobacteria utilize specialized photosynthetic pigments and antenna systems to harvest these far-red wavelengths. By sampling the natural environment and using custom-built far-red light growth chambers, I have isolated several species of oxygenic phototrophs …

Secretory Iga Enhances Gut B Cells Priming And Systemic Igg Responses Towards Commensals, You Zhou

Arts & Sciences Electronic Theses and Dissertations

IgA is the primary antibody response at mucosal surfaces and is reported to inhibit adaptive immune responses against gut bacteria. Here, we utilize an in vitro system to expand and screen IgA memory B cells for their ability to recognize gut bacteria in the context of secretory IgA (sIgA) deficiency in polymeric Ig receptor (Pigr–/–) mice. Contrary to the prevailing hypothesis that IgA provides an immune exclusionary function, we found that mice lacking sIgA showed decreased anti-bacterial IgA specificities as assessed using flow cytometry. IgA B cell responses against certain taxa such as those of order Bacteriodales showed greater dependence …

Quantitatively Studying Tissue Damage In Multiple Sclerosis Using Gradient Recalled Echo Mri Sequences, Biao Xiang

Arts & Sciences Electronic Theses and Dissertations

Multiple Sclerosis (MS) is an unpredictable, often disabling disease of the central nervous system (CNS) that disrupts the flow of information within the brain, and between the brain the body. MS is the most common progressive neurologic disease of young adults, affecting approximately 2.3 million people worldwide. It is estimated that more than 700,000 individuals are affected by MS in United States. While MS has been studied for decades, the cause of it is still not definite and a fully effective treatment for MS is not yet available. Magnetic resonance imaging (MRI) has been used extensively in MS diagnosis and …

Fast-Forward Protein Folding And Design: Development, Analysis, And Applications Of The Fast Sampling Algorithm, Maxwell Isaac Zimmerman

Arts & Sciences Electronic Theses and Dissertations

Molecular dynamics simulations are a powerful tool to explore conformational landscapes, though limitations in computational hardware commonly thwart observation of biologically relevant events. Since highly specialized or massively parallelized distributed supercomputers are not available to most scientists, there is a strong need for methods that can access long timescale phenomena using commodity hardware. In this thesis, I present the goal-oriented sampling method, Fluctuation Amplification of Specific Traits (FAST), that takes advantage of Markov state models (MSMs) to adaptively explore conformational space using equilibrium-based simulations. This method follows gradients in conformational space to quickly explore relevant conformational transitions with orders of …

Quantitatively Studying Tissue Damage In Multiple Sclerosis Using Gradient Recalled Echo Mri Sequences, Biao Xiang

Arts & Sciences Electronic Theses and Dissertations

Multiple Sclerosis (MS) is an unpredictable, often disabling disease of the central nervous system (CNS) that disrupts the flow of information within the brain, and between the brain the body. MS is the most common progressive neurologic disease of young adults, affecting approximately 2.3 million people worldwide. It is estimated that more than 700,000 individuals are affected by MS in United States. While MS has been studied for decades, the cause of it is still not definite and a fully effective treatment for MS is not yet available.

Magnetic resonance imaging (MRI) has been used extensively in MS diagnosis and …

Mechanism Of Activation Of Uvrd Helicase By A Processivity Factor Mutl, Yerdos Ordabayev

Arts & Sciences Electronic Theses and Dissertations

E. coli UvrD is a superfamily 1A helicase/translocase involved in DNA repair, recombination, and replication. I investigated the role of E. coli MutL, a regulatory protein involved in methyl-directed mismatch DNA repair, in the regulation of UvrD-catalyzed DNA unwinding. Using single molecule fluorescence resonance energy transfer (FRET) and single round stopped-flow DNA unwinding experiments I demonstrated that MutL can activate latent UvrD monomer helicase activity and also stimulate UvrD dimer helicase activity. Furthermore, using analytical ultracentrifugation experiments I determined that a single MutL dimer is sufficient to activate UvrD monomer helicase. DNA unwinding experiments with a series of DNA substrates …

Brain Blood Flow And Metabolism: Variable Relationships In Altered Metabolic States, Tyler M. Blazey

Arts & Sciences Electronic Theses and Dissertations

Brain metabolism is usually thought of in terms of energy production. Decades of research has shown that the brain derives the majority of its energy from the oxidative phosphorylation of glucose transported from the blood into the brain. Because of this, cerebral blood flow (CBF), the cerebral metabolic rate of glucose consumption (CMRglc), and the cerebral metabolic rate of oxygen consumption (CMRO2) generally are tightly coupled. Indeed, the coupling between CBF, CMRglc, and CMRO2 is robust enough such that many investigators believe them to be equivalent measures of brain activity. Nevertheless, research over the last few decades has shown that …

Isolating Item And Subject Contributions To The Subsequent Memory Effect, Jihyun Cha

Arts & Sciences Electronic Theses and Dissertations

The subsequent memory effect (SME) refers to the greater brain activation during encoding of subsequently recognized items compared to subsequently forgotten items. Previous literature regarding SME has been primarily focused on identifying the role of specific regions during encoding or factors that potentially modulate the phenomenon. The current dissertation examines the degree to which this phenomenon can be explained by item selection effects; that is, the tendency of some items to be inherently more memorable than others. To estimate the potential contribution of items to SME, I provided participants a fixed set of items during encoding, which allowed me to …

Siderophore-Dependent Transport Paradigms For Iron Across The Bacterial Cell Envelope In The Human Pathogen Staphylococcus Aureus, Nathaniel Endicott

Arts & Sciences Electronic Theses and Dissertations

This work is focused on iron trafficking through ABC transporters in Staphylococcus aureus and combatting the growing antimicrobial resistance crisis by exploiting virulence factors as therapeutic targets. Specifically, the goal was to understand the role of a siderophore-binding lipoprotein FhuD2 in S. aureus iron trafficking. While S. aureus endogenously produces three metallophores for metal sequestration from the host, FhuD2 is thought to scavenge metals from hydroxamate-based xenosiderophores encountered in the host environment. FhuD2 is a critical virulence factor and vaccine candidate (Novartis) for MRSA. Since xenosiderophore scavenging systems are often dispensable, it was hypothesized that FhuD2 must be playing another …

Understanding The Physiology Of Extracellular Electron Uptake In Purple Nonsulfur Bacteria, Michael Singh Guzman

Arts & Sciences Electronic Theses and Dissertations

Microbially catalyzed oxidation-reduction reactions drive nutrient cycling and energy flux on Earth. Photoautotrophs, which include the cyanobacteria (oxygenic) and purple and green sulfur bacteria (anoxygenic), transform light energy into chemical energy and are responsible for substantial global primary productivity. Anoxygenic phototrophs, in particular, play a crucial role in biogeochemical cycling in anoxic illuminated environments because of their ability to oxidize an array of inorganic compounds for CO2 fixation. Electron donors include molecular hydrogen, nitrite, and reduced sulfur compounds. Recent evidence has also suggested that solid-phase conductive substances (SPCSs), including rust (mixed-valent iron minerals) and their proxies (poised electrodes), can serve …

From Single Cells To Human Disease: High-Resolution Phenotyping Of Male Infertility Models Using Single-Cell Rna Sequencing, Min Jung

Arts & Sciences Electronic Theses and Dissertations

Male infertility is a complex disease that can result in significant emotional distress and treatment costs. Globally, male infertility affects 7% of males, and while its incidence is rising, its etiology remains elusive. In order to improve patient care, it is critical to identify the nature of spermatogenic failure in as many men as possible. The extensive cellular heterogeneity of testis has limited the application of bulk expression measurements to capture crucial information to dissect molecular mechanisms of defects in the infertile patients. Thus, the application of single-cell RNA-sequencing on male germ cells provides an amazing new set of scientific …

Determining The Genetic Contributions Of The Williams Syndrome Critical Region To Behavior Using Mouse Models And Human Genetics, Nathan David Kopp

Arts & Sciences Electronic Theses and Dissertations

Williams syndrome is a neurodevelopmental model caused by the deletion of 26-28 genes on chr7q11.23. The loss of these genes affects multiple organ systems resulting in severe cardiovascular disease, craniofacial dysmorphology, intellectual impairment, a specific Williams syndrome cognitive profile made up of deficits in visual-spatial processing with preserved language skills, and a characteristic hypersocial personality. The reciprocal duplication occurs at a lower frequency and manifests with diametric phenotypes to the deletion. This suggests that this locus harbors dosage sensitive genes that play a role in neurodevelopment. Large efforts have been taken to identify which genes are responsible for causing the …

Siderophore-Dependent Transport Paradigms For Iron Across The Bacterial Cell Envelope In The Human Pathogen Staphylococcus Aureus, Nathaniel Endicott

Arts & Sciences Electronic Theses and Dissertations

This work is focused on iron trafficking through ABC transporters in Staphylococcus aureus and combatting the growing antimicrobial resistance crisis by exploiting virulence factors as therapeutic targets. Specifically, the goal was to understand the role of a siderophore-binding lipoprotein FhuD2 in S. aureus iron trafficking. While S. aureus endogenously produces three metallophores for metal sequestration from the host, FhuD2 is thought to scavenge metals from hydroxamate-based xenosiderophores encountered in the host environment. FhuD2 is a critical virulence factor and vaccine candidate (Novartis) for MRSA. Since xenosiderophore scavenging systems are often dispensable, it was hypothesized that FhuD2 must be playing another …

Mechanism Of Activation Of Uvrd Helicase By A Processivity Factor Mutl, Yerdos Ordabayev

Arts & Sciences Electronic Theses and Dissertations

E. coli UvrD is a superfamily 1A helicase/translocase involved in DNA repair, recombination, and replication. I investigated the role of E. coli MutL, a regulatory protein involved in methyl-directed mismatch DNA repair, in the regulation of UvrD-catalyzed DNA unwinding. Using single molecule fluorescence resonance energy transfer (FRET) and single round stopped-flow DNA unwinding experiments I demonstrated that MutL can activate latent UvrD monomer helicase activity and also stimulate UvrD dimer helicase activity. Furthermore, using analytical ultracentrifugation experiments I determined that a single MutL dimer is sufficient to activate UvrD monomer helicase. DNA unwinding experiments with a series of DNA substrates …

High-Density Diffuse Optical Tomography During Passive Movie Viewing: A Platform For Naturalistic Functional Brain Mapping, Andrew Kelsey Fishell

Arts & Sciences Electronic Theses and Dissertations

Human neuroimaging techniques enable researchers and clinicians to non-invasively study brain function across the lifespan in both healthy and clinical populations. However, functional brain imaging methods such as functional magnetic resonance imaging (fMRI) are expensive, resource-intensive, and require dedicated facilities, making these powerful imaging tools generally unavailable for assessing brain function in settings demanding open, unconstrained, and portable neuroimaging assessments. Tools such as functional near-infrared spectroscopy (fNIRS) afford greater portability and wearability, but at the expense of cortical field-of-view and spatial resolution. High-Density Diffuse Optical Tomography (HD-DOT) is an optical neuroimaging modality directly addresses the image quality limitations associated with …

A Physics-Based Intermolecular Potential For Biomolecular Simulation, Joshua Andrew Rackers

Arts & Sciences Electronic Theses and Dissertations

The grand challenge of biophysics is to use the fundamental laws of physics to predict how biological molecules will move and interact. The atomistic HIPPO (Hydrogen-like Intermolecular Polarizable Potential) force field is meant to address this challenge. It does so by breaking down the intermolecular potential energy function of biomolecular interactions into physically meaningful components (electrostatics, polarization, dispersion, and exchangerepulsion) and using this function to drive molecular dynamics simulations. This force field is able to achieve accuracy within 1 kcal/mol for each component when compared with ab initio Symmetry Adapted Perturbation Theory calculations. HIPPO is capable of this accuracy because …

Force Requirements And Force Generation During Endocytosis In Yeast, Jonah Kyle Scher-Zagier

Arts & Sciences Electronic Theses and Dissertations

Endocytosis is a process by which cells bring external materials into the intracellular environment and perform other essential biological functions. The main drivers of endocytosis include clathrin and actin, which help shape the membrane and form the endocytic invagination. In mammalian cells and other cells lacking a wall, the primary barriers to endocytosis are the bending rigidity of the cell membrane and surface tension. However, in cells with a rigid cell wall, such as those of yeast, this process is opposed by a substantial pressure within the cell, known as the turgor pressure, which is generated by a difference in …

Electron Decoupling With Chirped Microwave Pulses For Magic Angle Spinning Dynamic Nuclear Polarization Nuclear Magnetic Resonance Spectroscopy, Edward Paul Saliba

Arts & Sciences Electronic Theses and Dissertations

Dynamic nuclear polarization (DNP) is a method of generating hyperpolarization of nuclear spins for nuclear magnetic resonance (NMR) spectroscopy. Coherent, time domain techniques make the possibility of DNP directly to spins of interest at room temperature and higher feasible in magic angle spinning (MAS) NMR, allowing for optimal experimental repetition times to be limited by the T_1 of the electron, rather than a much longer T_1DNP, with excellent resolution. The strong hyperfine couplings that make such direct DNP transfers possible, however, can lead to short nuclear relaxation times that result in broadening of nuclear resonances and reduce sensitivity. This dissertation …

Individual Differences In Human Brain Functional Network Organization, Benjamin A. Seitzman

Arts & Sciences Electronic Theses and Dissertations

The human brain is organized at many spatial scales, including the level of areas and systems. Resting-state functional magnetic resonance imaging is a non-invasive technique that allows for the study of areal- and systems-level brain organization in vivo. Over two decades of research has sought to identify and characterize the functional communities that comprise the brain’s network architecture. Consequently, a convergent description of group-average functional network organization in healthy adults has emerged. Recent advances have allowed for the study of such organization in single individuals. Investigation of functional network organization in highly sampled individuals has revealed brain regions that deviate …

A Combinatorial Approach Of Ionomics, Quantitative Trait Locus Mapping, And Transcriptome Analysis To Characterize Element Homeostasis In Maize, Alexandra Asaro

Arts & Sciences Electronic Theses and Dissertations

In plant systems, genetic and biochemical pathways impact uptake of elements from the soil. These environment-sensitive pathways often act in the root tissue to impact element concentrations throughout the plant. In order to characterize element regulation as well as apply ionomics to understand plant adaptation, perspectives are needed from multiple tissues and environments and from approaches that take interactions between elements into account. The work described in this thesis includes multi-environment and multi-tissue experiments that connect variation in genetic sequence, and in gene expression, with variation in element accumulation. The associations found here include those that are sensitive to environment, …

Exploring Infant Leukemia Through Exome Sequencing And An In Vitro Model Of Hematopoietic Development, Mark Cannon Valentine

Arts & Sciences Electronic Theses and Dissertations

Cancer is a heterogeneous disease with myriad causes and outcomes. Many of the cancers that occur in adult populations have become increasingly well characterized with the advent of affordable high-throughput sequencing. These studies have revealed that cancer is largely a disease of somatic mutation in the adult population. In strong contrast to this, childhood cancers have an exceedingly low rate of somatic mutation. At the extreme end of this spectrum is Infant Leukemia (IL). Sequencing of IL has revealed that these tumors frequently have one or fewer somatic SNP. In the absence of a somatic explanation for IL, many other …

A Formative Assessment Of The Vulnerability Context Of Three Indigenous Communities In Rural Ecuador For Improved Intervention Design, Ivy Blackmore

Arts & Sciences Electronic Theses and Dissertations

Nearly 20 % of the current world population are small-scale producers living in rural areas who rely on agriculture and related activities to support their families (IFAD, 2016; World Bank, 2008). Despite the almost 76 billion USD of official development assistance committed to agriculture improvement projects and associated activities over the past decade, many of the intended beneficiaries remain poor and struggle to meet their basic needs. The lack of success in addressing rural poverty highlights the need for quality research focused on understanding what type of intervention/s could help rural communities sustainably improve their livelihood security.

The goal of …

Development Of Enteric Neurons And Muscularis Macrophages, Marina Avetisyan

Arts & Sciences Electronic Theses and Dissertations

The enteric nervous system (ENS) is a complex interconnected network of neurons and glia in the bowel wall that regulates intestinal motility, blood flow, and epithelial function. The ENS also controls aspects of inflammatory signaling within the bowel. To perform these tasks, there are at least 20 types of enteric neuron and four types of enteric glia. Although much is known about early events in ENS development, signals governing the development of specific neuronal subtypes and communication with neighboring cell types within the bowel remain poorly understood. One fundamental hypothesis is that diverse trophic factors support distinct neuronal populations in …

Spatio-Temporal Principles Of Infra-Slow Brain Activity, Anish Mitra

Arts & Sciences Electronic Theses and Dissertations

In the study of systems where basic laws have eluded us, as is largely the case in neuroscience, the simplest approach to progress might be to ask: what are the biggest, most noticeable things the system does when left alone? Without any perturbations or fine dissections, can regularities be found in the basic operations of the system as a whole? In the case of the brain, it turns out that there is an amazing amount of activity even in the absence of explicit environmental inputs or outputs. We call this spontaneous, or resting state, brain activity. Prior work has shown …

The Role Of Tumor Stromal Discoidin Domain Receptor 2 (Ddr2) In Breast Cancer Metastasis., Samantha Van Hove Bayer

Arts & Sciences Electronic Theses and Dissertations

Characteristics of breast tumor stroma, including altered collagen architecture and increased stiffness, are known to contribute to tumor invasion and metastasis. However, the cellular and molecular mechanisms by which these changes occur are not fully understood. To address this question, we used a mouse genetic model to delete Discoidin Domain Receptor 2 (DDR2) from mouse tumor stromal cells and interrogated breast cancer associated fibroblasts (CAFs) to determine the molecular events downstream of DDR2 action that may lead to changes in the tumor extracellular matrix (ECM). Our work revealed that the action of DDR2 in breast stromal cells is required for …

Characterizing The Humoral Response To Flavivirus Infection, Estefania Fernandez

Arts & Sciences Electronic Theses and Dissertations

Flaviviruses are positive (+) sense, single-stranded RNA viruses of the Flaviviridae family that are transmitted by mosquitoes. For our studies, we focused on Zika virus (ZIKV) and Japanese encephalitis virus (JEV). Most human infections with ZIKV historically resulted in a mild self-limiting febrile illness. However, since 2013, a worldwide spread and increase in ZIKV infections has been observed. Notably, ZIKV has been associated with autoimmune ascending paralysis (Guillain-Barré Syndrome) and ophthalmologic effects in adults and intrauterine growth restriction and microcephaly in developing fetuses. Current vaccine efforts utilize technologies implemented for related flaviviruses (yellow fever virus (YFV), Dengue virus (DENV), and …

Defining Gastric Epithelial Cell Population Dynamics At Homeostasis And Following Injury, Joseph Ronald Burclaff

Arts & Sciences Electronic Theses and Dissertations

Gastric diseases affect many people around the world, yet surprisingly little is known about the basic dynamics of gastric epithelial cells. Loss of acid-secreting parietal cells has long been observed to precede pre-cancerous gastric metaplasias like Spasmolytic Polypeptide-Expressing Metaplasia (SPEM), yet no signaling component from dying parietal cells has yet been implicated in initiating the metaplastic responses. Also, experiments pulsing 3H-thymidine and or examining intracellular components suggest that gastric mucous neck cells are short-lived transient intermediates between the gastric stem cell and mature zymogenic “chief” cells, yet specifics about this transition remain elusive. Here, we develop a novel mouse line …