Life Sciences Commons^™

Interactions Among Sex, Apolipoprotein E Genotype, And 17-Beta Estradiol In A Mouse Model Of Alzheimer's Disease, Lisa Taxier

Theses and Dissertations

Alzheimer’s disease (AD) is the most common form of dementia, yet its cause remains a mystery and no truly effective treatments exist. The high incidence of AD, coupled with its devastating health and economic impacts, highlight the urgent need for continued research into the etiology of this disease (Ernst & Hay, 1994; Rice et al., 1993). Although existing and efficacious treatments for AD are lacking, several risk factors for AD have been identified. One such factor is apolipoprotein E genotype, which is the greatest genetic risk factor for AD (Ertekin-Taner, 2007; van der Flier et al., 2011). Another factor is …

Effects Of Seat And Axle Position On Pain, Pathology, And Independence In Pediatric Manual Wheelchair Users With Spinal Cord Injury, Hannah Frank

Theses and Dissertations

Manual wheelchair (MWC) users with spinal cord injury (SCI) rely heavily on their upperextremities to complete daily occupations. Due to repetitive shoulder use during wheelchair mobility and propulsion, MWC users are at greater risk of shoulder pain and shoulder pathology, and thus decreased independence, and lower quality of life. The relative fit of the wheelchair and its parameters are critical and can further impact the user’s propulsion biomechanics. Parameters such as seat angle and axle position may put the user in detrimental shoulder positions for longer periods of time, impacting health outcomes even more. Although the effects of wheelchair setup …

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 …

Microbial Communities Hosted By Carnivorous Pitcher Plants: Diversity, Recruitment, Functions And Succession In Sarracenia Purpurea Microbiomes, Jacob Jeffrey Grothjan

Theses and Dissertations

The pitcher plant Sarracenia purpurea supplements nutrient acquisition through carnivory, capturing insect prey which are digested by a food web community of eukaryotes and bacteria. Analysis of both bacterial and eukaryotic diversity, and an understanding of bacterial recruitment into pitchers and succession of bacterial and eukaryotic communities over time have not been well explored. This thesis presents three studies designed to address these gaps using field sampling and manipulative greenhouse experiments. Study I compared bacterial and eukaryotic composition and diversity of pitcher communities within and between populations of plants in two distinct wetland habitats. Genetic sequence analysis revealed an underappreciated …

The Study Of The Phytopathogen Dickeya Dadantii 3937 Cpx Signaling On The Regulation Of Virulence And Antimicrobial Resistance, Daqing Jiang

Theses and Dissertations

Bacteria respond to environmental cues through a variety of mechanisms. Two-component systems (TCSs) are a conserved mechanism used by bacteria to accurately respond and sense environmental changes. The monitoring of envelope perturbance is linked to TCS CpxA/CpxR in animal-infecting pathogens. The study of the TCS response regulator (RR) CpxR is largely unexplored in phytopathogens. This work focuses on the genetic linkage between cpxR and T3SS expression regulation. We identified the multiple roles of CpxR on several T3SS regulators and its participation in the bacterial second messenger (c-di-GMP) signaling cascade. Moreover, a compound library screening revealed a novel Cpx inducer CHIR-090, …

The Use Of A Biopsychosocial Framework In Evaluating And Treating Patellofemoral Pain, Jennifer Thorpe

Theses and Dissertations

Patellofemoral pain (PFP) is a chronic pain condition of the knee that afflicts approximately 25% of the population, and may lead to long-term complaints of pain and dysfunction. In the current literature, PFP is primarily studied using the framework of the pathomechanical model of biomechanical and muscular factors that increase patellofemoral joint loading. However, PFP may be better understood examining it through the Biopsychosocial Model of Sport Injury Rehabilitation (Brewer et al., 2002) as a conceptual framework to explore how injury characteristics, sociodemographic factors, and intermediate biopsychosocial outcomes may impact a patient’s perceptions of pain and function. These relationships may …

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 …

Effect Of Neighborhood Socioeconomic Disadvantage On Brain Functional Connectivity And Structural Properties In Trauma-Exposed Adults, Elisabeth Kathleen Webb

Theses and Dissertations

Though there has been substantial progress towards understanding brain-behavior relationships and characterizing the neurobiology of psychiatric disorders, research has not translated as expected into novel prevention and treatment of mental health conditions. One limitation may be the emphasis on individual-level variables (e.g., income) and omission of relevant area-level factors (e.g., neighborhood socioeconomic disadvantage). Recently, attention has been directed towards identifying the biological mechanisms by which neighborhoods impact mental health. The chronic stress associated with living in a disadvantaged neighborhood promotes a cascade of maladaptive events, which in turn impact brain structure and functioning. The processes affected by chronic neighborhood stressors …

Central Sensitization, Muscle Function, And Knee Kinematics In Females With Patellofemoral Pain, Kemery Jean Sigmund

Theses and Dissertations

Context: Females with patellofemoral pain (PFP) are at higher risk, have higher rates, and experience worse long-term outcomes than males. Structural and functional changes have been observed in pain networks and neuromuscular systems in individuals with PFP. Central sensitization describes dysfunctional pain modulation which could lead to altered neuromuscular control. Evidence examining relationships between central sensitization and muscle function in PFP is lacking.

Objective: The purpose of this study is to determine whether females with PFP exhibit signs of central sensitization compared to pain-free females. Then, after grouping each individual based on her quantitative sensory test results into a centrally …

Protein-Ligand Binding As A Tool To Identify Antiviral Drugs., Rajdeep Virdi

Theses and Dissertations

Viruses are the most abundant biological entities on the planet. A virus is a collection of essential genetic material encapsulated in a protein coat that is incapable of replicating without a host. A virus must inject its genetic material into a suitable host cell to utilize host machinery to replicate. During the process of replication, a virus hijacks cellular functions, avoids or inhibits host antiviral defenses, and sometimes causes disease in the host organism. One effective way to fight viral infection is to identify molecules that inhibit the function of essential viral proteins. The studies described in this dissertation focus …

Assessing The Trophic Positions Of Lake Michigan Fishes Using Stable Carbon And Nitrogen Isotopes, Benjamin Alan Turschak

Theses and Dissertations

Lake Michigan is the second largest Laurentian Great Lake and is characterized by broad spatiotemporal variation in ecosystem processes such as nutrient cycling and energy flow. Variation in ecosystem processes—such as those induced by invasive dreissenid mussels—and subsequent changes in the spatiotemporal distribution of resources (i.e. prey or habitat) has resulted in major changes in Lake Michigan’s fish community. The ability of fish species to cope with spatiotemporal resource dynamics is at least partially dependent on their ability to shift apparent trophic position along various resource gradients. The objectives of this research were to quantify trophic positions of Lake Michigan …

Round Goby, Neogobius Melanostomus, Abundance And Productivity In The Rocky Nearshore Zone Of Lake Michigan, Graceanne Kay Tarsa

Theses and Dissertations

Few organisms are well adapted to efficiently feed on invasive dreissenid mussels, a dominant primary consumer in Lake Michigan and other lower Great Lakes. As a result, these mussels represent a potential trophic dead-end. However, round gobies (Neogobius melanostomus), an invasive species introduced to the Great Lakes region at the end of the 20th century, possess several adaptive advantages that allow them to make dreissenid mussels a significant portion of their diet. Since their invasion, round gobies have become the predominant shallow nearshore fish in Lake Michigan and their success, along with the success of dreissenid mussels, has caused major …

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 …

Resting State Functional Connectivity In The Default Mode Network: Relationships Between Cannabis Use, Gender, And Cognition In Adolescents And Young Adults, Megan Ritchay

Theses and Dissertations

Introduction: Cannabis is the most commonly used illicit substance in the United States, and nearly 1 in 4 young adults are current cannabis users. The psychoactive component of cannabis, THC, is active at cannabinoid receptors, type 1, or CB1 receptors. CB1 receptors play a critical role in neural development, and chronic cannabis use causes desensitization and downregulation of these receptors. Chronic cannabis use is associated with changes in resting state functional connectivity (RSFC) in the default mode network (DMN) in adolescents and young adults, although results are somewhat inconsistent across studies, likely due to differing methodologies. Additionally, cannabis effects appear …

Roles Of Secreted Proteins And Iron Utilization Proteins In Virulence Of The Fish Pathogen Flavobacterium Columnare, Rachel Conrad

Theses and Dissertations

The Gram-negative bacterium Flavobacterium columnare is the causative agent of columnaris disease and is responsible for significant economic losses in aquaculture. Little is known regarding the virulence factors produced by F. columnare, and control measures are limited. Like many members of the phylum Bacteroidetes, F. columnare uses the type IX secretion system (T9SS) to secrete enzymes, adhesins, and proteins involved in gliding motility. When a core component of this system was deleted in the wild type strain, the resulting mutant was avirulent in zebrafish, rainbow trout, and channel catfish infection studies. This suggests that the individual secreted proteins may function …

Resting-State Versus Breath-Hold For Testing Functional Magnetic Resonance Imaging Integrity In Pre-Surgical Planning, Nooshin Jafari Fesharaki

Theses and Dissertations

The neuro-vascular coupling mechanism responsible for blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) signals can be focally disrupted by various pathological factors (such as brain tumors) while leaving the underlying neurons functionally intact. Such neuro-vascular uncoupling (NVU) can pose serious complications for clinical use of fMRI. Mapping of cerebrovascular reactivity (CVR), which is a measure of the dilatory function of cerebral vasculature, can be a useful approach for detecting potential NVU. The widely-accepted approach for non-invasive CVR mapping requires the patient to perform a breath-hold challenge, which may have practical disadvantages for many patient populations. Thus, a …

Negative Regulation Of The Kinase Lin-45 By The E3/E4 Ubiquitin Ligase Ufd-2, Augustin Deniaud

Theses and Dissertations

The serine/threonine kinase BRAF is a key part of the Ras-Raf-MEK-ERK pathway, an inducer of cell growth, differentiation, and survival. In humans, activating mutations, most commonly BRAF(V600E), have been detected in several cancers, including melanoma and thyroid cancer. In the Caenorhabditis elegans ortholog LIN-45, the equivalent mutation LIN-45(V627E) results in elevated Raf-MEK-ERK signaling. We performed an unbiased genetic screen to identify negative regulators of LIN-45(V627E). Here, we report the identification of the E3/E4 ubiquitin ligase UFD-2, and show it is a negative regulator of LIN-45 protein activity and levels. Loss of UFD-2 leads to accumulation of wild-type LIN-45 protein as …

Effects Of A Novel, Non-Toxic Histone Deacetylase Inhibitor On Hippocampal Memory Formation, Histone Acetylation, And Bdnf Gene Expression In Male Mice, Sarah Brianna Beamish

Theses and Dissertations

Memory dysfunction is a common symptom of aging, neuropsychiatric disorders, and neurodegenerative disorders, yet truly effective treatments for memory loss do not exist. De novo gene transcription is a molecular requirement for long-term memory formation. The transcription of genes related to synaptic plasticity and learning are regulated in part by histone acetylation, an epigenetic mechanism that regulates chromatin accessibility. Pharmacological compounds that maintain histone acetylation, called histone deacetylase inhibitors (HDACi), enhance memory by preventing deacetylation of core histone proteins, which initiates binding of transcriptional machinery to open chromatin. Therefore, HDACi are potentially promising therapeutics that could be used to prevent …

Neural Substrates Of Fear Generalization And Its Associations With Anxiety And Intolerance Of Uncertainty, Ashley Ann Huggins

Theses and Dissertations

Fear generalization - the tendency to interpret ambiguous stimuli as threatening due to perceptual similarity to a learned threat – is an adaptive process. Overgeneralization, however, is maladaptive and has been implicated in a number of anxiety disorders. Neuroimaging research has indicated several regions sensitive to effects of generalization, including regions involved in fear excitation (e.g., amygdala, insula) and inhibition (e.g., ventromedial prefrontal cortex). Research has suggested several other small brain regions may play an important role in this process (e.g., hippocampal subfields, bed nucleus of the stria terminalis [BNST], habenula), but, to date, these regions have not been examined …

Behavioral And Neural Correlates Of Episodic Memory Regulation, Mrinmayi Kulkarni

Theses and Dissertations

Episodic memory retrieval, while critical for daily living, needs to be regulated to maintain goal-directed behavior. Past work has shown that episodic memory regulation engages brain regions involved in cognitive control, such as the dorsolateral and ventrolateral prefrontal cortex. These regions interact with the medial temporal lobe structures to control retrieval processes. In the current study, I paired eye-tracking, a sensitive index of memory, with fMRI in a novel paradigm to address several open questions in the field of episodic memory regulation. Participants initially encoded three celebrity faces and three tools with multiple indoor and outdoor scenes. In a subsequent …

Study Of Binding Induced Mechanical Stabilization Of Proteins Using A Single Molecule Approach, Narayan Prasad Dahal

Theses and Dissertations

Proteins operating under force are involved in several biological processes and perform multiple roles. While the structures and roles of numerous proteins are ubiquitous, their involvement in binding-induced stabilization is currently poorly understood. Most protein systems operating under force interact with their binding partners in a force-dependent manner. Such systems are related to bacterial adhesion, cellular mechano-transduction, and muscle contraction. With a goal of understanding mechanical stability induced through ligand binding, I used single-molecule magnetic tweezers to study several protein systems. This approach involves protein engineering and hetero-covalent attachment chemistry, which, combined with magnetic tweezers, allows us to characterize the …

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, …

Investigating Mechanisms Of Nanotoxicity Of A Next-Generation Lithium Cobalt Oxide Nanomaterial, Nicholas Joseph Niemuth

Theses and Dissertations

Commercial use of engineered nanomaterials (ENMs; materials in the range of 1-100 nm) has grown dramatically since the discovery of the means to observe, characterize, and controllably synthesize these materials at the end of the 20th century. Today, ENMs represent a global market valued in the trillions of dollars, incorporated into products because of the unique properties they confer, including increased strength, catalytic activity, and interactions with light. In this time, ENMs have also grown from relatively simple first-generation materials, such as Au, Ag, and carbon ENMs, to complex next-generation materials incorporating numerous elements into materials with complex secondary structures, …

Longitudinal Changes In Resting-State Functional Connectivity Of The Salience Network Among Individuals At-Risk For Ptsd Development, Kyrie Sellnow

Theses and Dissertations

Predicting post-traumatic stress disorder (PTSD) following a traumatic event has been a focus of recent neuroimaging research in the hopes of identifying key biomarkers that contribute to the disorder’s development. One possibility relies on understanding the connectivity between intrinsic connectivity networks (ICNs), including the salience network (SN). Prior research has consistently identified hyperconnectivity among SN regions among those with chronic PTSD, and this study aimed to examine the role of SN connectivity over time on PTSD symptom development. To do so, this study recruited individuals presenting to the Emergency Department with traumatic injuries to complete two resting-state fMRI scans: one …

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 …

Behavioral, Physiological, And Molecular Characterization Of Long-Term Administration Of A Novel Estrogen Receptor Beta Agonist In A Mouse Model Of Menopause, Aaron William Fleischer

Theses and Dissertations

The menopausal loss of circulating hormones, including estrogens, is associated with negative symptoms, such as hot flashes, anxiety and depression, cognitive decline, and weight gain. Although estrogenic hormone therapies (HT) prevent many of the negative symptoms related to the menopausal transition, these same therapies are associated with increased health risks, such as the development of breast and ovarian cancers, which is mediated by the activation of the a (ERa), but not b (ERb), estrogen receptor isoform. Furthermore, ERb agonism has previously been shown to reduce preclinical indices of hot flashes, memory decline, anxiety, and depression. As most ERb agonists are …

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 …

Neural Correlates Underlying The Interactions Between Anxiety And Cannabis Use In Predicting Motor Response Inhibition, Richard Ward

Theses and Dissertations

The ability to effectively withhold an inappropriate response is a critical feature of cognitive control. Prior research indicates alterations in neural processes required for motor response inhibition in anxious individuals, including those with posttraumatic stress disorder (PTSD), and those who engage in regular cannabis use. However, thus far most research has examined how anxiety-related symptoms and cannabis use influence response inhibition in isolation of one another. The current study examined the interactions between anxious symptomology and recent cannabis use in a sample that recently experienced a traumatic event using functional magnetic resonance imaging (fMRI) during the completion of a Stop-Signal …

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 …