Life Sciences Commons^™

Retroviral Infection Dynamics In Maine's Wild Turkeys, Stephanie A. Shea

Electronic Theses and Dissertations

Widespread wild turkey reintroductions in the late 1900s have led to increases in population density and geographic distribution across North America. This rapid population expansion has put them into proximity with closely-related wild and domestic avian species, increasing the risks of pathogen transmission. Lymphoproliferative disease virus (LPDV) is an avian oncogenic retrovirus detected in wild turkeys in 2009, and previously known to infect domestic turkeys. Following its initial detection, surveys reported variable LPDV prevalence across eastern North America with most wild turkeys being asymptomatic, however diagnostic cases revealed 10% mortality of LPDV-infected individuals. Given its recent detection, little is known …

An Examination Of Bone Loss During Space Travel With Differential Gene Expression Analysis, Claudia Vo

Master's Projects

Spaceflight poses many risks to human health due to the harsh conditions of microgravity, cosmic radiation, and confinement. One of the impacts that spaceflight entails is bone loss, which is a risk to astronauts as future space missions will require long travel durations. To elucidate the role of genetics in spaceflight bone loss, in this study differential gene expression analysis was performed using Nextflow-RCP, an adaptation of NASA Genelab’s RNA-Seq Consensus pipeline. The dataset for this project was GLDS-241, which contained samples from mice femoral skin. To gain a comprehensive understanding of the genes involved in bone loss, the results …

Mrna-Sequencing Pipeline For Differential Gene Expression Analysis, Crystal Han

Master's Projects

Endothelial cells (ECs) line the insides of blood vessels and play a key role in the coagulation and vascular repair system. Under normal circumstances, ECs are constantly expressing anticoagulants to prevent clots and maintain healthy blood flow. But when there is an injury to the vessel, endothelial cells become centrally involved in orchestrating the complex series of events that would lead to the clotting of the wound. Thus, ECs are dynamic and respond accordingly based on changes in their local environment. Unfortunately, endothelial cells can sometimes misinterpret cues from the environment and initiate coagulation when there is no vessel damage …

Effective Cancer Detection Using Higher-Order Genome Architecture And Chromatin Interactions, My Chung

Master's Projects

Cancer is a complex disease which requires interactions between cell-intrinsic alterations and tumor microenvironment. The connection between epigenetics and genomic structure plays a key role in chromatin interaction which promotes enhancer-promoter interactions for transcriptional activities. Alterations of chromatin states in oncogenic signaling pathway potentially cause cancer cell-intrinsic changes and inappropriate instructions to normal cell cycles, leading to abnormal cell growth. Resulting phenotypic changes are correlated to underlying changes in higher-order chromatin structure such as topologically associating domains (TADs) and compartments. In cancer cells, TAD structure is usually altered to facilitate the communication between enhancers and promoters in addition to higher …

Molecular Investigation Into The Biologic And Prognostic Elements Of Peripheral T-Cell Lymphoma With Regulators Of Tumor Microenvironment Signaling Explored In Model Systems, Tyler Herek

Theses & Dissertations

Peripheral T-cell lymphoma (PTCL) is heterogenous group of mature T-cell neoplasms characterized by distinctive transcriptional and genetic lesions. Herein, we investigated DNMT3A mutations in angioimmunoblastic T-cell lymphoma (AITL, n = 176) and novel molecular subtypes (i.e., PTCL-GATA3, n = 61 and PTCL-TBX21, n = 80) within PTCL- NOS and observed significant biological and prognostic differences associated with DNMT3A mutations. DNMT3A-mutated PTCL-TBX21 cases showed inferior overall survival (OS; p < 0.005), with DNMT3A mutations (DNMT3A-MT) skewed toward the methyltransferase domain and in the dimerization domain (S881-R887). Transcriptional profiling demonstrated significant enrichment of activated CD8⁺ T-cell cytotoxic gene signatures in the tumor microenvironment of DNMT3A-MT PTCL-TBX21 cases. Genome-wide methylation analysis of DNMT3A-R882/Q886 versus wild-type in PTCL-TBX21 cases demonstrated hypomethylation in target genes regulating T-cytotoxic genes, TCR …

Functional Characterization Of Cancer-Associated Dna Polymerase Ε Variants, Stephanie R. Barbari

Theses & Dissertations

Replicative DNA polymerases ε (Polε) and δ (Polδ) achieve high fidelity DNA synthesis through a precise balance of polymerization and exonucleolytic proofreading. Errors that escape proofreading are corrected by DNA mismatch repair (MMR). Ultramutated human cancers with proficient MMR carry alterations in the exonuclease domain of Polε, which were initially predicted to abolish proofreading. However, functional studies in yeast of the most recurrent Polε-P286R variant suggested defects beyond a loss of exonuclease activity. Indeed, biochemical analysis of the yeast Polε-P286R analog revealed increased polymerization capacity in addition to decreased proofreading, which enables efficient mismatch extension and bypass of replication-blocking non-B …

Nuclear Receptor Coactivator 3 In Endoplasmic Reticulum Stress And Stress Granule Dynamics In Pancreatic Cancer, Andrew Kisling

Theses & Dissertations

Pancreatic cancer is predicted to be the second-leading cause of cancer-related deaths within the next decade. Nuclear receptor coactivator 3 (NCOA3/SRC3/AIB1) regulates an array of metabolic and signaling pathways and has been established by our group and others as a critical regulator pancreatic cancer progression and metastasis. A recent study demonstrated NCOA3 regulation by the IRE1α-XBP1 axis of the unfolded protein response (UPR), suggesting a link between NCOA3 and cellular stress management. Furthermore, NCOA3 has been shown to directly bind to a scaffolding protein of stress granules (SGs). Since SG assembly is regulated by the UPR, we hypothesized that NCOA3 …

Usp11 And Usp7 Deubiquitinases Regulate Sprtn Auto-Proteolysis And Sprtn-Mediated Dna-Protein Crosslink Repair, Megan C. Perry

Theses & Dissertations

DNA repair pathways that recognize and remove damaged DNA are vital for maintenance of genomic stability and prevention of tumorigenesis. Conversely, these pathways may be robust in tumor cells, thus diminishing the anti-cancer potential of available therapies. DNA-protein crosslinks (DPCs) are particularly deleterious DNA adducts that occur when proteins become irreversibly covalently bound to the DNA. DPCs represent a diverse group of lesions, as any protein can be crosslinked to the DNA duplex by non-specific crosslinking agents like reactive aldehydes and radiation. Additionally, functional DNA-binding proteins such as topoisomerases may become permanently crosslinked to DNA ends by abortive enzymatic processes …

A Pkcα-Mediated Growth Suppressive Mek-Erk Signaling Axis In Intestinal Epithelial Cells, Navneet Kaur

Theses & Dissertations

Members of the protein kinase C (PKC) family of serine/threonine kinases are involved in regulation of fundamental cellular functions, including proliferation, differentiation, survival, migration, and transformation. Increasing evidence points to anti-proliferative and tumor suppressive role of PKCs. Our laboratory and others have reported that the classical PKC isozyme, PKCαnegatively regulates proliferation and tumorigenesis in the intestinal epithelium. Our laboratory has further determined that PKCα signaling induces a program of cell cycle withdrawal in intestinal epithelial cells that involves downregulation of the pro-proliferative proteins, cyclin D1 and Id1, and upregulation of the cyclin dependent kinase (CDK) inhibitor, p21^Cip1. Unexpectedly, …

Immunological Factors Associated With Siv/ Shiv Persistence In Diverse Tissue Niches, Omalla A. Olwenyi

Theses & Dissertations

The significant challenge towards a successful HIV cure lies in eradicating persistent viral reservoirs across diverse tissue niches. As a result, HIV-infected individuals have to resort to lifelong antiretroviral therapy. Recent news of supposed HIV eradication in a second patient has further re-invigorated the fields of HIV cure. However, a few barriers remain, such as the lack of currently available assays to accurately quantify viral reservoirs, limited information on cellular factors associated with persistence, and varied dynamics of the viral reservoir in various body compartments. Lastly, HIV-infected individuals live different lifestyles stemming from comorbid substance abuse including consumption of morphine, …

Utilization Of Secondary Processing Mill Residues In Maine To Produce Raw Materials For Manufacturing Wood-Plastic Composites (Wpcs), Geeta Pokhrel

Electronic Theses and Dissertations

The overall objective of this study was to explore the potential of utilizing secondary processing mill residues generated in Maine (1.6 million tons annually) in Wood-Plastic Composites (WPCs). Attributable to the huge shipping costs for transporting wood flour over long distances, wood pellets are explored as alternative feedstock for WPCs manufacturing. The mill residues from four species based on their abundance and potential applicability for utilization in WPCs manufacturing were used to make the two different feedstocks. The properties of the wood flour and pellets were studied along with the comparison of the properties of polypropylene-based WPCs using both of …

Food Safety And Functionality Assessment Of Kombucha Systems Through Bacillus Cereus Spore And Probiotic Inoculations, Alexandria L. Bromley

Electronic Theses and Dissertations

Kombucha is a SCOBY-fermented tea beverage known for its taste, sensorial qualities, and high endogenous microbial load. In recent years, kombucha has become a popular functional food with a compound annual growth rate of 25% from 2015 to 2020 in American kombucha sales alone, and sales are predicted to keep increasing significantly over the next decade. However, kombucha is lacking in scientific research, and there is still much to be explored regarding its safety and native probiotic content. This research looked into the various routes of contamination of several kombucha systems as well as the feasibility of the producing a …

Coyote Management In San Francisco, Matthew Greer

Master's Projects and Capstones

As cities in North America grow, coyotes have become progressively more important species in urban ecosystems. Moreover, as coyotes increasingly use these urban spaces, human-coyote conflicts have become more common, creating a need for new management strategies. This paper will explore how the city of San Francisco could create a new coyote management plan for its highly visible coyote population. San Francisco has had a persistent coyote population since the early 2000s (Todd, 2018). Currently, the coyote population is close to 100 individuals and is still growing (J. Young, Presidio Trust, pers. comm.). To explore this topic a literature review …

Joint Management Of Upland & Aquatic Habitat For The California Red-Legged Frog & California Tiger Salamander, Kyle E. Verblaauw

Master's Projects and Capstones

As federally and state protected amphibians, the California tiger salamander (Ambystoma californiense) and the California red-legged frog (Rana draytonii) are recipients of ample management focus. Both species face a variety of threats, including habitat loss and alteration, introduction of non-native species, spread of disease, and effects of climate change. While management plans for the California tiger salamander and California red-legged frog exist, they frequently do not consider both species in tandem and often contain multiple shortcomings. This document aims to address the shortfalls of current management by providing practical recommendations for jointly managing the upland and …

Development Of Polymeric Cxcr4 Targeting Carriers For Sirna Delivery To Treat Acute Kidney Injury, Weimin Tang

Theses & Dissertations

Acute kidney injury (AKI) is a major kidney disease that is characterized by a sudden loss of renal function which manifests by a decrease in urine output and an increase in serum creatinine. AKI is a global healthcare burden associated with high morbidity, mortality, and increasing cost. Currently there are no effective pharmacological treatments available. Apoptosis induced by p53 has been demonstrated as an important pathological mechanism for the development of AKI. Meanwhile, CXCR4/SDF-1 axis has been associated with the inflammation during AKI, and CXCR4 is overexpressed on injured tubules. This dissertation hypothesized that polycations with CXCR4 targeting ability could …

Integrative Analysis Of Multi-Omics Kinome Data And Virtual Screening Of Identified Targets With Pan-Cancer Application, Siddesh Southekal

Theses & Dissertations

Cancer is a heterogeneous disease characterized by the uncontrolled growth and dissemination of abnormal cells. Unfortunately, it is also challenging to treat due to the heterogeneous nature of the tumors and the lack of known drugs that are effective against all tumor subpopulations.

The human protein kinases represent an essential and diverse family of enzymes and are often dysregulated in cancer. The human kinome comprises only around 2% of all coding genes of the human genome but phosphorylates about 30% of cellular proteins critical for regulating various biological processes such as cell proliferation, cell cycle progression, apoptosis, motility, growth, differentiation, …

Understanding The Impact Of Chlamydia Trachomatis Infection On Host Vesicular Trafficking, Lisa M. Jorgenson

Theses & Dissertations

Chlamydia trachomatis is a highly evolved obligate intracellular bacterial pathogen. During infection, organisms reside within a host epithelial cell in a membrane-bound vacuole called the inclusion. The inclusion membrane contains both pathogen and host components, including unique chlamydial type III effector proteins called Incs and host lipids like cholesterol and sphingomyelin. The inclusion membrane serves as the main barrier between the bacteria and the host cytosol, and thus, functions as the platform supporting host-chlamydial interactions. Via the inclusion membrane, C. trachomatis intercepts components of host vesicular traffic including many host SNARE proteins, which are a conserved family of eukaryotic proteins …

Development Of A Muc16-Targeted Near-Infrared Antibody Probe For Fluorescence-Guided Surgery Of Pancreatic Cancer, Madeline T. Olson

Theses & Dissertations

Pancreatic cancer (PDAC) is an extremely lethal disease with an overall survival rate of 10%. Surgery remains the only potentially curative treatment option, but resections are complicated by infiltrative disease, proximity of critical vasculature, peritumoral inflammation, and dense stroma. Surgeons are limited to tactile and visual cues to differentiate cancerous tissue from normal tissue. Furthermore, translating preoperative images to the intraoperative setting poses additional challenges for tumor detection, and can result in undetected and unresected lesions. Thus, PDAC has high rates of incomplete resections, and subsequently, disease recurrence. Fluorescence-guided surgery (FGS) has emerged as a method to improve intraoperative detection …

The Rotator Cuff Tendon-To-Bone Interface: Maturation, Aging, And 3d Bioprinting For Regeneration, Xiping Jiang

Theses & Dissertations

Rotator cuff tendon injuries often occur at the tendon-to-bone interface (i.e., enthesis) area with a high prevalence for the elderly population. In addition, regeneration of the gradient structure of the enthesis is still a significant clinical challenge. Our studies aim to identify the histological, molecular, and biomechanical alterations of the rotator cuff enthesis with maturation and aging, and develop a novel therapeutic method using three-dimensional (3D) bioprinting technique to regenerate a functional enthesis. Striking variations of the entheses were observed both histologically and biomechanically during the maturation process. The histological features did not show many differences at the insertion site …

Metabolic Heterogeneity And The Roles Of Cody And Ccpa In Central Metabolism And S. Aureus Biofilm Formation., Logan L. Bulock

Theses & Dissertations

Staphylococcus aureus is a metabolically versatile human pathogen, causing disease in many areas of the body. Its versatility can be attributed to the fact that it utilizes a variety of tools to adapt to many different environments, including toxins to scavenge from the host and multiple transporters to compete for its preferred carbon sources. S. aureus can also survive in harsh conditions through biofilm development, which are notoriously recalcitrant to antibiotics and immune defenses. Biofilms exhibit marked heterogeneity, with division of labor for production of matrix components and differential gene expression among various niches within the biofilm.

In this study, …

Fear Of The Human "Super-Predator" In African Mammals, Nikita R. Frizzelle

Electronic Thesis and Dissertation Repository

Humans’ exploitive killing of virtually every mammal species globally may result in a perception of humans as feared, ultra-lethal predators. In Africa, mammals are central to the continent’s tourism industry; however, it is largely unknown whether African mammals fear the presence of tourists. Firstly, I aimed to review how the presence of humans on the landscape affects African mammal behaviour. Of 31 studies, most authors reported that humans alter mammal behaviour in a manner that may negatively impact survival. To test if a fear of humans can pervade communities, I simulated the presence of humans, hunting, lions, and birds using …

Pushing It To The Limit: Determining Asian Elephant (Elephas Maximus) Olfactory Sensitivity And Discrimination Through A Behavioral Choice Task, Matthew S. Rudolph

Theses and Dissertations

Elephants have shown remarkable olfactory capabilities. Their sense of smell impacts their foraging choices, behavior, and ultimately, survival. Being able to detect a target odor can allow elephants to locate specific resources, identify threats, and find receptive conspecifics. Previous studies have shown that elephants can consistently detect target odors, but have not identified the limits of this detection. Thus, to investigate the extent of elephants’ odor detection capabilities, we tested Asian elephants in a two-step odor discrimination task. First, we investigated whether elephants could detect odors at varying levels of dilution after a training procedure, and then whether they could …

Effects Of Catharanthine On Dopamine Release In The Nucleus Accumbens And Ethanol Consumption, Emily Baldwin

Undergraduate Honors Theses

This thesis discusses the history of catharanthine and related compounds, and their potential anti-addictive properties. Current research is exploring possible mechanisms of these properties. Past studies have found catharanthine has effects on neurons that project to the mesocorticolimbic system, an area implicated in addiction. We have seen that catharanthine decreases evoked dopamine (DA) release but increases basal DA release. This is the first study to investigate catharanthine’s effect on DA transmission in vivo. Using microdialysis, we determined the effect of catharanthine on DA in the nucleus accumbens of the striatum. This study determines the effect of different doses of …

Comparing Macroinvertebrate Total Abundance And Total Biomass On Five Substrate Types From Upstream To Downstream On The North Branch Of The Au Sable River, Paul David Dingman

Masters Theses

The North Branch of the Au Sable River is located in the northern lower peninsula of Michigan and is known for prolific hatches of Ephemeroptera (mayflies), Trichoptera (caddisflies), and Plecoptera (stoneflies). Macroinvertebrates play an important role in processing and recycling organic material in rivers and are a valuable food source for trout. In 2018, anglers were reporting catching fewer numbers of brook and brown trout (Salmo trutta and Salvelinus fontinalis). The Michigan Department of Natural Resources (MDNR) determined significantly lower abundance than the historical average. We hypothesized that trout abundances were lower due to a lack of prey …

Intrinsically Disordered Protein Regions In Human Evolution And As Therapeutic Targets, Karen Paco Mendivil

KGI Theses and Dissertations

Intrinsically disordered proteins (IDPs) and IDP regions (IDPRs) fail to form stable structures but have important biological functions via interacting with various molecular partners (proteins, DNA, RNA, glycosaminoglycans). We hypothesized that IDPRs are potential targets for therapeutics development because they are reservoirs of evolutionary innovation, and they play crucial roles in adaptation to pathogens.

We first studied the evolution of IDPRs in the human proteome and compared it with the proteome of non-human primates. We have found that evolutionary young protein-coding genes have included low conserved regions in the N-terminal part of proteins, and such regions are linked to high …

Energetic Tradeoffs, Infection, And Immunity In Wild Chimpanzees Of Uganda And Tanzania, Sarah Renee Phillips

Anthropology ETDs

Infectious disease is a primary source of mortality for most mammal species, but scientists have little understanding of factors driving variation in infection and immunity between individuals, populations, and species in the wild. Life history theory provides an evolutionary framework for delineating distribution of available energy to competing physiological demands, including growth, reproduction, and maintenance. Early life reproduction should be favored over late life survival, but, in long-lived species, reproductive success is strongly tied to survival to old age. Slower pace of reproduction could allow investment in immunity, reducing risk of morbidity and mortality to infectious disease. Additionally, several host …

Exploring The Biofilm Of Candida Auris As It Relates To Persistence In Clinical Setting And Susceptibility To Antimicrobials, Bethany Butts

Master of Science in Integrative Biology Theses

The rapid rise of drug-resistant pathogens is a global health concern. Known pathogens are acquiring resistance to many commonly used drugs, while new drug-resistant pathogens are emerging. These resistant pathogens are responsible for many healthcare-associated infections (HAI) [1, 2]. Candida auris is among these emerging drug-resistant pathogens, first described in 2009. The CDC labels C. auris at the highest level of global public health threat [3,4]. Effective methods of decolonization and control of the organisms have yet to be established, as it is resistant to many agents used for microbial control. Recent research has found that C. auris has the …

Molecular Mechanisms Of Aberrant Protein Glycosylation In Pancreatic Cancer Stemness And Metastasis, Frank Leon

Theses & Dissertations

A myriad of genetic and other abnormal changes underlies the aggressiveness and dissemination properties observed in pancreatic cancer (PC). Aberrant protein glycosylation is a commonly observed feature in PC. The modification of protein O-glycosylation is mediated by glycosyltransferases, which attach and sequentially elongate monosaccharides on Serine/Threonine (Ser/Thr) motifs. Aberrant glycosylation is recognized as an emerging hallmark of cancer where a disruption in normal glycosylation results in irregular O-glycans.

This dissertation research has investigated the consequences of aberrant protein glycosylation on stemness and enhancement of metastatic properties in pancreatic ductal adenocarcinoma (PDAC). Several publications have reported aberrant O-glycosylation increases in oncogenic …

Restricted Microbial Presence, Activity, And Community Structuring Within Dry Valley Soils Of Antarctica, Scott Fillerup George

Theses and Dissertations

The McMurdo Dry Valley region is the largest ice-free area of Antarctica. Harsh abiotic conditions of the polar desert ecosystem, including extreme cold, aridity, and limited nutrient availability select for unique taxa. The comparatively simple terrestrial ecosystem is well-suited for investigating edaphic influences on microbial presence, activity, and community structuring. The Dry Valleys are viewed as a useful analog for Mars astrobiology investigations. However, most biotic investigations have been focused on lower elevations, where an understanding of edaphic effects on microbial communities within its generally more favorable conditions has emerged. Transiently wetted Dry Valley water tracks may be analogous to …

Utilizing Isothermal Titration Calorimetry For Measuring Beta-Galactosidase Activity In Liquid Dairy Products, Eliza Anne Brock

Theses and Dissertations

This research explores Isothermal Titration Calorimetry as a method for measuring beta-galactosidase activity directly and continuously in milk, sweet whey, sweet whey permeate, acid whey, and acid whey permeate. Beta-galactosidase in various concentrations was injected into each of the liquid dairy products spiked with lactose to verify if the heat rate from the enzymatic reaction could be observed. In addition, a consistent concentration of beta-galactosidase was injected into various concentrations of lactose in the products, to observe the heat rates from the enzymatic reaction. There was exothermic activity that never returned to baseline demonstrated in milk, sweet whey, and sweet …