Life Sciences Commons^™

Mathematical Modeling And Analysis Of Inflammation And Tissue Repair: Lung Inflammation And Wound Healing In Corals Under Stress, Quintessa Hay

Theses and Dissertations

A variety of insults, including tissue injury and/or exposure to pathogen, elicit an immune response in many organisms. An improperly regulated immune response can result in deleterious effects to the organism. Here we present models for lung injury in young and old mice and models for wound healing in coral reefs.

It is well known that the immune response becomes less effective in older individuals. This is of particular interest in pulmonary insults such as ventilator induced lung injury (VILI) or lung infection. We extended a mathematical model for the inflammatory response to VILI and used experimental data to select …

Sphingosine Kinase 2 Depletion Dysregulates Hepatic Redox Metabolism And Enhances Inflammation In Early Metabolic Dysfunction-Associated Steatohepatitis (Mash), Kaitlyn Georgene Jackson

Theses and Dissertations

Metabolic dysfunction-associated steatotic liver disease (MASLD) currently affects one in three people worldwide; its prevalence is growing alongside other cardiometabolic disorders. Aberrations to redox and sphingolipid metabolism contribute to MASLD pathologic progression. Sphingosine-1-phosphate (S1P) is an active lipid, meaning that S1P participates in biochemical processes within the cell. S1P is generated by two distinct isoenzymes, sphingosine kinase (SphK)1 and SphK2. The localization of the SphK enzyme dictates S1P function. While cytosolic SphK1-generated S1P is well-characterized, nuclear and mitochondrial SphK2-generated S1P is less known. Moreover, SphK2 depletion effects on cellular redox processes and inflammation are not well-defined.

This study defines the …

The Role Of Hdac6 In Periodontal Inflammation, Hannah S. Lohner

Theses and Dissertations

Periodontal disease is a polymicrobial infection-induced chronic inflammatory disease and results in irreversible tissue damage and bone loss. While bacteria play a large role in the initiation of this disease, excessive and prolonged inflammatory immune responses are fundamental for its progression, making host directed therapy (HDT) a possible and potentially valuable treatment. Histone Deacetylase 6 (HDAC6) is an enzyme that removes acetyl groups from both histone and non-histone proteins, giving it a potential role in regulating inflammation initiated by pathogenic oral bacteria. Previous studies indicated that HDACs act as a bivalent regulator in inflammatory responses; however, the role that HDAC6 …

Role Of Human Intermediate Form Prl Receptor I-Tail In The Pathogenesis Of Breast Cancer, Shanwei Shen

Theses and Dissertations

Breast cancer continues to be the second most common cancer in women in the United States. The neuroendocrine hormone human prolactin (hPRL) plays an important role in normal mammary gland development and growth, stimulating normal breast tissue proliferation and differentiation. Considerable evidence has shown that hPRL is involved in the malignant transformation of human breast tissue. hPRL enhances viability, invasiveness, and proliferation of breast cancer cells in vitro. Evidence from epidemiologic and genetic studies also implicates role of hPRL in the pathogenesis of breast cancer. Its cognate receptor the human prolactin receptor (hPRLr) is required for the action of hPRL. …

Investigation Of Brain Function And Structural Development As Risk Factors Of Suicidal Thoughts And Behaviors, Yi Zhou

Theses and Dissertations

Background: Identifying risk factors for suicidal thoughts and behaviors, especially causal ones, will be imperative to improving screening and treatment interventions. To identify replicable brain-based risk factors, there is increasing evidence indicating the need for large sample sizes, in the hundreds to thousands, in order to achieve a sufficient level of statistical power to detect them. Furthermore, longitudinal studies of brain and behavioral factors will be essential to understanding how suicide develops, especially the transition from suicide ideation to attempt. While experimental studies may not be feasible or ethical, genetically informed methods for testing evidence for causation are an alternative …

Mild Traumatic Brain Injury In Yucatan Minipigs: Assessing Changes In Approachability And Mechanical Nociception Following Diffuse Central Fluid Percussion Injury, Mark D. Pavlichenko

Theses and Dissertations

Traumatic brain injury (TBI) is a major healthcare concern affecting millions. Symptoms of TBI include sensory sensitivity and social changes that may persist long-term. Due to similarities in cytoarchitecture, metabolism, and inflammation, higher order minipig models are advantageous for translational TBI research, however, there remains a shortage of information regarding their behavioral and sensory sequelae following injury. Therefore, in this study, we assessed changes in sociability and somatosensation in adult male and female Yucatan minipigs for up to one-week following a sham or central fluid percussion injury (cFPI). Specifically, the voluntary human approach task (VHAT) and the forced human approach …

Re-Programming Transcription Factor Function For Neuroscience Research Of Addiction: Investigating The Role Of Zinc Finger Proteins In Driving Cocaine Reinforcement In Mice, Joseph A. Picone

Theses and Dissertations

Administration of addictive drugs like cocaine or morphine initiates aberrant gene transcription within brain reward circuitry neurons, which contributes to the lasting behavioral maladaptations that define addiction. The drug-induced expression and function of key brain transcription factors (TFs) is one major mechanism through which these drugs are able to regulate transcription, and as a consequence, lasting damaging drug-related behaviors including compulsive drug use. The goal of this dissertation is to more fully understand the molecular mechanistic drug-specific actions of TFs within the rodent nucleus accumbens (NAc). The findings from these studies could serve as the basis to identify novel candidate …

An Exploratory Study Of The Effects Of Bis-Substituted Triazolium Bromide Salts On The Proliferation Of Wi-38 Lung Cells And H-1299 Lung Cancer Cells, Rakaiya Martin

Theses and Dissertations

Lung cancer is the leading cause of cancer deaths worldwide. The battle against this disease continues to challenge physicians and scientists daily, due to its various forms, treatments, and responses. Depending on the grade and stage of the disease, treatments can be extensive, encompassing surgery, chemotherapy, and radiation therapy. Though these therapeutics can prolong a patient’s life, they often have significant ramifications. For instance, radiation therapy has an extensive list of side effects, from organ damage to loss of fertility. These outcomes have driven scientists to explore the applicability of novel cancer treatments. Imidazolium and benzimidazolium salts have been shown …

Facilitative And Competitive Interactions Among Dune Grass Species In Monoculture And Polyculture Communities, Anne M. Sciolino

Theses and Dissertations

Coastal dunes are natural barriers between land and sea and are imperative to the protection and preservation of inland ecosystems and human infrastructure. However, due to global warming, seal level rise, and coastal development, coastal dunes are under constant threat of destruction. Restoration efforts have been implemented to rebuild the protective function of dunes through the planting of dune building grasses. Dune grasses build and maintain these vital sand dunes. However, little is known about facilitative and competitive relationships among the grasses. In order to maximize restoration efforts, research is needed to better understand the biotic interactions among restorative grass …

Evaluation Of Alternative Methods For Dna Recovery Of Compromised Skeletal Remains, Ciara N. Rhodes

Theses and Dissertations

Skeletal remains frequently serve as the sole source of genetic material available for developing a profile in cases concerning unidentified human remains or mass casualties. Nevertheless, as unidentified skeletal remains age and are exposed to uncontrolled environmental conditions, the success rates of conventional methods of bone analysis diminish significantly. The physical and mechanical processing of skeletal remains into fine powder for DNA isolation and downstream analysis can substantially impact the quality and quantity of recoverable genetic information. This concern may be exacerbated when dealing with degraded forensic skeletal remains. Few studies have explored whether pulverization of bone samples contributes to …

Investigations Of A Nox2 Activator, P47phox, Px Domain Membrane Anchoring Interactions And Inhibition, Angela Develin

Theses and Dissertations

The regulation of cellular signaling across plasma membranes is a well-organized process through cross-talk of biomolecules such as proteins and membranes. Peripheral membrane proteins (PMPs) are a class of water soluble, membrane associated, proteins that play a critical role in transducing such signals. Due to the dynamic nature of their membrane interactions, relatively smooth surfaces, and general lack of deep ligand binding pockets, PMPs are commonly associated with an approximate 85% of the human proteome that is classified as ‘undruggable’ by current drug discovery methodologies. One such PMP, p47^phox, contains a PX domain which is essential in activation …

Dynamic Mathematical Approaches To Understanding Pain In Sickle Cell Disease, Quindel Jones

Theses and Dissertations

In the last 50 years, pain in Sickle Cell Disease (SCD) has become more widely studied thanks to advancements in technology and awareness. Clinical studies, population surveys, pharmaceutical trials, and computational models have been created and conducted to elucidate the mechanisms, treatments, and prediction of Sickle Cell disease pain episodes. Computational models have become quite useful in unraveling disease pathology with the rise in data collection accessibility and advanced computational power. In particular, dynamic mathematical models have been used to investigate Sickle Cell disease pathology and treatment. In this work we conduct a literature review of mathematical models used in …

Investigating The Protein Interactome Of Escherichia Coli To Understand Metabolic Regulation When Proteins Bind: A Systems Biology Study., Shomeek Chowdhury

Theses and Dissertations

Proteins bind other proteins and work together as machines to perform many biological functions. Metabolic enzymes governing the life-sustaining metabolic reactions and therefore, metabolism are proteins which also binds other proteins. In this dissertation work, I have explored proteins when they interact with metabolic enzymes, play any role in regulating the cell’s metabolism. I study this phenomenon in Escherichia coli whose protein-protein interaction data is readily available in public databases with proper reference to the experimental study. Another good reason is the predictions we make in this computational study can be tested and validated in E. coli as it is …

Single-Molecule Pulldown (Simpull) For Detection Of Gpcr Complexes In Mammalian Cells, Julie M. Kraft

Theses and Dissertations

G protein-coupled receptors (GPCRs) constitute the most numerous and diverse superfamily of cell membrane receptors. While GPCRs can perform signal transduction as monomers, evidence suggests they also function as homo- and hetero- dimers and oligomers. These diverse quaternary structures can affect GPCRs’ downstream cellular signaling, pharmacological properties, and regulation of internalization.

The single-molecule pulldown (SiMPull) assay combines a co-immunoprecipitation assay with single-molecule total internal reflection fluorescence (TIRF) microscopy and can be used to probe the stoichiometry of GPCR oligomers in mammalian cells.

This project replicates the SiMPull assay by confirming the quaternary structure of mGluR2 homodimers. Plasmid constructs SNAP-mGluR2-HA and …

Investigating The Impact Of Chronic Inflammatory Pain On Ethanol Consumption In Mouse Models., Joshua L. Hunt

Theses and Dissertations

Chronic pain affects nearly 20% of Americans annually and for many alcohol provides a convenient and legally acquired palliative. Population-based studies have suggested a link between increased alcohol use and reduced pain, but chronic or excessive alcohol use potentiates the risk to develop alcohol dependence and neuropathy. However, sex differences in chronic pain and alcohol abuse are still not well understood. In the present study, we investigated whether chronic inflammatory pain using the inflammatory agent Complete Freund’s Adjuvant (CFA) model could alter ethanol consumption in male and female C57BL/6J mice. We observed that only CFA-treated male mice increased their ethanol …

Leaf To Canopy Functional Resilience: Plant Physiological And Carbon Cycling Stability Following Disturbances, Lisa T. Haber

Theses and Dissertations

Ecological disturbances impact core ecosystem functions, including production and biogeochemical cycling, by precipitating changes in biodiversity, physical environmental variables, vegetation structure, and functional trait distributions. As disturbance patterns intensify and abruptly transition to novel regimes under global change, future trajectories of ecosystem functions, including carbon (C) uptake and storage, are uncertain. A more complete understanding of the mechanisms underpinning ecosystem stability (or ability to return to baseline functioning) following disturbance is needed to forecast future C cycling.

Replicated ecosystem-scale disturbance experiments, particularly when coupled with modeling, are required to rigorously test hypothesized trajectories of ecosystem structural and functional change following …

Exploring Serotonin 1b Autoreceptor Mediated Regulation Of Serotonin Transporter In Female Mice, Sanyukta Jalihalkar

Theses and Dissertations

Rationale: Serotonin (5-HT) is a crucial neurotransmitter involved in regulating various physiological processes. Dysregulation of the serotonergic system has been implicated in several neuropsychiatric disorders. Though numerous 5-HT receptors exist, the 5-HT transporter (SERT) is responsible for 5-HT clearance in the brain and periphery. 5-HT_1Bautoreceptors regulate 5-HT release and interact with glycogen synthase kinase-3β (GSK3β), which can modulate SERT function via specific Ser44/48 phosphorylation sites. While these findings suggest a potential interplay between 5-HT_1Band GSK3β-mediated SERT phosphorylation in regulating extracellular 5-HT, the primary causal molecular link remains unknown.

Objectives: To investigate if 5-HT_1B activation by …

The Genetic Architecture Of Cervical Change During Pregnancy: From Modeling To Mechanism — Does The Cervix Mediate Maternal Risk For Spontaneous Preterm Birth?, Hope M. Wolf

Theses and Dissertations

This project leverages clinical data and biospecimens from a prospective longitudinal cohort of pregnant women to study the genetic and phenotypic relationships between cervical shortening and the duration of pregnancy. Sonographic cervical length (CL) was measured throughout pregnancy in a cohort of 5,160 Black/African American women in Detroit, Michigan. Maternal DNA samples were sequenced with a next-generation low-pass whole genome platform. The heritability of cervical change during pregnancy and its genetic correlation with gestational age at delivery (GAD) were estimated using Genome-Wide Complex Trait Analysis. These estimates suggest that cervical change is heritable (h²CL = 51%) and highly polygenic trait. …

Plk1 Overexpression Drives Tumorigenesis In A Prostate Cancer Mouse Model, Emile Kachouh

Theses and Dissertations

Prostate cancer is the leading cause of cancer-related deaths among men worldwide, and the development of resistance to existing treatments necessitates the exploration of new therapeutic strategies, including combination therapies. This study investigates the role of Polo-like kinase 1 (PLK1), located on chromosome 16p12.2, as an oncogene in prostate cancer. We generated a transgenic mouse model with prostate-specific overexpression of PLK1 to closely mimic human prostate cancer progression. Quantitative PCR (qPCR) analysis was employed to characterize the molecular profile of PLK1, revealing its implication in multiple pathways. To further elucidate the functional consequences of PLK1 overexpression, we confirmed phenotypic progression …

Characterization Of Tonneau1 Recruiting Motif Proteins And Ton2 Signaling Functions, Tyler Falk

Theses and Dissertations

Plants cells are fixed in place. As a result they have to carefully divide in order to function properly. Plants use a number of complex microtubule arrays to ensure proper division and orientation including the preprophase band (PPB) and the phragmoplast. The PPB orients the cell prior to division and marks the cortical division site, which is where the phragmoplast is guided to. The phragmoplast is a dynamic microtubule array that builds the cell plate which later becomes the cell wall that divides daughter cells. Proteins involved with PPB formation include Tonneau1 (TON1) and Tonneau2 (TON2) which localize to and …

Genetic And Transcriptomic Investigations Of Progressive Ethanol Consumption In The Diversity Outbred Mouse, Zachary Tatom

Theses and Dissertations

As a complex genetic disorder, alcohol use disorder (AUD) is thought to be influenced by many genes each contributing only a small effect to the overall disease liability. Dozens of genes have been implicated as potentially affecting risk for AUD and alcohol consumption. However, understanding the full genetic architecture of AUD – what genes are involved, to what extent, and how these genes are regulated – remains a challenging step in identifying novel treatments. Gene expression studies in humans have attempted to augment GWAS of alcohol consumption but are often confounded by environmental factors; the difficulty of collecting tissue from …

Biodistribution Comparison Of Fentanyl And Morphine Following Acute And Repeated Expsoure, Rosamond M. Goodson

Theses and Dissertations

The ongoing opioid crisis constitutes a dire public health threat that has resulted in staggering loss of life. In 2021, opioids were implicated in over 75% of the approximately 107,000 deaths attributed to drug overdose (CDC), and synthetic opioids such as fentanyl and its analogues are key drivers of the surge in opioid fatalities in recent years. Although fentanyl is a μ opioid receptor agonist, it has several distinct attributes compared to other drugs in this category, such as morphine. These include enhanced lipophilicity, heightened potency to induce respiratory depression, more rapid entry into the central nervous system, reduced sensitivity …

Carotenoids And The Associations With Gut Microbiota Bacterial Populations In Chronic Kidney Disease Hemodialysis Patients, Andrea Kendall

Theses and Dissertations

Background: With increased prevalence and mortality of chronic kidney disease (CKD), treatment by renal replacement therapy using hemodialysis (HD) has increased in parallel. Emerging evidence suggests that gut microbiota play an important role in the progression of CKD; influential dietary factors have not been studied exhaustively to date.

Objective: To explore the relationships between dietary carotenoid intake, the abundance of specific gut microbiota, and symptom-related outcomes in patients with CKD on HD.

Methods: This cross-sectional study investigated the gut microbiota characteristics relative to carotenoid intake in CKD subjects on HD in central Illinois (n = 20). The Block Dialysis …

Bridging The Gaps: Characterizing Alzheimer's Disease In Native Hawaiian And Pacific Islander Populations, Justina P. Tavana

Theses and Dissertations

This dissertation addresses critical gaps in dementia research in Native Hawaiian and Pacific Islander (NHPI) communities. Focusing on Samoan and Tongan communities, the study successfully adapted and validated the AD8 informant interview and the Clinical Dementia Rating (CDR) scale in native languages, establishing these instruments as reliable tools for detecting cognitive impairment in these populations. The research process prioritized meaningful community engagement and forged partnerships with indigenous professionals, ensuring alignment with and responsiveness to the specific needs of the community. These invaluable connections were the foundation of making this difficult work possible. Subjects assessed with these adapted instruments were enrolled …

Plant Material Selection And Seed Enhancement Technologies Improve Seed-Based Restoration In Dryland Systems, Travis G. Sowards

Theses and Dissertations

The restoration of large-scale heterogeneous landscapes is typically approached using seed-based restoration as a cost-effective means to achieve project goals and objectives. However, seeding is often met with low survival rates primarily driven by low seedling emergence and establishment. This dissertation investigates opportunities to enhance restoration focusing on 1) seed treatments, 2) plant materials, and 3) a synthesis of seeding strategies. • Fungal pathogenesis can cause high seedling mortality. Fungicide seed coatings used in the agriculture industry are novel to wildland restoration. We assess the effect a fungicide seed coating has on the recruitment of Pseudoroegneria spicata seedlings across a …

Effect Of Timing Of Energy Intake On Blood Glucose And Body Composition In Women With Overweight Or Class One Obesity, Michael Wade Smith

Theses and Dissertations

Overweight and obesity has increased in the U.S. Unfortunately, this increases the risk of metabolic dysfunction, such as diabetes. Meal timing has recently shown promise as viable options to minimize the risk of overweight or obesity and metabolic dysfunction. The primary purpose of this study, therefore, was to investigate the effect of timing of energy intake on blood glucose in females with overweight or class one obesity (BMI=27-35 kg/m2). This study utilized crossover design with two conditions counterbalanced in random order. Participants completed two 2-week 1500kcal dietary interventions: 1) a big breakfast diet or BB (50% of energy intake between …

Linking Individual Behavior With Physiology To Understand Complex Life Histories, Doreen Cabrera

Theses and Dissertations

Life history strategies encompass a suite of co-evolved traits crucial for ensuring an individual's fitness, often evolving from trade-offs between traits competing for the same resources. Adult male crayfish in the Cambaridae family undergo seasonal morphological changes linked to reproductive status, a process called cyclic dimorphism. In this dissertation, we attempt to understand how cyclic dimorphism evolved in non-native northern crayfish (Faxonius virilis). First, in Chapter 1, we review empirical studies that have assessed animal personality across developmental periods. The results show that personality traits tend to be stable within life stages but not across developmental events. In Chapter 2, …

Techniques In Multi-Omics Data Integration To Develop A Novel Proteogenomics Framework For Identification Of Proteoforms, Kanishka Manna

Theses and Dissertations

Multi-omics experimental approaches are becoming a mainstream practice in systems biology underlining the need to design new integrative techniques and applications to enable the multi-scale characterization of different types of diseases for targeted therapy. Proteogenomics, a sub-field within the broad field of multi-omics incorporates techniques to integrate genomics, transcriptomics and proteomics data for efficient identification of novel proteoforms or protein isoforms. There are multitude of challenges when applying proteogenomics analyses, such as improper integration of each omics data type, missing structural annotations, inefficient identification of splice-junctions, novel genes, etc. This dissertation will outline a novel and integrative proteogenomics pipeline that …

Isolation And Characterization Of Nut Shell Proteins From Arachis Hypogea Linn. And Cocos Nucifera Linn. And Its Effect On Macrophage Activation To Treat Visceral Leishmaniasis, Suhatha S

Theses and Dissertations

Glycoproteins are among several immunomodulatory agents known to activate the innate immune system. Plant derived glycoproteins are a generous source of glycoproteins that could be utilized as cost effective preparations for therapeutics. Isolating glycoproteins from agricultural by- products with the intention to use them against Visceral Leishmaniasis (VL) was the focus in this doctoral study. The two nut shells, Arachis hypogea L. (Groundnut) and Cocos nucifera L. (Coconut), were used for the isolation of glycoprotein used in the study. Crude glycoproteins from the A. hypogea L. (AHP-C) were isolated and fractioned. AHP-F2 was identified as 28.37 kDa Mannose/Glucose binding lectin …

Investigating The Impact Of Transcription On Mutation Rates, Sarah Patterson

Theses and Dissertations

tRNA genes are highly transcribed and perform one of the most fundamental cellular functions. Although a universal pattern observed across all three domains of life is that highly transcribed genes tend to evolve slowly, tRNA genes have been shown previously to evolve rapidly. This rapid sequence evolution could result from relaxed selection, increased mutation rate, or a combination of both. Here, we use mutation-accumulation line sequencing data to show that tRNA genes accumulate more mutations than other gene types. Our results indicate that this elevated mutation rate is a consequence of both elevated transcription-associated mutagenesis and a lack of transcription-coupled …