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Dean's Report- Winter-Spring 2025, Marina K. Holz

GSBMS Dean’s Report

No abstract provided.

Chronic Alcohol Consumption Induces Phenotypic And Functional Alterations Consistent With A Hyper-Inflammatory State In Peripheral Blood Mononuclear Cell-Derived Microglia In A Rhesus Macaque Model, Hami Hemati, Madison B. Blanton, Heather E. True, Jude Koura, Rupak Khadka, Kathleen A. Grant, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Alcohol-induced dysregulation of microglial activity is associated with neuroinflammation, cognitive decline, heightened risk for neurodegenerative diseases, alcohol dependence, and escalation of alcohol drinking. Given the challenge of longitudinally sampling primary microglia, we optimized an in vitro method to differentiate peripheral blood mononuclear cells (PBMC) from rhesus macaque (RM) into induced microglia-like cells (RM-iMGLs). The RM-iMGLs displayed transcriptional profiles distinct from monocyte progenitors and closely resembling primary microglia. Notably, morphological features showed that differentiated RM-iMGLs derived from subjects with chronic alcohol consumption (CAC), while bigger, exhibited a bipolar-like morphology. Additionally, dysregulation in key inflammatory and regulatory markers, along with increased baseline …

Investigating Regulation And The Regulome Of The Nucleic Acid Binding Protein Spovg Within Borrelia Burgdorferi, Timothy C. Saylor

Theses and Dissertations--Medical Sciences

Prior studies indicated Borrelia burgdorferi SpoVG protein was regulated, SpoVG binds specifically to a number of nucleic acids, and SpoVG binds to the non-variable section of the major virulence factor vlsE. Although a direct transcriptional activator or inhibitor was not elucidated, it is shown that SpoVG is regulated based on cell culture density independent of the growth rate of B. burgdorferi, indicating that SpoVG regulation is outside the scope of the alternative sigma factor RpoS. Using a dCas9 CRISPRi construct to target SpoVG resulted in protein expression trending towards upregulation of the BosR-RpoS regulon, and a marked decrease …

Cellular And Behavioral Consequences Of Psychedelic Drug Action In The Claustrum, Tanner L. Anderson

Theses and Dissertations--Neuroscience

Psychedelics are rapidly garnering research attention for their ability to successfully treat a variety of psychiatric diseases after one or a handful of treatments in recent clinical research. Among the conditions treated is substance use disorder (SUD), which afflicted 48.5 million (16.7%) Americans aged 12 and older in 2023 (NSDUH). As clinical trial results continue to show lasting positive effects of psychedelic psychotherapy, there remains an enormous gap in knowledge regarding how these drugs cause lasting changes in the brain to achieve these therapeutic effects. It has been suggested that psychedelics must induce rapid and long-lasting neuronal plasticity in order …

Leveraging Clinical Standards To Improve The Translational Relevance Of Therapies For Experimental Spinal Cord Injury, Aaron L. Silverstein

Theses and Dissertations--Neuroscience

Efforts to improve treatment of spinal cord injury (SCI) often use animals to develop effective therapeutics, intending to improve the survival and the quality of life of persons with SCI. Over half of all SCIs in the United States occur at the cervical level and often cause locomotor deficits and life-threatening breathing dysfunction. Thus, my dissertation is focused on this important patient population.

After beginning with a description of translational research and surveying SCI from a clinical standpoint, I turned to describe experimental models of cervical SCI and more detailed neuroimmunological findings relevant to my work. Then, I conducted a …

Immune Dynamics And B Cell Contributions To Neuroplasticity And Recovery After Stroke, Thomas A. Ujas

Theses and Dissertations--Neuroscience

This dissertation explores the dynamic interplay between the immune system and the brain across stroke and aging using clinical, post-mortem, and pre-clinical models. The immune system plays critical roles in shaping brain function, responding to injury, and mediating recovery. These studies aim to enhance our understanding of neuroimmune dynamics across spatial and temporal dimensions.

In the first part, we conducted longitudinal sampling of aneurysmal subarachnoid hemorrhage (aSAH) patients to track immune cell and cytokine changes at days 3, 5, 7, 10, and 14 post-stroke, with a focus on delayed cerebral ischemia (DCI), a common complication. We observed distinct temporal patterns, …

Anxiolytic Intervention: Modulation Of Cell Types Due To Nicotine Withdrawal, Taylor Elder

Theses and Dissertations--Pharmacy

Nicotine use disorder (NUD) remains a leading cause of preventable disease, yet the neurobiological mechanisms underlying nicotine withdrawal are incompletely understood. Emerging evidence implicates neuroimmune signaling and astrocytic regulation of glutamate in shaping the withdrawal-associated affective phenotype. This dissertation investigated these processes using multiple nicotine administration paradigms including osmotic minipump implant, cigarette smoke exposure, and nicotine vapor inhalation to model diverse routes of human nicotine intake.

Chapter 2 examines the effects of these three modes of administration on neuroinflammation and validation of nicotine delivery. Nicotine exposure was confirmed through receptor [³H]Epibatidine nAChR binding assay and serum cotinine measurements. …

Biochemical And Biophysical Properties Of Failing Myocardium In Rare Patient Populations, Gregory Nathaniel Milburn

Theses and Dissertations--Physiology

Heart failure has diverse underlying etiologies, complicating research. While some types, like ischemic disease or inherited mutations, are well-studied, research on rarer forms has lagged. Understanding the molecular drivers in these populations may enhance diagnostics and therapies. This work examines two rare groups: patients with ATTR cardiac amyloidosis and those receiving mechanical assist device support. We show that myocardium from patients with amyloidosis has increased fibrosis and reduced force production without changes in cross-bridge kinetics. Additionally, we show that the passive stiffness of amyloidosis myocardium is not different from non-failing myocardium, indicating increased ventricular wall thickness may cause restrictive filling. …

Biochemical Properties Of Cardiac Sarcomeres In Human Heart Failure, Austin Grey Wellette-Hunsucker

Theses and Dissertations--Physiology

Heart failure (HF) exhibits considerable heterogeneity, posing significant challenges for research involving human cohorts. Diastolic dysfunction is a common pathophysiological feature; however, its molecular mechanisms remain incompletely elucidated. Sarcomeric proteins are integral to cardiac contraction and relaxation. Nonetheless, the phosphoproteome and the structural remodeling effects of these proteins on diastolic function within the context of HF have not been comprehensively characterized. This study examined sarcomeric modifications in diastolic dysfunction in human HF, focusing on Dilated and Ischemic HF, with non-failing donor hearts as controls. Analyzing myocardial samples from ~150 patients using electrophoretic and biochemical techniques, it found significant titin remodeling …

Fabricating Silver-Ceria Polymer Nanocomposite Scaffolds For Biomedical Therapeutic Applications, Shreya S. Pawar

Honors Undergraduate Theses

Improper healing of bone fractures and limited regeneration of bone following bone tumor resection remain a prevalent complication worldwide. Long-term effects of this include joint instability, limited movement, and arthritis. Bone infections (osteomyelitis), reactive oxygen species (ROS) generation via excessive inflammation, and underlying conditions such as osteoporosis can contribute to suboptimal bone tissue regeneration. ROS accumulation stimulates osteoblast apoptosis, while promoting osteoclast differentiation. These processes inhibit mineralization and osteogenesis. Conventional therapeutics involve the utilization of drugs and bone grafts. However, these approaches pose limitations and can result in subsequent complications. Microbial infections, ROS accumulation, and excessive inflammations are factors that …

Attacking Diabetes One Day At A Time, Kyla Duncan

Theses and Dissertations

The "Attacking Diabetes One Day at a Time" initiative targets the growing concern of public health, type 2 diabetes, among under-reserved communities. This comprehensive care program emphasizes the importance of prevention through education, improving lifestyles, and access to care. Based on insights from the Self-Care Management Theory, this initiative seeks to provide individuals with sound, culturally tailored strategies that reduce disease risk and help them manage healthy lifestyles. Major components include educational workshops, and resource navigation. The success of this program, from community engagement through evaluation on a phased implementation plan, is guaranteed. The expected outcomes of this work will …

Impact Of Obesity On The Gut Microbiome And Inflammatory Markers During Siv Infection And Antiretroviral Therapy, Casey M. Mcguire, Isaac R. Cinco, Diana Takahashi, Kristin A. Sauter, Melissa Kirigiti, Ilhem Messaoudi, Jonah B. Sacha, Charles T. Roberts, Paul Kievit

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Dysbiosis and impaired gut barrier integrity contribute to chronic immune activation associated with both obesity and HIV infection. Given the increased incidence of obesity in people living with HIV, we explored the impact of obesity on the gut microbiome and microbial translocation (MT) biomarkers during HIV infection and antiretroviral therapy (ART). Lean and obese rhesus macaques were infected with simian immunodeficiency virus (SIV) and subsequently treated with ART. Obese animals exhibited higher initial MT and inflammation biomarkers that remained constant throughout the study, while lean animals exhibited significant increases in these biomarkers that approached levels observed in obese animals. Lean …

Lis1 Depletion In Adult Mouse Projection Neurons Causes Neurodegeneration And Severe Neurological Phenotypes, Anne Ventrone

Theses and Dissertations

Proper LIS1 function is crucial for human brain development, as mutations in LIS1 lead to lissencephaly, a severe neurodevelopmental disorder caused by defective proliferation, differentiation and migration of neural precursors. Our understanding of LIS1's functions after brain development is limited. LIS1 regulates cytoplasmic dynein 1 (dynein), an essential microtubule motor protein in cell division and migration, but also a cellular transport motor. We previously showed that tamoxifen (TX)-induced global knockout of LIS1 using a Cre/Lox system (Act-Lis1iKO) in young adult mice results in severe neurological defects and rapid lethality. This strongly supports LIS1's critical post- developmental role, but the underlying …

Limiting H1n1 Replication Via The Dsrnai Pathway Using Sequence-Specific Ldsrna, Shawn Marie Sharon Carr, Stephanie Dewitte-Orr

Theses and Dissertations (Comprehensive)

The seasonal influenza virus causes a common respiratory illness that can be life threatening to the immunocompromised, the very young, and the elderly. The current strategies for avoiding a serious influenza virus infection are good hygiene practices and the annual influenza vaccine. Unfortunately, last year’s influenza virus vaccine effectiveness ranged between 32-60% for children and adolescents and 46-54% for adults. These low efficacy rates are due to the vaccine often targeting hemagglutinin, a highly variable surface protein. This thesis seeks to create a prophylactic treatment via the RNA interference (RNAi) response that targets the virus’s conserved genes that are integral …

Effect Of Nonsurgical Periodontal Therapy On Oxidative Stress Biomarkers And Glycemic Control In Type 2 Diabetic Patients, Eman Taha, Eman Shawki, Fady Kyrillos, Mohamed A. Al-Shahat

Mansoura Journal of Dentistry

Objective Reactive oxygen species are increasingly being linked to the pathophysiology of periodontal tissue damage. The one of the sensitive significant markers used for assessing oxidative damage in several conditions is 8-hydroxy-deoxyguanosine (8- OHdG). The current study aims to estimate the effects of non-surgical treatment for periodontal disease on the concentrations of 8-OHdG in plasma and saliva as oxidative stress biomarker, as well as its impact on glycemic control in individuals with type 2 diabetes (T2D) and periodontitis. Subjects and Methods The study involved 50 nonsmoking patients. 20 T2D patients with periodontitis. 20 nondiabetic with periodontitis. 10 healthy non-diabetic without …

A Limb-Speed-Driven Locomotor Control System And Its Ability To Adapt, Emily Marie Herrick

Graduate Theses, Dissertations, and Problem Reports (ETD)

Despite how simple walking may seem, the locomotor control system is structurally and functionally complex. Its hierarchical organization of supraspinal and spinal networks with forward and feedback pathways has many interactions at multiple levels that are dependent on the dynamics of a high-dimensional musculoskeletal system. Having a comprehensive understanding of sensorimotor integration within a healthy locomotor control system is crucial for understanding changes to the system due to age or neurologic disease and developing effective technologies to recover mobility in those populations. In this dissertation, we address persistent gaps in knowledge pertaining to how the nervous system controls locomotion.

In …

Sex-Specific Roles Of The Adipocyte Mineralocorticoid Receptor In Obesity And Early Life Stress, Meghan B. Turner

Theses and Dissertations--Pharmacology and Nutritional Sciences

Obesity is a burgeoning health epidemic caused by chronic overnutrition and exacerbated by genetic, environmental and developmental factors. The adipocyte mineralocorticoid receptor (MR), a transcriptionally active nuclear receptor, is speculated to contribute to metabolic dysfunction in the obese state. MR expression is increased in obese adipose tissue, and MR modulates the expression of fat-derived hormones such as leptin and adiponectin. In women, obesity can be exacerbated by early life stress, such as adverse childhood experiences (ACEs). Studies show that women display a positive association between cumulative ACE exposures and increased body mass index. Previously, we demonstrated that maternal separation and …

Fructose Induces Metabolic Changes Distinctly Different From Glucose In A N2a Cell Line., Catherine A. Ghigleri

All Master's Theses

Over the last 50 years, there has been a rise in diagnoses of Alzheimer’s Disease and other dementias associated with metabolic stress. This parallels an increase in fructose consumption and has led to research on the effects of fructose on the hippocampus, a brain structure responsible for learning and long-term memory formation. The hippocampus is also a region of the brain that metabolizes fructose. Experiments using animals fed diets containing fructose have shown a correlation between fructose consumption, learning impairment, and structural changes to the hippocampus in animals’ brains. However, the effects of fructose on hippocampal neurons have not been …

Identification Of Potential Prophylactic Medical Countermeasures Against Acute Radiation Syndrome (Ars), Kia T. Liermann-Wooldrik, Arpita Chatterjee, Elizabeth A. Kosmacek, Molly Myers, Oluwaseun Adebisi, Louise Monga-Wells, Liu Mei, Michelle P. Takacs, Patrick H. Dussault, Daniel R. Draney, Robert Powers, James W. Checco, Chittibabu Guda, Tomáš Helikar, David B. Berkowitz, Kenneth W. Bayles, Alan H. Epstein, Lynnette Cary, Daryl J. Murry, Rebecca E. Oberley-Deegan

Journal Articles: Pathology and Microbiology

Acute radiation syndrome (ARS) occurs when hematopoietic or gastrointestinal cells are damaged by radiation exposure causing DNA damage to the bone marrow and gastrointestinal epithelial stem cell populations. In these highly proliferative cell types, DNA damage inhibits stem cell repopulation. In humans and animals, this inability to regenerate stem cells is lethal. Within this manuscript, several compounds, Amifostine, Captopril, Ciprofloxacin, PrC-210, 5-AED (5-androstene-3β,17β-diol), and 5-AET (5-androstene-3β,7β,17B-triol), are assessed for their ability to protect against ARS in an in vitro and/or in vivo setting. ARS was accomplished by irradiating mouse bone marrow cells or rat intestinal epithelial (IEC-6) cells in vitro …

Alpha-Synuclein Interaction With Gedunin, Tony Matundura Nyabayo

Graduate Theses/Dissertations

Parkinson’s disease (PD) and other Proteinopathies develop when α-synuclein misfolds and aggregates into toxic amyloids. While existing treatments for PD are primarily focused on managing its symptoms, a viable solution for slowing down the progress of Parkinson’s disease involves targeting the toxic α-synuclein amyloids. Gedunin, a natural inhibitor of heat shock protein 90, has been extensively used to treat malaria. Also, recent research investigations have shed light on its potential beyond malaria therapy, indicating that Gedunin may offer a possible solution for treating a variety of neurodegenerative diseases. Using plate-based assays, we examined how Gedunin influences α-synuclein fibrillation and its …

Characterizing A Rad23 Dependent Ultraviolet Radiation Resistance In Tetrahymena Thermophila, Emma June Liimatta

Graduate Theses/Dissertations

In 2020, 10 million deaths were attributed to cancer, with multidrug resistance being responsible for over 90% of deaths in cancer patients receiving treatment. This study utilized the model organism Tetrahymena thermophila to study how cells become resistant to Ultraviolet Radiation (UV) radiation, a process similar to multidrug resistance, specifically focusing on the nucleotide excision repair and ubiquitin shuttle protein Rad23. The National Cancer Institute documented 30-60% of cancers tested had a mutation in RAD23. Knockdown of RAD23 in Tetrahymena thermophila demonstrated a UV resistance phenotype with decreased nucleotide excision repair and differential expression of proteins active within caspase-independent …

Microglial Trem2 Promotes Phagocytic Clearance Of Damaged Neurons After Status Epilepticus, Dale B Bosco, Vaclav Kremen, Koichiro Haruwaka, Shunyi Zhao, Lingxiao Wang, Blake A Ebner, Jiaying Zheng, Manling Xie, Aastha Dheer, Jadyn F Perry, Abhijeet Barath, Aivi T Nguyen, Gregory A Worrell, Long-Jun Wu

The Brown Foundation: Institute of Molecular Medicine

In the central nervous system, triggering receptor expressed on myeloid cells 2 (TREM2) is exclusively expressed by microglia and is critical for microglial proliferation, migration, and phagocytosis. Microglial TREM2 plays an important role in neurodegenerative diseases, such as Alzheimer's disease and amyotrophic lateral sclerosis. However, little is known about how TREM2 affects microglial function within epileptogenesis. To investigate this, we utilized male TREM2 knockout (KO) mice within the intra-amygdala kainic acid seizure model. Electroencephalographic analysis, immunocytochemistry, and RNA sequencing revealed that TREM2 deficiency significantly promoted seizure-induced pathology. We found that TREM2 KO increased both the severity of acute status epilepticus …

Assessing Reproductive Health In Zoo-Managed African Elephant Bulls (Loxodonta Africana), Kaitlyn Marie Campbell

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Populations of zoo-managed African elephant (Loxodonta Africana) exhibit substantial individual- and population-level variation in reproductive success, yet research has largely focused on females, leaving male fertility poorly understood. Subfertility in bulls, characterized by low libido and inconsistent semen quality, poses significant challenges to genetic management and long-term population sustainability. This study a) systematically evaluates semen quality, b) identifies physiological, behavioral, social, and environmental determinants of fertility, and c) advances ex situ conservation through the expansion of the African elephant sperm bank. Between January 2023 and July 2025, 209 semen collection events were conducted from 13 sexually mature bulls …

Effect Of Integrated Neuromuscular Inhibition Technique On Iliotibial Band Friction Syndrome, Esraa Tarek Farouk Ahmed, Amir Mohamed Saleh, Hassan Hussien Ahmed, Doaa Rafat El Azab

Journal of Medicine in Scientific Research

Background: It was reported that, 25% of adults experience limited mobility and a diminished quality of life due to knee pain. The iliotibial band friction syndrome (ITBFS) is a frequent overuse injury that causes lateral knee pain. It is marked by recurrent lateral knee pain as well as motor impairment in the lower extremities. Pain worsens with exercise and weight-bearing activities, especially at 30° of knee flexion, and patients usually have a history of overuse caused by knee flexion and extension.Objective: To determine the impact of the integrated neuromuscular inhibition technique on pain intensity, knee range of motion and knee …

Contact Pathway Factors As Potential Modifiers Of Bleeding Related To Factor Xi Deficiency, Ivy R. Han, Leah Rosenfeldt, Courtney Young, Bal Krishan Phd, Rachel Cantrell Phd, Cassie Sprague, Mousa Kharnaf, William Abplanalp, Joseph Palumbo Md

Williams Honors College, Honors Research Projects

Factor XI (FXI) deficiency, also known as Hemophilia C, is characterized by mild to moderate bleeding symptoms. However, the factors that modify bleeding severity in FXI deficiency are not fully understood. In this study, we investigated whether components of the contact activation pathway can act as modifiers of bleeding in the context of FXI deficiency. Using a tail vein transection (TVT) model in rats, we assessed bleeding in four experimental groups: wild-type Sprague-Dawley rats, Prekallikrein knockout (PKK^-/-) rats, rats treated with a FXI-inhibiting antibody, and PKK-/- rats treated with the FXI antibody.

Under anesthesia, each rat underwent a …

Effects Of Energy Drinks On Crayfish Physiology, Melyna Sweeney

Williams Honors College, Honors Research Projects

Energy drinks have become the drink of choice among many college students due to the rush of energy it provides via the megadose of caffeine (Vercammen et al. 2019). Because of their newfound popularity, there is much research to be done about the effects on human physiology. Energy drinks are known to increase endurance in muscles of rat subjects (Imagawa et al. 2009) and stimulate enhanced “alertness” (Smit & Rogers, 2002). The purpose of this research was to uncover the potential effects that energy drinks have on metabolic rate and/or stress responses in crayfish (Procambarus clarkii), with the …

Astrocyte Specific Enhancers In The Cortex And Striatum Of Mice, Mikaela Kottelich

Williams Honors College, Honors Research Projects

Among glial cells, astrocytes have a prevalent influence on supporting neuronal function and overall brain health. Specifically targeting this cell type for disease treatment is an existing issue. Other cell types tend to express the desired treatment, which is not always wanted and can lead to unintended, negative consequences. Astrocytes contribute largely to maintaining the blood brain barrier, which is disrupted in Parkinson’s disease. Certain genes are thought to be the reason for this disruption, so if they can be specifically targeted in astrocytes with a specific enhancer, the disruption of the disease could be reversed. In our experiment, we …

Impact Of Tetrahydrocannabinol (Thc) On Daphnia Magna Heart Rate, Ashley Cosgrave

Williams Honors College, Honors Research Projects

Marijuana (Cannabis) is currently federally illegal within the United States and classified as a Schedule I drug. This leaves a large research gap on the impacts of Tetrahydrocannabinol (THC) use. Daphnia magna are frequently used as a model organism for the human heart and toxicology screenings due to their myogenic heart, similarities in physiological pathways, and sensitivity to toxins. As such, in order to bridge the research gap and uncover potential use of Daphnia magna as a model organism for humans in regard to impact on heart rate, we hypothesized that if Daphnia magna possess CB1 receptors or an equivalent …

Neuropsychological Assessment Accuracy In Diagnosing Early-Onset Alzheimer’S Disease, Elise Thomas

Master's Theses and Doctoral Dissertations

Early-onset Alzheimer’s disease (EOAD), a progressive neurological condition, is often difficult to diagnose before substantial neuronal damage. Neuropsychological assessments offer a more cost-effective and accessible method for detecting early cognitive decline, yet limited research exists on optimal combinations for EOAD identification. This study analyzed data from 24 clinical studies to determine the diagnostic accuracy of FDA-approved EOAD assessments used in combination. No single combination was found to be superior across all diagnostic metrics. MMSE + MoCA + ADAS-Cog showed the highest sensitivity, MMSE + MoCA + RBANS the highest specificity, MMSE + RBANS the highest AUC value, and MMSE + …

Depletion Of Adipose Stroma-Like Cancer-Associated Fibroblasts Potentiates Pancreatic Cancer Immunotherapy, Joseph Rupert, Alexes Daquinag, Yongmei Yu, Yulin Dai, Zhongming Zhao, Mikhail G Kolonin

Faculty, Staff and Student Publications

This study shows that populations of CAFs have distinct effects on pancreatic cancer progression and shows that depletion of CAFs expressing adipose markers potentiates tumor/metastasis suppression effects of immune checkpoint blockade.