Cell and Developmental Biology Commons^™

Antioxidant Biomarkers And Nutraceutical Therapeutics In Neurodegeneration And Neurotrauma, Lilia A. Koza

Electronic Theses and Dissertations

Mild traumatic brain injury (mTBI), yielding a Glascow Coma Scale of 13-15, is the most commonly occurring severity of TBI. Pathology from mTBI consists of blood brain barrier disruption, neuroinflammation, oxidative stress, excitotoxicity, mitochondrial dysfunction, protein aggregation, axonal degeneration, and resulting neuronal death. These processes deplete the body’s endogenous antioxidant system. We report a retrospective analysis of antioxidant blood biomarkers in patients with a history of mTBI from a local sports medicine clinic, Resilience Code. We found persistent sex-specific antioxidant depletions in mTBI patients associated with worsened symptomology.

Certain populations, such as athletes, are at high risk for repetitive mTBI …

Organellar Zn2+ Homeostasis And The Role Of Trpml Channels In Neuronal Lysosome Physiology And Axonal Transport, Taylor Franklin Minckley

Electronic Theses and Dissertations

Zinc (Zn²⁺) is crucial for proper cellular function, and as such it is important to measure and track Zn²⁺ dynamics in living cells. Fluorescent sensors have been used to estimate Zn²⁺ content of subcellular compartments, but little is known about endolysosomal Zn2+ homeostasis. Similarly, although numerous sensors have been reported, it is unclear whether and how Zn²⁺ can be released from intracellular compartments into the cytosol due to a lack of probes that can detect physiological dynamics of cytosolic Zn²⁺. My dissertation started with comparing and characterizing different Zn²⁺ sensors including the …

The Effects Of Neuronal Growth Factors On Lps-Activated Schwann Cells, Caitlyn E. Henry, Peyton Kimmel, Angela Asirvatham Ph.D.

Student Research Poster Presentations 2022

Schwann cells (SCs) are the principal support cells of neurons in the peripheral nervous system, that both myelinate axons for the rapid conduction of electrical impulses as well as assist in axonal repair during nerve injury. During nerve injury, SCs secrete tumor necrosis factor alpha (TNF-α)^1,5,6 and other proinflammatory mediators^1,6, attracting macrophages to the site of injury to induce inflammation and clear myelin debris.^1,6 Once the debris is cleared, the neuron stimulates SC proliferation by secreting neuronal mitogens, such as heregulin^3,4, and an unknown factor that activates the cAMP pathway³, an important …

Simulation Of An Inflammatory Model Using Schwann Cells, Caitlyn Henry, Peyton Kimmel, Angela Asirvatham

Student Research Poster Presentations 2022

During peripheral nerve injury, the myelin surrounding the neuronal axons is damaged, initiating an inflammatory response to remove myelin debris. Once myelin debris is cleared, Schwann cells acquire a proliferating phenotype which allows them to grow and divide so that remyelination can occur. The neuron stimulates Schwann cell division by secreting growth factors, like heregulin, and an unknown growth factor that activates the cAMP pathway. Although the role of cAMP in axonal regeneration is well-known, not much has been explored about its function in Schwann cells during nerve injury and inflammation. To simulate an inflammatory environment, the S16 Schwann cell …

Generalizing Frameworks For Sentience Beyond Natural Species, Michael Levin

Animal Sentience

Crump et al. (2022) offer a well-argued example of an essential development: a rigorous framework for assessing sentience from the perspective of moral concern over an agent’s welfare. Current and forthcoming developments in bioengineering, synthetic morphology, artificial intelligence, biorobotics, and exobiology necessitate an expansion and generalization of this effort. Verbal reports (the Turing Test) and homology to human brains are utterly inadequate criteria for assessing the status of novel, unconventional agents that offer no familiar touchstone of phylogeny or anatomy. We must develop principled approaches to evaluating the sentience of (and thus, our responsibility to) beings of unfamiliar provenance and …

A Novel Chelator For Pb-212/Bi-212-Based Alpha-Particle Radiotherapy For Cancers, Eric Doorn, Mengshi Li, Brianna Cagle, Nicholas Baumhover, Zhiming Dai, Dijie Liu, Ivy Vance, Frances Johnson, Michael K. Schultz

Summer Research

Lead-212 ( 212Pb) has been identified as a promising candidate for alpha(α)- particle radiotherapies for cancers in preclinical and clinical studies. Using a low molecular weight peptide, the radiotherapy will target with high affinity selective markers highly expressed in cancer cells but found in low concentration in healthy tissue. A radiometal is coupled to a chelator moiety linked to the peptide to deliver the α-particle radiation destroying cancer cells.

To develop a novel Pb specific chelator (PSC) that will provide high affinity to Pb212 and improve the in vitro and in vivo binding pharmacokinetics and stability of progeny of the …

Exploring The Role Of Ahr Activation In Bladder Cancer Models, Hyeon Jin Kim, Peter Jones, Josh Jang, Justin Kulchycki

Summer Research

Immune checkpoint inhibitor therapy was designed to reinvigorate immune cells to bind and kill cancer cells. However, the treatment that was intended to help patients resulted in hyper progressive disease (when the tumor shows accelerated growth, leading to an explosion of tumor growth in a short period of time). We searched for a particular gene that could function as a biomarker for hyperprogression. Upon inspecting tumor samples, we discovered a biomarker called CYP1A1. We thought to test if a tumor that expressed high levels of endogenous CYP1A1, treated with immunotherapy, ultimately led to hyper progression. Every step of the project …

Targeting Histone Reader Enl With Protac Degrader, Josiah Harsh, Zhaoyu Xue, Fan Xuan, Xiaobing Shi, Hong Wen

Summer Research

ENL is a histone reader that is part of the super elongation complex and is primarily involved in chromatin and gene expression regulation. ENL has also been found to play an essential role in the progression of a spectrum of acute myeloid leukemia (AML). Some hotspot mutations of its reader module, the YEATS domain, have been found to be oncogenic. For this reason, we explored the efficacy of a newly developed ENL PROTAC degrader in its ability to degrade wild-type and mutant ENL protein and suppress oncogene expression in cancer cells.

The Role Of Integrins In Hiv-1 Infection Of Intestinal Endothelial Cell Stimulated Resting Cd4+ T Cells, Jessica Eddy, Fisher Pham, Nathan Dapprich, Anding Shen

Summer Research

A major barrier to eradicating HIV is latent reservoirs in resting CD4+ T cells. Antiretroviral therapy is effective in bringing the viral load down to undetectable levels but is unable to eradicate the latent reservoir. Previous data from our lab revealed that when stimulated by intestinal endothelial cells (IEC), resting CD4+ T cells can be directly infected while remaining in a resting state, allowing formation of latent reservoirs. An additional study found that integrins, which are cell surface molecules, play a role in the interactions between endothelial cells (EC) and T cells. Our research further examines the role of integrins …

A Tale Of Two Toxicants: How Trichloroethylene (Tce) And Perchloroethylene (Pce) Metabolites Affect Immune Cell Viability Upon Co-Exposure With Lipopolysaccharide (Lps), Eleanor Scheeres, Sean Harris, Erica Boldenow

Summer Research

• TCE and PCE are volatile organic solvents used in industrial processes, such as metal degreasing and dry cleaning, and known human carcinogens.
• GBS is a common bacteria in the vaginal flora but can lead to complications such as preterm birth during pregnancy.
• Lipopolysaccharide (LPS) is a gram-negative bacterial cell wall component that induces inflammatory immune responses and is used as an infection model.
• Co-treatment (GBS+DCVC) in placental membranes lead to inhibition of pathogen stimulated cytokine secretion (Fig. 1).
• We hypothesized that DCVC and TCVC (PCE’s metabolite) would produce decreased cell viability, and DCVC+LPS would produce further immune inhibitory effects, which …

Er-Golgi In Membrane Repair In Cardiomyocytes, Visakuo Tsurho, Hsin-Yu Chen, Daniel Michele

Summer Research

Impaired membrane repair leads to muscular dystrophies like Miyoshi Myopathy and LGMD2B1. The mechanism behind membrane repair is not well understood, and there are few studies on membrane repair in cardiomyocytes. Research in nonmuscle cells suggest that lysosomes are a source of membranes for repairing injuries2. Few lysosomes were found in cardiomyocytes compared to non cardiomyocytes. Therefore, we investigated the ER and Golgi as potential organelles involved in membrane repair in cardiomyocytes. We used Sec22b to investigate ER to Golgi in membrane repair in cardiomyocytes because it is an ER-Golgi protein involved in membrane fusion and Golgi vesicle trafficking in …

Characterization Of Cofilin And Its Potential Role In The Epha4 Pathway, Brian Donald Condron

Master's Theses and Doctoral Dissertations

EphA4 is a receptor tyrosine kinase that is responsible for cellular adhesion and locomotion using repulsion signaling in early development of Xenopus laevis. EphA4 regulates cellular locomotion by controlling proteins within its signal transduction pathway, which may include the protein cofilin. Cofilin actively severs and removes actin monomers, thus altering the actin cytoskeleton, leading to the cessation of cellular crawl. During the gastrulation phase of embryonic development, individual cells are relocating to create the three primary germ layers of the organism. Failure of this process to occur results in attrition of the embryos, frequently by way of embryonic exogastrulation. …

Intestinal Endothelial Cells Promote Hiv Latent Infection In Resting And Activated Cd4+ T-Cells, Nathan Dapprich, Jessica Eddy, Fisher Pham, Anding Shen

Summer Research

No abstract provided.

Phosphatidylserine Externalization On Non-Apoptotic Cells And Lipid Scramblases In C. Elegans, Julia Frondoni

Electronic Theses and Dissertations

Cell corpse clearance is key for animals to avoid inflammation and autoimmune disease. To better understand the “eat me” signal of phosphatidylserine (PS) exposure for non-apoptotic corpse clearance, we attempted to disrupt the externalization of PS on C. elegans polar bodies. The second polar body undergoes a non-apoptotic form of cell death, loses membrane integrity, externalizes PS and is cleared by embryonic cells during early development. During apoptotic and necrotic cell death, PS asymmetry is disrupted by lipid scramblases, which translocate phospholipids between the leaflets of the lipid bilayer. We found neither apoptotic nor necrotic scramblases are required for PS …

Emerging Biomedical Applications Of The Vesicular Stomatitis Virus Glycoprotein, Sheeba Rehman, Suman Bishnoi, Rajarshi Roy, Anshu Kumari, Harikrishnan Jayakumar, Sharad Gupta, Parimal Kar, Asit K. Pattnaik, Bebasis Nayak

School of Veterinary and Biomedical Sciences: Faculty Publications

Nanoparticles (NPs) made of metals, polymers, micelles, and liposomes are increasingly being used in various biomedical applications. However, most of these NPs are hazardous for long- and short-term use and hence have restricted biomedical applications. Therefore, naturally derived, biocompatible, and biodegradable nanoconstructs are being explored for such applications. Inspired by the biology of viruses, researchers are exploring the viral proteins that hold considerable promise in biomedical applications. The viral proteins are highly stable and further amenable to suit specific biological applications. Among various viral proteins, vesicular stomatitis virus glycoprotein (VSV-G) has emerged as one of the most versatile platforms for …

Phip-Seq Reveals Autoantibodies For Ubiquitously Expressed Antigens In Viral Myocarditis, Mahima T. Rasquinha, Ninaad Lasrado, Erika M. Petro-Turnquist, Eric A. Weaver, Thiagarajan Venkataraman, Daniel R. Anderson, H. Benjamin Larman, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Simple Summary: Myocarditis is the inflammation of the heart muscle, and viral infections are a common cause of this disease. Myocarditis in some patients can progress to dilated cardiomyopathy (DCM). The mouse model of coxsackievirus B3 (CVB3) is commonly used to understand this disease progression in DCM patients. In this paper, we have attempted to analyze antibodies for heart antigens that could be produced as a result of heart damage in animals infected with CVB3 using a technique called Phage ImmunoPrecipitation Sequencing (PhIP-Seq). The analyses led us to identify antibodies for several proteins that were not previously reported that may …

The Electronic Structure Of Atoms: A New Approach, Jackson Ross, Krista Zogg, Katherine Selvaggio, Roger Dekock

Summer Research

No abstract provided.

One Cell’S Trash Is Another Cell’S Treasure: The Role Of Exosomes In Stress Physiology Of The Brown Anole (Anolis Sagrei), Anna Kaza

Honors Program Theses

Exosomes are a type of extracellular vesicle that is produced by cells through an endosomal pathway and secreted into bodily fluids. Exosomes deliver bioactive cargo from their parent cells to target cells as a form of intercellular communication. While most research has studied exosomes in the context of disease, less is known about their role in normal physiology when disease is absent. Using the brown anole (Anolis sagrei) as a model organism, we investigated how stress exposure affects exosome concentrations in the plasma of anoles, and whether exosome release is necessary for the response to stress. We hypothesized that stress …

Investigation Of Nuclear Envelope-Associated Progeria Proteins During Nuclear Envelope Rupture, Rhiannon Marie Sears

Dissertations and Theses

The nuclear envelope (NE) is a specialized extension of the endoplasmic reticulum critical for the proper protection and organization of the genome. This interphase-only structure is host to several proteins and their interacting constituents that have various and diverse cellular roles. Mutations in NE constituents are associated with several human diseases. A subset of these diseases, known as progeria syndromes, are characterized by the premature presentation of physiological aging in a variety of tissues. Mutations in the genes LMNA and BANF1, which encode the A-type lamins and barrier-to-autointegration factor (BAF), can lead to these multisystem progeroid diseases. Though the underlying …

Serotonin's Proliferative Effects On Lung Cancer Cell Lines, Jessy K. Ntabo

Honors Undergraduate Theses

Serotonin has been widely explored in the brain. Recently, there have been new findings on how serotonin works in the periphery. Serotonin is introduced to the periphery by the enterochromaffin cells and metabolized by the liver and lung. Studies have shown that serotonin plays a role in controlling lung cancer. However, the mechanism by which it initiates tumor formation has not been fully explored. Cell viability was measured in several lung adenocarcinoma cell lines treated with serotonin to study this effect. In GFP-labelled cells, fluorescence intensity was measured for quantification of cell viability. Our data showed an overall increase in …

Cellular Activation Following Acute And Chronic Ethanol In Glutamatergic Projection Neurons, Annalise Hassan, Sam Gottlieb, Michael F. Miles Md, Phd

IRBEH/Spit for Science Publications and Presentations

No abstract provided.

Phip Variants Associated With Chung–Jansen Syndrome Disrupt Replication Fork Stability And Genome Integrity, Neysha Tirado-Class, Caitlin Hathaway, Wendy K. Chung, Huzefa Dungrawala

Molecular Biosciences Faculty Publications

Chung–Jansen syndrome (CJS) is a rare, autosomal dominant disorder characterized by developmental delay, intellectual disability/cognitive impairment, behavioral challenges, obesity, and dysmorphic features. CJS is associated with heterozygous variants in PHIP (Pleckstrin-Homology Interacting Protein), a gene that encodes one of several substrate receptors for Cullin4-RING (CRL4) E3 ubiquitin ligase complex. Full-length PHIP, also called DCAF14, was recently identified to function as a replication stress response protein. Herein, we report the identification of two PHIP missense variants identified by exome sequencing in unrelated individuals with CJS. The variants p.D488V and p.E963G occur in different functional elements of DCAF14-WD40 repeat domain and pleckstrin …

Sequence Properties Of An Intramolecular Interaction That Inhibits P53 Dna Binding, Emily Gregory, Gary W. Daughdrill

Molecular Biosciences Faculty Publications

An intramolecular interaction between the p53 transactivation and DNA binding domains inhibits DNA binding. To study this autoinhibition, we used a fragment of p53, referred to as ND WT, containing the N-terminal transactivation domains (TAD1 and TAD2), a proline rich region (PRR), and the DNA binding domain (DBD). We mutated acidic, nonpolar, and aromatic amino acids in TAD2 to disrupt the interaction with DBD and measured the effects on DNA binding affinity at different ionic strengths using fluorescence anisotropy. We observed a large increase in DNA binding affinity for the mutants consistent with reduced autoinhibition. The ΔΔG between DBD and …

Alternatively Spliced Csf3r In Human Health And Disease, Borwyn A. Wang

Theses and Dissertations

Elevated alternative colony stimulating factor 3 receptor (CSF3R) isoforms are observed in myelodysplastic syndromes (MDS) and other myeloid neoplasms, but their role in driving disease progression has not been fully explained. In this study we report on the role of an MDS-associated splicing factor SRSF2 and its effects on the production of Class III and Class IV CSF3R isoforms and granulopoiesis. Class IV add-back in Csf3r-null mice showed impaired neutrophil differentiation with increased number of CFU-G, which largely consisted of metamyelocytes, while Class III showed greater dysgranulopoiesis accompanied by dysmorphic neutrophils. Alternative CSF3R isoforms were elevated in …

Identifying Adaptor Proteins For Selective Mrna Export In S. Cerevisiae, Chloe Baker, Rebecca Adams

Science University Research Symposium (SURS)

The export of mature mRNA from the nucleus of the cell to the cytoplasm is crucial for a cell’s survival, as this process is necessary to produce proteins encoded by these transcripts. In S. cerevisiae (yeast) cells, a protein known as Mex67 must bind to the mRNA while it’s in the nucleus so it can cross through the nuclear pore complex (NPC). Mex67 cannot bind to the mRNA directly, instead it needs to be accompanied by adaptor proteins to aid it in getting across the NPC. Stress conditions such as heat shock interferes with the function of these adaptor …

Adenoviral-Vectored Centralized Consensus Hemagglutinin Vaccine Provides Broad Protection Against H2 Influenza A Virus, Erika M. Petro-Turnquist, Brianna L. Bullard, Matthew J. Pekarek, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Several influenza pandemics have occurred in the past century, one of which emerged in 1957 from a zoonotic transmission of H2N2 from an avian reservoir into humans. This pandemic caused 2–4 million deaths and circulated until 1968. Since the disappearance of H2N2 from human populations, there has been waning immunity against H2, and this subtype is not currently incorporated into seasonal vaccines. However, H2 influenza remains a pandemic threat due to consistent circulation in avian reservoirs. Here, we describe a method of pandemic preparedness by creating an adenoviral-vectored centralized consensus vaccine design against human H2 influenza. We also assessed the …

The Application Of The Skin Virome For Human Identification, Ema H. Graham, Jennifer Clarke, Samodha Fernando, Joshua Herr, Michael Adamowicz

Nebraska Center for Virology: Faculty Publications

The use of skin virome offers a unique approach for human identification purposes in instances where a viable and statistically relevant human DNA profile is unavailable. The skin virome may act as an alternative DNA profile and/or an additional form of probative genetic material. To date, no study has attempted to investigate the human virome over a time series across various physical locations of the body to identify its diagnostic potential as a tool for human identification. For this study, we set out to evaluate the stability, diversity, and individualization of the human skin virome. An additional goal was to …

Functionalization Of Chitosan Based Microparticles For In Vitro 3d Culture Of Human Liver Cells, William Imes

Williams Honors College, Honors Research Projects

Previous work involving 3D culture of human liver cells with fluorinated chitosan based microparticles has shown that their incorporation provides needed structural cues that the culture of cells alone does not provide, such as increased gas transport. However, using bare microparticles to grow large 3D cellular structures is not practical as they tend to collapse before any meaningful research can be done on them. It is proposed that this is because of the lack of extracellular matrix (ECM)components within pure cell culture in vitro, which in their absence cannot adequately facilitate biochemical communication and adhesion between cells. It is …

Analysis Of Hematocrit Levels In Walleye Sander Vitreus From Similar Waterbodies, Alyssa Hauser

Journal of Earth and Life Science

Walleye Sander vitreus are a popular fish among anglers and hold a prominent place in Minnesotan’s identity as their state fish. Because of this, multiple management practices are used to ensure the continued health of their populations within Minnesota waters. In this study, the process of analyzing hematocrit levels was used to determine if the analysis of hematological parameters could be a useful tool in detecting differences in population health. To evaluate this, blood samples were acquired from age-0 and age-1 fish from two similar lakes and run through a hematocrit centrifuge to separate platelets from plasma to read the …

A Novel Drug To Induce Apoptosis In Advanced Prostate Cancer Cells, Parshva A. Sanghvi

Honors Undergraduate Theses

Prostate cancer is one of the leading causes of death for men in America as approximately 1 in 41 men will have prostate cancer. In this research, we focus on enzalutamide-resistant prostate cancer cells as cell resistance to enzalutamide is a prevalent obstacle in treating prostate cancer. We tested a novel compound library at different doses and observed each compound's efficacy in inducing apoptosis in enzalutamide-resistant cells. Furthermore, we analyzed the mechanism by which apoptosis was induced in compounds that showed a high efficacy at lower doses. Overall, we found that Darapladib shows promising results in treating cells that have …