Disease Modeling Commons^™

Role Of Chronic Stress-Induced Neuroinflammation In Rodent Locus Coeruleus Physiology And Anxiety-Like Behaviors, Arthur Anthony A. Reyes

Graduate School of Biomedical Sciences Theses and Dissertations

The locus coeruleus (LC), the primary site of brain norepinephrine (NE), is a key anatomical brain region implicated in the stress response. Stress is a neuroendocrine physiologic response to a stressor that promotes organism survival through adaptive change and restoration of homeostasis. The central stress response, which drives behavioral and physiological change, is primarily mediated by activating the hypothalamic-pituitary-adrenal (HPA) axis. While advantageous in the short term, chronic stress exposure can lead to HPA axis and LC dysregulation, which are thought to contribute to the etiology of anxiety disorders. Previous studies demonstrate the effects of acute stress in increasing LC …

Relative Efficacy Of Resource Constrained Forward And Backward Contact Tracing In An Open Population, Nicholas Roberts

Biology and Medicine Through Mathematics Conference

No abstract provided.

Functional Evaluation Of A Novel Rpl30 Mutation And Its Role In Diamond Blackfan Anemia (Dba), Alexandra Prosser, Alexandria Cockrell, Danny Miller, Chris Seidel, Tamara Potapova, John M. Perry, Midhat Farooqi, Erin M. Guest, Jennifer Gerton

Research Days

Background: Bone marrow failure is life-threatening and requires prompt, intensive treatment, which is dependent upon identification of genetic drivers. Although there has been investigation into associated genetic mutations, especially in Diamond Blackfan anemia (DBA), the relationship between genotype and phenotype remains unclear.DBA has been identified as a ribosomopathy, also known as a disease associated with defects in ribosome biogenesis. We identified a novel heterozygous variant (c.167+769C >T) in the noncoding region of RPL30 in a patient with clinical diagnosis of DBA. Clinical RNA sequencing (RNA-seq) suggests the variant generates a novel splice acceptor site resulting in truncated RPL30 transcripts. Elucidation …

The Role Of Food Accessibility In Weight Loss In A Rat Model Of Parkinson’S Disease, Anjali Kikkisetti, Nicole Charles, Francois Gould

Stratford Campus Research Day

Parkinson’s disease (PD) is a neurodegenerative disorder that causes a variety of motor and non-motor symptoms. The goal of this project was to understand whether the weight loss seen with Parkinson’s disease was due to the lack of being able to access the food because of the food placement or because of inability to chew the food due to degeneration of muscles required for chewing food. Both treatment groups, Adjusted Diet and Unadjusted Diet, lost weight after injections started, whereas control weights were stable throughout the experiment. There is no statistically significant difference in weight loss between adjusted and unadjusted …

Differential Degeneration Of Neurons In A Mouse Model Of Canavan Disease, Vibha Chauhan, Quy Nguyen, Jeremy Francis, Paola Leone

Stratford Campus Research Day

Canavan disease (CD) is an inherited leukodystrophy caused by inactivating mutations to the glial enzyme aspartoacylase (ASPA). ASPA catabolizes neuronal N-acetylaspartate (NAA) into free acetate and aspartate and loss of this function results in the chronic elevation of non-catabolized NAA and the failure of developmental myelination. Elevated NAA is thought to cause damage to myelin and myelin-producing cells (oligodendrocytes, but the viability of neurons in CD is relatively unexplored. We compare here the progressive degeneration of neurons in two regions of the CD mouse brain, the thalamus and the cortex, distinguished by differing degrees of vacuolation, and show that the …

Cardiovascular Disease Prediction Modelling: A Machine Learning Approach, Usmaan Al-Shehab, Maduka Gunasinghe, Yousuf Elkhoga, Nimay Patel, Juliana Yang

Stratford Campus Research Day

The objective of this project is to utilize the UCI Heart Disease dataset to identify physiological biomarkers that are highly correlated with heart disease incidence. A predictive model can then be developed using these biomarkers to estimate the likelihood of someone having or developing a heart-related condition. This study compares the efficacy of predicting cardiovascular disease as an outcome using three machine learning algorithms: Support Vector Machine, Gaussian Naive Bayes, and logistic regression. Support Vector Machine works by creating hyperplanes between data points to conduct classification. Gaussian Naive Bayes works by using the conditional probabilities of events to classify the …

Swallowing Disrupts Tongue-Jaw Coordination During Chewing In A Rat Model Of Parkinson's Disease, Meejan Palhang, N. Charles, Francois Gould

Stratford Campus Research Day

The primary motor symptoms of Parkinson’s disease, including bradykinesia, rigidity, and tremor, are associated with difficulties regulating transitions between motor behaviors due to basal ganglia dysfunction. Chewing and swallowing, which are disordered in most patients with Parkinson’s disease, are two complex motor behaviors which overlap in time and share some neuromuscular components. The objective of this study is to identify how Parkinson’s disease affects the coordination of chewing and swallowing. We hypothesize that as a result of impaired regulation of shift between motor patterns, chewing cycles that occur with a swallow will be more affected that chewing cycles occurring in …

Development Of A Computational Model To Investigate Pathways And The Effects Of Treatment In Fanconi Anemia, Sabrina Kellett

Biological Sciences Undergraduate Honors Theses

Fanconi Anemia (FA) is a rare type of anemia that is not easily studied and can have very detrimental effects. This disease compromises the bone marrow, resulting in decreased hemopoiesis. Symptoms of FA also include abnormalities in the brain and spinal cord, incorrect formation of the kidneys, abnormal formation of the heart and lungs, and a dramatically increased risk of developing cancer. FA can be caused by various mutations in any of the 22 genes that encode for proteins involved in what is called the FA DNA repair pathway. In healthy individuals, this pathway specifically repairs interstrand cross-links (ICLs) recognized …

Immunomodulatory Effects Of Resolvin D2 In A Model Of Infection, Prem Yugandhar Kadiyam Sundarasivarao

Graduate School of Biomedical Sciences Theses and Dissertations

Dysregulated hyperinflammatory host immune response to underlying bacterial infections is a characteristic of sepsis. In sepsis, bacteria often trigger abnormal hyperinflammatory responses which can cause multiple organ failure and if sustained can lead to an immunosuppressive phase where the host is susceptible to secondary infections caused by opportunistic bacteria like Pseudomonas aeruginosa (P. aeruginosa). In our studies, we used a 2-hit model of cecal ligation and puncture (CLP) followed by P. aeruginosa secondary lung infection to investigate cellular and molecular mechanisms in the beneficial action of resolvin D2 (RvD2). Resolvins of the D-series are a group of fatty acids known …

Validating A New In Vivo Model To Study Als, Izabela J. Cimachowska

Student Theses and Dissertations

Buildup of oxidative stress and mitochondrial dysfunction are well known characteristics of both sporadic and hereditary amyotrophic lateral sclerosis (ALS). While both forms of the disease seem to arise from common cellular dysfunction, the genetic disease is studied to a much greater extent. Engineering novel animal models of the sporadic form of the disease is crucial for development of druggable targets to treat ALS and understand the underlying mechanisms. Interestingly, accumulation of oxidative stress by exacerbated emission of reactive oxygen species (ROS) from presynaptic mitochondria is a hallmark of both hereditary and sporadic ALS. Previous work by our laboratory showed …

Protective Effect Of Betulinic Acid Administration On Kidney Damage In Acetaminophen-Induced Nephrotoxicity Model, Eda Dokumacioglu, Hatice İskender, Armagan Hayirli, Guler Yenice, Kubra Asena Terim Kapakin, Ismail Bolat, Esra Manavoglu Kirman

Makara Journal of Health Research

Background: Acetaminophen (APAP) is the most widely used analgesic drug worldwide, but it may induce renal toxicity. Betulinic acid (BA) ameliorates the oxidative stress and inflammatory response to renal damage. The present study aimed to investigate the potential protective effects of BA treatment through an experimental kidney damage rat model administered with APAP.

Methods: Sprague–Dawley male rats were randomly divided into four groups: control, BA (25 mg/kg for 15 days), APAP (1 g/kg), and APAP + BA groups. BA was administered via oral gavage at a dose of 25 mg/kg for 15 days. APAP was dissolved in hot …

Localization Of Ctg-Repeat-Containing Transgenes In Drosophila Melanogaster Myotonic Dystrophy Models, Andrea Waltrip

Student Research Submissions

Myotonic Dystrophy Type 1, DM1, is a multi-systemic muscle wasting disorder that results from expression of expanded CTG repeats in the DMPK gene in humans. Three transgenic Drosophila melanogaster lines have been created containing 60, 250, or 480 CTG repeats to model DM1. The transgenic repeats are expressed using the GAL4/UAS system. Expression of long-repeat transgenes ((CTG)₂₅₀ and i(CTG)₄₈₀) produces phenotypes consistent with DM1, relative to control lines ((CTG)₆₀). The precise chromosomal location of insertion of the transgenes has not been reported. We used classical genetic approaches to localize CTG-repeat transgene insertion to a specific …

Modeling Immune System Dynamics During Hiv Infection And Treatment With Differential Equations, Nicole Rychagov

CODEE Journal

An inquiry-based project that discusses immune system dynamics during HIV infection using differential equations is presented. The complex interactions between healthy T-cells, latently infected T-cells, actively infected T-cells, and the HIV virus are modeled using four nonlinear differential equations. The model is adapted to simulate long term HIV dynamics, including the AIDS state, and is used to simulate the long term effects of the traditional antiretroviral therapy (ART). The model is also used to test viral rebound over time of combined application of ART and a new drug that blocks the reactivation of the viral genome in the infected cells …

A Look Into The Physiological Impacts Of Childhood Cancers And Modeling Of Tumor Growth Rate, Erica Steiner, Kimberly Hansen, Marissa Stanton

Honors Theses, University of Nebraska-Lincoln

Cancer is one of the deadliest diseases present in the world. Children have different reactions to diseases and treatments; thus, it is important to study those reactions specifically in children. Knowing how children are impacted by these factors can be helpful in diagnosis and treatment of cancer. I performed this study by researching the different types of cancer I was interested in and using MATLAB to code for and simulate a growth curve of a brain tumor. I found that there are many different physiological impacts of different cancers in children. As for the modeling, I was able to get …

Longitudinal Ultrasound Imaging And Network Modeling In Rats Reveal Sex-Dependent Suppression Of Liver Regeneration After Resection In Alcoholic Liver Disease, Benjamin K. Barnhart, Toshiki Kan, Ankita Srivastava, Corinne E. Wessner, John Waters, Manju Ambelil, John R. Eisenbrey, Jan B. Hoek, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Liver resection is an important surgical technique in the treatment of cancers and transplantation. We used ultrasound imaging to study the dynamics of liver regeneration following two-thirds partial hepatectomy (PHx) in male and female rats fed via Lieber-deCarli liquid diet protocol of ethanol or isocaloric control or chow for 5–7 weeks. Ethanol-fed male rats did not recover liver volume to the pre-surgery levels over the course of 2 weeks after surgery. By contrast, ethanol-fed female rats as well as controls of both sexes showed normal volume recovery. Contrary to expectations, transient increases in both portal and hepatic artery blood flow …

Vitamin C Contributes To Epigenetic Regulation Of Genes Related To Diabetic Retinopathy In Retinal Endothelial Cells, Elizabeth L. Turner, Jonathon Reynolds, Walker Kay, Marianne Becnel, Matthew Conway, Alexander Kim, John A. Kriak, Kyle B. Bills, David W. Sant

Annual Research Symposium

No abstract provided.

Cost-Benefit Analysis Of Increased Water Treatment Plant Service Goals On Reducing Water Quality Risk, Briton Polen, Kendra Sanner

Williams Honors College, Honors Research Projects

To treat water to make it safe to drink, disinfection processes are used in water treatment plants. These disinfection processes produce disinfection byproducts (DBPs) through the reaction of organic matter and the disinfectant, such as chlorine. DBPs have been shown to pose a cancer risk to consumers. In this report, the focus is on two types of DBPs, trihalomethanes (THMs) and haloacetic acids (HAAs). The cancer risks associated with DBPs are analyzed through ingestion and inhalation pathways. Ingestion and inhalation consist of common water uses like drinking, cooking, or bathing. In addition to this, DBPs have been shown to increase …

Marineepi: A Gui-Based Matlab Toolbox To Simulate Marine Pathogen Transmission, Gorka Bidegain, Tal Ben-Horin, Eric N. Powell, John M. Klinck, Eileen E. Hofmann

CCPO Publications

The Graphical User Interface (GUI) MarineEpi is presented as a Matlab toolbox for easily (i) constructing disease transmission models for different marine host-pathogen systems, (ii) running simulations by specifying initial conditions and model parameters, and (iii) interpreting the resulting time series of the host and pathogen population dynamics. MarineEpi users can generate models for systems in which pathogen transmission occurs through contact with infected individuals (SI), contact with dead infected individuals (SID), contact with environmental pathogens released by infected individuals (SIP), and contact with environmental pathogens released by dead infected individuals (SIPD). MarineEpi is a freely available GUI that provides …

Establishment Of An In Vivo Streptozotocin-Induced Type 1 Diabetes Model Recapitulating Early Brain And Retinal Fibrosis, Kia Bourdot, Lucy Dawson, Igor Kuzin, Arturo Bravo Nuevo, Zeus Antonello

Cooper Rowan Medical Journal

INTRODUCTION: Diabetes has risen to one of the top American public health concerns. The hyperglycemic state of chronic diabetes leads to microvascular and macrovascular changes that predispose patients to delayed wound healing and organ fibrosis. The validation of models to specifically detect early, quantifiable fibrotic changes seen in the diabetic state is of fundamental importance for understanding the diabetic pathophysiology and exploring earlier management options. Here, we investigated if we could detect early signs of internal fibrosis in a streptozotocin (STZ) diabetic mouse model by quantifying α-SMA expression in various organs using flow cytometry.

METHODS: We used a low-dose STZ-induced …

Physics-Informed Neural Networks For Informed Vaccine Distribution In Heterogeneously Mixed Populations, Alvan Arulandu, Padmanabhan Seshaiyer

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.