Disease Modeling Commons^™

Investigation Of The Safety Of Focused Ultrasound-Induced Blood-Brain Barrier Opening In A Natural Canine Model Of Aging, Meaghan Anne O'Reilly, Ryan Matthew Jones, Edward Barrett, Anthony P. Schwab, Elizabeth Head, Kullervo Hynynen

Sanders-Brown Center on Aging Faculty Publications

Rationale: Ultrasound-mediated opening of the Blood-Brain Barrier(BBB) has shown exciting potential for the treatment of Alzheimer's disease(AD). Studies in transgenic mouse models have shown that this approach can reduce plaque pathology and improve spatial memory. Before clinical translation can occur the safety of the method needs to be tested in a larger brain that allows lower frequencies be used to treat larger tissue volumes, simulating clinical situations. Here we investigate the safety of opening the BBB in half of the brain in a large aged animal model with naturally occurring amyloid deposits.

Methods: Aged dogs naturally accumulate plaques and show …

Dnmt3a Haploinsufficiency Provokes Hematologic Malignancy Of B-Lymphoid, T-Lymphoid, And Myeloid Lineage In Mice, Garland Michael Upchurch

Theses & Dissertations

DNA methyltransferase 3A (DNMT3A) is a master epigenetic regulator of benign and malignant hematopoiesis. To dissect the biological consequences of homozygous and heterozygous Dnmt3a inactivation in malignant hematopoiesis, we generated Dnmt3a homozygous null (Dnmt3a^Δ/Δ) and Dnmt3a heterozygous (Dnmt3a^+/–) mice and compared the presentations of hematologic malignancies between cohorts. Bi-allelic inactivation of Dnmt3a results in the presentation of mature lymphoid neoplasms resembling chronic lymphocytic leukemia (CLL; B220⁺CD19⁺CD5⁺; 88% penetrance (37/42)) and CD8+ peripheral T-cell lymphoma (PTCL; TCRβ⁺CD3⁺CD8⁺CD4^—; 40% penetrance (17/42)). …

Application Of Support Vector Machine Modeling And Graph Theory Metrics For Disease Classification, Jessica M. Rudd

Published and Grey Literature from PhD Candidates

Disease classification is a crucial element of biomedical research. Recent studies have demonstrated that machine learning techniques, such as Support Vector Machine (SVM) modeling, produce similar or improved predictive capabilities in comparison to the traditional method of Logistic Regression. In addition, it has been found that social network metrics can provide useful predictive information for disease modeling. In this study, we combine simulated social network metrics with SVM to predict diabetes in a sample of data from the Behavioral Risk Factor Surveillance System. In this dataset, Logistic Regression outperformed SVM with ROC index of 81.8 and 81.7 for models with …

A Multiscale Modeling Study Of The Mammary Gland, Joseph D. Butner

Biomedical Engineering ETDs

Multiscale, hybrid computer modeling has emerged as a valuable tool in the fields of computational systems biology and mathematical oncology. In this work, we present an overview of the motivations for, and development and implementation of, three hybrid multiscale models of the mammary gland system and early stage ductal carcinoma in situ (DCIS) in the gland. Pubertal mammary gland development was described first using a two-dimensional, lattice-based hybrid agent-based model description of the mammary terminal end bud (TEB), and then with a three-dimensional lattice-free TEB model. Both models implement a discrete, agent-based description of the cell scale, and a continuum, …

Mechanistic Mathematical Models: An Underused Platform For Hpv Research, Marc Ryser, Patti Gravitt, Evan R. Myers

Global Health Faculty Publications

Health economic modeling has become an invaluable methodology for the design and evaluation of clinical and public health interventions against the human papillomavirus (HPV) and associated diseases. At the same time, relatively little attention has been paid to a different yet complementary class of models, namely that of mechanistic mathematical models. The primary focus of mechanistic mathematical models is to better understand the intricate biologic mechanisms and dynamics of disease. Inspired by a long and successful history of mechanistic modeling in other biomedical fields, we highlight several areas of HPV research where mechanistic models have the potential to advance the …

Simulating Within-Vector Generation Of The Malaria Parasite Diversity, Lauren M. Childs, Olivia F. Prosper

Mathematics Faculty Publications

Plasmodium falciparum, the most virulent human malaria parasite, undergoes asexual reproduction within the human host, but reproduces sexually within its vector host, the Anopheles mosquito. Consequently, the mosquito stage of the parasite life cycle provides an opportunity to create genetically novel parasites in multiply-infected mosquitoes, potentially increasing parasite population diversity. Despite the important implications for disease transmission and malaria control, a quantitative mapping of how parasite diversity entering a mosquito relates to diversity of the parasite exiting, has not been undertaken. To examine the role that vector biology plays in modulating parasite diversity, we develop a two-part model framework …

Light Dependent Endolysosomal Defects In A Photoreceptor Model Of Alzheimer's Disease, Michelle S. Smith

Undergraduate Honors Theses

Alzheimer’s disease (AD) is a neurodegenerative disease which is the 6^th leading cause of death in the US. AD pathology is thought to be linked to the accumulation and aggregation of toxic proteins, amyloid-beta and tau. AD development and neurodegeneration is proposed to be caused by the toxic effects of these protein accumulations, specifically amyloid-beta, as postulated by the amyloid-cascade hypothesis. To study the relationship between amyloid-beta and overall neuronal health, a study was carried out using an amyloid-expressing fruit fly photoreceptor model. Using this model, toxicity of amyloid in a stressed lysosomal system induced by light, an established …

The Kinetics Of Type I Interferons During Influenza Virus Infection, Margaret A. Myers

Biology and Medicine Through Mathematics Conference

No abstract provided.

Control Policies And Sensitivity Analysis In A Cutaneous Leishmaniasis Model: A Case Study In Cusco Region, Peru., Rocio M. Caja-Rivera, Ignacio Barradas

Biology and Medicine Through Mathematics Conference

No abstract provided.

Computational Modeling Of Contrast Sensitivity And Orientation Tuning In Schizophrenia, Steven M. Silverstein, Docia L. Demmin, James A. Bednar

MODVIS Workshop

Computational modeling is being increasingly used to understand schizophrenia, but, to date, it has not been used to account for the common perceptual disturbances in the disorder. We manipulated schizophrenia-relevant parameters in the GCAL (gain control, adaptation, laterally connected) model (Stevens et al., 2013), run using the Topographica simulator (Bednar, 2012), to model low-level visual processing changes in the disorder. Our models incorporated: separate sheets for retinal, LGN, and V1 activity; gain control in the LGN; homeostatic adaptation in V1 based on a weighted sum of all inputs and limited by a logistic (sigmoid) nonlinearity; lateral excitation and inhibition in …

Lymphoid Hematopoiesis And The Role Of B-Cells In Transgenic Mouse Model Of Sickle Cell Disease, Christina Cotte

University Scholar Projects

Sickle cell disease (SCD) has been shown to be associated with decreased baseline immunity and thus increased susceptibility to infection. I sought to discern possible causes of this by looking into the correlations between SCD and hematopoiesis, the immune system and the neuroendocrine system, and ultimately by conducting experiments surrounding the impaired immune system of SCD. These experiments focused on the potential causes and effects of the diminution of B-1a cells in the SCD spleen. Adoptive transfers, infections with Streptococcus pneumoniae, and histologic imaging were conducted to establish if the diminution of the B-1a cells in the SCD spleen …

Dox Inducible Idh2 R140q Expression In Stem Cells Results In Cell Death, Opposite Of Cancerous Overgrowth, Reuben Hogan

Undergraduate Research Symposium Posters

Mutations in isocitrate dehydrogenase (IDH) 1 or 2 are found in about 23% of acute myeloid leukemia (AML) samples and about 90% of gliomas. Mutations result in neomorphic function of the IDH enzyme that yields the novel molecule 2-hydroxyglutarate (2HG) instead of alpha-ketoglutarate (aKG). 2HG is known to be associated with hypermethylation of DNA and histones, a phenotype seen in AML. Our lab intends to study the mechanism by which hypermethylation is achieved and how this mechanism relates to the onset of cancer. In this experiment, we utilized a line of H9 stem cells which we had developed. These cells …

Integrative Analysis Of Omics Data In Adult Glioma And Other Tcga Cancers To Guide Precision Medicine, Xin Hu, Xin Hu

Dissertations and Theses (Open Access)

Transcriptomic profiling and gene expression signatures have been widely applied as effective approaches for enhancing the molecular classification, diagnosis, prognosis or prediction of therapeutic response towards personalized therapy for cancer patients. Thanks to modern genome-wide profiling technology, scientists are able to build engines leveraging massive genomic variations and integrating with clinical data to identify “at risk” individuals for the sake of prevention, diagnosis and therapeutic interventions. In my graduate work for my Ph.D. thesis, I have investigated genomic sequencing data mining to comprehensively characterise molecular classifications and aberrant genomic events associated with clinical prognosis and treatment response, through applying high-dimensional …

A Mixed-Methods Study: Self-Efficacy And Barriers To Participation In Workplace Wellness Programs, Massiel Perez-Calhoon

Dissertations

America needs a healthy workforce to sustain the country. The scourge of obesity continues to plague Americans despite government initiatives such as the Affordable Care Act and wellness programs in the workplace to combat this epidemic. However, despite initiatives to make America healthy, barriers continued to impede the nation’s health. Lack of awareness and sensitivity to what motivates individual participants versus group participants built formidable barriers to accessing all workplace employees equitably. The purpose of this study was twofold. First, the intent of this study was to explore the relationship between self-efficacy and the impact on participation and engagement when …

Persistent Neurobehavioral Traits In A Mouse Model Of Prenatal Ethanol Exposure, Jill M. Lawrence

Neuroscience Honors Papers

Fetal Alcohol Spectrum Disorders (FASD) effect an estimated 2% of the population, causing a range of symptoms: from craniofacial defects to inhibited cortical growth (May, et al., 2009; Murawski, et al., 2015). Impaired medial forebrain function apparent in FASD is associated with lifelong cognitive behavioral deficits, but these consequences may be avoided with early diagnosis and intervention (Streissguth, et al., 2004). Our goal is to identify early neurobehavioral abnormalities that persist into adulthood that could potentially serve as early indicators for FASD. Mouse models of prenatal ethanol exposure were developed using a voluntary drinking paradigm that introduced a sweetened ethanol …

Npy1 Receptor Agonist Modulates Development Of Depressive-Like Behavior And Gene Expression In Hypothalamus In Sps Rodent Ptsd Model, Lidia Serova, H Mulhall, Esther Sabban

NYMC Faculty Publications

Delivery of neuropeptide Y (NPY) to the brain by intranasal infusion soon after traumatic stress has shown therapeutic potential, and prevented development of many behavioral and neuroendocrine impairments in the single prolonged stress (SPS) animal model of PTSD. Therefore, we examined whether the Y1R preferring agonist [Leu(31)Pro(34)]NPY is sufficient to prevent development of SPS induced depressive-like behavioral changes, and hypothalamic gene expression as obtained with intranasal NPY intervention. Male Sprague-Dawely rats were given intranasal infusion of either NPY (150 mug/rat), a low (68 mug /rat), or high (132 mug/rat) dose of [Leu(31)Pro(34)]NPY or vehicle immediately following the last SPS stressor, …

A Comparative Study Of Three Different Types Of Stem Cells For Treatment Of Rat Spinal Cord Injury, Jiri Ruzicka, L Machova-Urdzikova, John Gillick, T Amemori, N Romanyuk, K Karova, K Zaviskova, J Dubisova, S Kubinova, Raj Murali, E Sykova, Meena Jhanwar-Uniyal, P Jendelova

NYMC Faculty Publications

Three different sources of human stem cells-bone marrow-derived mesenchymal stem cells (BM-MSCs), neural progenitors (NPs) derived from immortalized spinal fetal cell line (SPC-01), and induced pluripotent stem cells (iPSCs)-were compared in the treatment of a balloon-induced spinal cord compression lesion in rats. One week after lesioning, the rats received either BM-MSCs (intrathecally) or NPs (SPC-01 cells or iPSC-NPs, both intraspinally), or saline. The rats were assessed for their locomotor skills (BBB, flat beam test, and rotarod). Morphometric analyses of spared white and gray matter, axonal sprouting, and glial scar formation, as well as qPCR and Luminex assay, were conducted to …

Transcriptional Signatures Of Brain Aging And Alzheimer's Disease: What Are Our Rodent Models Telling Us?, Kendra E. Hargis, Eric M. Blalock

Pharmacology and Nutritional Sciences Faculty Publications

Aging is the biggest risk factor for idiopathic Alzheimer’s disease (AD). Recently, the National Institutes of Health released AD research recommendations that include: appreciating normal brain aging, expanding data-driven research, using open-access resources, and evaluating experimental reproducibility. Transcriptome data sets for aging and AD in humans and animal models are available in NIH-curated, publically accessible databases. However, little work has been done to test for concordance among those molecular signatures. Here, we test the hypothesis that brain transcriptional profiles from animal models recapitulate those observed in the human condition. Raw transcriptional profile data from twenty-nine studies were analyzed to produce …

P35. Investigating The Effect Of Maternal Immune Activation On Sensory Filtering, Social Behaviour And Attention, Faraj Haddad

Western Research Forum

Background

Altered brain development is associated with many neuropsychiatric disorders like Autism Spectrum Disorder (ASD) and schizophrenia. Environmental insults can interfere with neurodevelopment, and a prominent example is maternal infection during pregnancy. Epidemiological studies show that children born to mothers who were infected during pregnancy display a higher risk of developing ASD and schizophrenia, and this effect is mainly due to the maternal immune response. Polyinosinic-polycytidilic acid (Poly I:C) is a double stranded RNA molecule that mimics viral markers and elicits an immune response. When injected in pregnant rodents, this model produces offspring that exhibit core symptoms of ASD and …

Modification Of The Ruiz-Moreno Chikungunya Seir Model, Joseph Devlin

UNO Student Research and Creative Activity Fair

The Ruiez-Moreno CHIKV model predicts the outcome of the Chikungunya disease. Chikungunya, a disease similar to the Zika virus, is vector-borne with very little treatment for patients. This experiment looks to find ways to improve the model. The model will still need further improvement, as there is no model that can predict with full certainty. However, a method of modification has been made to expedite the process, the code has been rearranged for easy input and to minimize possibility of unwanted changes, and the control files for comparison have been created. The method to modify the model can be superimposed …