Cell and Developmental Biology Commons^™

Molecular Mechanism Of Neurodegeneration Induced By 4-Nonylphenol, Michelle Alejandra Aranda

Open Access Theses & Dissertations

Neurodegeneration, a progressive loss of nerve cells, occurs in many neurological disorders, including Alzheimer's disease (AD) and Parkinson's diseases (PD), as well as in dementia. The pathogenesis of these diseases is unknown, and recent evidence suggests that environmental factors, which act as endocrine-disrupting compounds (EDCs) could play a significant role in developing the disease process. 4-Nonylphenol (4-NP), an EDC, and a ubiquitous environmental toxin has been shown to affect brain development and may cause neurodegeneration. 4-NP is produced in large quantities in the U.S. and used as raw materials for making detergents, pesticides, plastics, paints, cosmetics, rubber, and other industrial/household …

Hspg2 Mediates Mandibular Jaw Joint Development, Barbara Samantha Castellanos

Open Access Theses & Dissertations

We present a patient diagnosed with a multiple congenital anomaly syndrome characterized by scoliosis, intellectual disabilities, and craniofacial defects. Trio-based whole exome sequencing identified compound heterozygous variants in the HSPG2 gene: a maternally inherited c.5998-7A>G variant in the promoter region and a paternally inherited c.4916C>T variant in the coding sequence. HSPG2 encodes for perlecan, a large proteoglycan that plays an important role in cartilage formation, cell adhesion, and basement membrane stability. Mutations in HSPG2 have been associated with Schwartz-Jampel syndrome and Dyssegmental Dysplasia Silverman-Handmaker Type, two disorders characterized by skeletal abnormalities (1). These data indicate a function for …

Evaluating Lactobacillus Acidophilus As A Model Organism For Co-Culture Cancer Studies, Samuel A. Mikhail

Honors Undergraduate Theses

The causality dilemma between dysbiosis and cancer has given rise to numerous studies both exploring the mechanisms behind cancer progression and the associative shifts in the microbiota upon carcinogenesis. Aside from the hallmark study of Dr. Barry Marshall in establishing the true causal relationship between Helicobacter pylori and gastric adenocarcinoma, studies have only been successful in adding associative links of carcinogenesis mediated by bacteria to the literature. The current field is limited in its ability to establish causative relationships, and further work is needed to construct a reference community whose physiological responses reflect global community responses. In this thesis, the …

Bioinformatic And Experimental Analyses Of Axolotl Regeneration, Nour W. Al Haj Baddar

Theses and Dissertations--Biology

Salamanders have an extraordinary ability to regenerate appendages after loss or amputation, irrespective of age. My dissertation research explored the possibility that regenerative ability is associated with the evolution of novel, salamander-specific genes. I utilized transcriptional and genomic databases for the axolotl to discover previously unidentified genes, to the exclusion of other vertebrate taxa. Among the genes identified were multiple mmps (Matrix metalloproteases) and a jnk1/mapk8 (c-jun-N-terminal kinase) paralog. MMPs function in extracellular matrix remodeling (ECM) and tissue histolysis, processes that are essential for successful regeneration. Jjnk1/mapk8 plays a pivotal role in regulating transcription in response to cellular stress stimuli, …

Tgf-Β, Wnt, And Fgf Signaling Pathways During Axolotl Tail Regeneration And Forelimb Bud Development, Qingchao Qiu

Theses and Dissertations--Neuroscience

Tgf-β, Wnt, and Fgf signaling pathways are required for many developmental processes. Here, I investigated the requirement of these signaling pathways during tail regeneration and limb development in the Mexican axolotl (Ambystoma mexicanum).

Using small chemical inhibitors during tail regeneration, I found that the Tgf-β signaling pathway was required from 0-24 and 48-72 hours post tail amputation (hpa), the Wnt signaling pathway was required from 0-120 hpa, and the Fgf signaling pathway was required from 0-12hpa. Tgf-β1 was upregulated after amputation and thus may mediate Tgf-β signaling pathway during tail regeneration. Both Smad-mediated and non-Smad mediated Tgf-β signaling …

Effects Of A Systemic High Urea Concentration On The Endometrial And Embryonic Transcriptomes Of The Mare, Yatta Linhares Boakari

Theses and Dissertations--Veterinary Science

Pregnancy loss remains a major source of economic cost to the equine industry. Frequently, the exact causes of pregnancy loss remain unknown. It has been shown, in other species, that increased dietary protein leading to elevated blood urea nitrogen concentrations (BUN) can be a factor in decreased survival of the early embryo. Our studies provided novel information regarding the effects of elevated BUN on endometrium and embryos from mares as well as insights on changes in their gene expression. Our first objective was to develop an experimental model to elevate BUN during diestrus using intravenous urea infusion. We analyzed the …

Ultrasound/Elastography Techniques, Lipidomic And Blood Markers Compared To Magnetic Resonance Imaging In Non-Alcoholic Fatty Liver Disease Adults, Irene Cantero, Mariana Elorz, Itziar Abete, Bertha Araceli Marin, Jose Ignacio Herrero, Jose Ignacio Monreal, Alberto Benito, Jorge Quiroga, Ana Martínez, Pilar Huarte, Juan Isidro Uriz-Otano, Josep Antoni Tur, John Kearney, J. Alfredo Martinez, M. Angeles Zulet

Articles

Introduction: Non-alcoholic fatty liver disease (NAFLD) may progress to steatohepatitis, cirrhosis and complicated hepatocellular carcinoma with defined differential symptoms and manifestations. Objective: To evaluate the fatty liver status by several validated approaches and to compare imaging techniques, lipidomic and routine blood markers with magnetic resonance imaging in adults subjects with non-alcoholic fatty liver disease. Materials and methods: A total of 127 overweight/obese with NAFLD, were parallelly assessed by Magnetic Resonance Imaging (MRI), ultrasonography, transient elastography and a validated metabolomic designed test to diagnose NAFLD in this cross-sectional study. Body composition (DXA), hepatic related biochemical measurements as well as the Fatty …

Evaluating The Effects Of Antibody-Conjugated Multi-Walled Carbon Nanotubes In Combination With Microwave Irradiation, Amy Chall

College of Graduate Studies: Theses & Dissertations

Cancer remains one of the largest public health concerns of our day, particularly in developed countries where technological advances have allowed populations to live well into their eighth decade. In America, those in their 80’s have a 1 in 2 chance of developing cancer in their lifetime. Prostate cancer, specifically is the second leading cause of cancer deaths in males. Traditional cancer therapies cause high levels of toxicity to the patient due to mechanisms of action that often attack cancer cells and healthy cells alike. The holy grail of cancer research is to find a treatment that targets the cancer …

Monocytes And Monocyte-Derived Antigen-Presenting Cells Have Distinct Gene Signatures In Experimental Model Of Multiple Sclerosis, Kelly L. Monaghan, Wen Zheng, Gangqing Hu, Edwin C. K. Wan

Faculty & Staff Scholarship

Multiple sclerosis (MS) is a chronic inflammatory disease mediated by a complex interaction between the autoreactive lymphocytes and the effector myeloid cells within the central nervous system (CNS). In a murine model of MS, experimental autoimmune encephalomyelitis (EAE), Ly6Chi monocytes migrate into the CNS and further differentiate into antigen-presenting cells (APCs) during disease progression. Currently, there is no information about gene signatures that can distinguish between monocytes and the monocyte-derived APCs. We developed a surface marker-based strategy to distinguish between these two cell types during the stage of EAE when the clinical symptoms were most severe, and performed transcriptome analysis …

Examining The Effects Of Fadrozole, An Aromatase Inhibitor, On Testosterone And Estrogen Production Of Domestic Chicken Embryos (Gallus Gallus), Abby E. Joseph

Honors Theses

The hypothalamic-pituitary-gonadal (HPG) axis is responsible for the production of the hormones testosterone and estradiol, and testosterone is thought to contribute to regulation of the axis through a negative feedback mechanism. Regulation by negative feedback involves the product of a pathway turning off that pathway when enough product is made. However, because the enzyme P450 aromatase converts testosterone to estradiol, estradiol may also contribute to regulation of the HPG axis and other phenomena that have been attributed to testosterone, like the inhibition of immune function. Previous studies have injected birds with an aromatase inhibitor (presumably reducing estradiol production) and shown …

Exploring The Efficacy Of Natural Products In Alleviating Alzheimer’S Disease Using Animal Models, Prajakta Deshpande, Neha Gogia, Amit Singh

Biology Faculty Publications

Alzheimer’s disease (hereafter AD) is a progressive neurodegenerative disorder that affects the central nervous system. There are multiple factors that cause AD, viz., accumulation of extracellular Amyloid-beta 42 plaques, intracellular hyper-phosphorylated Tau tangles, generation of reactive oxygen species due to mitochondrial dysfunction and genetic mutations. The plaques and tau tangles trigger aberrant signaling, which eventually cause cell death of the neurons. As a result, there is shrinkage of brain, cognitive defects, behavioral and psychological problems. To date, there is no direct cure for AD. Thus, scientists have been testing various strategies like screening for the small inhibitor molecule library …

Ehdv-2 Infection Prevalence Varies In Culicoides Sonorensis After Feeding On Infected White-Tailed Deer Over The Course Of Viremia, Sandra Y. Mendiola, Mary K. Mills, Elin Maki, Barbara S. Drolet, William C. Wilson, Roy D. Berghaus, David E. Stallknecht, Jonathan Breitenbach, D. Scott Mcvey, Mark G. Ruder

School of Veterinary and Biomedical Sciences: Faculty Publications

Epizootic hemorrhagic disease viruses (EHDVs) are arboviral pathogens of white-tailed deer and other wild and domestic ruminants in North America. Transmitted by various species of Culicoides, EHDVs circulate wherever competent vectors and susceptible ruminant host populations co-exist. The impact of variation in the level and duration of EHDV viremia in white-tailed deer (Odocoileus virginianus) on Culicoides infection prevalence is not well characterized. Here we examined how infection prevalence in a confirmed North American vector of EHDV-2 (Culicoides sonorensis) varies in response to fluctuations in deer viremia. To accomplish this, five white-tailed deer were experimentally infected with EHDV-2 and colonized C. …

Misexpression Of Cancer/Testis (Ct) Genes In Tumor Cells And The Potential Role Of Dream Complex And The Retinoblastoma Protein Rb In Soma-To-Germline Transformation, Sabha M. Alhewati

Dissertations, Master's Theses and Master's Reports

Misexpression of germline genes like Cancer Testis (CT) genes, called a soma-to-germline transformation, is a phenomenon linked to tumorigenesis. However, the mechanisms underlying this phenomenon are poorly understood. A soma-to-germline transformation in Caenorhabditis elegans occurs due to the loss function of the highly conserved DREAM (Dp, Retinoblastoma (Rb)-like, E2F, and MuvB) transcriptional repressor complex. In mammalian cells, the DREAM complex (Muvb core complex, E2F4/5, DP1/2, and p130/p107 proteins), as well as the Retinoblastoma protein (pRb), are implicated in transcriptional repression of cell cycle genes in quiescence or G0. We hypothesize that the expression of CT genes in malignant cells occurs …

Disruption Of Cul3-Mediated Ubiquitination Causes Proximal Tubule Injury And Kidney Fibrosis, Turgay Saritas, Catherina A. Cuevas, Mohammed Z. Ferdaus, Christophe Kuppe, Rafael Kramann, Marcus J. Moeller, Jurgen Floege, Jeffrey Singer, James A. Mccormick

Biology Faculty Publications and Presentations

Cullin 3 (CUL3) is part of the ubiquitin proteasomal system and controls several cellular processes critical for normal organ function including the cell cycle, and Keap1/Nrf2 signaling. Kidney tubule-specific Cul3disruption causes tubulointerstitial fibrosis, but little is known about the mechanisms. Therefore, we tested the hypothesis that dysregulation of the cell cycle and Keap1/Nrf2 pathway play a role in initiating the kidney injury upon Cul3 disruption. Cul3 deletion increased expression of cyclin E and p21, associated with uncontrolled proliferation, DNA damage, and apoptosis, all of which preceded proximal tubule injury. The cdk2-cyclin E inhibitor roscovitine did not prevent the effects …

Mutations Of Fus Cause Aggregation Of Rna Binding Proteins, Disruptions In Protein Synthesis, And Dysregulation Of Nonsense Mediated Decay, Marisa Elizabeth Kamelgarn

Theses and Dissertations--Toxicology and Cancer Biology

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron death and subsequent muscle atrophy. Approximately 15% of ALS cases are inheritable, and mutations in the Fused in Sarcoma (FUS) gene contribute to approximately 5% of these cases, as well as about 2% of sporadic cases. FUS performs a diverse set of cellular functions, including being a major regulator of RNA metabolism. FUS undergoes liquid- liquid phase transition in vitro, allowing for its participation in stress granules and RNA transport granules. Phase transition also contributes to the formation of cytoplasmic inclusions found in the …

Exosomes Mediate Zika Virus Transmission Through Smpd3 Neutral Sphingomyelinase In Cortical Neurons, Wenshuo Zhou, Michael Woodson, Michael B. Sherman, Girish Neelakanta, Hameeda Sultana

Biological Sciences Faculty Publications

The harmful effects of ZIKA virus (ZIKV) infection are reflected by severe neurological manifestations such as microcephaly in neonates and other complications associated with Guillain-Barre syndrome in adults. The transmission dynamics of ZIKV in or between neurons, or within the developing brains of the foetuses are not fully understood. Using primary cultures of murine cortical neurons, we show that ZIKV uses exosomes as mediators of viral transmission between neurons. Cryo-electron microscopy showed heterogeneous population of neuronal exosomes with a size range of 30-200 nm. Increased production of exosomes from neuronal cells was noted upon ZIKV infection. Neuronal exosomes contained both …

Put Your Money Where Your Mouth Is: Reforming Organized Dentistry To Address Persistent Oral Health Disparities In The U.S., Aparna Chintapalli

Pomona Senior Theses

The importance of oral health has been largely neglected from the conventional standards of healthcare in terms of public understanding & prioritization, the industrial infrastructure, and the scope of prevention & early-intervention services. Its adjunctive locus to the field of medicine has lead to the bifurcation of the oral cavity from the rest of the human body. As a result of this divide, there have been multiple factors that have allowed socially stratified oral health outcomes to manifest. This thesis examines the determinants of oral health disparities through a multidisciplinary lens (i.e. biology, public policy, infrastructure), and offers evidence of …

The Effects Of Bisphenol F On Embryonic Cardiac Output In Zebrafish, Kyle Monnot

Williams Honors College, Honors Research Projects

Bisphenol F (BPF) is an analog compound of the xenoestrogen bisphenol A (BPA). BPA utilization has decreased dramatically due to its detrimental effects as an endocrine disrupter. In place of BPA, BPF is growing to be a ubiquitous chemical in epoxy resin manufacturing. Recent research has begun to investigate the possible endocrinal effects of BPF as an analog of BPA. This study was performed to examine the potential effects of BPF exposure on cardiac parameters of zebrafish (Danio rerio) embryos. Embryos were exposed to 50 µg/L BPF for 48 hours, and cardiac parameters (stroke volume, heart rate, and …

Identifying Critical Genes For Cholesterol Metabolism In Macrophages Using Crispr-Cas9 Whole-Genome Screens, Kevin Wanniarachchi

Electronic Theses and Dissertations

Macrophage foam cells contribute to atherosclerotic plaque formation, a pathology that underlies heart disease, peripheral arterial disease and stroke. Foam cells form when macrophages take up excessive amounts of low-density lipoprotein (LDL) leading to elevated cellular levels of neutral lipids, which are packaged into lipid droplet organelles. Despite the high public health priority motivating research of cardiovascular disease processes, current understanding of macrophage cholesterol metabolism including mechanisms of LDL uptake, cholesterol trafficking, lipid droplet biogenesis, lipid droplet degradation and cholesterol efflux is limited. Here, we implemented a CRISPR-Cas9 whole genome screening strategy to identify critical genes regulating macrophage cholesterol metabolism. …

Optimization Of Primary Cilia Detection In Musculoskeletal Tissue, Ragen Engel

Williams Honors College, Honors Research Projects

The objective of this research project was to optimize a laboratory technique for visualizing primary cilia in musculoskeletal tissue of young swine, specifically the growth plate of long bones. This was accomplished through varying fixation procedures, antigen retrieval methods, antibody concentrations, and incubation times. By varying these parameters, a reproducible procedure was developed to examine the primary cilia in multiple tissues including ligament, fascia, and growth plate. This experiment introduced variances in fixation methods, with methanol or formalin. Paraffin and frozen embedding techniques were also varied for comparison with regards to cilia visualization. Results from the acetylated alpha tubulin (aTUB) …

Microarray Data Analysis And Classification Of Cancers, Grant Gates

Williams Honors College, Honors Research Projects

When it comes to cancer, there is no standardized approach for identifying new cancer classes nor is there a standardized approach for assigning cancer tumors to existing classes. These two ideas are known as class discovery and class prediction. For a cancer patient to receive proper treatment, it is important that the type of cancer be accurately identified. For my Senior Honors Project, I would like to use this opportunity to research a topic in bioinformatics. Bioinformatics incorporates a few different subjects into one including biology, computer science and statistics. An intricate method for class discovery and class prediction is …

Sprouty4 Is A Negative Regulator Of Erk/Mapk Signaling In Breast Cancer And Plays A Role In The Transition From In Situ To Invasive Disease, Ethan Brock

Wayne State University Dissertations

Breast ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive ductal carcinoma (IDC). It is still unclear which DCIS will become invasive and which will remain indolent. Previous data by our group found that Sprouty4 transcript was differentially expressed between three DCIS cell lines and a non-transformed breast epithelial cell line. Sprouty proteins are important regulators of ERK/MAPK signaling, and have been studied in various cancers. We hypothesized that Sprouty4 is an endogenous inhibitor of ERK/MAPK signaling and that its loss/reduced expression is a mechanism by which DCIS lesions progress toward IDC, including triple-negative disease. Using immunohistochemistry we …

Stress-Dependent Regulation Of A Major Node Of The Insulin-Like Peptide Network That Modulates Survival, Rashmi Chandra

Wayne State University Dissertations

Chronic stress disrupts insulin signaling, predisposing human populations to diabetes, cardiovascular disease, Alzheimer’s Disease, and other metabolic and neurological disorders, including post-traumatic disorders (PTSD). Thus, efficient recovery from stress optimizes survival. However, stress recovery in humans is difficult to study, but is much easier to dissect in model organisms. The worm genetic model Caenorhabditis elegans can switch between stressed and non-stressed states, and this switch is largely regulated by insulin signaling. Previously, the Alcedo lab proposed that insulin-like peptides (ILPs), which exist as multiple members of a protein family in both C. elegans and humans, implements a combinatorial coding strategy …

The Balance Between Prostaglandin E2 Ep3 And Ep4 Receptors Determines Severity Of Cardiac Damage In Myocardial Infarction And An Angiotensin Ii-Induced Model Of Hypertension, Timothy Dean Bryson

Wayne State University Dissertations

According to the center for disease control about 610,000 people die every year in the United States from heart disease, of which, coronary heart disease is the most common form. One major risk factor for heart attack is hypertension, which affects nearly half of all Americans [472, 473]. PGE2 plays an important role in regulating cardiovascular function and mediating inflammation, both of which contribute to the development of hypertension and/or heart disease. Prostaglandin E2 can act as a vasodilator or vasoconstrictor depending on which of its receptor subtypes are activated.

In general, activation of the EP1 and EP3 receptors is …

Sonic Hedgehog Is Expressed By Hilar Mossy Cells And Regulates Cellular Survival And Neurogenesis In The Adult Hippocampus, Luis E. Gonzalez-Reyes, Chia-Chu Chiang, Mingming Zhang, Joshua Johnson, Manuel Arrillaga-Tamez, Nicholas H. Couturier, Neha Reddy, Lev Starikov, Jeffrey R. Capadona, Andreas H. Kottmann, Dominique M. Durand

Publications and Research

Sonic hedgehog (Shh) is a multifunctional signaling protein governing pattern formation, proliferation and cell survival during embryogenesis. In the adult brain, Shh has neurotrophic function and is implicated in hippocampal neurogenesis but the cellular source of Shh in the hippocampus remains ill defined. Here, we utilize a gene expression tracer allele of Shh (Shh-nlacZ) which allowed the identification of a subpopulation of hilar neurons known as mossy cells (MCs) as a prominent and dynamic source of Shh within the dentate gyrus. AAV-Cre mediated ablation of Shh in the adult dentate gyrus led to a marked degeneration …

The Functional Role Of Rna Binding Protein Rbms3 As A Tumor Promoter In Triple-Negative Breast Cancer Cells, Yuting Zhou

Theses and Dissertations--Molecular and Cellular Biochemistry

RBMS3 belongs to the family of c-myc gene single-strand binding proteins (MSSPs) that play important roles in transcriptional regulation. Here, we show that RBMS3 functions as a tumor promoter in triple-negative breast cancer (TNBC), a highly aggressive BC subtype. Analysis of RBMS3 expression shows that RBMS3 is upregulated at both mRNA and protein levels in TNBC cells. Functionally, overexpression of RBMS3 increases cell migration, invasion and cancer stem cell (CSC) behaviors. Moreover, RBMS3 induces expression of epithelial-mesenchymal transition (EMT) and CSC markers. Conversely, loss of RBMS3 in TNBC BT549 cells inhibits cell proliferation, migration and mesenchymal phenotype. Correlation analysis shows …

The Effects Of A Ketone Body On Synaptic Transmission, Alexandra Elizabeth Stanback

Theses and Dissertations--Biology

The ketogenic diet is commonly used to control epilepsy, especially in cases when medications cannot. The diet typically consists of high fat, low carb, and adequate protein and produces a metabolite called acetoacetate. Seizure activity is characterized by glutamate excitotoxicity and therefore glutamate regulation is a point of research for control of these disorders. Acetoacetate is heavily implicated as the primary molecule responsible for decreasing glutamate in the synapse; it is believed that acetoacetate interferes with the transport of glutamate into the synaptic vesicles. The effects on synaptic transmission at glutamatergic synapses was studied in relation to the ketogenic diet …

P4ha1 Is A New Regulator Of The Hif-1 Pathway In Breast Cancer, Ren Xu

Markey Cancer Center Faculty Publications

Hypoxia-Inducible Factor (HIF)-1 is a transcription factor that plays the key role in response to low oxygen concentrations, or hypoxia. Activation of the HIF-1 pathway is not only crucial for normal tissue development and function, but also involved in disease progression, such as cancer. Cancer cells proliferate rapidly in solid tumors, and thus, solid tumors consume much more oxygen and nutrients than normal tissue and generate oxygen tension. It is well established that oxygen tension in solid tumor tissue induces the aberrant activation of the HIF-1 pathway, and subsequently promotes angiogenesis and tumor progression. Breast cancer is a heterogeneous disease …

A Poxvirus Pseudokinase Represses Viral Dna Replication Via A Pathway Antagonized By Its Paralog Kinase, Annabel T. Olson, Zhigang Wang, Amber B. Rico, Matthew S. Wiebe

Nebraska Center for Virology: Faculty Publications

Poxviruses employ sophisticated, but incompletely understood, signaling pathways that engage cellular defense mechanisms and simultaneously ensure viral factors are modulated properly. For example, the vaccinia B1 protein kinase plays a vital role in inactivating the cellular antiviral factor BAF, and likely orchestrates other pathways as well. In this study, we utilized experimental evolution of a B1 deletion virus to perform an unbiased search for suppressor mutations and identify novel pathways involving B1. After several passages of the ΔB1 virus we observed a robust increase in viral titer of the adapted virus. Interestingly, our characterization of the adapted viruses reveals that …

Persistent Viral Reservoirs In Lymphoid Tissues In Siv-Infected Rhesus Macaques Of Chinese-Origin On Suppressive Antiretroviral Therapy, Summer Siddiqui, Stefanie Perez, Yong Gao, Lara Doyle-Meyers, Brian T. Foley, Qingsheng Li, Binhua Ling

Nebraska Center for Virology: Faculty Publications

Understanding HIV latent reservoirs in tissues is essential for the development of new strategies targeting these sites for eradication. Here, we assessed the size of latent reservoirs and the source of residual viruses in multiple lymphoid tissues of SIV-infected and fully suppressed rhesus macaques of Chinese-origin (cRMs). Eight cRMs were infected with SIVmac251 and treated with tenofovir and emtricitabine daily for 24 weeks initiated 4 weeks post-infection. Four of the eight animals reached sustained full viral suppression with undetectable viremia. The levels of cell-associated SIV DNA varied in peripheral blood mononuclear cells (PBMCs) and multiple lymphoid tissues, but with higher …