Cell and Developmental Biology Commons^™

Mechanisms Of Trinucleotide Repeat Instability During Dna Synthesis, Kara Y. Chan

Theses and Dissertations--Toxicology and Cancer Biology

Genomic instability, in the form of gene mutations, insertions/deletions, and gene amplifications, is one of the hallmarks in many types of cancers and other inheritable genetic disorders. Trinucleotide repeat (TNR) disorders, such as Huntington’s disease (HD) and Myotonic dystrophy (DM) can be inherited and repeats may be extended through subsequent generations. However, it is not clear how the CAG repeats expand through generations in HD. Two possible repeat expansion mechanisms include: 1) polymerase mediated repeat extension; 2) persistent TNR hairpin structure formation persisting in the genome resulting in expansion after subsequent cell division. Recent in vitro studies suggested that a …

Expression Of Alternative Oxidase In The Copepod T. Californicus When Exposed To Environmental Stressors, Carly Tward

Theses and Dissertations (Comprehensive)

In addition to the typical electron transport system in animal mitochondria responsible for oxidative phosphorylation, some species possess an alternative oxidase (AOX) pathway, which causes electrons to bypass proton pumping complexes. Although AOX appears to be energetically wasteful, studies have revealed its wide taxonomic distribution, and indicate it plays a role in environmental stress tolerance. AOX discovery in animals is recent, and further research into its expression, regulation, and physiological role has been impeded by the lack of an experimental model organism. DNA database searches using bioinformatics revealed an AOX sequence present in the arthropod Tigriopus californicus. Multiple sequence …

Investigating The Antiviral Effects Of Vig-3 From Rainbow Trout, Shanee Herrington-Krause

Theses and Dissertations (Comprehensive)

Rainbow trout is the most farmed fish in Ontario, and thus is economically important to the province. Despite this, there is a lack of understanding regarding fish innate immunity, specifically with regards to interferon-stimulated genes (ISGs) and their antiviral effector functions. ISGs are the workhorses of the innate antiviral response, operating together to limit each step of virus replication. The Viral Hemorrhagic Septicemia Virus (VHSV) induced gene (Vig)-3 is a newly identified ISG within many fish species and is homologous to ISG-15 in mammals. It is a small ubiquitin-like protein inducible by type I interferon (IFN-I), and is suggested to …

Novel Amphiphilic Cyclobutene And Cyclobutane Cis-C18 Fatty Acid Derivatives Inhibit Mycobacterium Avium Subsp. Paratuberculosis Growth, Denise K. Zinniel, Wantanee Sittiwong, Darrell D. Marshall, Govardhan Rathnaiah, Isin T. Sakallioglu, Robert Powers, Patrick H. Dussault, Raul G. Barletta

School of Veterinary and Biomedical Sciences: Faculty Publications

Mycobacterium avium subspecies paratuberculosis (Map) is the etiologic agent of Johne’s disease in ruminants and has been associated with Crohn’s disease in humans. An effective control of Map by either vaccines or chemoprophylaxis is a paramount need for veterinary and possibly human medicine. Given the importance of fatty acids in the biosynthesis of mycolic acids and the mycobacterial cell wall, we tested novel amphiphilic C₁₀ and C₁₈ cyclobutene and cyclobutane fatty acid derivatives for Map inhibition. Microdilution minimal inhibitory concentrations (MIC) with 5 or 7 week endpoints were measured in Middlebrook 7H9 base broth media. We compared the …

Investigation Of Congestive Heart Failure In Beef Cattle In A Feedyard At A Moderate Altitude In Western Nebraska, Rodney A. Moxley, David R. Smith, Dale M. Grotelueschen, Tom Edwards, David Steffen

School of Veterinary and Biomedical Sciences: Faculty Publications

Right-sided congestive heart failure (brisket disease) commonly occurs in cattle raised at elevations >2,500– 3,500 m. We investigated clinical cases resembling brisket disease at a western Nebraska feedyard at a moderate altitude (1,369 m). Over a 15-mo period (2009–2010), we examined 17 cases (16 steers and 1 heifer), all purebred Angus. All animals had clinical right-sided heart failure: brisket and ventral abdominal edema, and severe chronic passive congestion of the liver. Gross examination confirmed right ventricular hypertrophy (left ventricle plus septum: right ventricle weight ratio mean: 1.33 vs. 2.8–4.0 reference interval). Microscopically, all 17 cases had interstitial fibrosis (mean score: …

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 …

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 …

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 …

Is The Blood An Alternative For Programmed Cell Death Ligand 1 Assessment In Non-Small Cell Lung Cancer?, Emmanuel Acheampong, Isaac Spencer, Weitao Lin, Melanie Ziman, Michael Millward, Elin Gray

Research outputs 2014 to 2021

Anti-programmed cell death (PD)-1/PD-ligand 1 (L1) therapies have significantly improved the outcomes for non-small cell lung cancer (NSCLC) patients in recent years. These therapies work by reactivating the immune system and enabling it to target cancer cells once more. There is a general agreement that expression of PD-L1 on tumour cells predicts the therapeutic response to PD-1/PD-L1 inhibitors in NSCLC. Hence, immunohistochemical staining of tumour tissue biopsies from NSCLC patients with PD-L1 antibodies is the current standard used to aid selection of patients for treatment with anti-PD-1 as first line therapy. However, issues of small tissue samples, tissue heterogeneity, the …

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 …

Non-Contact Trapping And Stretching Of Biological Cells Using Dual-Beam Optical Stretcher On Microfluidic Platform, Aotuo Dong, Balaadithya Uppalapati, Shariful Islam, Brandon Gibbs, Ganesan Kamatchi, Sacharia Albin, Makarand Deo

Electrical & Computer Engineering Faculty Publications

Optical stretcher is a tool in which two counter-propagating, slightly diverging, and identical laser beams are used to trap and axially stretch microparticles in the path of light. In this work, we utilized the dual-beam optical stretcher setup to trap and stretch human embryonic kidney (HEK) cells and mammalian breast cancer (MBC) cells. Experiments were performed by exposing the HEK cells to counter-propagating laser beams for 30 seconds at powers ranging from 100 mW to 561 mW. It was observed that the percentage of cell deformation increased from 16.7% at 100 mW to 40.5% at 561 mW optical power. The …

End-To-End Learning Via A Convolutional Neural Network For Cancer Cell Line Classification, Darlington A. Akogo, Xavier-Lewis Palmer

Electrical & Computer Engineering Faculty Publications

Purpose: Computer vision for automated analysis of cells and tissues usually include extracting features from images before analyzing such features via various machine learning and machine vision algorithms. The purpose of this work is to explore and demonstrate the ability of a Convolutional Neural Network (CNN) to classify cells pictured via brightfield microscopy without the need of any feature extraction, using a minimum of images, improving work-flows that involve cancer cell identification.

Design/methodology/approach: The methodology involved a quantitative measure of the performance of a Convolutional Neural Network in distinguishing between two cancer lines. In their approach, they trained, validated and …

No Causal Effect Of Telomere Length On Ischemic Stroke And Its Subtypes: A Mendelian Randomization Study, Weijie Cao, Xingang Li, Xiaoyu Zhang, Jie Zhang, Qi Sun, Xizhu Xu, Ming Sun, Qiuyue Tian, Qihuan Li, Hao Wang, Jiaonan Liu, Xiaoni Meng, Lijuan Wu, Manshu Song, Haifeng Hou, Youxin Wang, Wei Wang

Research outputs 2014 to 2021

Background: Epidemiological studies observing inconsistent associations of telomere length (TL) with ischemic stroke (IS) are susceptible to bias according to reverse causation and residual confounding. We aimed to assess the causal association between TL, IS, and the subtypes of IS, including large artery stroke (LAS), small vessel stroke (SVS), and cardioembolic stroke (CES) by performing a series of two-sample Mendelian randomization (MR) approaches. Methods: Seven single nucleotide polymorphisms (SNPs) were involved as candidate instrumental variables (IVs), summarized from a genome-wide meta-analysis including 37,684 participants of European descent. We analyzed the largest ever genome-wide association studies of stroke in Europe from …