Cell and Developmental Biology Commons^™

Understanding The Effects Of Embryonic Hyperglycemia On Retinal Development And Maintenance, Kayla Titialii-Torres

Theses and Dissertations--Biology

Hundreds of millions of people are affected by diabetes worldwide. Whether they are diagnosed with prediabetes or Type I or II diabetes, there are a variety of mechanisms in the pathogenesis of diabetes. Diabetes is a disease which consists of recurring states of hyperglycemia that can be difficult to manage due to either lack of insulin production or improper utilization of insulin. While these mechanisms of action differ, complications induced by diabetes occur in both poorly regulated Type I and II. Common complications of diabetes include nerve damage, kidney damage, and eye damage. Eye damage specifically is called diabetic retinopathy …

Identifying Epidermal Enriched Genes Required For Planarian Regeneration- Sp. Schmidtea Mediterranea, Pallob Barai

Theses and Dissertations--Biology

The outer epithelial layer covering an organism, commonly known as the epidermis, is crucial for maintaining homeostasis and for the wound healing processes after injury. The planarian epidermis allows flatworms to heal their wounds and virtually restore any missing tissues. Immediately after amputation, planarians contract their muscle and stretch their epidermis to heal the wound area. However, how the planarian epidermis coordinates with other tissues and mechanisms after the initial wound healing processes begins is not understood in detail. I hypothesized that epidermal cell stretching upon wound healing induces transcriptional changes that are required for effective regeneration. To test this …

The Role Of Protein Tyrosine Phosphatase Receptor Type F In Intestinal Homeostasis And Colorectal Cancer, Ashley T. Skaggs

Theses and Dissertations--Molecular and Cellular Biochemistry

Protein phosphorylation defines one of the most important regulatory mechanisms in cell signaling. PTPRF, protein tyrosine phosphatase receptor type F, belongs to the class I R2A subfamily of protein tyrosine phosphatases (PTP). The overall objective of this dissertation is to investigate the molecular mechanisms by which PTPRF regulates normal and cancer stem cells by controlling Wnt signaling.

Dysregulation of Wnt signaling promotes the initiation and progression of colorectal cancer (CRC). We first determined the functional important of PTPRF in regulating Wnt signaling in CRC. Combining cell culture, 3D tumor organoid and xenograft models, results from our study establish PTPRF as …

A Multidisciplinary Characterization Of The Enzymology And Biology Of Reversible Glucan Phosphorylation In Toxoplasma Gondii , Robert Murphy

Theses and Dissertations--Molecular and Cellular Biochemistry

Toxoplasma gondii is an opportunistic, protozoan parasite of all warm-blooded animals, infecting roughly one-third of humans worldwide. Humans acquire infections by consuming T. gondii tissue cysts in undercooked meat or from oocysts shed in cat feces. Encysted parasites convert into rapidly growing tachyzoites that disseminate throughout the body, defining the acute phase of infection. Under host immune pressure, tachyzoites convert into bradyzoites that populate tissue cysts found in CNS or muscle tissue and persist for the lifetime of the host, defining the chronic phase of infection. Tissue cysts are responsible for transmission via carnivory, but also possess the ability to …

Determinants Of Virus Variation, Evolution, And Host Adaptation, Katherine Latourrette, Hernan Garcia-Ruiz

Nebraska Center for Virology: Faculty Publications

Virus evolution is the change in the genetic structure of a viral population over time and results in the emergence of new viral variants, strains, and species with novel biological properties, including adaptation to new hosts. There are host, vector, environmental, and viral factors that contribute to virus evolution. To achieve or fine tune compatibility and successfully establish infection, viruses adapt to a particular host species or to a group of species. However, some viruses are better able to adapt to diverse hosts, vectors, and environments. Viruses generate genetic diversity through mutation, reassortment, and recombination. Plant viruses are exposed to …

Immunogenicity And Protective Efficacy Of A Recombinant Pichinde Viral-Vectored Vaccine Expressing Influenza Virus Hemagglutinin Antigen In Pigs, Sushmita Kumari, Jayeshbhai Chaudhari, Qinfeng Huang, Phillip Gauger, Marcelo Nunes De Almeida, Yuying Liang, Hinh Ly, Hiep Vu

Nebraska Center for Virology: Faculty Publications

Influenza A virus of swine (IAV-S) is an economically important swine pathogen. The IAV-S hemagglutinin (HA) surface protein is the main target for vaccine development. In this study, we evaluated the feasibility of using the recombinant tri-segmented Pichinde virus (rPICV) as a viral vector to deliver HA antigen to protect pigs against IAV-S challenge. Four groups of weaned pigs (T01–T04) were included in the study. T01 was injected with PBS to serve as a non-vaccinated control. T02 was inoculated with rPICV expressing green fluorescence protein (rPICV-GFP). T03 was vaccinated with rPICV expressing the HA antigen of the IAV-S H3N2 strain …

Evaluation Of Ivermectin Antiviral Activity Against Avian Infectious Bronchitis Virus Using A Chicken Embryo Model, Donald L. Reynolds, E. Barry Simpson

School of Veterinary and Biomedical Sciences: Faculty Publications

Ivermectin is widely used in both animals and humans as an FDA-approved parasiticide. Ivermectin has also been reported to have antiviral activity against several viruses including coronaviruses. There are reports that indicate ivermectin may have some role in diminishing the disease caused by SARS-CoV-2, but the evidence is inconclusive. The objective of this study was to determine if ivermectin was efficacious in inhibiting avian infectious bronchitis virus (IBV, a coronavirus) replication in chicken embryos. Briefly, our approach was to use the Massachusetts vaccine strain of IBV in combination with various doses of ivermectin and then inoculate these preparations into chicken …

Structural Variant-Based Pangenome Construction Has Low Sensitivity To Variability Of Haplotype-Resolved Bovine Assemblies, Alexander S. Leonard, Danang Crysnanto, Zih-Hua Fang, Michael P. Heaton, Brian L. Vander Ley, Carolina Herrera, Heinrich Bollwein, Derek M. Bickhart, Benjamin D. Rosen, Hubert Pausch

School of Veterinary and Biomedical Sciences: Faculty Publications

Advantages of pangenomes over linear reference assemblies for genome research have recently been established. However, potential effects of sequence platform and assembly approach, or of combining assemblies created by different approaches, on pangenome construction have not been investigated. Here we generate haplotype-resolved assemblies from the offspring of three bovine trios representing increasing levels of heterozygosity that each demonstrate a substantial improvement in contiguity, completeness, and accuracy over the current Bos taurus reference genome. Diploid coverage as low as 20x for HiFi or 60x for ONT is sufficient to produce two haplotype-resolved assemblies meeting standards set by the Vertebrate Genomes Project. …

Does Swab Type Matter? Comparing Methods For Mannheimia Haemolytica Recovery And Upper Respiratory Microbiome Characterization In Feedlot Cattle, William B. Crosby, Lee Pinnell, John T. Richeson, Cory Wolfe, Jake Castle, John Dustin Loy, Sheryl P. Gow, Keun Seok Seo, Sarah F. Capik, Amelia R. Woolums, Paul S. Morley

School of Veterinary and Biomedical Sciences: Faculty Publications

Background: Bovine respiratory disease (BRD) is caused by interactions among host, environment, and pathogens. One standard method for antemortem pathogen identification in cattle with BRD is deep-guarded nasopharyngeal swabbing, which is challenging, costly, and waste generating. The objective was to compare the ability to recover Mannheimia haemolytica and compare microbial community structure using 29.5 inch (74.9 cm) deep-guarded nasopharyngeal swabs, 16 inch (40.6 cm) unguarded proctology swabs, or 6 inch (15.2 cm) unguarded nasal swabs when characterized using culture, real time-qPCR, and 16S rRNA gene sequencing. Samples for aerobic culture, qPCR, and 16S rRNA gene sequencing were collected from the …

Rna Nanovaccine Protects Against White Spot Syndrome Virus In Shrimp, Yashdeep Phanse, Supraja Puttamreddy, Duan Loy, Julia Vela Ramirez, Kathleen A. Ross, Ignacio Alvarez-Castro, Mark Mogler, Scott Broderick, Krishna Rajan, Balaji Narasimhan, Lyric C. Bartholomay

School of Veterinary and Biomedical Sciences: Faculty Publications

In the last 15 years, crustacean fisheries have experienced billions of dollars in economic losses, primarily due to viral diseases caused by such pathogens as white spot syndrome virus (WSSV) in the Pacific white shrimp Litopenaeus vannamei and Asian tiger shrimp Penaeus monodon. To date, no effective measures are available to prevent or control disease outbreaks in these animals, despite their economic importance. Recently, double-stranded RNA-based vaccines have been shown to provide specific and robust protection against WSSV infection in cultured shrimp. However, the limited stability of double-stranded RNA is the most significant hurdle for the field application of these …

Understanding The Cellular And Physiological Mechanisms Of Fertilization And Early-Stage Seed Development, Mohammad Foteh Ali

Theses and Dissertations--Plant and Soil Sciences

Flowering plants have evolved a unique double-fertilization process. Two sperm cells fuse with two female gametophytic cells, the egg and central cells within the ovule, giving rise to the embryo and endosperm, respectively. Sperm cells in flowering plants are nonmotile and delivered in close proximity to the egg and central cells by the pollen tube. Flowering plants have established filamentous actin (F-actin) based sperm nuclear migration system for successful fertilization. Prior to fertilization, the female gamete forms a mesh-like structure of F-actin that shows constant inward movement from the plasma membrane periphery to the center of the cell where the …

Development Of Novel Pyridazine Derivatives And Drug Delivery Systems Against Dengue, Janae A. Culmer

College of Graduate Studies: Theses & Dissertations

The lack of approved vaccines, medications and treatment regimens has significantly contributed to the rapid spread of mosquito-borne viruses such as Dengue and Zika virus. The complex immunopathology of these viruses presents limitations for the development and implementation of a definitive, safe and effective approach to combat infections.Previous research has demonstrated that vector control strategies such as the elimination of larval habitats, larviciding with insecticides, the use of biological agents and the application of adulticides have been unsuccessful in the reduction of viral transmission leading to the need for the continued development of antivirals. This research proposes an approach for …

Elucidating The Role Of Polycomb Repressive Complex 2 In Lung Stem Cell Fate And Lung Disease, Aria Byrd

Theses and Dissertations--Toxicology and Cancer Biology

The average human lungs take ~22,000 breaths and inhale ~2,000 gallons of air each day. This organ is the primary conduit for the transfer of oxygen to the internal organs, making it crucial for the sustainment of life. Consequently, mechanical malfunction of the lungs and/or pollution of inhaled air negatively impact internal organ function and ultimately put survival in jeopardy. Epigenetics, by nature, is a plastic phenomenon in which environmental stimuli influence short term, long term, and generational gene expression patterns. Chronic exposure of harmful stimuli to the lung epithelium has also been shown to alter epigenetic pathways, engender aberrant …

Extracellular Vesicles And Cancer Therapy: An Insight Into The Role Of Oxidative Stress, Jenni Ho

Theses and Dissertations--Toxicology and Cancer Biology

As a result of improvements in cancer detection and treatment methods, a growing population of cancer survivors are living with side effects associated with their cancer therapy. Oxidative stress plays a significant role in the development of cancer and as a mechanism for cancer therapy to exert its therapeutic effects, resulting in off-target tissue damage. Radiation has been long established as a means to utilize the generation of reactive oxygen species to kill cancer cells, and 50% of chemotherapy agents currently used are associated with inducing oxidative stress. One major side effect observed in cancer survivors is a decline in …

Overcoming Resistance To Sg-Aris In Castration-Resistant Prostate Cancer, Chaohao Li

Theses and Dissertations--Toxicology and Cancer Biology

Prostate cancer (PCa) ranks as the most diagnosed type of cancer and the second leading cause of death in men. Androgen receptor (AR) signaling plays a pivotal function in promoting the survival and progression of PCa. Therefore, medication for PCa mainly focuses on the inhibition of AR pathway, which is termed androgen deprivation therapy (ADT). However, the disease eventually progresses and develops to a lethal stage called castration-resistant prostate cancer (CRPC) that is characterized by resistance to canonical ADT. To deal with this situation, several second-generation AR inhibitors (SG-ARIs) have been created that have better efficacy against AR, including Enzalutamide …

Tissue And Sex-Specific Rna Editing During Induced Acute Inflammation, Claire E. Nichols

Graduate Theses/Dissertations

A-to-I RNA editing is a process where select adenosine (A) nucleotides are deaminated by an editing enzyme, ADAR, to become inosines (I) in RNA transcripts. RNA editing can affect the sequence of the encoded protein and the regulation of the RNA. ADAR1 also plays a role in regulating innate immunity and its expression is upregulated during inflammation. Current data on the effects of increasing ADAR1 on RNA editing is limited, and most studies are completed only in male animals. We are interested in expanding RNA editing data to include female animals. Lipopolysaccharide (LPS) was used to induce acute inflammation and …

Elucidating The Role Of Hemodynamic Force In Regulating The Attachment Of Vascular Smooth Muscle Cells (Vsmcs) To Maturing Vessels During Mouse Embryonic Development, Israt Jahan

Graduate Theses/Dissertations

Blood vessel maturation is characterized by the recruitment and attachment of vascular smooth muscle cells (vSMCs) around immature blood vessels, which ultimately form the tunica media. Improper maturation can lead to vascular birth defects ranging from minor birthmarks to lethal brain aneurysms. Previously, our lab demonstrated that hemodynamic force plays an important role to regulate vSMCs recruitment from neighboring low-flow to high-flow vessels followed by the attachment of these vSMCs to the high-flow vessels. To understand the reason for the preferred attachment of vSMCs to high-flow vessels, instead of low-flow vessels, I hypothesize that hemodynamic force modulates the expression of …

Identification Of A Novel Protein Interaction That Elucidates The Mechanism Of Idiopathic Recurrent Miscarriages In Women With Nlrp2 Mutations, Nayeon Son

Graduate Theses/Dissertations

The protein NOD-Like receptor pyrin domain containing 2 (NLRP2) is one member of a larger family of protein receptors that plays an important role in our innate immune system. In humans, the NLR family consists of 22 proteins. However, only about a half of NLRs’ functions are known, but many are pro-inflammatory, causing inflammation. NLRP2 has been identified to be a maternal effect gene regulating early embryo development in idiopathic recurrent miscarriages. In previous studies, mutations in the NLRP2 gene resulted in genetic maternal imprinting disorders due to NLRP2 regulating DNA methylation. However, the exact mechanisms involved in recurrent miscarriages …

Nutrient Scarcity And Cellular Cooperation In A Clonal Hydroid, Weam S. El Rahmany

Graduate Research Theses & Dissertations

Biological complexity forms when lower-level units (e.g., genes, cells, organisms) cooperatively band together. This complexity may be exemplified by multicellularity, the cooperation between the cells of the same species, or symbiosis, cooperation between the cells of different species. This cooperation is under continual threat, as defection, the opposite of cooperation, is favored by default by lower-level units (i.e., cells). Animal cancers may be the most well-known phenomena that exemplify the concept of cellular defection. Cancer cells have been shown to feature morphological and metabolic traits, developed through differential gene expression or mutations, that favor their growth at the cost of …

Xrcc4 And Mre11 Roles And Transcriptional Response To Repair Of Talen-Induced Double-Strand Dna Breaks, Ronald Benjamin, Atoshi Banerjee, Xiaogang Wu, Corey Geurink, Lindsay Buczek, Danielle Eames, Sara G. Trimidal, Janice M. Pluth, Martin R. Schiller

Health Physics and Diagnostic Sciences Faculty Research

Double-strand breaks (DSB) are one of the most lethal forms of DNA damage that, if left unrepaired, can lead to genomic instability, cellular transformation, and cell death. In this work, we examined how repair of transcription activator-like effector nuclease (TALEN)-induced DNA damage was altered when knocking out, or inhibiting a function of, two DNA repair proteins, XRCC4 and MRE11, respectively. We developed a fluorescent reporter assay that uses TALENs to introduce DSB and detected repair by the presence of GFP fluorescence. We observed repair of TALEN-induced breaks in the XRCC4 knockout cells treated with mirin (a pharmacological inhibitor of MRE11 …

Assessment Of Combined Modality Therapy For Non-Small-Cell Lung Carcinoma: A Simulation Study Concerning Concurrent Chemo-Brachytherapy, Hadi Rezaei, Hesameddin Mostaghimi, Ali Reza Mehdizadeh

Electrical & Computer Engineering Faculty Publications

Although surgery is the treatment of choice for early-stage non-small-cell lung carcinoma, almost two-thirds of patients do not have acceptable pulmonary function for extensive surgeries. The alternative approach for this large group of patients is sublobar resection along with low-dose-rate (LDR) brachytherapy (BT). However, patients with resected lungs have a high risk of recurrence and are often treated with platinum-based (Pt-based) chemotherapy (CT). In this study, we aimed to evaluate the absorbed doses of lung and other thoracic organs, considering concurrent chemo-BT with LDR sources in two modalities: conventional vs. unconventional Pt-based CT. We used the MCNPX code for simulations …

Cell-Engineered Vesicles For Therapeutic Delivery And Immunomodulatory Applications, Khaga Neupane

Theses and Dissertations--Chemistry

Development of a new kind of drug delivery system (DDS) that could efficiently deliver therapeutics to the cell of interest would allow us to accomplish cell-specific drug delivery while eliminating systemic toxicity. Although nanocarriers including endogenously released extracellular vesicles (EEVs), liposomes, and small molecules seem to be promising drug delivery systems, biological challenges persist for their use in clinical applications. Here, we demonstrate nanovesicles engineered by fragmenting cellular membranes can be exploited as versatile DDSs for therapeutics delivery as well as immunomodulatory functions. Cell-engineered vesicles were produced by cavitating cells using nitrogen gas at high pressure followed by serial centrifugation. …

Protein Charge Parameters That Influence Stability And Cellular Internalization Of Polyelectrolyte Complex Micelles, Rachel A. Kapelner, Rachel S. Fisher, Shana Elbaum-Garfinkle, Allie C. Obermeyer

Advanced Science Research Center

Proteins are an important class of biologics, but there are several recurring challenges to address when designing protein-based therapeutics. These challenges include: the propensity of proteins to aggregate during formulation, relatively low loading in traditional hydrophobic delivery vehicles, and inefficient cellular uptake. This last criterion is particularly challenging for anionic proteins as they cannot cross the anionic plasma membrane. Here we investigated the complex coacervation of anionic proteins with a block copolymer of opposite charge to form polyelectrolyte complex (PEC) micelles for use as a protein delivery vehicle. Using genetically modified variants of the model protein green fluorescent protein (GFP), …

Alternative Splicing Regulates The Innate Immune Response To Viral Infection, Luke A. White

Graduate Student Theses, Dissertations, & Professional Papers

Rift Valley fever virus (RVFV) is a mosquito-borne RNA virus that infects humans and livestock in sub-Saharan Africa and the Arabian peninsula, causing disease ranging from a mild flu-like illness to liver damage, blindness, hemorrhagic fever, death, and, especially in livestock animals, high rates of abortive pregnancies. There is no approved vaccine for RVFV, and as a disease with a high rate of spread that causes severe illness, it is listed as a Category A pathogen by the USA CDC. A better understanding of RVFV’s molecular virology will be instrumental to combating RVFV as climate change causes its mosquito host …

Determining Haplotype Specific X Chromosome Inactivation State And Related Epigenetic Features In Female X-Linked Genes, Ariah Dawn Mackie

Cal Poly Humboldt theses and projects

Females with heterozygous X-linked mutations are prone to pseudo-haploinsufficiency because random X chromosome inactivation (XCI) silences one of their two X chromosomes. A prior study explored the theory that reactivating the silenced healthy allele could be a treatment for pseudo-haploinsufficient females. The next step was to evaluate this approach in a clinically relevant stem cell model of the rare neurological disease CDKL5 Deficiency Disorder (CDD). It was necessary to validate X-inactivation state with respect to CDKL5 allele expression in one of these models. We explored CDKL5 allele expression in two populations of CDD female patient-derived induced pluripotent stem cells (iPSCs) …

Employers’ General Knowledge, Social Attitudes, Experience, And Employability Of Level 1 Autism Spectrum Disorder Adults, Jennifer C. Kiselica

Walden Dissertations and Doctoral Studies

AbstractAutism spectrum disorders (ASD) is a neurodevelopmental disorder which causes an individual to have abnormalities in socialization and communication, and unusual behaviors and interests. Each year about a half million young adults with ASD transition from high school to adulthood; however, only 57% become employed. The current study’s purpose was to investigate how general knowledge of ASD and social interactions with those with ASD affected employers’ social attitudes and perceptions of those with ASD being employed by them. Social Contact theory employers who have more social interaction with individuals with ASD have more social knowledge about ASD.. The population for …

Regulation Of Ppp1r15a (Gadd34) And Ppp1r15b (Crep) Mrna Expression And Localization In The Unfolded Protein Response, Krithika Giresh

University of the Pacific Theses and Dissertations

The failure to balance protein synthesis, folding, and degradation in the endoplasmic reticulum (ER) leads to the accumulation of unfolded proteins, leading to ER stress. Cells respond to this stress by activating a response signaling pathway known as the Unfolded Protein Response (UPR). One of the branches of the UPR induces the phosphorylation of eIF2α (Eukaryotic Initiation Factor 2) to attenuate global protein synthesis, allowing for a chance to clear misfolded and unfolded proteins. This phosphorylation of eIF2α is opposed by a phosphatase, containing a catalytic subunit, Protein Phosphatase 1, and a scaffolding protein, either GADD34 or CReP. Inhibition of …

Elucidating The Role Of Kmt2d In Her2+ Breast Cancer, Emily Ma

Dissertations

Breast cancer is the second leading cause of cancer-related deaths among women in the US. Histone modifications are common epigenetic changes that have been implicated in several breast cancers, including HER2+ breast cancers. Current therapies, such as trastuzumab, block the HER2 receptor to reduce tumor growth. Unfortunately, HER2+ breast cancers have found ways to overcome these therapies, leading to tumor resistance, metastases, and poor survival outcomes. A better understanding of the underlying mechanisms contributing to HER2+ breast cancer resistance may lead to the discovery of novel therapeutic strategies to improve patient outcomes.One prognostic marker for poor survival in women with …

Modification Of Culture Medium And Identification Of Microbial Contaminants For Improved In Vitro Propagation Of Freshwater Mussels, Raquel M. Wetzell

Theses and Dissertations

In vitro propagation efforts play an essential role in conserving and restoring threatened freshwater mussel populations by circumventing the need for a fish host. Across a broad range of taxa, transformation is induced with an artificial M199 medium and rabbit serum. However, such formulation may not be sufficient in culturing critical species with more specific physiological requirements. In this study, multiple serum mixtures were tested to improve in vitro transformation of two freshwater mussel species: yellow lampmussel (Lampsilis cariosa) and tidewater mucket (Atlantaconcha ochracea). These species were selected because they parasitize similar fish host species but …

Identifying The Human Homologs Of Yeast Rab Proteins Ypt10 & Ypt11 And A Global-Scale Louse Endosymbiont Genome Variation, Nathaniel P. Smith

Theses and Dissertations

Amyotrophic lateral sclerosis (ALS) is a late-onset fatal neurodegenerative disease that causes loss of upper and/or lower motor neurons, and currently has no treatment or cure available. Over 90% of cases occur spontaneously with unknown causes, highlighting the complexity of the disease, and only 10% of cases are linked to heritable genetic mutations. Numerous ALS-linked genes are conserved through evolution, and model organisms may therefore provide opportunities to understand disease pathology at a molecular or cellular level, proving instrumental in identifying therapeutic targets. ALS subtype 8 (ALS8) is caused by an autosomal dominant P56S mutation in the VAPB gene that …