Cell and Developmental Biology Commons^™

The Role Of Sox4 In Regulating Choroid Fissure Closure And Retinal Neurogenesis, Wen Wen

Theses and Dissertations--Biology

The development of the vertebrate eye is tightly controlled by precise genetic regulations. From a single ocular primordium to bilateral eyes with complex structures and cell types, it requires intensive proliferation and migration for cells in both the ectoderm and mesoderm to accomplish ocular morphogenesis, and during this process cell differentiation and interaction takes place to establish the complex composition of ocular cell types and cellular connections. Genetic defects can lead to severe abnormalities in eye morphogenesis and cell differentiation during ocular development. A tremendous amount of work has been done to identify both intrinsic and extrinsic factors that regulate …

Role Of Hairy-Related (Her) Genes During Vertebrate Retinal Development And Regeneration, Stephen G. Wilson

Theses and Dissertations--Biology

Development and regeneration of the vertebrate eye are the result of complex interactions of regulatory networks and spatiotemporally controlled gene expression events. During embryonic retinal development, the coordination of cell signaling and transcriptional regulation allows for a relatively homogenous sheet of neuroepithelial cells to proliferate and differentiate in-to a multilayered, light sensitive retinal tissue. Following injury, the retinas of many cold-blooded vertebrates, such as the zebrafish, undergo a proliferative response that results not only in new retinal cells of the correct type in the correct location, but also functional integration of these cells and restoration of vision. In order for …

Elucidating Proteasome Catalytic Subunit Composition And Its Role In Proteasome Inhibitor Resistance, Kimberly C. Carmony

Theses and Dissertations--Pharmacy

Proteasome inhibitors bortezomib and carfilzomib are FDA-approved anticancer agents that have contributed to significant improvements in treatment outcomes. However, the eventual onset of acquired resistance continues to limit their clinical utility, yet a clear consensus regarding the underlying mechanisms has not been reached.

Bortezomib and carfilzomib are known to target both the constitutive proteasome and the immunoproteasome, two conventional proteasome subtypes comprising distinctive sets of catalytic subunits. While it has become increasingly evident that additional, ‘intermediate’ proteasome subtypes, which harbor non-standard mixtures of constitutive proteasome and immunoproteasome catalytic subunits, represent a considerable proportion of the proteasome population in many cell …

Homocysteine And Csrp-3 Protein In Migrating Neural Crest Cells: A Quantitative And Qualitative Confocal Microscopy Study, Allysan R. White

Dissertations and Theses @ UNI

Congenital heart defects are one of the leading causes of infant death. High maternal blood serum levels of the amino acid homocysteine and the frequency of heart defects are correlated, but the immediate cause is unknown. During early embryonic development, a distinctive population of cells arises dorsally as the neural tube closes, forming the brain and spinal cord. These are the neural crest cells, which play a crucial role in the development of the nervous system, head skeletal, certain endocrine and connective tissues, and, notably, the heart’s outflow region. These migratory cells will follow specific pathways and respond to signals …

The Effect Of Rearing Temperature On Somite Formation And Skeletal Development In The Zebrafish, Danio Rerio, Sarah Jean Freeland

Honors Program Theses

The purpose of this study is to explore the effect temperature may have on development of elements of the Weberian apparatus in relation to the other regions of the vertebral column. The goals of this study were three-fold 1. To test rapid whole-mount staining techniques to quickly determine effect of temperature on somite number. 2. To examine the effect of extreme low and extreme high rearing temperature on somite formation. 3. To examine the effect of extreme low and extreme high rearing temperature on skeletal development in the Weberian apparatus

Excess Folic Acid As A Potential Competitor Of Glutamate May Interfere With Neural Development, Benjamin Fick

Honors Program Theses

Folic acid, Vitamin B9, is strongly advised as a supplement taken by pregnant woman to maintain the health of the embryo, and deficiency increases the risk of neural tube defects. However, a safe upper limit of folate to consume has not been established, and an excess of dietary folate may interfere with neurodevelopmental metabolism, increasing the risk of adverse outcomes, including autism spectrum disorder (ASD). It has been suggested that folate affects connectivity among neurons as the brain develops. Glutamate is important in the regulation of neural tissue development, as it is a common excitatory neurotransmitter that binds to synaptic …

Radio-Frequency Plasma Polymerized Biodegradable Carrier For In Vivo Release Of Cis-Platinum, Sudhir Bhatt, Fatemeh Valamanesh, Jerome Pulpytel, Rea Lo Dico, Aliby Baiyukha, Iman Al-Dybiat, Marc Pocard, Farzaneh Arefi-Khonsari, Massoud Mirshahi

Bioelectrics Publications

A low pressure plasma process based on plasma deposition has been used to develop a drug delivery strategy. In this study, a drug delivery system based on different layers of plasma co-polymerized Poly ε-caprolactone-Polyethylene glycol (PCL-PEG) co-polymers was deposited on biocompatible substrates. Cis-platinum (118 μgm/cm²) was used as an anti-cancer drug and incorporated for local delivery of the chemotherapeutic agent. The co-polymer layers and their interaction with cancer cells were analyzed by scanning electron microscopy. Our study showed that the plasma-PCL-PEG coated cellophane membranes, in which the drug, was included did not modify the flexibility and appearance of …

Autoantibody Production In Cancer—The Humoral Immune Response Toward Autologous Antigens In Cancer Patients, Pauline Zaenker, Elin Solomonovna Gray, Melanie Ruth Ziman

Research outputs 2014 to 2021

A link between autoimmune responses and cancer via autoantibodies was first described in the 1950s. Since, autoantibodies have been studied for their potential use as cancer biomarkers, however the exact causes of their production remain to be elucidated. This review summarizes current theories of the causes of autoantibody production in cancer, namely:

1) defects in tolerance and inflammation,

2) changes in protein expression levels,

3) altered protein structure, and

4) cellular death mechanisms.

We also highlight the need for further research into this field to improve our understanding of autoantibodies as biomarkers for cancer development and progression.

Confirmation Of Emx2 Protein Binding Partners, Cody Gillman

All Master's Theses

The neocortex is a structure within mammalian brains that processes sensory input from eyes, ears, and touch receptors and mediates the conscious use of skeletal muscles. The processing of information related to each of these types of functions is localized within discrete areas of the neocortex, which are separated by sharp borders. Proper development of these functional areas is regulated during embryogenesis by several transcription factors that are expressed in distinct gradients across the progenitor layer of the neocortex, the ventricular zone. Despite the vast amount of progress that has been made in describing how these transcription factors impact the …

The Impact Of Oxygen On Bacterial Enteric Pathogens, Nathan Wallace, Ashley N. Zani, Elizabeth A. Abrams, Yvonne Sun

Biology Faculty Publications

Bacterial enteric pathogens are responsible for a tremendous amount of foodborne illnesses every year through the consumption of contaminated food products. During their transit from contaminated food sources to the host gastrointestinal tract, these pathogens are exposed and must adapt to fluctuating oxygen levels to successfully colonize the host and cause diseases. However, the majority of enteric infection research has been conducted under aerobic conditions. To raise awareness of the importance in understanding the impact of oxygen, or lack of oxygen, on enteric pathogenesis, we describe in this review the metabolic and physiological responses of nine bacterial enteric pathogens exposed …

Comparative Proteomic Analysis Of Extracellular Vesicles From Prostate Cancer-Derived Cell Lines, Gloria Polanco

Open Access Theses & Dissertations

Prostate cancer (PCa) is the leading non-cutaneous malignancy and the second deadliest among American men. PCa mortality rates among African American men are much higher than any other ethnic group, and the same is true for men of African ancestry world-wide. There is also a lack of reliable diagnostic markers and effective treatment options. Extracellular vesicles (EVs) have been observed to play an important role in cancer processes such as promotion of tumor growth and metastasis. They are also a promising source of diagnostic markers. This study addresses these problems by studying the proteome of EVs derived from PCa cells …

Defining And Characterizing The Step In The Hiv-1 Viral Life Cycle Affected By Fullerene Derivatives, Zachary Sean Martinez

Open Access Theses & Dissertations

Fullerene derivatives, both C60 and C70, were synthesized and characterized to test their activity against HIV-1 infection. The derivatives tested have previously been reported to inhibit HIV-1 replication and/or in vitro activity of reverse transcriptase. It was found that viruses produced in the presence of low micromolar concentrations of most of these fullerene derivatives exhibit a reduction in viral infectivity greater than 99%. Quantification of virion-associated viral RNA and p24 indicates that RNA packaging and viral production were unremarkable in these viruses. These compounds did not affect infectivity of mature virions, indicating no effect on the early steps of the …

Elucidating The Molecular Mechanism Of Action By Which Rs1-208b Induces Apoptosis In Hematological Cancers, Ruben Israel Calderon

Open Access Theses & Dissertations

The 26S proteasome has been successfully targeted to treat multiple myeloma. However, the effect can sometimes be reversed as cells acquire resistance to chemotherapy. Recently, combining proteasome inhibitors with indirect proteasome inhibitors has been proposed in order to delay and even reverse resistance. Small molecules derived from 4-piperidinone that maintain an unsaturated β-carbonyl group are thought to interact with the thiol group of catalytically active cysteine residues in deubiquitinases that associate with the 26S proteasome, effectively inhibiting the proteasome.

RS1-208b was selected following a high-throughput screening of a small library of 4-piperidinone derived curcumin structural analogs due to its selectivity …

Human Anatomy And Physiology Preparatory Course: Part 1 Of 4 (Interactive), Carlos Liachovitzky

Open Educational Resources

The overall purpose of these preparatory course set of learning objectives is to help students familiarize with some terms and some basic concepts they will find later in the Human Anatomy and Physiology I course.

These 40+ learning objectives to prepare for Human Anatomy and Physiology can be downloaded and played in a desktop, or laptop (windows exe file).

The entire course has four parts:

• Part 1
• Part 2
• Part 3
• Part 4

Each learning objective is followed by a set of multiple choice question similar to those found later in a Human Anatomy and Physiology course.

The organization and …

Human Anatomy And Physiology Preparatory Course: Part 4 Of 4 (Interactive), Carlos Liachovitzky

Open Educational Resources

The overall purpose of these preparatory course set of learning objectives is to help students familiarize with some terms and some basic concepts they will find later in the Human Anatomy and Physiology I course.

These 40+ learning objectives to prepare for Human Anatomy and Physiology can be downloaded and played in a desktop, or laptop (windows exe file).

The entire course has four parts:

• Part 1
• Part 2
• Part 3
• Part 4

Each learning objective is followed by a set of multiple choice question similar to those found later in a Human Anatomy and Physiology course.

Integrin Α6Β4 Promotes Pancreatic Cancer Invasion By Altering Dna Repair-Mediated Epigenetics, Brittany L. Carpenter

Theses and Dissertations--Molecular and Cellular Biochemistry

Integrin α6β4 is upregulated in pancreatic carcinoma, where signaling promotes metastatic properties, in part by altering the transcriptome. Such alterations can be accomplished through DNA demethylation of specific promoters, as seen with the pro-metastatic gene S100A4. I found that signaling from integrin α6β4 dramatically upregulates expression of amphiregulin (AREG) and epiregulin (EREG), ligands for the epidermal growth factor receptor (EGFR), and that these ligands promote pancreatic carcinoma invasion. To determine if AREG and EREG are regulated by DNA methylation, pancreatic cancer cells with low AREG and EREG expression were treated with the DNA methyltransferase inhibitor 5-aza-2’-deoxycytidine (5-Aza-CdR), resulting in stable …

The Role Of E-Cadherin Force In The Maintenance Of Homeostasis In Epithelial Acini, Fnu Vani Narayanan

Theses and Dissertations

Numerous three-dimensional model systems have emerged for emulating the biochemical and physiological states of native tissue. Yet little is known about the effects of mechanical forces on cell behavior in the context of an organized tissue structure in three-dimensional cell-culture. Epithelial cells cultured in a three-dimensional environment comprised of extracellular matrix proteins form spheroids of polarized cells. Cellular responses to mechanical cues, generated from dynamic interactions with the extracellular matrix and neighboring cells, are known to influence cellular behavior to a great extent. Previous studies have shown that tumorigenic progression has been frequently linked to the down regulation of E-cadherin, …

Intrinsic And Extrinsic Regulation Of Pineal Melatonin Rhythms, Ye Li

Theses and Dissertations--Biology

Circadian rhythm is a biological rhythm with period of about 24 hours. Circadian rhythm is universal in phyla from bacteria to mammals and exists in different level from gene expression to behavior. Circadian system consists of three components: 1) a self-sustained oscillator; 2) an input pathway which can alter the phase of the oscillator; and 3) an output such as gene expression, enzyme activity, hormone production, heart rate, body temperature or locomotor activities. The way the oscillator regulates its outputs is complicated, in that on one hand usually the oscillator is not the only factor affecting the outputs, and on …

Characterization Of Somatically-Eliminated Genes During Development Of The Sea Lamprey (Petromyzon Marinus), Stephanie A. Bryant

Theses and Dissertations--Biology

The sea lamprey (Petromyzon marinus) undergoes programmed genome rearrangements (PGRs) during early development that facilitate the elimination of ~20% of the genome from the somatic cell lineage, resulting in distinct somatic and germline genomes. To improve our understanding of the evolutionary/developmental logic of PGR, we generated computational predictions to identify candidate germline-specific genes within a transcriptomic dataset derived from adult germline and the embryonic stages encompassing PGR. Validation studies identified 44 germline-specific genes and characterized patterns of transcription and DNA loss during early embryogenesis. Expression analyses reveal that several of these genes are differentially expressed during early embryogenesis …

Complete Genome Sequence Of Highly Virulent Porcine Reproductive And Respiratory Syndrome Virus Variants That Recently Emerged In The United States, Aspen M. Workman, Timothy P.L. Smith, Fernando A. Osorio, Hiep L.X. Vu

Nebraska Center for Virology: Faculty Publications

A recent outbreak of particularly virulent disease caused by porcine reproductive and respiratory syndrome virus has occurred in swine herds across the United States. We report here the complete genome sequence of eight viral isolates from four Nebraska herds experiencing an outbreak of severe disease in 2016.

Domain I Of The 5′ Non-Translated Genomic Region In Coxsackievirus B3 Rna Is Not Required For Productive Replication, L. Jaramillo, S. Smithee, S. Tracy, N. M. Chapman

Nebraska Center for Virology: Faculty Publications

Domain I is a cloverleaf-like secondary structure at the 5′ termini of all enterovirus genomes, comprising part of a cis-acting replication element essential for efficient enteroviral replication. 5′ genomic terminal deletions up to as much as 55% of domain I can occur without lethality following coxsackie B virus infections. We report here that the entire CVB structural domain I can be deleted without lethality.

Reversion To Wildtype Of A Mutated And Nonfunctional Coxsackievirus B3cre(2c), Shane Smithee, Steven Tracy, Nora M. Chapman

Nebraska Center for Virology: Faculty Publications

The cis-acting replication element (CRE) in the 2C protein coding region [CRE(2C)] of enteroviruses (EV) facilitates the addition of two uridine residues (uridylylation) onto the virus-encoded protein VPg inorder for it to serve as the RNA replication primer. We demonstrated that coxsackievirus B3 (CVB3) is replication competent in the absence of a native (uridylylating) CRE(2C) and also demonstrated that lackof a functional CRE(2C) led to generation of 5’ terminal genomic deletions in the CVB3 CRE-knock-out (CVB3-CKO) population. We asked whether reversion of the mutated CRE(2C) occurred, thus permitting sustained replication, and when were 5’ terminal deletions generated during replication. Virions …

Replicating Single-Cycle Adenovirus Vectors Generate Amplified Influenza Vaccine Responses, Catherine M. Crosby, William E. Matchett, Stephanie S. Anguiano-Zarate, Christopher A. Parks, Eric A. Weaver, Larry R. Pease, Richard J. Webby, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Head-to-head comparisons of conventional influenza vaccines with ade- novirus (Ad) gene-based vaccines demonstrated that these viral vectors can mediate more potent protection against influenza virus infection in animal models. In most cases, Ad vaccines are engineered to be replication-defective (RD-Ad) vectors. In contrast, replication-competent Ad (RC-Ad) vaccines are markedly more potent but risk causing adenovirus diseases in vaccine recipients and health care workers. To harness antigen gene replication but avoid production of infectious virions, we de- veloped “single-cycle” adenovirus (SC-Ad) vectors. Previous work demonstrated that SC-Ads amplify transgene expression 100-fold and produce markedly stronger and more persistent immune responses than …

Autoimmunity In Picornavirus Infections, Chandirasegara Massilamany, Andreas Koenig, Jay Reddy, Sally Huber, Iwona Buskiewicz

School of Veterinary and Biomedical Sciences: Faculty Publications

Enteroviruses are small, non-enveloped, positive-sense singlestrand RNA viruses, and are ubiquitously found throughout the world. These viruses usually cause asymptomatic or mild febrile illnesses, but have a propensity to induce severe diseases including type 1 diabetes and pancreatitis, paralysis and neuroinflammatory disease, myocarditis, or hepatitis. This pathogenicity may result from induction of autoimmunity to organ-specific antigens. While enterovirus-triggered autoimmunity can arise from multiple mechanisms including antigenic mimicry and release of sequestered antigens, the recent demonstration of T cells expressing dual T cell receptors arising as a natural consequence of Theiler’s virus infection is the first demonstration of this autoimmune mechanism.

Genome-Wide Search For Host Association Factors During Ovine Progressive Pneumonia Virus Infection, Jesse Thompson, Fangrui Ma, Meghan Quinn, Shi-Hua Xiang

School of Veterinary and Biomedical Sciences: Faculty Publications

Ovine progressive pneumonia virus (OPPV) is an important virus that causes serious diseases in sheep and goats with a prevalence of 36% in the USA. Although OPPV was discovered more than half of a century ago, little is known about the infection and pathogenesis of this virus. In this report, we used RNA-seq technology to conduct a genome-wide probe for cellular factors that are associated with OPPV infection. A total of approximately 22,000 goat host genes were detected of which 657 were found to have been significantly up-regulated and 889 down-regulated at 12 hours post-infection. In addition to previously known …

Guidelines For The Use And Interpretation Of Assays For Monitoring Autophagy (3rd Edition), Daniel J. Klionsky, Rodrigo Franco, More Than 2,000 Co-Authors

School of Veterinary and Biomedical Sciences: Faculty Publications

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes.

For example, a key point that needs to be emphasized is that …

From Crystal Structure Of Α-Conotoxin Gic In Complex With Ac-Achbp To Molecular Determinants Of Its High Selectivity For Α3Β2 Nachr, Bo Lin, Manyu Xu, Xiaopeng Zhu, Yong Wu, Xi Liu, Dongting Zhangsun, Yuanyan Hu, Shi-Hua Xiang, Igor E. Kasheverov, Victor I. Tsetlin, Xinquan Wang, Sulan Luo

School of Veterinary and Biomedical Sciences: Faculty Publications

Acetylcholine binding proteins (AChBPs) are unique spatial homologs of the ligand-binding domains of nicotinic acetylcholine receptors (nAChRs), and they reproduce some pharmacological properties of nAChRs. X-ray crystal structures of AСhBP in complex with α-conotoxins provide important insights into the interactions of α-conotoxins with distinct nAChR subtypes. Although considerable efforts have been made to understand why α-conotoxin GIC is strongly selective for α3β2 nAChR, this question has not yet been solved. Here we present the structure of α-conotoxin GIC in complex with Aplysia californica AChBP (Ac-AChBP) at a resolution of 2.1 Å. Based on this co-crystal structure complemented with molecular docking …

From Crystal Structure Of Α-Conotoxin Gic In Complex With Ac-Achbp To Molecular Determinants Of Its High Selectivity For Α3Β2 Nachr, Bo Lin, Manyu Xu, Xiaopeng Zhu, Yong Wu, Xi Liu, Dongting Zhangsun, Yuanyan Hu, Shi-Hua Xiang, Igor E. Kasheverov, Victor I. Tsetlin, Xianquan Wang, Sulan Luo

School of Veterinary and Biomedical Sciences: Faculty Publications

Acetylcholine binding proteins (AChBPs) are unique spatial homologs of the ligand-binding domains of nicotinic acetylcholine receptors (nAChRs), and they reproduce some pharmacological properties of nAChRs. X-ray crystal structures of AСhBP in complex with α-conotoxins provide important insights into the interactions of α-conotoxins with distinct nAChR subtypes. Although considerable efforts have been made to understand why α-conotoxin GIC is strongly selective for α3β2 nAChR, this question has not yet been solved. Here we present the structure of α-conotoxin GIC in complex with Aplysia californica AChBP (Ac-AChBP) at a resolution of 2.1 Å. Based on this co-crystal structure complemented with molecular docking …

A Synthetic Porcine Reproductive And Respiratory Syndrome Unprecedented Levels Of Heterologous Protection, Hiep Vu, Fangrui Ma, William W. Laegreid, Asit K. Pattnaik, David Steffen, Alan R. Doster, Fernando A. Osorio

School of Veterinary and Biomedical Sciences: Faculty Publications

Current vaccines do not provide sufficient levels of protection against divergent porcine reproductive and respiratory syndrome virus (PRRSV) strains circulating in the field, mainly due to the substantial variation of the viral genome. We describe here a novel approach to generate a PRRSV vaccine candidate that could confer unprecedented levels of heterologous protection against divergent PRRSV isolates. Using a set of 59 non-redundant, full genome sequences of type-2 PRRSV, a consensus genome (designated as PRRSV-CON) was these 59 PRRSV full genome sequences, followed by selecting the most common nucleotide found at each position of the alignment. Next, the synthetic PRRSV-CON …

Overview Of Rhabdo- And Filoviruses, Asit K. Pattnaik, Michael A. Whitt

School of Veterinary and Biomedical Sciences: Faculty Publications

Enveloped viruses with a negative-sense, single-stranded monopartite RNA genome have been classified into the order Mononegavirales. Five families of viruses that constitute the order are: Rhabdoviridae, Filoviridae, Paramyxoviridae, Bornaviridae and Nyamiviridae. Members of these families possess a helical nucleocapsid core containing the viral genome and a host-derived lipid envelope containing viral proteins. This introductory chapter provides a brief overview of the Rhabdoviridae and the Filoviridae, the two families of viruses that are the subject of this book. Many members of these two families are highly significant human and animal pathogens. The rationale and goal of the book is to …