Cell and Developmental Biology Commons^™

Kinetics Of Hiv-1 Uncoating In C20 Microglial Cells, Melanie Anne Taylor

Graduate Theses/Dissertations

Uncoating is a poorly understood yet required step of HIV-1 replication that is defined as the disassembly of the viral capsid structure. The goal of this project is to characterize uncoating in C20 microglial cells. These cells are a natural target of HIV-1 that are infected to establish latent viral reservoirs and HIV-associated neurological disorders. A stable C20 cell line that expresses TRIM-CypA was established to study the kinetics of uncoating with the CsA washout assay. The expression of TRIM-CypA was confirmed by western blot and the functionality of the protein was confirmed by a viral infectivity assay. Using this …

Further Characterization Of The Skeletal Phenotype In A Hurler Syndrome Mouse Model And The Ethical Treatment Of Children In Medicine, Anna Marie Mcwoods

Graduate Theses/Dissertations

Mucopolysaccharidosis type I (MPS I) is a rare, autosomal recessive disorder caused by the deficiency of the lysosomal enzyme α-L-iduronidase (IDUA). Absence of IDUA results in the accumulation of dermatan and heparin sulfate and ultimately causes multi-system dysfunction. The most severe form of MPS I is Hurlers syndrome, a rapidly progressive disorder that, if left untreated, is fatal. Current treatment options for diagnosed individuals includes hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT). These treatments are able to ameliorate the majority of symptoms with the exception of the bone phenotype. This investigation aimed to further characterize the bone …

Development Of A Sonically Powered Biodegradable Nanogenerator For Bone Regeneration, Avi S. Patel

University Scholar Projects

Background: Reconstruction of bone fractures and defects remains a big challenge in orthopedic surgery. While regenerative engineering has advanced the field greatly using a combination of biomaterial scaffolds and stem cells, one matter of difficulty is inducing osteogenesis in these cells. Recent works have shown electricity’s ability to promote osteogenesis in stem cell lines when seeded in bone scaffolds; however, typical electrical stimulators are either (a) externally housed and require overcomplex percutaneous wires be connected to the implanted scaffold or (b) implanted non-degradable devices which contain toxic batteries and require invasive removal surgeries.

Objective: Here, we establish a biodegradable, piezoelectric …

Development Of A Sonically Powered Biodegradable Nanogenerator For Bone Regeneration, Avi Patel

Honors Scholar Theses

Background: Reconstruction of bone fractures and defects remains a big challenge in orthopedic surgery. While regenerative engineering has advanced the field greatly using a combination of biomaterial scaffolds and stem cells, one matter of difficulty is inducing osteogenesis in these cells. Recent works have shown electricity’s ability to promote osteogenesis in stem cell lines when seeded in bone scaffolds; however, typical electrical stimulators are either (a) externally housed and require overcomplex percutaneous wires be connected to the implanted scaffold or (b) implanted non-degradable devices which contain toxic batteries and require invasive removal surgeries.

Objective: Here, we establish a biodegradable, piezoelectric …

Analyzing The Effect Of Apoptotic Mutations On The State Of The Nascent-Polypeptide Associated Complex In Caenorhabditis Elegans, Monica Gerber

Senior Honors Projects, 2010-2019

Cells experiencing misfolded protein stress can become debilitated and die, contributing to the onset of disease. The nascent polypeptide-associated complex (NAC) is a heterodimeric translational chaperone that protects against misfolded protein stress by mediating proper protein folding and localization during translation. Depletion of this complex results in misfolded protein accumulation in the endoplasmic reticulum (ER). To determine the importance of the NAC to proteostasis, we have previously depleted the complex in C.elegans via RNA interference and observed numerous dose-dependent effects, including apoptosis of neuronal cells and changes in gene expression of hypodermal cells. While we have observed these cell-specific responses …

The Role Of Zyxin And Limd1 In Mitosis And Cancer, Jiuli Zhou

Theses & Dissertations

The Hippo signaling pathway, originally discovered in Drosophila, consists of a core kinase cascade and has been subsequently demonstrated to control tissue growth and tumorigenesis. The core of this pathway contains MST1/2 (Mammalian sterile 20-like kinase 1/2), LATS1/2 (large tumor suppressor 1/2) and downstream effector named Yes-associated protein (YAP) and PDZ-binding motif (TAZ). MST1/2 transduce their kinase activity mainly through directly phosphorylating LATS1/2. Once phosphorylated and activated, LATS1/2 subsequently phosphorylate and inhibit YAP/TAZ from translocating to nucleus, thereby suppressing the expression of downstream pro-growth and survival genes. While recent studies provide important insight into the tumor suppressor properties of …

Identification Of Pathways Required For The Survival Of Inversion(16) Acute Myeloid Leukemia, Yiqian Wang

Theses & Dissertations

Inversion of chromosome 16 [inv(16)] acute myeloid leukemia (AML) generates a fusion gene CBFB-MYH11. Approximately half of inv(16) AML patients eventually relapse mainly due to the existence of leukemia stem cells (LSCs). Previous work using a Cbfb-MYH11 knockin mouse model showed that the LSCs are enriched within CSF2RB^- population. Another gene upregulated by Cbfb-MYH11 encodes the cytokine receptor IL1RL1. Using Cbfb-MYH11 knockin mice, we showed that LSCs exist in multiple sub-populations defined by their immunophenotype, and IL1RL1 is expressed by cell populations with high LSC activity. We also found that treatment of IL-33, the ligand for IL1RL1, promoted …

Developing Targeted Therapy Against Pancreatic Cancer, Garima Kaushik

Theses & Dissertations

Not available.

Anti-Crispr Vs. Crispr: The Evolutionary Arms Race Between Microorganisms, Rachael M. St. Jacques

Masters Theses, 2010-2019

CRISPR arrays are a defense mechanism employed by bacteria against viral invaders. Cas proteins do the work in detecting, capturing, and integrating the viral DNA into the CRISPR array (Barrangou et al., 2007). Anti-CRISPR proteins are produced by phages, viruses that infect bacteria, to stop the bacterial host’s CRISPR-Cas complex from interrupting the phage life cycle (Bondy-Denomy, et al., 2015).

SEA-PHAGES is a course-based bacteriophage research network composed of 120 colleges and known at James Madison University as Viral Discovery. JMU uses the unsequenced Streptomyces griseus ATCC10137 as a host for bacteriophage discovery and propagation, and in this study we …

Yfmk Is A Novel Nε-Lysine Acetyltransferase That Directly Acetylates The Histone-Like Protein Hbsu In Bacillus Subtilis, Valerie J. Carabetta, Todd M. Greco, Ileana M. Cristea, David Dubnau

Rowan-Virtua Research Day

Recently, N^e-lysine acetylation was realized to be a prevalent bacterial post-translational modification (PTM), contrary to the historical notion that this was a rare occurrence. Acetylation can impact protein function in multiple ways, by modifying conformation, interactions, subcellular localization or activity. In bacteria, hundreds of proteins are known to be acetylated, including those involved essential processes such as DNA replication, nucleoid organization, translation, cell shape, central carbon metabolism, and even several virulence factors. Despite the growing recognition that numerous proteins are acetylated, the biological significance of the vast majority of these modifications in any bacteria remains largely unknown. Previously, …

Times Of Action And Evolutionary Conservation Of Heterochronic Genes, Maria Ivanova, Eric G. Moss

Rowan-Virtua Research Day

Specific genes called heterochronic genes control the timing and sequence of developmental events during larval stages of C. elegans. Mutations in heterochronic genes can cause skipping or reiteration of cell fates associated with certain larval stages. lin-14 and lin-28 are two well-studied heterochronic genes. LIN-14 acts during the first larval stage (L1) and controls events of the L1 and L2 stages, LIN-28 acts during the L2 stage and controls its events.

A Dedicated Chaperone Mediates The Safe Transfer Of Mitoribosomal Proteins To Their Site Of Assembly, Gabrielle Ashley Hillman

Graduate School of Biomedical Sciences Theses and Dissertations

Mitochondrial ribosomes are functionally specialized for the synthesis of several essential inner membrane proteins of the respiratory chain. While remarkable progress has recently been made towards understanding the structure of mitoribosomes, the unique pathways and factors that facilitate their biogenesis remain largely unknown. This dissertation defines the physiological role of an evolutionarily conserved yeast protein called Mam33 in mitochondrial ribosome assembly. The biomedical relevance of this finding stems from the fact that mutations or changes in its expression of the human ortholog p32 result in mitochondrial dysfunction. In human patients, bi-allelic mutations cause severe multisystemic defects in mitochondrial energy metabolism, …

The Signaling Pathways Of Metallothionein-Mediated Chemotaxis In Breast Cancer, Jennifer Messina

University Scholar Projects

Metallothionein (MT) is a small, thiol rich protein released into the extracellular environment in response to stress. Elevated expression of MT has been linked to many inflammatory diseases including inflammatory bowel diseases, diabetes, and cancer. In breast cancer, high expression of MT has been associated with poor patient prognosis. Previous studies have shown that MT acts as a chemoattractant in lymphocytes, and that UC1MT, a monoclonal anti-MT antibody, can block this chemotactic response. In addition, it has been shown that both Cholera toxin and Pertussis toxin, which are known antagonists of G-protein coupled receptors, can inhibit MT-mediated chemotaxis. Here, I …

Pcr Cloning: New Parameters For Managing Alzheimer’S Dementia, Asra Khan, Rehana Rehman, Saara Ahmad

Department of Biological & Biomedical Sciences

No abstract provided.

Developing A Modern Microbiology Laboratory Manual To Enhance Student Learning, Alexander Yonchak

Senior Honors Projects

My project has been addressing the issue of incorporating recent developments in biosafety and pedagogical approaches for lab-courses into our existing educational curriculum by developing a new, modern lab manual aimed at improving experiential learning for introductory microbiology teaching labs. Through researching the most recent safety regulations, industry standards, & guidelines for such teaching labs, my manual clearly delineates learning outcomes to match the skills expected of undergraduates completing degrees within the life sciences. In addition, the lab manual that I have designed has been modernized to incorporate the most recent recommended safety precautions and is written in a user-friendly …

The Role Of Ppal In The Moss Physcomitrella Patens., Noela M. Botaka

College of Arts & Sciences Senior Theses

Protein prenylation is a post-translational modification that involves the addition of lipid groups to the carboxy end of a target protein and is necessary for protein activity. Prenylation has important roles in the cell: targeting and localizing proteins to subcellular compartments and promoting protein-protein interactions. As a highly conserved process in eukaryotes, prenylation is especially important for plant development. In contrast to other eukaryotes, in which loss of prenylation components can be lethal, in the flowering plant Arabidopsis thaliana and the moss Physcomitrella patens, most are viable. Prior studies have shown that prenylation is involved in ABA hormone responses, …

Human Anatomy And Physiology I: Course Map With Expected Learning Outcomes, Carlos Liachovitzky

Open Educational Resources

This document contains a list with all the Anatomy and Physiology I expected learning outcomes organized by topics, and grouped into ten units: 1. Introduction to A&P: body plan & organization; 2. Introduction to A&P: homeostasis; 3. The chemical level of organization; 4. Levels of organization: the cellular level of organization; 5. Levels of organization: the tissue level of organization; 6. Support and movement: integumentary system; 7. Support and movement: skeletal system & articulations; 8. Support and movement: muscular system; 9. Regulation, integration, and control: nervous system; 10. Regulation, integration, and control: special senses

Each learning outcome is referred to …

Attenuated Responses To Inflammatory Cytokines In Mouse Embryonic Stem Cells: Biological Implications And The Molecular Basis, Bohan Chen

Master's Theses

Embryonic stem cells (ESCs) have attracted intense interest due to their great potential for regenerative medicine. However, their immune property is an overlooked but a significant issue that needs to be thoroughly investigated not only to resolve the concern for therapeutic applications but also for further understanding the early stage of organismal development. Recent studies demonstrated that ESCs are deficient in innate immune responses to viral/bacterial infections and inflammatory cytokines. Inflammatory conditions generally inhibit cell proliferation, which could be detrimental to ESCs, since cell proliferation is their dedicated task during early embryogenesis. Thus, I hypothesize that the attenuated innate immunity …

An Oxanthroquinone Derivative Disrupts Ras Plasma Membrane Localization And Function By Inhibition Of Acylpeptide Hydrolase And Perturbation Of Sphingomyelin Metabolism, Lingxiao Tan

Dissertations and Theses (Open Access)

Oncogenic RAS proteins are commonly expressed in human cancer. To be functional, RAS proteins must undergo post-translational modification and localize to the plasma membrane (PM). Therefore, compounds that prevent RAS PM targeting have potential as putative RAS inhibitors. Here we examined the mechanism of action of oxanthroquinone G01 (G01), a recently described inhibitor of KRAS PM localization. We show that G01 mislocalized HRAS and KRAS from the PM with similar potency and disrupted the spatial organization of RAS proteins remaining on the PM. G01 also inhibited recycling of epidermal growth factor receptor and transferrin receptor, but did not impair internalization …

Embryonic Lethality Of Cranial Neural Crest Deletion Of Cdc73, Lilia Shen

Honors Scholar Theses

Hyperparathyroidism-jaw tumor (HPT-JT) syndrome is a disease characterized by parathyroid tumors, renal cysts or tumors, uterine tumors, and ossifying jaw fibromas. The cause of this syndrome is linked to a tumor suppressor gene called Cdc73, which encodes the protein product parafibromin. The loss of proper expression of Cdc73/parafibromin is implicated in the development of the tumors typical of HPT-JT, although the exact mechanisms of tumorigenesis are unclear. In particular, not much is understood about the development of ossifying fibromas (OF) of the jaw in this syndrome. OF is a benign bone neoplasm that can affect the mandible and …

The Signaling Pathways Of Metallothionein-Mediated Chemotaxis In Breast Cancer, Jennifer Messina

Honors Scholar Theses

Metallothionein (MT) is a small, thiol rich protein released into the extracellular environment in response to stress. Elevated expression of MT has been linked to many inflammatory diseases including inflammatory bowel diseases, diabetes, and cancer. In breast cancer, high expression of MT has been associated with poor patient prognosis. Previous studies have shown that MT acts as a chemoattractant in lymphocytes, and that UC1MT, a monoclonal anti-MT antibody, can block this chemotactic response. In addition, it has been shown that both Cholera toxin and Pertussis toxin, which are known antagonists of G-protein coupled receptors, can inhibit MT-mediated chemotaxis. Here, I …

Spatial Reorganization Of Histone-Like Nucleoid Structuring Proteins Caused By Silver Nanoparticles, Meaad Alqahtany

Graduate Theses and Dissertations

Silver nanoparticles (AgNPs) and ions (Ag+) can be the new generation of antibiotics due to their antimicrobial effects against bacteria and other microbes. Many studies have shown that AgNPs and suppress the growth of bacteria and damage the cell walls of the microbes; therefore, treating bacterial cells with AgNPs may be a promising method to terminate multi-resistant bacteria. In this work, the effect of AgNPs with two different surface coatings on the spatial reorganization of histone-like nucleoid structuring (H-NS) proteins in Escherichia coli bacteria was investigated using quantitative super-resolution fluorescence microscopy to understand the toxicity and antimicrobial mechanism of AgNPs. …

A Novel Kinesin Adapter Directly Mediates Dendritic Mrna Localization During Synapse Development, Hao Wu

Dissertations, Theses, and Capstone Projects

Cytoskeleton based active transport with motor proteins is essential for mRNA localization and local protein translation in animal cells, yet how mRNA granules interact with motor proteins remains poorly understood. Using an unbiased screen for interaction between mRNA binding proteins (RBP) and motor proteins, we identified protein interacting with APP tail 1 (PAT1) as a potential direct adapter between the β-actin mRNA Zipcode-binding protein 1 (ZBP1) and Kinesin-1 motor complex.

Mouse PAT1 is similar to the Kinesin Light Chain (KLC) in amino acid sequence and binds directly to KLC. High-resolution images from structured illumination microscopy (SIM) indicates that synaptic stimulation …

The Role And Regulation Of Alternative Polyadenylation In The Dna Damage Response, Michael R. Murphy

Dissertations, Theses, and Capstone Projects

Cellular homeostasis is achieved by the dynamic flux in gene expression. Post-transcriptional regulation of coding and non-coding RNA offers a fast method of adapting to a changing cellular environment, including deadenylation, microRNA (miRNA) pathway, and alternative polyadenylation (APA). In this dissertation, I explored some of the mechanisms involved in the post-transcriptional regulation of gene expression. The main hypothesis in these studies is that a single APA event after DNA damage is governed by specific conditions and factors outside of current known regulators of APA, and that the resultant transcript has a role in the DNA damage response (DDR). My aims …

The Molecular Mechanisms Underlying The Cancer Killing Effect Of Interleukin-24, Leah Eshanie Persaud

Dissertations, Theses, and Capstone Projects

Interleukin-24 (IL-24) is an immunomodulatory cytokine that also displays specific anti-tumor effects across many cancer cell types. The tumor suppressor activities of IL-24 include inhibition of angiogenesis, metastasis, toxic autophagy, cancer-specific apoptosis, and sensitization to traditional cancer treatments like chemotherapy and radiation. Overexpression of IL-24 can selectively induce apoptosis in various cancer cells while having no adverse effects on normal cells. Due to this favorable killing effect, IL-24 is currently in phase II clinical trials. There is accumulating evidence that IL-24’s anti-cancer activity is primarily through the endoplasmic reticulum (ER) stress pathway but other pathways leading to cell death are …

The 5-Ht1a-R Knockout Mouse As A Model Of Later Life Anxiety Disorders: Implications For Sex Differences, Tatyana Budylin

Dissertations, Theses, and Capstone Projects

Anxiety affects nearly twice as many women as it affects men across all cultures and economic groups. Importantly, girls have a higher chance of inheriting anxiety disorders than boys, and many anxiety disorders appear at a very young age. However, little is known about sex differences in brain and behavioral development and how they relate to anxiety in adulthood. Serotonin 1A receptor (5-HT_1A-R) mediated signaling has been implicated in depression and anxiety, however most studies that focus on the involvement of the 5-HT_1A-R have been conducted in adults. Little is known about how the 5-HT_{1A …}

Platiscity Of C. Elegans Germline Stem Cells Under Nutritional And Metabolic Stress, Kenneth Trimmer

Dissertations and Theses (Open Access)

Stem cells are integral for tissue maintenance and fertility. Therefore, understanding how stem cells are regulated under stress is imperative. When confronted with acute starvation, stem cells must conserve energy and metabolites to cope with the lack of an external source. Caenorhabditis elegans germline stem cells (GSCs) are an excellent model for studying stem cell properties and regulation as they can divide throughout the life of the organism. While GSCs are an adult stem cell population, their cell cycle structure more closely mimics mouse and human embryonic stem cells with short G1 and long S phases. In this thesis, I …

Thiol-Based Misfolding: Linking Redox Balance To Cytosolic Proteostasis, Ford Amy

Dissertations and Theses (Open Access)

The eukaryotic cytosolic proteome is vulnerable to changes in proteostatic and redox balance caused by temperature, pH, oxidants and xenobiotics. Cysteine-containing proteins are especially at risk as the thiol side chain is subject to oxidation, adduction and chelation by thiol-reactive compounds. All of these thiol-modifiers have been demonstrated to induce the heat shock response and recruit protein chaperones to sites of presumed protein aggregation in the budding yeast Saccharomyces cerevisiae. However, endogenous targets of thiol stress toxicity responsible for these outcomes are largely unknown. Furthermore, I hypothesize proteins identified as redox-active are prone to misfolding and aggregation by thiol-specific …

Evaluating The Potential Of Repurposing Commercially Available Drugs For The Treatment Of Viral Infections, Brennan Connor Mcewan

Undergraduate Honors Capstone Projects

Viral infections that are often overlooked as common seasonal illnesses such as influenza can rapidly become a public threat. They threaten society as new, more dangerous strains of these common viruses emerge and as strains develop resistance to current vaccines and antiviral treatments (Kochanek, Murphy, Xu, & Tejada-Vera, 2014). To combat this, the development of antiviral treatments with novel mechanisms of action is essential. Repurposing drugs instead of developing new drugs can save years of development time and hundreds of millions of dollars (DiMasi, Hansen, & Grabowski, 2003). To support the effort to discover drugs with unique mechanisms of action, …

The Effects Of Vascular Endothelial Growth Factor On The Characteristics Of Pluripotent Dental Pulp Stem Cells, Cale Forgues

UNLV Theses, Dissertations, Professional Papers, and Capstones

Many believe that stem cells hold the key to regenerative medicine. Therefore, research with stem cells has become increasingly popular over the years. Three specific groups of study have become present in literature. The first group has focused much of their research on harvesting and cultivating stem cell lines to retain their pluripotent ability. Stem cells can be tricky to cultivate and preserve over time as they will often differentiate or die. Another group examines the specific characteristics that a pluripotent stem cell has and how to retain, or even create, a cell with pluripotent potential. Lastly, the third group …