Cell and Developmental Biology Commons^™

Cyclophilin A Enhances Hiv-1 Reverse Transcription In Human Microglial Cells, Zachary Michael Ingram

Graduate Theses/Dissertations

Parenchymal microglia represent a susceptible cell type to HIV infection and contribute to HIV Associated Neurocognitive Disorders (HAND). Currently, HIV host-protein interactions in microglia are understudied, but relevant to the design of antiviral drugs. HIV replication events rely on host and viral proteins to evade an immune response while improve replication success. Post-fusion the HIV capsid is released into the cytoplasm and begins trafficking towards the nucleus. During transit viral RNA is transcribed to DNA through reverse transcription (RT). In addition, the HIV capsid that protects the reverse transcription complex disassembles in a step termed uncoating. Once the pre-integration complex …

Mechanisms And Consequences Of Myb Gene Activation In Salivary Gland Tumors, Candace Frerich

Biomedical Sciences ETDs

Salivary gland adenoid cystic carcinoma (ACC) is an aggressive tumor with a tendency to infiltrate surrounding nerves and metastasize to distant sites. The standard treatment often fails to control local tumor recurrence and distant metastases and no approved targeted therapeutic options exist for these tumors. The goal of our studies was to reveal the molecular mechanisms driving ACC tumor development and novel drug targets to improve patient morbidity and mortality.

We first analyzed clinical and RNA-sequencing (RNA-seq) data for 68 formalin-fixed paraffin-embedded (FFPE) ACC tumor samples and described previously unappreciated molecular heterogeneity that predicts patient outcome. The poor outcome subgroup …

Functional Importance Of Lipin Phosphorylation, Stephanie Elizabeth Hood

Graduate Theses and Dissertations

Highly conserved throughout evolution, lipins are dual functioning proteins found from yeast to humans. Functioning in the cytoplasm as phosphatidate phosphatase enzymes (PAP), lipins produce diacylglycerol that serves as a precursor for neutral fats and membrane phospholipids. Alternatively, nuclear lipins are responsible for the regulation of metabolic genes. Interestingly, both the mammalian lipin 1 paralog and the single Drosophila Lipin ortholog are highly phosphorylated proteins. Target of rapamycin (TOR) has previously been identified as one of the kinases that controls the subcellular localization of both lipin 1 and Drosophila Lipin. However, other serine and threonine kinases are predicted to be …

Natural Variation In Yeast Stress Signaling Reveals Multiple Paths To Similar Phenotypes, Amanda N. Scholes

Graduate Theses and Dissertations

Natural environments are dynamic, and organisms must sense and respond to changing conditions. One common way organisms deal with stressful environments is through gene expression changes, allowing for stress acclimation and resistance. Variation in stress sensing and signaling can potentially play a large role in how individuals with different genetic backgrounds are more or less resilient to stress. However, the mechanisms underlying how gene expression variation affects organismal fitness is often obscure.

To understand connections between gene expression variation and stress defense phenotypes, we have been exploiting natural variation in Saccharomyces cerevisiae stress responses using a unique phenotype called acquired …

A Novel Switch-Like Function Of Delta-Catenin In Dendrite Development, Ryan Baumert

Dissertations and Theses (Open Access)

The formation of neuronal networks in the brain is tightly regulated, and dependent on the morphology of dendrites, the branch-like signal-receiving structures extending from neurons. Disruptions in dendrite development, or dendritogenesis, can lead to the atypical neuronal connectivity associated with multiple neurodevelopmental diseases. My research addresses molecular processes that underlie dendritogenesis via analysis of a pair of novel interactions involving the protein delta-catenin.

In neurons, delta-catenin localizes to dendrites and synapses, where it functions in their development and maintenance. Structurally, delta-catenin possesses a central Armadillo domain and a C-terminal PDZ-binding motif. This motif associates with PDZ domain-containing proteins, and is …

Uncovering The Zeb1 Interactome To Identify Novel Regulators Of Metastatic Non-Small Cell Lung Cancer, Roxsan Manshouri

Dissertations and Theses (Open Access)

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death in the United States, due in part to the robust affinity of lung cancer cells to metastasize. Understanding the processes that contribute to metastasis provides promise for the discovery of novel therapeutic targets. Epithelial-tomesenchymal transition (EMT) is a proposed model for the initiation of metastasis. During EMT cell adhesion and polarity is reduced, allowing epithelial cancer cells to dissociate from the primary tumor and invade distant organs. The transcription factor zinc finger E-box-binding homeobox 1 (ZEB1) has been reported to uniquely correlate with NSCLC disease progression and to …

The Role Of Membrane Domains In Protein And Lipid Sorting During Endocytic Traffic, Blanca B. Diaz-Rohrer

Dissertations and Theses (Open Access)

The lipid and protein composition of the plasma membrane (PM) must be tightly controlled to maintain cellular functionality, despite constant, rapid endocytosis. Because de novo synthesis of proteins and lipids is energetically costly, the cell depends on active recycling to return endocytosed membrane components back to the PM. For most proteins, the mechanisms and pathways of their PM retention remain unknown. The work presented here shows that association with ordered membrane microdomains is fully sufficient for PM recycling and that abrogation of raft partitioning leads to their degradation in lysosomes. These findings support a model wherein ordered membrane domains mediate …

Toward Understanding The Mechanism Of Protein Targeting In The Chloroplast Signal Recognition Particle Pathway, Mercede Furr

Graduate Theses and Dissertations

Protein targeting is a vital cellular function. The signal recognition particle (SRP) pathway is a universally conserved targeting system present in the cytosol and used to co-translationally target many proteins to the inner membrane of prokaryotes and the endoplasmic reticulum of eukaryotes. The chloroplast has a homologous SRP system which post-translationally targets light harvesting chlorophyll binding proteins (LHCPs) to the thylakoid membrane for integration. The chloroplast SRP (cpSRP) is a heterodimer with a 54 kDa subunit equivalent to SRP54 in the canonical pathway. In addition, cpSRP contains a novel 43 kDa subunit which is a unique and irreplaceable component. cpSRP43 …

Quantitative Study Of The Antimicrobial Effects Of Silver On The Motility Of Escherichia Coli, Benjamin Russell

Graduate Theses and Dissertations

In recent decades, the number of antibiotic-resistant bacterial infections has grown to become a serious global threat. This rise can be attributed to the widespread misuse of antibiotics and the lack of newly developed drugs to fight resistant organisms. Novel bactericidal substances have, therefore, garnered significant research interest. Silver, due to its powerful antimicrobial effects, is one such substance. Silver is typically most effective in cationic form; however, advancements in nanotechnology have paved the way for the controlled fabrication of nano-silver. Silver nanoparticles have been shown to have increased antibacterial potency for a variety of reasons, including the release of …

Anti-Inflammatory Effects Of Cruciferous And Apiaceous Vegetables In C57bl/6j Mice Colon, Rosa Moreno Narvaez

Graduate Theses and Dissertations

Previous studies have demonstrated chemo-preventive potential of cruciferous and apiaceous vegetables against colon cancer. Colon inflammation is one condition closely related with colon cancer initiation. Therefore, we wanted to compare if total western diet (TWD) was as pro-inflammatory as died-induced obesity (DIO) and a better dietary model for human conditions, and determine if diet supplementation with cruciferous (broccoli, watercress and cabbage) or apiaceous vegetables (celery and parsnip) could reduce dietary inflammation, and which vegetable was more effective.

Male CBL57/6J mice were fed chow for seven days, on day eight, mice were assigned to one of the following diets: American Institute …

Comprehensive Investigation Of Bioactive Steroidal Alkaloids In Veratrum Californicum, Matthew West Turner

Boise State University Theses and Dissertations

Veratrum californicum, commonly referred to as corn lily or Californian false hellebore, grows in high mountain meadows and produces bioactive steroidal alkaloids, including cyclopamine. Cyclopamine is a potent inhibitor of the Hedgehog (Hh) signaling pathway. Our lab has optimized methods to extract cyclopamine and related steroidal alkaloids from V. californicum, and implemented in-house Hh signaling bioactivity evaluation of these steroidal alkaloids using a Shh-Light II cell assay. A survey of extraction methods and solvents resulted in the identification of conditions most favorable for alkaloid extraction yield and antagonist activity in the Shh-Light II cell assay. The highest amount …

A Systematic Comparison Of Lipopolymers For Sirna Delivery To Multiple Breast Cancer Cell Lines: In Vitro Studies, Hamidreza Montazeri Aliabadi, Remant Bahadur Kc, Emira Bousoik, Ashley Barbarino, Bindu Thapa, Melissa Coyle, Parvin Mahdipoor, Hasan Uludağ

Pharmacy Faculty Articles and Research

Small interfering RNA (siRNA) therapy is a promising approach for treatment of a wide range of cancers, including breast cancers that display variable phenotypic features. To explore the general utility of siRNA therapy to control aberrant expression of genes in breast cancer, we conducted a detailed analysis of siRNA delivery and silencing response in vitro in 6 separate breast cancer cell models (MDA-MB-231, MDA-MB-231-KRas-CRM, MCF-7, AU565, MDA-MB-435 and MDA-MB-468 cells). Using lipopolymers for siRNA complexation and delivery, we found a large variation in siRNA delivery efficiency depending on the specific lipopolymer used for siRNA complexation and delivery. Some lipopolymers were …

Function-Driven Single-Cell Genomics Uncovers Cellulose-Degrading Bacteria From The Rare Biosphere, Devin F. R. Doud, Robert M. Bowers, Frederik Schulz, Markus De Raad, Kai Deng, Angela Tarver, Evan Glasgow, Brian Fox, Sam Deutsch, Yasuo Yoshikuni, Trent Northen, Brian P. Hedlund, Steven W. Singer, Natalia Ivanova, Tanja Woyke

Life Sciences Faculty Research

No abstract provided.

Dynamical Modeling In Cell Biology With Ordinary Differential Equations, Renee Marie Dale

LSU Doctoral Dissertations

Dynamical systems have been of interest to biologists and mathematicians alike. Many processes in biology lend themselves to dynamical study. Movement, change, and response to stimuli are dynamical characteristics that define what is 'alive'. A scientific relationship between these two fields is therefore natural. In this thesis, I describe how my PhD research variously related to biological, mathematical, and computational problems in cell biology. In chapter 1 I introduce some of the current problems in the field. In chapter 2, my mathematical model of firefly luciferase in vivo shows the importance of dynamical models to understand systems. Data originally collected …

Lung Cancer Cells Survive Egfr Tki Exposure Through Upregulation Of Cholesterol Synthesis, Mark Howell

USF Tampa Graduate Theses and Dissertations

Lung cancer is the number one cause of cancer related death in both males and females. About 20% of all non-small cell lung cancer (NSCLC) patients are expected to harbor an epidermal growth factor receptor (EGFR) activating mutation. EGFR inhibitors have been shown to provide clinical benefits over chemotherapy for lung cancer patients with EGFR activating mutations. However, despite the initial clinical responses to these EGFR targeted therapies, long-term efficacy is not possible because acquired drug resistance hampers the effectiveness of these therapies. We found that a fiber inspired smart scaffold (FiSS) platform established in our laboratory allows growth of …

The Role Of Atypical Protein Kinase C In Colorectal Cancer Cells Carcinogenesis, S M Anisul Islam

USF Tampa Graduate Theses and Dissertations

Colorectal cancer (CRC) is the third most common malignancy and the fourth most common cause of cancer-related death worldwide. CRC is a life-threatening disease due to therapy-resistant cancerous cells. The exact mechanisms of cell growth, survival, metastasis and inter & intracellular signaling pathways involved in CRC are still a significant challenge. Moreover, the treatment of metastatic CRC considered palliative for many years aimed for an improved life, with little hope of a cure, highlighting the need for developing novel targeted therapy for CRC. Hence, investigating new molecular mechanism(s) that lead to colorectal carcinogenesis may give insight into the therapeutic target. …

Genome-Wide Variation In Potyviruses, Deepti Nigam, Katherine Latourrette, Pedro F.N. Souza, Hernan Garcia Ruiz

Nebraska Center for Virology: Faculty Publications

Potyviruses (family Potyviridae, genus Potyvirus) are the result of an initial radiation event that occurred 6,600 years ago. The genus currently consists of 167 species that infect monocots or dicots, including domesticated and wild plants. Potyviruses are transmitted in a non-persistent way by more than 200 species of aphids. As indicated by their wide host range, worldwide distribution, and diversity of their vectors, potyviruses have an outstanding capacity to adapt to new hosts and environments. However, factors that confer adaptability are poorly understood. Viral RNA-dependent RNA polymerases introduce nucleotide substitutions that generate genetic diversity. We hypothesized that selection imposed by …

Macrophage-Associated Wound Healing Contributes To African Green Monkey Siv Pathogenesis Control, Fredrik Barrenas, Kevin Raehtz, Cuiling Xu, Lynn Law, Richard R. Green, Guido Silvestri, Steven E. Bosinger, Andrew Nishida, Qingsheng Li, Wuxun Lu, Jianshui Zhang, Matthew J. Thomas, Jean Chang, Elise Smith, Jeffrey M. Weiss, Reem A. Dawoud, George H. Richter, Anita Trichel, Dongzhu Ma, Xinxia Peng, Jan Komorowski, Cristian Apetrei, Ivona Pandrea, Michael Gale Jr.

Nebraska Center for Virology: Faculty Publications

Natural hosts of simian immunodeficiency virus (SIV) avoid AIDS despite lifelong infection. Here, we examined how this outcome is achieved by comparing a natural SIV host, African green monkey (AGM) to an AIDS susceptible species, rhesus macaque (RM). To asses gene expression profiles from acutely SIV infected AGMs and RMs, we developed a systems biology approach termed Conserved Gene Signature Analysis (CGSA), which compared RNA sequencing data from rectal AGM and RM tissues to various other species. We found that AGMs rapidly activate, and then maintain, evolutionarily conserved regenerative wound healing mechanisms in mucosal tissue. The wound healing protein fibronectin …

Clpc Affects The Intracellular Survival Capacity Of Staphylococcus Aureus In Non-Professional Phagocytic Cells, Gubesh Gunaratnam, Lorena Tuchscherr, Mohamed I. Elhawy, Ralph Bertram, Janina Eisenbeis, Christian Spengler, Thomas Tschernig, Bettina Löffler, Greg A. Somerville, Karin Jacobs, Mathias Herrmann, Markus Bischoff

School of Veterinary and Biomedical Sciences: Faculty Publications

Invasion and persistence of bacteria within host cells requires that they adapt to life in an intracellular environment. This adaptation induces bacterial stress through events such as phagocytosis and enhanced nutrient-restriction. During stress, bacteria synthesize a family of proteins known as heat shock proteins (HSPs) to facilitate adaptation and survival. Previously, we determined the Staphylococcus aureus HSP ClpC temporally alters bacterial metabolism and persistence. This led us to hypothesize that ClpC might alter intracellular survival. Inactivation of clpC in S. aureus strain DSM20231 significantly enhanced long-term intracellular survival in human epithelial (HaCaT) and endothelial (EA.hy926) cell lines, without markedly affecting …

Aniseed 2019: 4d Exploration Of Genetic Data For An Extended Range Of Tunicates, J. Dardaillon, D. Dauga, P. Simion, E. Faure, T. A. Onuma, M. B. Debiasse, A. Louis, K. R. Nitta, M. Naville, L. Besnardeau, W. Reeves, K. Wang, M. Fagotto, M. Guéroult-Bellone, S. Fujiwara, R. Dumollard, M. Veeman, J.-N. Volff, H. Roest Crollius, E. Douzery, J. F. Ryan, Bradley Justin Davidson , '91, H. Nishida, C. Dantec, P. Lemaire

Biology Faculty Works

ANISEED (https://www.aniseed.cnrs.fr) is the main model organism database for the worldwide community of scientists working on tunicates, the vertebrate sister-group. Information provided for each species includes functionally-annotated gene and transcript models with orthology relationships within tunicates, and with echinoderms, cephalochordates and vertebrates. Beyond genes the system describes other genetic elements, including repeated elements and cis-regulatory modules. Gene expression profiles for several thousand genes are formalized in both wild-type and experimentally-manipulated conditions, using formal anatomical ontologies. These data can be explored through three complementary types of browsers, each offering a different view-point. A developmental browser summarizes the information in a gene- …

Why Did The Eisenhower Administration Decide To Deploy Jupiter Missiles In Turkey: A Case Study In Nuclearization Of Nato Strategy, Murat Iplikci

Theses and Dissertations

Looking out at the international political landscape of the late 1940s and the early 1950s, the Eisenhower administration was determined to challenge the evident appeal of Communism, particularly in Western Europe. NATO, which was a fragile organization due to the devastation of World War II (WWII), and its members were prone to any communist attack, either by military forces or through political parties. They had to be defended. The Eisenhower administration saw nuclear weapons as the only means to defend the alliance against the massive threat of the Soviet Union. Therefore, President Eisenhower committed nuclear weapons to NATO as a …

Discovery Of An Egfr Inhibitor For The Treatment Of Lung And Other Cancers, Jodie Meng '20

Student Publications & Research

The Epidermal Growth Factor Receptor (EGFR), a transmembrane protein involved in the regulation of signaling pathways, is frequently overexpressed in epithelial tumors. First generation EGFR TKIs, such as erlotinib and gefitinib, traditionally improved outcomes for non-small-cell lung carcinoma and pancreatic cancer patients by attaching competitively and reversibly to the ATP binding domain of EGFR. Second-generation EGFR TKIs have been developed to combat resistance among patients, despite demonstrating toxic side effects. In the present study, 1400 selective inhibitors were designed based on the molecular scaffolds of first and second generation EGFR TKIs. Results were refined by parameters outlined in Lipinski’s rule. …

The Democratization And Development Of Cell-Free Protein Synthesis, Max Z. Levine

Master's Theses

Cell-free protein synthesis (CFPS) using crude lysates has developed into a robust platform technology over the last 60 years to express numerous types of recombinant proteins. The open-nature, elimination of reliance on cell viability, and focus of all energy towards production of the protein of interest represent substantial advantages of CFPS over in vivo protein expression methods. CFPS has provided new opportunities across a series of research fields that include metabolic engineering, therapeutic and vaccine development, education, biosensors, and many more. In recent years, optimizations of CFPS have even allowed the platform to reach the industrial level of protein production. …

Updating Molecular Diagnostics For Detecting Methicillin- Susceptible And Methicillin-Resistant Staphylococcus Aureus Isolates In Blood Culture Bottles, Fred C. Tenover, Isabella A. Tickler, Victoria M. Le, Scott Dewell, Rodrigo E. Mendes, Richard V. Goering, Mrsa Consortium

Biology Faculty Publications

Molecular diagnostic tests can be used to provide rapid identification of staphylococcal species in blood culture bottles to help improve antimicrobial stewardship. However, alterations in the target nucleic acid sequences of the microorganisms or their antimicrobial resistance genes can lead to false-negative results. We determined the whole-genome sequences of 4 blood culture isolates of Staphylococcus aureus and 2 control organisms to understand the genetic basis of genotypephenotype discrepancies when using the Xpert MRSA/SA BC test (in vitro diagnostic medical device [IVD]). Three methicillin-resistant S. aureus (MRSA) isolates each had a different insertion of a genetic element in the staphylococcal cassette …

Cul3 Regulates Cyclin E1 Protein Abundance Via A Degron Located Within The N-Terminal Region Of Cyclin E, Brittney Marie Davidge, Katia De Oliveira Rebola, Larry N. Agbor, Curt D. Sigmund, Jeffrey D. Singer

Biology Faculty Publications and Presentations

mammalian cells. Increased levels of cyclin E are found in some cancers. Additionally, proteolytic removal of the cyclin E N-terminus occurs in some cancers and is associated with increased cyclin E–Cdk2 activity and poor clinical prognosis. Cyclin E levels are tightly regulated and controlled in part through ubiquitin-mediated degradation initiated by one of two E3 ligases, Cul1 and Cul3. Cul1 ubiquitylates phosphorylated cyclin E, but the mechanism through which Cul3 ubiquitylates cyclin E is poorly understood. In experiments to ascertain how Cul3 mediates cyclin E destruction, we identified a degron on cyclin E that Cul3 targets for ubiquitylation. Recognition of …

Dynamics Of Trophoblast Differentiation In Peri-Implantation–Stage Human Embryos, Rachel C. West, Hao Ming, Deirdre M. Logsdon, Jiangwen Sun, Sandeep K. Rajput, Rebecca A. Kile, William B. Schoolcraft, R. Michael Roberts, Rebecca L. Krisher, Zongliang Jiang, Ye Yuan

Computer Science Faculty Publications

Single-cell RNA sequencing of cells from cultured human blastocysts has enabled us to define the transcriptomic landscape of placental trophoblast (TB) that surrounds the epiblast and associated embryonic tissues during the enigmatic day 8 (D8) to D12 peri-implantation period before the villous placenta forms. We analyzed the transcriptomes of 3 early placental cell types, cytoTB (CTB), syncytioTB (STB), and migratoryTB (MTB), picked manually from cultured embryos dissociated with trypsin and were able to follow sublineages that emerged from proliferating CTB at the periphery of the conceptus. A unique form of CTB with some features of STB was detectable at D8, …

Fetal Programming Of Intrauterine Growth Restricted Skeletal Muscle Stem Cell Function, Micah Most

Honors Program: Senior Projects (Public)

Intrauterine growth restriction (IUGR) reduces skeletal muscle mass in fetuses and offspring. The objective of this study was to determine if myoblasts (skeletal muscle stem cells) from maternal inflammation induced intrauterine growth-restricted (MI-IUGR) fetuses are less responsive to proliferation-stimulating factors in culture. Ovine MI-IUGR fetal myoblasts were isolated at 125 days of gestational age (dGA, term = 150 dGA), grown for 72 hours in complete growth media spiked with insulin, tumor necrosis factor α (TNFα), or unspiked (basal), and analyzed for ex vivo proliferative capacity via a 2 hour EdU pulse. A second set of myoblasts were differentiated in differentiation …

All Nuts And No Bolts: The Evolution Of Undergraduate Research At A Small State School, James Hawker

Florida Statewide Symposium: Best Practices in Undergraduate Research

In fall of 2017, students first started doing research with their biology instructor, and just a few terms later, two students have earned Portz Interdisciplinary Fellowships. In some ways, the program is going well with students participating in high numbers, but organizers still have questions about the “nuts and bolts” of establishing the program within the institution. Enthusiasm is high! However, key metrics are not being tracked and the workload needs to be distributed more evenly. The organizers will be talking with the audience about different ways to integrate UGR into the institution.

Equine Hoof Stratum Internum K14+Cd105+ Progenitor Cells: Culture, Characterization, And Model Of Epithelial To Mesenchymal Transition, Qingqiu Yang

LSU Doctoral Dissertations

For the potential benefit of progenitor cells to be realized in cell-based clinical therapies, it is vital to investigate the mechanism between progenitor cells and abnormal tissue formation. Laminitis is a fatal condition that is often presented by equine hoof inflammation and hoof tissue disarrangement. The persistence of abnormal tissue formation after the resolution of equine laminitis suggests there is progenitor cell compromise. So far, there is limited information about equine hoof progenitor cells and the effects of inflammation on hoof progenitor cells. To pursue a better understanding of both hoof progenitor cell and hoof growth as well as find …

Phenylethynyl-Substituted Benzenes And Heterocycles For The Treatment Of Cancer, David S. Watt, Chunming Liu, Vitaliy M. Sviripa, Wen Zhang, Markos Leggas

Molecular and Cellular Biochemistry Faculty Patents

Halogenated phenylethynyl-substituted heterocycles that possess either an N-alkylamino or N,N-dialkylamino group attached to the heterocycle or halogenated phenylethynyl-substituted benzenes that a nitrogen-containing heterocycle attached to the benzene inhibit the proliferation cancer cells and are useful antineoplastic agents.