Cell Biology Commons^™

Towards An In Vitro Model Of Testing Osteoblast Cellular Function In Contact With Various Surfaces, Raheleh Miralami

Theses & Dissertations

Past studies have shown that the success of total joint replacements depends on the biocompatibility of orthopaedic materials, which can be improved by modifying the implant surface. However, the exact roles of these modifications and their effective mechanisms are poorly understood. The objective of this study was to develop and evaluate a model system to investigate the impact of nano-structured surfaces, produced by the ion beam-assisted deposition (IBAD) technique, on biomarkers of osteointegration using an in vitro model. The IBAD technique was employed to deposit zirconium oxide (ZrO₂), Titanium oxide (TiO₂), and Titanium (Ti) nano-films on …

Regulation Of Canonical And Non-Canonical Hippo Pathway Components In Mitosis And Cancer, Seth Stauffer

Theses & Dissertations

The Hippo pathway is conserved regulator of organ size through control of proliferation, apoptosis, and stem-cell self-renewal. In addition to this important function, many of the canonical signaling members have also been shown to be regulated during mitosis. Importantly, Hippo pathway components are frequently dysregulated in cancers and have attracted attention as possible targets for improved cancer therapeutics. Further exploration of Hippo-YAP (yes-associated protein) signaling has revealed new regulators and effectors outside the canonical signaling network and has revealed a larger non-canonical network of signaling proteins in which canonical Hippo pathway components crosstalk with important cellular homeostasis and apoptosis signaling …

Intra- And Inter-Molecular Signaling In A Cardiac Connexin: Role Of Cytoplasmic Domain Dimerization And Phosphorylation, Andrew J. Trease

Theses & Dissertations

As critical mediators of cell-to-cell communication, gap junctions (GJs) are comprised of membrane channels that directly link the cytoplasm of adjacent coupled cells thereby allowing for the passage of ions, small metabolites, and secondary messengers. Each channel is formed by the apposition of two connexons from adjacent cells, each composed of six connexin (Cx) proteins. Each GJ channel functions to promote signal propagation and synchronization of cells and tissues in organs. Furthermore, GJs are essential for proper propagation of cardiac action potentials from one cell to the next, leading to the coordinated contraction and relaxation of heart muscle powering circulation. …

Investigating The Impact Of Oxidative Stress On Tetrahymena Thermophila Sirtuin,Thd 18, Emmanuel Dubuisson

Publications and Research

Sirtuins are a family of enzymes that fulfill various important biological functions. Investigators have looked for the implication of Sirtuin genes in cell signaling mechanisms, in the formation and silencing of heterochromatin, in the regulation of ion channels, and in the modulation of the cellular redox reactions[2]. Different model organisms have been previously used to conduct these studies; among them, there are yeasts, nematodes, and fruit flies. Each one has made some valuable contribution into the vast body of knowledge related to this field.

However, gaps in the understanding of Sirtuins functions still remain to be filled. In this optic, …

Engineering Yeast To Evaluate Human Proteins Involved In Selective Rna Packaging During Hiv Particle Production, Ryan M. Bitter

Master's Theses

Despite recent advances in antiretroviral therapy, nearly 37 million people continue to live with human immunodeficiency virus (HIV). Basic and applied research on the assembly of HIV could be enhanced by using a genetically tractable organism, such as yeast, rather than mammalian cells. While previous studies showed that expression of the HIV Gag polyprotein in Saccharomyces cerevisiae spheroplasts resulted in the production of virus-like particles (VLPs), many questions regarding the utility of yeast in HIV assembly remain uninvestigated. Here, we report use of S. cerevisiae for both the production of VLPs with selectively packaged RNA and to evaluate the human …

Il-12 Gene Electrotransfer Triggers A Change In Immune Response Within Mouse Tumors, Guilan Shi, Chelsea Edelblute, Sezgi Arpag, Cathryn Lundberg, Richard Heller

Bioelectrics Publications

Metastatic melanoma is an aggressive skin cancer with a relatively low survival rate. Immune-based therapies have shown promise in the treatment of melanoma, but overall complete response rates are still low. Previous studies have demonstrated the potential of plasmid IL-12 (pIL-12) delivered by gene electrotransfer (GET) to be an effective immunotherapy for melanoma. However, events occurring in the tumor microenvironment following delivery have not been delineated. Therefore, utilizing a B16F10 mouse melanoma model, we evaluated changes in the tumor microenvironment following delivery of pIL-12 using different GET parameters or injection of plasmid alone. The results revealed a unique immune cell …

Structure-Activity Relationship Of Novel Rgd-Containing Cyclic Peptides Against Αvβ3 Integrin, Aaron Silva

Honors Theses

The αvβ3 integrin, a receptor for many extracellular matrix proteins with the RGD sequence motif, is involved in multiple physiological processes. The integrin is highly expressed on tumor cells, therefore making it a target for cancer therapy and imaging. Efforts have been made to develop an RGD-containing ligand against the αvβ3 integrin.

A series of RGD-containing cyclic octapeptides (LXW analogs) were previously synthesized, tested in vitro, and screened as integrin antagonists with a different binding affinity (Xiao et al., 2010; Wang et al., 2015), but the structure-activity relationship remains to be elucidated. In the current study, the structures of three …

Polyglutamine Repeat Proteins Disrupt Actin Structure In Drosophila Photoreceptors., Annie Vu, Tyler Humphries, Sean Vogel, Adam Haberman

Biology: Faculty Scholarship

Expansions of polygutamine-encoding stretches in several genes cause neurodegenerative disorders including Huntington's Disease and Spinocerebellar Ataxia type 3. Expression of the human disease alleles in Drosophila melanogaster neurons recapitulates cellular features of these disorders, and has therefore been used to model the cell biology of these diseases. Here, we show that polyglutamine disease alleles expressed in Drosophila photoreceptors disrupt actin structure at rhabdomeres, as other groups have shown they do in Drosophila and mammalian dendrites. We show this actin regulatory pathway works through the small G protein Rac and the actin nucleating protein Form3. We also find that Form3 has …

Epidermal Growth Factor-Like Ligands Regulate Dimer Selection., Jamie S. Rush

Electronic Theses and Dissertations

There are thirteen known endogenous EGF-like ligands. We previously reported that Betacellulin (BTC) increases ligand-mediated corneal wound healing more than Epidermal Growth Factor (EGF) [Peterson et al. (2014) IOVS 55(5):2870-80], although the molecular reason for this is unknown. Despite being better at promoting wound healing via enhanced cell migration, BTC has reduced receptor affinity and weaker induction of EGFR phosphorylation. These data indicate that BTC’s response is not due to enhanced affinity or EGFR-kinase activity. Receptor phosphorylation and proximity ligation assays indicate that BTC treatment significantly increases ErbB3 phosphorylation and EGFR:ErbB3 heterodimers. BTC traffics EGFR at a faster rate than …

Impedance Sensing Of Cancer Cells Directly On Sensory Bioscaffolds Of Bioceramics Nanofibers, Hanan Alismail

Graduate Theses and Dissertations

Cancer cell research has been growing for decades. In the field of cancer pathology, there is an increasing and long-unmet need to develop a new technology for low-cost, rapid, sensitive, selective, label-free (i.e. direct), simple and reliable screening, diagnosis, and monitoring of live cancer and normal cells in same shape and size from the same anatomic region. For the first time on using an impedance signal, the breast cancer and normal cells have been thus screened, diagnosed and monitored on a smart bioscaffold of entangled nanowires of bioceramics titanate grown directly on the surface of implantable Ti-metal and characterized by …

Prioritizing Chemical Constituents In Tobacco Products And Smoke To Predict Developmental Osteotoxicity In Human Embryonic Stem Cells, Joseph Madrid

Electronic Theses, Projects, and Dissertations

Though it is well known that tobacco related products can cause prenatal maldevelopment, very little is known on how tobacco products affect bone tissue as it develops in the embryo. Identifying which chemicals can induce the greatest harm to the prenatal skeletal system is an improbable task as there are over 7,000 chemicals in tobacco smoke alone. We hypothesized that the Toxicological Priority Index (ToxPI) program can be used to rank osteogenic cytotoxicity potential to aid in the assessment of what chemicals out of the thousands can cause osteogenic differentiation inhibition. ToxPI aggregates information from various assays and incorporates them …

Microenvironmental Forces Regulate Notch Signaling Through Integrins, Michael Allen Detweiler

Boise State University Theses and Dissertations

The extracellular microenvironment contributes significantly to a cell’s function and behavior. For instance, cell-cell interactions, cell-substrate interactions, and physical forces are all factors of the extracellular environment that can alter cellular behavior. Cells can receive these signals and forces through various membrane channels and receptors that transmit the signals from the extracellular to the intracellular space. Canonical Notch signaling is induced by ligand interactions with neighboring cells, but recent evidence has revealed that Notch signaling can occur through a variety of extracellular stimuli including hyperglycemia, hypoxia, multiple growth factors, fluid shear stress, and extracellular matrix (ECM) composition. Although Notch activation …

Data On Spectrum-Based Fluorescence Resonance Energy Transfer Measurement Of E. Coli Multidrug Transporter Acrb, Yuguang Cai, Thomas E. Wilkop, Yinan Wei

Chemistry Faculty Publications

This paper presented the dataset of correction parameters used in the determination of the energy transfer efficiencies from the spectrum-based fluorescence resonance energy transfer (FRET) measurement in a trimeric membrane protein AcrB. The cyan fluorescent protein (CFP) and yellow fluorescent protein (YPet) were used as the donor and acceptor, respectively. Two AcrB fusion proteins were constructed, AcrB-CFP and AcrB-YPet. The proteins were co-expressed in Escherichia coli cells, and energy transfer efficiency were determined in live cells. To obtain reliable energy transfer data, a complete set of correction parameters need to be first determined to accommodate for factors such as background …

The Roles Of Primary Cilia In Cardiovascular Diseases, Rajasekharreddy Pala, Maha Jamal, Qamar Alshammari, Surya M. Nauli

Pharmacy Faculty Articles and Research

Primary cilia are microtubule-based organelles found in most mammalian cell types. Cilia act as sensory organelles that transmit extracellular clues into intracellular signals for molecular and cellular responses. Biochemical and molecular defects in primary cilia are associated with a wide range of diseases, termed ciliopathies, with phenotypes ranging from polycystic kidney disease, liver disorders, mental retardation, and obesity to cardiovascular diseases. Primary cilia in vascular endothelia protrude into the lumen of blood vessels and function as molecular switches for calcium (Ca2+) and nitric oxide (NO) signaling. As mechanosensory organelles, endothelial cilia are involved in blood flow sensing. Dysfunction in endothelial …

Prenylation In The Moss Physcomitrella Patens, Noela Botaka, Susana Perez-Martinez, Liang Bao, Parul Singh, Mark Running

Posters-at-the-Capitol

Protein prenylation is a post-translational modification that involves the addition of lipid groups to the 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. Recently, we have found Protein Prenyltransferase Alpha Subunit-like (PPAL), which shares structural similarities to known prenylation enzymes. However, the biochemical function of PPAL is still unknown. PPAL is present in a single copy in other plants examined to date but is present in two copies in moss. Knockouts in our lab of either PpPAL1 or PpPAL2 …

Fatty Acid Amides And Their Biosynthetic Enzymes Found In Insect Model Systems, Ryan L. Anderson

USF Tampa Graduate Theses and Dissertations

A fatty acid amide is precisely as the name suggests: A fatty acid (CHn-COOH), in which the hydroxyl group of the carboxylic acid is displaced by an amine functional group from a biogenic amine (R-NH2), ultimately forming an amide bond. Furthermore, these fatty acid amides can be composed of a variety of different acyl chain lengths donated by the fatty acid and a myriad of different biogenic amines. Thus, these molecules can be subdivided in a number of different ways including the separation of short chain (acetyl to heptanoyl) and long chain (palmitoyl to arachidonoyl) and also based off the …

Actinomycin D And Telmisartan Combination Therapy Targets Lung Cancer Stem Cells, Ryan Green

USF Tampa Graduate Theses and Dissertations

The failure of lung cancer treatments has been attributed partly to the development of drug resistance, however the underlying cellular and molecular mechanisms are poorly understood. It has been suggested that a very small group of specific cells within the heterogeneous tumors, cancer initiating stem cells (CSC), develop resistance to treatment, survive and later initiate the growth of new tumors. Due to their pivotal role in maintenance and relapse of tumors following the acquisition of drug resistance, we reasoned that novel drugs targeting cancer cells and CSC might provide the most effective treatments, if not a cure. To this end, …

Hnrnpa2 Mediated Acetylation Reduces Telomere Length In Response To Mitochondrial Dysfunction, Manti Guha, Satish Srinivasan, F. Bradley Johnson, Gordon Ruthel, Kip Guja, Miguel Garcia-Diaz, Brett A. Kaufman, M. Rebecca Glineburg, Jikang Fang, Hiroshi Nakagawa, Jeelan Basha, Tapas Kundu, Narayan G. Avadhani

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Telomeres protect against chromosomal damage. Accelerated telomere loss has been associated with premature aging syndromes such as Werner’s syndrome and Dyskeratosis Congenita, while, progressive telomere loss activates a DNA damage response leading to chromosomal instability, typically observed in cancer cells and senescent cells. Therefore, identifying mechanisms of telomere length maintenance is critical for understanding human pathologies. In this paper we demonstrate that mitochondrial dysfunction plays a causal role in telomere shortening. Furthermore, hnRNPA2, a mitochondrial stress responsive lysine acetyltransferase (KAT) acetylates telomere histone H4at lysine 8 of (H4K8) and this acetylation is associated with telomere attrition. Cells containing dysfunctional mitochondria …

Investigating The Roles Of Fucosylation And Calcium Signaling In Melanoma Invasion, Tyler S. Keeley

USF Tampa Graduate Theses and Dissertations

Melanoma is the deadliest form of skin cancer. Prognosis for early stage melanoma patients is excellent, and surgery is often curative for these patients. However, once patients have presented with invasive disease, the average 5-year survival rate drops significantly from over 90% to between 10 and 15%. Several therapies have been developed to target a commonly mutated oncogene BRAF, or its downstream effectors. Unfortunately, while these treatments show robust initial response, most patients relapse within a year. Moreover, therapy-resistant tumors are often more invasive and metastatic. Therefore, it is important to investigate the molecular mechanisms underlying melanoma invasion and metastasis, …

Investigation Of Anemarrhena Asphodeloides And Its Constituent Timosaponin-Aiii As Novel, Naturally Derived Adjunctive Therapeutics For The Treatment Of Advanced Pancreatic Cancer, Catherine B. Marelia

USF Tampa Graduate Theses and Dissertations

Pancreatic adenocarcinoma (PDAC) remains one of the most lethal cancer types, with 92% of patients succumbing to the disease within five years. One of the hallmarks of this intractable disease is its nearly universal resistance to chemotherapeutic intervention. The deoxycytidine analog gemcitabine persists as the primary chemotherapy for advanced PDAC patients despite little improvement to its toxicity and tenuous efficacy over the past two decades. Plant-based drug discovery has a longstanding history and has led to some of the most significant drugs of the modern era, including some chemotherapeutic agents like paclitaxel and camptothecin. Our study analyzed the potential inhibitory …