Cell and Developmental Biology Commons^™

Cytoplasmic Polyadenylation Element Binding Protein 2 Alternative Splicing Regulates Hif1Α During Chronic Hypoxia, Emily M. Mayo

USF Tampa Graduate Theses and Dissertations

Chronic pulmonary hypoxia commonly results in the sustained expression of HIF1 (hypoxia inducible factor 1), a heterodimeric transcription factor, that, if unrestrained, can result in dramatic vasculature remodeling, pulmonary arterial hypertension, and right-sided heart failure. Together, these pulmonary disorders cost approximately $100 billion annually to treat due to the limited therapeutic targets designed to inhibit HIF1 expression. In this study, we introduce a translational regulator of HIF1 expression, known as Cytosolic polyadenylation element binding proteins 2 (CPEB2). Our lab has previously demonstrated in cancer cells that alternatively spliced isoforms of CPEB2 regulate the translation of the HIF1 oxygen-dependent subunit, HIF1α, …

The Effect Of Fluid Flow Shear Stress And Substrate Stiffness On Yes-Associated Protein (Yap) Activity And Osteogenesis In Murine Osteosarcoma Cells, Thomas R. Coughlin, Ali Sana, Kevin Voss, Abhilash Gadi, Upal Basu-Roy, Caroline M. Curtin, Alka Mansukhani, Oran D. Kennedy

Publications and Research

Osteosarcoma (OS) is an aggressive bone cancer originating in the mesenchymal lineage. Prognosis for metastatic disease is poor, with a mortality rate of approximately 40%; OS is an aggressive disease for which new treatments are needed. All bone cells are sensitive to their mechanical/ physical surroundings and changes in these surroundings can affect their behavior. However, it is not well understood how OS cells specifically respond to fluid movement, or substrate stiffness—two stimuli of relevance in the tumor microenvironment. We used cells from spontaneous OS tumors in a mouse engineered to have a bone-specific knockout of pRb-1 and p53 in …

Racial And Ethnic Minority Groups Are Under-Represented And Under-Reported In Guideline-Informing Heart Failure Clinical Trials, Gerardo Gamino

Undergraduate Honors Theses

Heart failure (HF) is a common cause of morbidity and mortality in the United States that may disproportionately affect certain racial/ethnic groups. Compared with White individuals, HF may affect Black individuals at a younger age with less favorable prognosis, and this excess risk may be partially explained by differences in HF risk factor burden. It is crucial for guideline informing HF clinical trials to adequately reflect the racial/ethnic diversity in the population. We assessed the extent of reporting and representation of race/ethnicity in HF clinical trials referenced in the 2013 ACC/AHA Guideline for the Management of Heart Failure and the …

Attenuated Strain Of Cvb3 With A Mutation In The Car‑Interacting Region Protects Against Both Myocarditis And Pancreatitis, Ninaad Lasrado, Arunakumar Gangaplara, Chandirasegaran Massilamany, Rajkumar Arumugam, Allison Shelbourn, Mahima T. Rasquinha, Rakesh H. Basavalingappa, Gustavo Delhon, Shi-Hua Xiang, Asit K. Pattnaik, David Steffen, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Coxsackievirus B3 (CVB3), is commonly implicated in myocarditis, which can lead to dilated cardiomyopathy, in addition to causing acute pancreatitis and meningitis. Yet, no vaccines are currently available to prevent this infection. Here, we describe the derivation of a live attenuated vaccine virus, termed mutant (Mt) 10, encoding a single amino acid substitution H790A within the viral protein 1, that prevents CVB3 infection in mice and protects from both myocarditis and pancreatitis in challenge studies. We noted that animals vaccinated with Mt 10 developed virus neutralizing antibodies, predominantly containing IgG2a and IgG2b, and to a lesser extent IgG3 and IgG1. …

Circrev1 Expression In Triple-Negative Breast Cancer, Meagan P. Horton

USF Tampa Graduate Theses and Dissertations

Triple-negative breast cancer (TNBC) comprises only 24% of breast cancer cases, yet is the second leading cause of cancer mortality in women due to its aggressive nature (1). This increase in mortality is due to the lack of receptors for three targetable growth factors (HER2, progesterone, and estrogen receptors). Our previous studies have indicated that these cancers are highly dysregulated in respect to alternative splicing. Hence, we undertook a study aimed at identifying circular RNAs (circRNAs) generated from back-splicing events which were dysregulated in TNBC. We have identified a novel circRNA transcript, circular REV1 (circREV1), which is upregulated in our …

Evaluation Of Somatic Mutations In Solid Metastatic Pan-Cancer Patients, Moom Roosan, Isa Mambetsariev, Rebecca Pharaon, Jeremy Fricke, Angel R. Baroz, Joseph Chao, Chen Chen, Mohd W. Nasser, Ramakanth Chirravuri-Venkata, Maneesh Jain, Lynette Smith, Susan E. Yost, Karen L. Reckamp, Raju Pillai, Leonidas Arvanitis, Michelle Afkhami, Edward W. Wang, Vincent Chung, Mihaela Cristea, Marwan Fakih, Marianna Koczywas, Erminia Massarelli, Joanne Mortimer, Yuan Yuan, Surinder K. Batra, Sumanta Pal, Ravi Salgia

Pharmacy Faculty Articles and Research

Metastasis continues to be the primary cause of all cancer-related deaths despite the recent advancements in cancer treatments. To evaluate the role of mutations in overall survival (OS) and treatment outcomes, we analyzed 957 metastatic patients with seven major cancer types who had available molecular testing results with a FoundationOne CDx^® panel. The most prevalent genes with somatic mutations were TP53, KRAS, APC, and LRP1B. In this analysis, these genes had mutation frequencies higher than in publicly available datasets. We identified that the somatic mutations were seven mutually exclusive gene pairs and an additional fifty-two co-occurring gene pairs. Mutations …

Temperature Regulation Of Plant Hormone Signaling During Stress And Development, Christian Castroverde, Damaris Dina

Biology Faculty Publications

Global climate change has broad-ranging impacts on the natural environment and human civilization. Increasing average temperatures along with more frequent heat waves collectively have negative effects on cultivated crops in agricultural sectors and wild species in natural ecosystems. These aberrantly hot temperatures, together with cold stress, represent major abiotic stresses to plants. Molecular and physiological responses to high and low temperatures are intricately linked to the regulation of important plant hormones. In this review, we shall highlight our current understanding of how changing temperatures regulate plant hormone pathways during immunity, stress responses and development. This article will present an overview …

Effect Of Her2 Expression On Nupl2 Protein In Cervical Cancer Cells, Mary E. Eichholz, Margaret J. Ballou, Tristan J. Haight, Jennifer L. Minton, Ryan N. Oates, Jacob J. Adler

Kentucky Journal of Undergraduate Scholarship

Recurring cervical cancer patients frequently present overexpressed Human Epidermal Growth Factor Receptor 2 (HER2) protein, which promotes the growth of the cancer. Some HER2-expressing cells and cervical cancer patients have enhanced gene expression of Nucleoporin-like 2 (NUPL2). As part of the nuclear pore complex, the NUPL2 protein serves to selectively export substances from the nucleus to the cytoplasm. In this experiment, HER2 was expressed in cervical cancer cells to examine its effect on NUPL2 protein expression and localization. Interestingly, there was no difference in NUPL2 protein levels between HER2-expressing and non-expressing cells. Importantly, consistent instances of NUPL2 protein …

Retinal Regeneration In A Genetic Mouse Model Of Glaucoma, Joshua Paris

Masters Theses

Glaucoma is a degenerative retinal disease characterized by progressive loss of retinal ganglion cells (RGCs). Previous studies have shown that application of a specific α7 nicotinic acetylcholine receptor agonist, PNU-282987 (PNU), onto the murine retina induces neurogenesis of numerous retinal cell types, including RGCs. The aim of this study is to characterize the short-term and long-term effects of PNU in a glaucoma model. The effects of PNU were analyzed in a DBA/2J mouse model that auto-induces a glaucoma-like condition in adulthood. These mice manifest an elevated intraocular pressure (IOP) starting at 6 months, followed by loss of RGCs. To assess …

Insights Into The Molecular Evolution Of Fertilization Mechanism In Land Plants, Vijyesh Sharma, Anthony J. Clark, Tomokazu Kawashima

Plant and Soil Sciences Faculty Publications

Land plants have evolved successive changes during their conquest of the land and innovations in sexual reproduction have played a major role in their terrestrialization. Recent years have seen many revealing dissections of the molecular mechanisms of sexual reproduction and much new genomics data from the land plant lineage, including early diverging land plants, as well as algae. This new knowledge is being integrated to further understand how sexual reproduction in land plants evolved, identifying highly conserved factors and pathways, but also molecular changes that underpinned the emergence of new modes of sexual reproduction. Here, we review recent advances in …

College Of Natural Sciences Newsletter, June 2021, College Of Natural Sciences

College of Natural Sciences Newsletters and Reports

Volume 2, Issue 6.

Page 1 Dean's Message
Page 2-6 Remembering the Life of Dr. Pengra and Celebrating His legacy for Entire Generations to Come.

Evolution And Development Of The Seed Coat In Gymnosperms, Cecilia Zumajo

Dissertations, Theses, and Capstone Projects

Gymnosperms and angiosperms are the most abundant plant lineages on earth and constitute a turning point in the evolution of plants because they are at the origin of the seed, a key morphological and developmental novelty in the evolution of land plant. Although the morphological variation of the seed, across seed plants, may on its own, explain the complexity of this structure, the origin, and evolution are even more, the understanding of these topics is still under discussion. Evidence shows that previous studies have often lacked the component of gene expression, particularly in species that are not model species. The …

Molecular Mechanisms Underlying Cell Fate Choice Within Specific Retinal Lineages, Estie Schick

Dissertations, Theses, and Capstone Projects

During development, retinal progenitor cells (RPCs) divide to form all of the cell types that make up the retina. Multipotent RPCs are competent to generate all retinal cell types, while restricted RPCs form specific lineages of cells. In particular, one genetically-defined RPC type preferentially gives rise to cone photoreceptors and horizontal cells. Many of the mechanisms that are responsible for directing cell fate choice within this lineage are unknown. This thesis largely focuses on examining the development of specific cell types and subtypes from restricted RPCs and on investigating the gene regulatory events that underlie cone photoreceptor and horizontal cell …

Immunological And Hematological Outcomes Following Protracted Low Dose/Low Dose Rate Ionizing Radiation And Simulated Microgravity, Amber M. Paul, Eliah G. Overbey, Willian A. Da Silveira, Nathaniel Szewczyk, Nina C. Nishiyama, Michael J. Pecaut, Sulekha Anand, Jonathan M. Galazka, Xiao Wen Mao

Publications

Using a ground-based model to simulate spaceflight [21-days of single-housed, hindlimb unloading (HLU) combined with continuous low-dose gamma irradiation (LDR, total dose of 0.04 Gy)], an in-depth survey of the immune and hematological systems of mice at 7-days post-exposure was performed. Collected blood was profiled with a hematology analyzer and spleens were analyzed by whole transcriptome shotgun sequencing (RNA-sequencing). The results revealed negligible differences in immune differentials. However, hematological system analyses of whole blood indicated large disparities in red blood cell differentials and morphology, suggestive of anemia. Murine Reactome networks indicated majority of spleen cells displayed differentially expressed genes (DEG) …

Reconstituting The Cyanobacterial Circadian Clock In Vitro, Pyong Hwa Kim

Dissertations

Cyanobacteria are photosynthetic organisms that are known to be responsible for oxygenating Earth’s early atmosphere. Having evolved to ensure optimal survival in the periodic light/dark cycle on this planet, their genetic codes are packed with various tools, including a sophisticated biological timekeeping system. Among the cyanobacteria is Synechococcus elongatus PCC 7942, the simplest clock-harboring organism with a powerful genetic tool that enabled the identification of its intricate timekeeping mechanism. The three central oscillator proteins—KaiA, KaiB, and KaiC—drive the 24 h cyclic gene expression rhythm of cyanobacteria, and the "ticking" of the oscillator can be reconstituted inside a test tube just …

Heparan Sulfate Proteoglycan Glypican‑1 And Pecam‑1 Cooperate In Shear‑Induced Endothelial Nitric Oxide Production, Anne Marie W. Bartosch, Rick Mathews, Marwa M. Mahmoud, Limary M. Cancel, Zahin S. Haq, John M. Tarbell

Publications and Research

This study aimed to clarify the role of glypican-1 and PECAM-1 in shear-induced nitric oxide production in endothelial cells. Atomic force microscopy pulling was used to apply force to glypican-1 and PECAM-1 on the surface of human umbilical vein endothelial cells and nitric oxide was measured using a fluorescent reporter dye. Glypican-1 pulling for 30 min stimulated nitric oxide production while PECAM-1 pulling did not. However, PECAM-1 downstream activation was necessary for the glypican-1 force-induced response. Glypican-1 knockout mice exhibited impaired flow-induced phosphorylation of eNOS without changes to PECAM-1 expression. A cooperation mechanism for the mechanotransduction of fluid shear stress …

Co-Targeting Plk1 And Dnmt3a In Advanced Prostate Cancer, Zhuangzhuang Zhang, Lijun Cheng, Qiongsi Zhang, Yifan Kong, Daheng He, Kunyu Li, Matthew Rea, Jianlin Wang, Ruixin Wang, Jinghui Liu, Zhiguo Li, Chongli Yuan, Enze Liu, Yvonne N. Fondufe-Mittendorf, Lang Li, Tao Han, Chi Wang, Xiaoqi Liu

Toxicology and Cancer Biology Faculty Publications

Because there is no effective treatment for late-stage prostate cancer (PCa) at this moment, identifying novel targets for therapy of advanced PCa is urgently needed. A new network-based systems biology approach, XDeath, is developed to detect crosstalk of signaling pathways associated with PCa progression. This unique integrated network merges gene causal regulation networks and protein-protein interactions to identify novel co-targets for PCa treatment. The results show that polo-like kinase 1 (Plk1) and DNA methyltransferase 3A (DNMT3a)-related signaling pathways are robustly enhanced during PCa progression and together they regulate autophagy as a common death mode. Mechanistically, it is shown that Plk1 …

Larval Chondrocranial And Internal Oral Morphology Of The Neotropical Treefrog Boana Crepitans (Wied-Neuwied, 1824; Amphibia, Anura, Hylidae), Marianna Isabella Rosa Rodrigues De Oliveira, Luiz Norberto Weber, Johnny Sousa Ferreira, Anna Evelin Coimbra Liborio, André Masahide Guimaraes Takazone, Rafael O. De Sá

Biology Faculty Publications

We describe the internal oral morphology and chondrocranial anatomy for Boana crepitans tadpoles, and compare them with available descriptions for other species in the subfamily Cophomantinae. Among species of the Boana faber group, the chondrocranial anatomy has been reported only for one species internal oral morphology and cranial anatomy are similar to other described species of Boana and Cophomantinae. B. crepitans lacks unique features in the oral cavity and chondrocranium that would distinguish it from other congeneric species. We identify six characters from the internal oral anatomy of tadpoles unique for Cophomantinae. In addition, Boana has infralabial papillae projections, buccal …

Component Causes Of Infectious Bovine Keratoconjunctivitis—Non-Moraxella Organisms In The Epidemiology Of Infectious Bovine Keratoconjunctivitis, John Dustin Loy, Kristin A. Clothier, Gabriele Maier

School of Veterinary and Biomedical Sciences: Faculty Publications

• Non-Moraxella organisms are associated with infectious bovine keratoconjunctivitis (IBK).

• Mycoplasma bovoculi can cause conjunctivitis and has a potential role in IBK pathogenesis.

• Other Non-Mycoplasma agents can cause disease that resembles IBK but is clinically different.

• Genomics and molecular technology are advancing research in this area.

• Classification and determination of pathogenesis potential of these organisms may be better understood through metagenomics and whole genome sequencing.

Analysis Of Symptom Expressions And Transmission Rates Caused By The Plant Pathogen Phytophthora Ramorum On Native Chaparral Plants From The Genus Arctostaphylos, Bharati Gaonker

Natural Sciences and Mathematics | Biological Sciences Master's Theses

Phytophthora ramorum is the causal agent of Sudden Oak death (SOD), ramorum dieback and ramorum leaf blight which affect both forest environments and nurseries. This oomycete pathogen has had a huge economic impact on the nursery and lumber industry. Forests in California have experienced substantial mortality of oaks affecting the forest dynamics and diversity. Our research investigates four native species and two ornamental cultivars of plants, which belong to the genus Arctostaphylos (manzanita) and are considered to be new hosts for P. ramorum in the chaparral ecosystem of California. Symptom expression and transmission rates were analyzed on Arctostaphylos glauca, …

Characterizing The Gene Regulatory Network Required To Specify The Excitatory Neurotransmitter Phenotype Of V0v Spinal Interneurons, Amber Kellie Woodard

Theses - ALL

The majority of neurons within the spinal cord are interneurons. Interneurons make important connections with other cells that allow signals to be relayed between the brain and the rest of the body, and aid in functions such as locomotion. One key functional characteristic of interneurons is the neurotransmitter that they use to communicate with other cells. Interneurons that use GABA or glycine neurotransmitters to communicate have an inhibitory phenotype, while interneurons that use glutamate neurotransmitters have an excitatory neurotransmitter phenotype. Without the correct neurotransmitter phenotype, connections within the central nervous system will malfunction. It is therefore important to understand how …

Characterizing The Gene Regulatory Network Required To Specify The Excitatory Neurotransmitter Phenotype Of V0v Spinal Interneurons, Amber Kellie Woodard

Theses - ALL

The majority of neurons within the spinal cord are interneurons. Interneurons make important connections with other cells that allow signals to be relayed between the brain and the rest of the body, and aid in functions such as locomotion. One key functional characteristic of interneurons is the neurotransmitter that they use to communicate with other cells. Interneurons that use GABA or glycine neurotransmitters to communicate have an inhibitory phenotype, while interneurons that use glutamate neurotransmitters have an excitatory neurotransmitter phenotype. Without the correct neurotransmitter phenotype, connections within the central nervous system will malfunction. It is therefore important to understand how …

Creating A Protein Chimera To Study Regulation Of Muscle Diversity, Shannon Scarboro

Symposium of Student Scholars

Creating a protein chimera to study regulation of muscle diversity.

Body muscles are made of many individual super-cells, called muscle fibers, that have distinct properties and determine every individual’s strength and endurance. Initially all muscle fibers have identical characteristics, but become differentiated into specific types in adults. The mechanism of such transition is not well understood, despite its obvious importance for shaping human physicality.

Remarkable conservation of the muscle tissue enables us to use fruit flies to study the mechanisms of muscle fiber diversity. We hypothesized that the transcription factor Mef2 acts as a molecular switch that activates structural genes …

Cancer Salt Nostalgia, Aashish S. Allu, Venkataswarup Tiriveedhi

Biology Faculty Research

High-salt (sodium chloride) diets have been strongly associated with disease states and poor health outcomes. Traditionally, the impact of salt intake is primarily studied in cardiovascular diseases, hypertension and renal diseases; however, recently there has been increasing evidence demonstrating the role of salt in autoimmune diseases. Salt has been shown to modulate the inflammatory activation of immune cells leading to chronic inflammation-related ailments. To date, there is minimal evidence showing a direct correlation of salt with cancer incidence and/or cancer-related adverse clinical outcomes. In this review article, we will discuss the recent understanding of the molecular role of salt, and …

Cnd-1/Neurod Is Required For Rme Head Neuron Cell Fate Specification In The Nematode Caenorhabditis Elegans., Genevieve Doxakis

Symposium of Student Scholars

cnd-1/NeuroD is required for RME head neuron cell fate specification in the nematode Caenorhabditis elegans.

Genevieve Doxakis (1), Illyana Weitzel (2), Amber Baldwin (1), Davron Hanley (1), and Martin L. Hudson (1)

(1) Department of Molecular and Cellular Biology, Kennesaw State University

(2) STEM Magnet Program, Wheeler High School

Transcription factors are proteins that control gene transcription. NeuroD is a deeply conserved transcription factor that regulates neuronal differentiation and pancreatic development. Mutations in this gene correlate with several neurological disorders, creating an imperative for further study. The nematode Caenorhabditis elegans has a NeuroD ortholog, cnd-1, which means we can use …

The Garden Of Extraterrestrial Deee-Lites, Jessica Bremehr

Graduate School of Art Theses

I present a delusion where you, the reader, are a hitchhiker on a journey toward an alternate realm guided by a god-like buffoon. While I take you on a journey through my daydreams and my musings on an alternate existence, a tour guide will lead the way to an otherworldly realm called The Garden of Extraterrestrial Deee-Lites, reflective of a tourist experience to a faraway destination. The tour will culminate in an uncanny space where curious life forms converge with familiar objects to encourage a sense of wonder while promoting ideas of interconnectedness within the world around us.

Igf1-Stimulated Posttraumatic Hippocampal Remodeling Is Not Dependent On Mtor, Erica L. Littlejohn, Anthony J. Desana, Hannah C. Williams, Rudy T. Chapman, Binoy Joseph, Jelena A. Juras, Kathryn E. Saatman

Physiology Faculty Publications

Adult hippocampal neurogenesis is stimulated acutely following traumatic brain injury (TBI). However, many hippocampal neurons born after injury develop abnormally and the number that survive long-term is debated. In experimental TBI, insulin-like growth factor-1 (IGF1) promotes hippocampal neuronal differentiation, improves immature neuron dendritic arbor morphology, increases long-term survival of neurons born after TBI, and improves cognitive function. One potential downstream mediator of the neurogenic effects of IGF1 is mammalian target of rapamycin (mTOR), which regulates proliferation as well as axonal and dendritic growth in the CNS. Excessive mTOR activation is posited to contribute to aberrant plasticity related to posttraumatic epilepsy, …

The Regulation Of Chemokinesis By The Soil Amoeba, Dictyostelium Discoideum, Julia Horan

Honors Scholar Theses

Many types of cells crawl on solid surfaces by amoeboid locomotion. Membrane protrusions, such as pseudopods, are generated by outward directed forces and the cell body retracts to allow the cell to migrate on the surface. The movement can be random, or can be directional in response to diffusible (chemotaxis) or surface associated signals (haptotaxis). It has been known for some time that chemotactic signals also lead to an increase in overall cell speed (chemokinesis), however the mechanism of this speed increase is unknown. This project investigates the cellular signaling pathways involved in the regulation of cell speed by ligands …

A Forward Genetic Screen To Identify Human Genes Of Interest And Their Roles In Ovarian Cancer, Susan A. Ihejirika

Honors College Theses

Drosophila melanogaster, fruit flies, are very important for modeling and studying human diseases. This study identifies human genes of interest and their contributions to epithelial ovarian carcinogenesis and progression as well as the roles orthologs of these genes play in Drosophila melanogaster. This is important because ovarian cancer is the most common cause of death among the gynecological cancers. This identification of genes was carried out using a forward genetic screen employing the widely used GMR-Gal4 driver/UAS-transgene system. The GMR-Gal4 driver is commonly utilized to express transgenes in the developing eye of the fruit fly. Transgenes that are expressed using …

Growth Suppression Of Erbb2-Driven Breast Cancers By P300/Cbp Inhibition, Sergelen Ariunbaatar

Natural Sciences and Mathematics | Biological Sciences Master's Theses

Breast cancer, which affects 1 in 8 women in the US, is divided into four major subtypes based on the overexpression or lack of expression of three different molecular markers: estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2, also referred to as ERBB2). About 20% of all newly diagnosed breast cancer cases are ERBB2-positive, and these breast cancer patients tend to have poorer prognosis with lower overall survival compared to hormone receptor-positive breast cancer (ACS, 2020). Although there are several anti-ERBB2 drugs available there are still many patients at both the early and metastatic stages …