Life Sciences Commons^™

Defining The Molecular Networks Necessary For Thymus Fate And Organogenesis, Kaitlin A. Reeh

Dissertations & Theses (Open Access)

The thymus and parathyroid (PT) glands originate from endodermal progenitors in the bilateral third pharyngeal pouches (3^rd pps). By E11.5 during mouse development, cells committed to the thymus lineage express Foxn1 whereas PT-fated cells express Gcm2. While these transcription factors are required for organ-specific differentiation, the exact molecular mechanisms that specify endodermal progenitors to either the thymus or parathyroid lineage are not well defined. Tbx1 is initially expressed throughout the 3^rd pp endoderm, as it is required for segmentation of the pharyngeal apparatus, but is downregulated in the thymus-fated domain by E10.5. Despite the widely held notion …

Preventing Thymus Involution In K5.Cyclin D1 Transgenic Mice Sustains The Naïve T Cell Compartment With Age, Michelle L. Bolner

Dissertations & Theses (Open Access)

The thymus maintains T cell receptor (TCR) repertoire diversity through perpetual release of self-MHC restricted naive T cells. However, thymus involution during the aging process reduces naïve T cell output, leading to defective immune responsiveness to newly encountered antigens. We have found that early thymus involution precipitates the age-associated shift favoring memory T cell dominancy in young control mice. Furthermore, we have shown that age-related thymus involution is prevented in mice expressing a keratin 5 promoter-driven Cyclin D1 (K5.D1) transgene in thymic epithelial cells (TECs). Thymopoiesis occurs normally in K5.D1 transgenic thymi and sustains T cell output to prevent the …

Molecular Regulation Of Vascular Calcification In Murine Models Of Atherosclerosis, Shanshan Gao

Dissertations & Theses (Open Access)

Background: Calcification occurs often in the atherosclerotic lesions of patients with coronary heart disease and animals with hypercholesterolemia, such as apolipoprotein-E deficient (ApoE-/-) mice. However, the mechanism(s) underlying the development of calcification in atherosclerosis remains unclear. ApoE acts as a lipid transporter, but also has been recognized as a potential regulator of osteogenesis. Little information is available as to whether ApoE has any direct impact on osteogenesis and calcification in vascular smooth muscle cells (VSMC). Several signal transduction pathways play a role in regulation of calcification, including the Wnt/β-catenin system and potentially GTAP, an ubiquitin-conjugating enzyme responsible for protein …

Leptin Regulates The Expression Of Autophagy-Related Genes In Chickens, Peter Olawale Ishola

Graduate Theses and Dissertations

Autophagy or cellular self-digestion, a lysosomal degradation pathway that is conserved from yeast to human, plays a key role in recycling cellular constituents, including damaged organelles. It also plays a pivotal role in the adaptation of cells to a plethora of distinct stressors including starvation. Autophagy has been extensively studied in mammals and yeast, but little is known in avian species. Thus, the major objective of the present study was to determine the effects of leptin on autophagy-related genes in chicken hypothalamus, muscle and liver. Leptin is an adipocytokine that is mostly produced by white adipose cells in mammals (as …

Transcriptomics Of Chicken Primordial Germ Cells, Nhung Thi Nguyen

Graduate Theses and Dissertations

Chicken primordial germ cells (PGCs) are derived from extraembryonic tissue of the embryo and first appear at stage X of development. They enter the bloodstream and migrate to the genital ridge, unite with somatic tissue to form a developing gonad, and then differentiate to sperm or ova (Fujimoto et al., 1976). Understanding molecular features of both male and female PGCs not only clarify the differentiation mechanism of such cells toward different germ lines, but will also help in selecting for highly productive types of commercial chicken. Most previous studies focused on the location of PGCs (Eyal-Giladi et al., 1981; Swift …

Problem Solving Skill And Obesity In Children, Caitlin R. Spano

The Eleanor Mann School of Nursing Undergraduate Honors Theses

Abstract:

Introduction: Childhood obesity is a problem that leads to many serious health effects including early maturation, decreased quality of life and increased risk for cardiovascular disease. In 2012, over one third of children were considered obese (Childhood Obesity Facts 2015). Efforts have been made to reduce this number but they have not been fully successful (Nutrition Standards for School Meals 2015, Prevalence of Childhood obesity in the United States 2011-2012 2015). What other factors are causing kids to choose foods that lead to weight gain.

Literature Review: In research regarding psychological motivations of overeating, there has been a correlation …

Identifying Protein Kinase Tbk1 As A Novel Inhibitor Of Intestinal Tumorigenesis, Amber L. Mathews

Dissertations & Theses (Open Access)

Colorectal cancer (CRC) is the third most common cancer diagnosed in women and men， causing almost 600,000 annual deaths worldwide. There is a clear need to understand how CRC forms and progresses in order to improve the strategies of CRC prevention and therapy. A major factor that drives the development of CRC is genetic mutations that lead to activation of oncogenes and inactivation of tumor suppressor genes in intestinal epithelial cells (IECs). In addition, the initiation and progression of CRC involve environmental and immunological factors. In particular, chronic inflammatory conditions are known as an important risk factor for CRC. Intestinal …

Normal Glycolytic Enzyme Activity Is Critical For Hypoxia Inducible Factor-1a Activity And Provides Novel Targets For Inhibiting Tumor Growth, Geoffrey Grandjean Phd

Dissertations & Theses (Open Access)

Normal Glycolytic Enzyme Activity is Critical for Hypoxia Inducible Factor-1α Activity and Provides Novel Targets for Inhibiting Tumor Growth

By Geoffrey Grandjean

Advisory Professor: Garth Powis, D. Phil

Unique to proliferating cancer cells is the observation that their increased need for energy is provided by a high rate of glycolysis followed by lactic acid fermentation in a process known as the Warburg Effect, a process many times less efficient than oxidative phosphorylation employed by normal cells to satisfy a similar energy demand ^[1]. This high rate of glycolysis occurs regardless of the concentration of oxygen in the cell and …

Characterization Of Embryonic Stem Cell-Differentiated Cells As Mesenchymal Stem Cells, Rachael N. Kuehn

Honors Theses

Embryonic stem cells (ESCs), due to their ability to differentiate into different cell types while still maintaining a high proliferation capacity, have been considered as a potential cell source in regenerative medicine. However, current ESC differentiation methods are low yielding and create heterogeneous cell populations. If transplanted in the human body, differentiated ESCs could be rejected by the immune system, form tumors, or may not function normally within the human body. On the other hand, mesenchymal stem cells (MSCs), a type of adult stem cell typically derived from bone marrow, have proved to be excellent candidates in clinical applications due …

The Effect Of Leucine Supplementation On Mitochondrial Biogenesis And Mitochondrial Protein Synthesis In Rats Fed A High-Fat Diet, David M. Skinner

Health, Human Performance and Recreation Undergraduate Honors Theses

This study aims to illuminate interaction between leucine supplementation and mitochondrial proteins concerned with synthesis and biogenesis. We hypothesized that supplementation with leucine will attenuate the weight gain of the high fat diet in comparison with the normal chow group, by enhancing mitochondrial biogenesis and content. We conducted a laboratory experiment using Western Blotting techniques to determine protein expression. Proteins of interest in this study include PGC-1α, COX-IV, TUFM, TFAM, and mtIF2. The findings from the research show a main effect of an increase in the expression of PGC-1 α in high fat diets. There was no difference in the …

Regulation Of The Retinoblastoma Tumor Suppressor By The Novel Ras Effector Nore1a., Thibaut François Barnoud

Electronic Theses and Dissertations

Ras is the most frequently mutated oncogene in human cancers. It acts as a critical branch point in signal transduction, regulating numerous downstream effectors involved in cell growth and differentiation. While Ras can activate many growth promoting pathways, it can paradoxically regulate growth inhibitory pathways leading to apoptosis and cell cycle arrest. One of the ways Ras can inhibit the growth of cells is via a family of effectors called the RASSF proteins. RASSF5 (NORE1A) is a tumor suppressor that is frequently inactivated in human tumors by epigenetic mechanisms. NORE1A binds directly to Ras and promotes Ras-induced senescence. We have …

The Ras Effector Nore1a Forms A Tumor Suppressor Complex With Brca1., Nicholas C Nelson

Electronic Theses and Dissertations

Ras proteins function as molecular signaling switches that can stimulate multiple mitogenic pathways in response to extracellular signaling. Oncogenic activation of Ras by structural mutation is a highly transforming event in ~1/3 of human cancers. However, aberrant Ras activation can also promote oncogene-induced senescence. This Ras-induced irreversible growth arrest is a physiological process that acts as a barrier to malignancy. The mechanisms by which Ras drives senescence and how this process is bypassed during Ras-driven transformation remains poorly understood.

Although mutations in the RAS gene are extremely rare in human breast cancer, the Ras signaling pathway is constitutively activated in …

Third Ventricle Width As A Metric For Fast And Efficient Detection Of Atrophy In Traumatic Brain Injury, Christopher Scott Finuf

Theses and Dissertations

In an average year more than 1.7 million people will experience a traumatic brain injury (TBI) in the United States. It is known that atrophy occurs across a spectrum for TBI patients, ranging from mild to severe. Current conventional magnetic resonance imaging (MRI) methods are inconsistent in detecting this atrophy on the milder end of the spectrum. Also more contemporary imaging tools, although efficient, are too time consuming for clinical applicability. It is for these reasons that a quick and efficient measurement for detecting this atrophy is needed by clinicians. The measuring of third ventricle width had the potential to …

Compounds Released From Biomass Deconstruction: Understanding Their Effect On Cellulose Enzyme Hydrolysis And Their Biological Activity, Angele Djioleu

Graduate Theses and Dissertations

The effect of compounds produced during biomass pretreatment on cellulolytic enzyme was investigated. Liquid prehydrolyzates were prepared by pretreating switchgrass using 24 combinations of temperature, time, and sulfuric acid concentration based on a full factorial design. Temperature was varied from 140°C to 180°C; time ranged from 10 to 40 min; and the sulfuric acid concentrations were 0.5% or 1% (v/v). Identified products in the prehydrolyzates included xylose, glucose, hydroxymethylfurfural (HMF), furfural, acetic acid, formic acid, and phenolic compounds at concentration ranging from 0 to 21.4 g/L. Pretreatment conditions significantly affected the concentrations of compounds detected in prehydrolyzates. When assayed in …

Dancing Through Life: Molecular Dynamics Simulations And Network-Centric Modeling Of Allosteric Mechanisms In Hsp70 And Hsp110 Chaperone Proteins, Gabrielle Stetz, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Hsp70 and Hsp110 chaperones play an important role in regulating cellular processes that involve protein folding and stabilization, which are essential for the integrity of signaling networks. Although many aspects of allosteric regulatory mechanisms in Hsp70 and Hsp110 chaperones have been extensively studied and significantly advanced in recent experimental studies, the atomistic picture of signal propagation and energetics of dynamics-based communication still remain unresolved. In this work, we have combined molecular dynamics simulations and protein stability analysis of the chaperone structures with the network modeling of residue interaction networks to characterize molecular determinants of allosteric mechanisms. We have shown that …

Endothelin-B Receptor Activation In Astrocytes Regulates The Rate Of Oligodendrocyte Regeneration During Remyelination., Timothy R. Hammond, Brian Mcellin, Paul D Morton, Matthew Raymond, Jeff Dupree, Vittorio Gallo

Medicine Faculty Publications

Reactive astrogliosis is an essential and ubiquitous response to CNS injury, but in some cases, aberrant activation of astrocytes and their release of inhibitory signaling molecules can impair endogenous neural repair processes. Our lab previously identified a secreted intercellular signaling molecule, called endothelin-1 (ET-1), which is expressed at high levels by reactive astrocytes in multiple sclerosis (MS) lesions and limits repair by delaying oligodendrocyte progenitor cell (OPC) maturation. However, as ET receptors are widely expressed on neural cells, the cell- and receptor-specific mechanisms of OPC inhibition by ET-1 action remain undefined. Using pharmacological approaches and cell-specific endothelin receptor (EDNR) ablation, …

Hepatic Nutrient And Hormonal Regulation Of The Pancreatic-Derived Factor (Pander) Promoter, Whitney Ratliff

USF Tampa Graduate Theses and Dissertations

PANcreatic-DERived factor (PANDER, FAM3B) has been shown to regulate glycemic levels via interactions with both pancreatic islets and the liver. Although PANDER is predominantly expressed from the endocrine pancreas, recent work has provided sufficient evidence that the liver may also be an additional tissue source of PANDER production. At physiological levels, PANDER is capable of disrupting insulin signaling and promoting increased hepatic glucose production. As shown in some animal models, strong expression of PANDER, induced by viral delivery within the liver, induces hepatic steatosis. However, no studies to date have explicitly characterized the transcriptional regulation of PANDER from the liver. …

The Transient Receptor Potential Melastatin 2 (Trpm2) Channel Contributes To Beta-Amyloid Oligomer-Related Neurotoxicity And Memory Impairment, Valeriy G. Ostapchenko, Megan Chen, Monica S. Guzman, Yu-Feng Xie, Natalie Lavine, Jue Fan, Flavio H. Beraldo, Amanda C. Martyn, Jillian C. Belrose, Yasuo Mori, John F. Macdonald, Vania F. Prado, Marco A. M. Prado, Michael F. Jackson

Anatomy and Cell Biology Publications

In Alzheimer's disease, accumulation of soluble oligomers of beta-amyloid peptide is known to be highly toxic, causing disturbances in synaptic activity and neuronal death. Multiple studies relate these effects to increased oxidative stress and aberrant activity of calcium-permeable cation channels leading to calcium imbalance. The transient receptor potential melastatin 2 (TRPM2) channel, a Ca2+-permeable nonselective cation channel activated by oxidative stress, has been implicated in neurodegenerative diseases, and more recently in amyloid-induced toxicity. Here we show that the function of TRPM2 is augmented by treatment of cultured neurons with beta-amyloid oligomers. Aged APP/PS1 Alzheimer's mouse model showed increased levels of …

Age-Associated Methylation Suppresses Spry1, Leading To A Failure Of Re-Quiescence And Loss Of The Reserve Stem Cell Pool In Elderly Muscle., Anne Bigot, William J Duddy, Zamalou G Ouandaogo, Elisa Negroni, Virginie Mariot, Svetlana Ghimbovschi, Brennan Harmon, Aurore Wielgosik, Camille Loiseau, Joseph Devaney, Julie Dumonceaux, Gillian Butler-Browne, Vincent Mouly, Stéphanie Duguez

Genomics and Precision Medicine Faculty Publications

The molecular mechanisms by which aging affects stem cell number and function are poorly understood. Murine data have implicated cellular senescence in the loss of muscle stem cells with aging. Here, using human cells and by carrying out experiments within a strictly pre-senescent division count, we demonstrate an impaired capacity for stem cell self-renewal in elderly muscle. We link aging to an increased methylation of the SPRY1 gene, a known regulator of muscle stem cell quiescence. Replenishment of the reserve cell pool was modulated experimentally by demethylation or siRNA knockdown of SPRY1. We propose that suppression of SPRY1 by age-associated …

The Role Of Endothelin 3 In Melanoma Progression And Metastasis, Nikeisha L. Chin

FIU Electronic Theses and Dissertations

Endothelin receptor b (Ednrb) and its ligand Endothelin 3 (Edn3) have been implicated in melanoma. Several studies have shown an upregulation of EDNRB and EDN3 at both the protein and mRNA levels, as melanoma becomes more aggressive. This study investigated the putative role played by Edn3 over-expression in melanoma progression and angiogenesis in vivo. We crossed Tg(Grm1)Epv transgenic mice that aberrantly express metabotropic glutamate receptor1 under the Dopachrome tautomerase promoter, leading to spontaneous melanocytic lesions in the ears and tails that do not metastasize, with transgenics that overexpress Edn3 under the Keratin 5 promoter ( …

The Chemopreventive Effect Of Polymethoxyflavones: Targeting The Colorectal Cancer Stem Cells, Fei Xu

Doctoral Dissertations

Among all the cancers, the death rate of colorectal cancer is one of the highest. Evidence from both murine xenograft model and human trials have shown cancer stem cells (CSCs) are responsible for the initiation, metastasis and recurrence of multiple cancers therefore targeting colorectal CSCs would be a promising chemo-preventive/ therapeutic strategy. Polymethoxyflavones including nobiletin (NBT) and 5-demethylatednobiletin (5DN) are exclusively found in citrus peels and have been shown to have anti-cancer effects. Our previous studies in the biotransformation and tissue distribution of NBT and 5DN have shown that in order to fuller evaluate the biological impact of those two …

How To Build A Spinal Cord: Exploring Radial Glial Proliferation And Their Contribution To Embryonic Neurogenesis, Kimberly A. Johnson

Doctoral Dissertations

During embryonic neural development, the concerted actions of neural stem cells (NSCs) populate and pattern the tissues that will give rise to the brain and spinal cord. This heterogeneous NSC population initially consists of neuroepithelial cells, which will generate the first neurons present in the central nervous system (CNS) prior to transitioning into radial glial cells. Classically, radial glial cells are known to play a wide range of roles during CNS development, from maintaining neuronal homeostasis, as a scaffold for neuronal migration, and as a permissive growth substrate for directed axon pathfinding. Recently, radial glial cells have been proposed to …

Characterization Of The Role Of Intrinsic And Extrinsic Factors During Murine Endoderm Development, Siyeon Rhee

Doctoral Dissertations

Yin Yang1 (YY1) is a ubiquitously expressed factor that plays multiple roles in early mouse development. We have found that an essential role of YY1 in the visceral endoderm (VE) of the yolk sac is the maintenance of VEGF. Furthermore, we have demonstrated that paracrine signals downstream of VEGF support the VE, assessed by maintenance of HNF4α. Because the VE is essential for yolk sac development, and thus for embryonic survival, we used an inducible-knockout strategy to demonstrate that YY1 is essential in the definitive endoderm (DE) for invasion of hepatoblasts into the surrounding mesenchyme. By E14.5 YY1-/- livers are …

Uncovering New Roles For The Cell Surface Protease Adam13 In Neural Crest Migration, Genevieve Abbruzzese

Doctoral Dissertations

ADAMs are a family of transmembrane metalloproteases that control cell behavior by cleaving both cell adhesion and signaling molecules. They play a variety of roles in diverse tissue types during development and can affect cell processes such as migration, differentiation, growth and survival. In the embryo, several ADAMs have proven to be integral components of the cranial of neural crest (CNC), which is a multipotent population of cells that gives rise to multiple structures of the face and head. These cells are highly motile and undergo a large-scale migration throughout the embryo that is essential for proper craniofacial development. The …

The Investigation Of Rhodiola Crenulata Root Extract Effects On Obesity Associated Inflammation And The Antineoplastic Mechanism In Breast Cancer Cells, Lotfi M. Bassa

Doctoral Dissertations

Obesity and breast cancer are two disease models that directly affect the United States population, as more than 35% of the adult population is obese [8], and more than 200,000 new cases of breast cancer are diagnosed in the United States per year [34]. Several diseases are associated with obesity including, cardiovascular disease, insulin resistance, increased inflammation and increased cancer risk [9,10]. Therefore it essential to understand the risks associated with obesity as well as to investigate possible preventive and/or therapeutic treatment strategies. Rhodiola crenulata is a Tibetan plant that has been used in Eastern traditional medicine to relieve depression, …

Behavioral And Neural Mechanisms Of Impulsive Choice, Jesse Mcclure

Doctoral Dissertations

Impulsive choice is defined as the preference for a small immediate reward over a larger delayed reward. Individual variablity in impulsive choice correlates with many socially relevant behaviors. Although forms of impulsive choice have been studied in both behavioral ecology and psychology, the exchange of knowledge between these fields is just beginning. Drawing from both of these fields will improve our research methods allowing for a more detailed understanding of this complex behavior. Existing tasks to measure impulsive choice conflate the delay and quantity of the reward. To address this, I have drawn from foraging research to establish a method …

Stochastic Models For Plant Microtubule Self-Organization And Structure, Ezgi Can Eren, Ram Dixit, Natarajan Gautam

Biology Faculty Publications & Presentations

One of the key enablers of shape and growth in plant cells is the cortical microtubule (CMT) system, which is a polymer array that forms an appropriately-structured scaffolding in each cell. Plant biologists have shown that stochastic dynamics and simple rules of interactions between CMTs can lead to a coaligned CMT array structure. However, the mechanisms and conditions that cause CMT arrays to become organized are not well understood. It is prohibitively time-consuming to use actual plants to study the effect of various genetic mutations and environmental conditions on CMT self-organization. In fact, even computer simulations with multiple replications are …

Chemical-Free Technique To Study The Ultrastructure Of Primary Cilium, Ashraf M. Mohieldin, Wissam A. Aboualaiwi, Min Gao, Surya M. Nauli

Pharmacy Faculty Articles and Research

A primary cilium is a hair-like structure with a width of approximately 200 nm. Over the past few decades, the main challenge in the study of the ultrastructure of cilia has been the high sensitivity of cilia to chemical fixation, which is required for many imaging techniques. In this report, we demonstrate a combined high-pressure freezing (HPF) and freeze-fracture transmission electron microscopy (FFTEM) technique to examine the ultrastructure of a cilium. Our objective is to develop an optimal high-resolution imaging approach that preserves cilia structures in their best natural form without alteration of cilia morphology by chemical fixation interference. Our …

Hyperactivity And Attention Deficits In Mice With Decreased Levels Of Stress-Inducible Phosphoprotein 1 (Stip1), Flavio H. Beraldo, Anu Thomas, Benjamin Kolisnyk, Pedro H. Hirata, Xavier De Jaeger, Amanda C. Martyn, Jue Fan, Daniela F. Goncalves, Matthew F. Cowan, Talal Masood, Vilma R.. Martins, Robert Gros, Vania F. Prado, Marco A. M. Prado

Anatomy and Cell Biology Publications

Stress-inducible phosphoprotein I (STIP1, STI1 or HOP) is a cochaperone intermediating Hsp70/Hsp90 exchange of client proteins, but it can also be secreted to trigger prion protein-mediated neuronal signaling. Some mothers of children with autism spectrum disorders (ASD) present antibodies against certain brain proteins, including antibodies against STIP1. Maternal antibodies can cross the fetus blood-brain barrier during pregnancy, suggesting the possibility that they can interfere with STIP1 levels and, presumably, functions. However, it is currently unknown whether abnormal levels of STIP1 have any impact in ASD-related behavior. Here, we used mice with reduced (50%) or increased STIP1 levels (fivefold) to test …

The Anatomy Of Porcine And Human Larynges: Structural Analysis And High Resolution Magnetic Resonance Imaging Of The Recurrent Laryngeal Nerve, Nena Lundgreen Mason

Theses and Dissertations

The recurrent laryngeal nerve (RLN) innervates all the intrinsic muscles of the larynx that are responsible for human vocalization and language. The RLN runs along the tracheoesophageal groove bilaterally and is often accidentally damaged or transected during head and neck surgical procedures. RLN palsy and vocal cord paralysis are the most common and serious post op complications of thyroid surgeries. Patients who suffer from RLN injury can develop unilateral or bilateral vocal fold paralysis (BVFP). Theoretically, selective reinnervation of the posterior cricoarytenoid muscle would be the best treatment for BVFP. The phrenic nerve has been shown in several studies to …