Cell Biology Commons^™

Effects Of Proline And Glycine On The Cnidocyte Discharge Of Hydra Magnipapillata, Janine R. Appleton

Honors Theses and Capstones

The sense of taste enables animals to utilize environmental cues to detect favorable foods. Through specialized sensory receptors, Cnidarians employ stinging cells called cnidocytes to perform a variety of activities such as locomotion, capturing prey, inducing of feeding responses, and defense. Their discharge is highly regulated by mechanical and chemical signals that are mediated by a complex system including the opsin and taste pathways. Taste 1 Receptors (T1R) have previously been isolated in vertebrates but only until recently, have been noted in invertebrates. Receptors specific to L- amino acids corresponding to the taste sensation of umami, were studied to determine …

Proteasome Inhibition As A Potential Anti-Breast Cancer Therapy: Mechanisms Of Action And Resistance-Reversing Strategies, Rahul Rajesinh Deshmukh

Wayne State University Dissertations

AMPK activation and Ubiquitin Proteasome System (UPS) inhibition have gained great attention as therapeutic strategies for the treatment of certain types of cancers. While AMPK serves as a master regulator of cellular metabolism, UPS regulates protein homeostasis. Although the crosstalk between them is suggested, the relationship between these two important pathways is not very clear. We observed that proteasome inhibition leads to AMPK activation in human breast cancer cells. We report that a variety of proteasome inhibitors activate AMPK in all of the tested cancer cell lines. Our data using Liver Kinase B1 (LKB1)-deficient cancer cells suggests that proteasome inhibitor-induced …

Brown Adipogenesis Of Mouse Embryonic Stem Cells In Alginate Microstrands, Andrea Mannarino Unser

Legacy Theses & Dissertations (2009 - 2024)

The ability of brown adipocytes (fat cells) to dissipate energy as heat shows great promise for the treatment of obesity and other metabolic disorders. Employing pluripotent stem cells, with an emphasis on directed differentiation, may overcome many issues currently associated with primary fat cell cultures. However, brown adipocytes are difficult to transplant in vivo due to the instability of fat, in terms of necrosis and neovascularization, once injected. Thus, 3D cell culture systems that have the potential to mimic adipogenic microenvironments are needed, not only to advance brown fat implantation, but also to better understand the role of brown adipocytes …

Myoepithelial Cell Morphogenesis And Differentiation In The Mouse Submandibular Salivary Gland In Development And Disease, Elise Marie Gervais

Legacy Theses & Dissertations (2009 - 2024)

Organogenesis is the process by which tissues organize, gain considerable size, and undergo cellular differentiation or specialization to form fully functional organs. To study the processes involved in organogenesis of branched organs, the mouse submandibular salivary gland is frequently used as a model system, as it can undergo morphogenesis and differentiation and be genetically manipulated ex vivo. The mouse submandibular salivary gland undergoes a specific process of outgrowth and invagination known as branching morphogenesis which allows for the significant increase in gland size and complexity, as well as maximization of surface area for secretion of saliva. Surrounding the mouse submandibular …

A Novel Method For Studying Gene Regulatory Elements In Vivo Reveals Essential Roles For Intron Splicing In Neurofilament Gene Expression, Chen Wang

Legacy Theses & Dissertations (2009 - 2024)

Axon outgrowth requires coordinated expression of critical cytoskeletal genes in response to extracellular cues. The spatial and temporal expression of these genes is regulated transcriptionally and posttranscriptionally. Such regulation is largely mediated through the activity of cis-regulatory elements within the cytoskeletal DNAs and RNAs, which recruit specific sets of trans-factors such as DNA- and RNA-binding proteins, as well as microRNAs. To identify the functionally active cis-elements, characterize their dynamically changing sets of trans-factors, and investigate the association between the two sets of regulators in the context of an intact developing nervous system, one needs to combine appropriate in vivo strategies …

Vitamin D Signaling And The Impact On Mouse Mammary Gland Epithelium, Donald Grant Matthews

Legacy Theses & Dissertations (2009 - 2024)

A strong correlation between vitamin D deficiency and increased breast cancer incidence and mortality has been well established, leading researchers to further examine the possibility of using vitamin D in treatment and prevention strategies. Our long term goal is to elucidate the mechanisms by which vitamin D pathway signaling impacts on breast cancer. Generation of the high-affinity vitamin D receptor (VDR) ligand 1,25-dihydroxyvitamin D (1,25-D) from 25-hydroxyvitamin D (25-D) is mediated by CYP27B1 which is present and developmentally regulated in multiple tissues including the mammary gland. We utilized transgenic mouse models combined with diet-induced vitamin D deficiency to determine whether …

Using A Novel Multiplexing Method To Track Cell Populations And Cytodifferentiation During Development Of The Submandibular Salivary Gland, Charles Thomas Manhardt

Legacy Theses & Dissertations (2009 - 2024)

The development of submandibular salivary glands is complex and requires coordination of specific signaling events. Submandibular salivary glands originate as an epithelial invagination into the adjacent mesenchyme that leads to a single stalk and end bud; this end bud will go through a clefting process. Numerous rounds of clefting will lead to a fully developed salivary gland by this process, which is known as branching morphogenesis. As the gland undergoes morphogenesis, specific cues leading to differentiation of multiple cell types and even epithelial sub classes are required. By the later stages of development the glands are fully innervated, have an …

Pharmacologic Induction Of The Melanocotin 1 Receptor (Mc1r) Pathway Provides Protection Against Sunburn And Enhances Expression Of Antioxidant Enzymes In The Skin, Alexandra Amaro-Ortiz

Theses and Dissertations--Toxicology and Cancer Biology

The inability to tan properly after sun exposure strongly correlates with increased incidence of skin cancer. The melanocortin 1 receptor (MC1R) is a transmembrane Gs-coupled cell surface receptor found on epidermal melanocytes that transmits pro-survival and pro-differentiation signals mediated by the second messenger cAMP. Humans carrying loss-of-function polymorphisms in MC1R signaling exhibit higher incidences of skin cancers including melanoma.

This study focused on the physiologic effects of topical application of forskolin, an adenylate cyclase activator, in extension (Mc1r^e/e) K14-SCF animals, which model the fair-skinned UV-sensitive human. Twice daily application of the drug promoted accelerated pigmentation, increased skin darkening …

Characterization Of Calbindin Positive Interneurons Within The Ventral Horn Of The Mouse Spinal Cord, Taylor L. Floyd, David R. Ladle

Celebration of Undergraduate & Graduate Research, Scholarship, and Creative Activities Materials

Sensory-motor circuits in the spinal cord integrate sensory feedback from muscles and modulate locomotor behavior. Although we know how the sensory-motor system generally works, the main issue lies in identifying all neurons involved and understanding their interrelationships. Many interneurons contribute to sensory-motor circuits and have been well studied. For example, Renshaw cells (RC) are inhibitory interneurons that prevent motor neurons from over-activity. A distinguishing feature of RCs is that they are the only interneurons within the ventral-most region of the spinal cord expressing the calcium binding protein calbindin (CB). Recent studies have found other subpopulations of ventral horn interneurons outside …

Regulation Of The Gαi - G-Protein Regulatory (Gpr) Module And The Biological Function Of Gpr-Containing Proteins In Chemokine Signal Processing Of Primary Leukocytes, William Gene Robichaux Iii

MUSC Theses and Dissertations

Activators of G-protein Signaling (AGS) proteins modulate G-protein signaling in diverse and unexpected ways and have functional roles in numerous physiological systems. The functions of AGS proteins in the immune system, where Gαi-coupled chemokine receptors are predominantly involved in dynamic signaling events, are poorly understood. The Group II AGS proteins AGS3 and AGS4 express multiple G-protein regulatory (GPR) motifs, each of which dock GDP-bound Gαi/o/t subunits and effectively compete with Gβγ for binding. This unique ability positions these proteins to modulate downstream signaling of Gαi and Gβγ, thus promoting signal diversity from seven-transmembrane receptors (7TMR). However, regulatory mechanisms and functional …

Dopaminergic Signaling Within The Primary Cilia In The Renovascular System, Kimberly F. Atkinson, Samred H. Kathem, Xingjian Jin, Brian S. Muntean, Wissam A. Aboualaiwi, Andromeda M. Nauli, Surya M. Nauli

Pharmacy Faculty Articles and Research

Activation of dopamine receptor type-5 (DR5) has been known to reduce systemic blood pressure, most likely by increasing renal vasodilation and enhancing natriuresis in the kidney. However, the mechanism of DR5 in natriuresis and vasodilation was not clearly known. We have previously shown that DR5 is localized to primary cilia of proximal renal epithelial and vascular endothelial cells. We here show that selective activation of DR5 specifically induces calcium influx only in the primary cilia, whereas non-selective activation of dopamine receptor induces calcium fluxes in both cilioplasm and cytoplasm. Cilia-independent signaling induced by thrombin only shows calcium signaling within cytoplasm. …

Effect Of Adjuvant And Neoadjuvant Anti-Telomerase With Anthracycline Based Chemotherapy On Triple Negative Breast Cancer Cells, Luke T. Pardy

Student Summer Scholars Manuscripts

Breast cancer is the second leading cause of cancer related death in women in the US. In addition, 20% of all breast cancer cases in the U.S. are from the subtype known as Triple-Negative Breast Cancer (TNBC), which is the most aggressive and invasive form of the disease. This type of breast cancer has the worst prognosis, a decreased survival rate, and no targeted therapy. Over the decades, interest in pre- (Neoadjuvant) and post- (Adjuvant) chemotherapy treatments, in the management of TNBC has increased. Therefore, we evaluated the Adjuvant and Neoadjuvant effects of anti-telomerases (BIBR 1532 and GV6) with anthracycline-based …

Altered Connexin 43 Expression Underlies Age-Dependent Decrease Of Regulatory T Cell Suppressor Function In Nonobese Diabetic Mice, Michel Kuczma, Cong-Yi Wang, Leszek Ignatowicz, Robert Gourdi, Piotr Kraj

Biological Sciences Faculty Publications

Type 1 diabetes is one of the most extensively studied autoimmune diseases, but the cellular and molecular mechanisms leading to T cell–mediated destruction of insulin-producing β cells are still not well understood. In this study, we show that regulatory T cells (T_regs) in NOD mice undergo age-dependent loss of suppressor functions exacerbated by the decreased ability of activated effector T cells to upregulate Foxp3 and generate T_regs in the peripheral organs. This age-dependent loss is associated with reduced intercellular communication mediated by gap junctions, which is caused by impaired upregulation and decreased expression of connexin 43. Regulatory …

Hrd1 Partners In Endoplasmic Reticulum-Associated Degradation, Aaron Alexander Burr

Wayne State University Dissertations

Protein Quality Control (PQC) comprises cellular pathways that regulate the turnover of short-lived, misfolded proteins. A main component of PQC is Endoplasmic Reticulum (ER)-Associated Degradation (ERAD), which controls the degradation of proteins synthesized in the ER. Aberrations in ERAD have been linked to malignancies such as sarcomas, breast, and pancreatic carcinomas, as well as neurodegenerative disease. The machinery in this system is complex and while significant progress has been made to understand ERAD, it is not clear how the different components come together, or how they are regulated. HRD1 is a resident ubiquitin ligase that has been proposed as a …

Soy Isoflavones Mediate Radioprotection Of Normal Lung Tissue By Modulating The Radiation-Induced Inflammatory Response, Lisa Marie Abernathy

Wayne State University Dissertations

Radiation-induced lung injury (RILI) is caused by an early inflammatory process triggered by damage to lung parenchyma, epithelial cells, vascular endothelial cells and stroma. Initially, oxidative injuries after radiation induce altered expression of pro-inflammatory cytokines. Infiltrating inflammatory cells are stimulated and activated, producing additional mediators, resulting in a cytokine cascade. The expansion and perpetual activation of inflammatory cells, as well as lung parenchyma, lead to clinical pneumonitis. Activated cells produce molecular mediators and growth factors that affect the proliferation and gene expression of lung fibroblasts. This process leads to increased collagen synthesis and deposition, eventually leading to the development of …

Adipocyte-Induced Inflammation In Prostate Tumor Progression In Bone: Role Of Cxcr2 And Osteopontin, Aimalie Lynnette Hardaway

Wayne State University Dissertations

Abstract

Prostate cancer (PCa) is the second leading cause of cancer-related deaths among men. Evidence suggests that age and obesity, conditions associated with adipocyte accumulation in the bone marrow, are linked to increased risk of developing PCa and progressing to metastatic disease. Studies presented in this dissertation were based on the hypothesis that metastatic progression in bone is a result of a cooperative effort between bone marrow adipocytes, macrophages, osteoclasts, and PCa cells. We specifically focused on two adipocyte-supplied chemokines, CXCL1 and CXCL2, and bone marrow macrophage-secreted osteopontin as key drivers of pro-inflammatory environment in the bone marrow and important …

Mach: A Model For Explaining Molecular And Cellular Mechanisms, Caleb M. Trujillo

Open Access Dissertations

Biologists use mechanistic explanations to understand behaviors of the immense complexity of molecular and cellular systems. In undergraduate biology courses, students are expected to explain molecular and cellular mechanisms, but teaching this skill presents many challenges due to the highly abstract, intangible nature of the cellular world, the influence of everyday language, and the tendency of students to overestimate how much they can explain. Therefore, across three studies this dissertation addresses these obstacles to teach undergraduate biology students to explain molecular and cellular mechanisms. ^ The first step was to model how biology experts explain molecular and cellular mechanisms, and …

Human Anatomy And Physiology Preparatory Course (1st Edition), Carlos Liachovitzky

Open Educational Resources

The overall purpose of this preparatory course textbook is to help students familiarize with some terms and some basic concepts they will find later in the Human Anatomy and Physiology I course.

The organization and functioning of the human organism generally is discussed in terms of different levels of increasing complexity, from the smallest building blocks to the entire body. This Anatomy and Physiology preparatory course covers the foundations on the chemical level, and a basic introduction to cellular level, organ level, and organ system levels. There is also an introduction to homeostasis at the beginning.

Adp-Ribosylation Factor 6 (Arf6) Regulates Integrin Αiibβ3 Trafficking, Platelet Spreading, And Clot Retraction, Yunjie Huang

Theses and Dissertations--Molecular and Cellular Biochemistry

Endocytic trafficking of platelet surface receptors plays a role in the accumulation of granule cargo (i.e. fibrinogen and VEGF) and thus could contribute to hemostasis, angiogenesis, or inflammation. However, the mechanisms of platelet endocytosis are poorly understood. The small GTP-binding protein, ADP-ribosylation factor 6 (Arf6), regulates integrin trafficking in nucleated cells; therefore, we posited that Arf6 functions similarly in platelets. To address this, we generated platelet-specific, Arf6 knockout mice. Arf6^-/- platelets had a storage defect for fibrinogen but not other cargo, implying Arf6’s role in integrin αIIbβ3 trafficking. Additionally, platelets from Arf6^-/- mice injected with biotinylated-fibrinogen, showed …

Physiological Function Of Fus: An Rna Binding Protein In Motor Neuron Disease, Liuqing Yang

Theses and Dissertations--Molecular and Cellular Biochemistry

FUS is an RNA binding protein implicated in the motor neuron disease— amyotrophic lateral sclerosis (ALS, also called Lou Gehrig’s disease). ALS is a fatal neurodegenerative disease characterized by progressive motor neuron death. Mutations in the FUS gene cause about 4% of familial ALS (FUS ALS). Mutated FUS protein mislocalizes from the motor neuron nucleus to the cytoplasm and forms inclusions in the cytoplasm. It is unclear how FUS mislocalization induces motor neuron dysfunction and degeneration. This dissertation research was designed to investigate the physiological functions of FUS in the nucleus, with a purpose to shed light on the pathogenesis …

Gene Expression And Alzheimer's Disease: Evaluation Of Gene Expression Patterns In Brain And Blood For An Alzheimer's Disease Mouse Model, Amanda Hazy

Senior Honors Theses

Previous studies have established a causative role for altered gene expression in development of Alzheimer’s disease (AD). These changes can be affected by methylation and miRNA regulation. In this study, expression of miRNA known to change methylation status in AD was assessed by qPCR. Genome-wide expression changes were determined by RNA-sequencing of mRNA from hippocampus and blood of control and AD mice. The qPCR data showed significantly increased expression of Mir 17 in AD, and sequencing data revealed 230 genes in hippocampus, 58 genes in blood, and 8 overlapping genes showing significant differential expression (p value ≤ 0.05). Expression data …

Detection And Tracking Of T Cells In Time-Lapse Imaging, Cody Arbuckle, Milton L. Greenberg, Erik J. Linstead

Mathematics, Physics, and Computer Science Faculty Articles and Research

The effective classification and tracking of cells obtained from modern staining techniques has significant limitations due to the necessity of having to train and utilize a human expert in the field who must manually identify each cell in each slide. Often times these slides are filled with noise cells that are not of particular interest to the researcher. The use of computational methods has the ability to effectively and efficiently enhance image quality, as well as identify and track target cell types over large data sets. Here we present a computational approach to the in vitro tracking of T cells …

Utilizing Galectin 3 As A Marker Of Ruptured Vesicles In Vivo, Jonathan London

Master's Theses

Ruptured vesicles have been associated with pathological forms of α-synuclein during the development of PD. Galectin 3 (Gal3) is readily recruited to these ruptured vesicles, making it a potentially useful marker of vesicle rupture in PD and other diseases associated with vesicle rupture and lysosomal dysfunction. We were able to visualize and quantify the differences in Gal3 levels during infection with pathological α-synuclein in the rat brain. Having significantly high basal levels of Gal3, we found that the differentiated monocytes showed a nearly100 percent increase in intercellular levels of Gal3 after treatment with pathological α-synuclein. By expressing only the Carbohydrate …

Pemetrexed, A Modulator Of Amp-Activated Kinase Signaling And An Inhibitor Of Wild Type And Mutant P53, Stuti Agarwal

Theses and Dissertations

New drug discoveries and new approaches towards diagnosis and treatment have improved cancer therapeutics remarkably. One of the most influential and effective discoveries in the field of cancer therapeutics was antimetabolites, such as the antifolates. The interest in antifolates increased as some of the antifolates showed responses in cancers, such as mesothelioma, leukemia, and breast cancers. When pemetrexed (PTX) was discovered, our laboratory had established that the primary mechanism of action of pemetrexed is to inhibit thymidylate 22 synthase (TS) (E. Taylor et al., 1992). Preclinical studies have shown that PTX has a broad range of antitumor activity in human …

Interaction Between Atm Kinase And P53 In Determining Glioma Radiosensitivity, Syed F. Ahmad

Theses and Dissertations

Glioblastoma multiforme (GBM) is the most common primary brain tumor. Studies have shown that targeting the DNA damage response can sensitize cancer cells to DNA damaging agents. Ataxia telangiectasia mutated (ATM) is involved in signaling DNA double strand breaks. Our group has previously shown that ATM inhibitors (ATMi) sensitize GBM cells and tumors to ionizing radiation. This effect is greater when the tumor suppressor p53 is mutated.

The goals of this work include validation of a new ATM inhibitor, AZ32, and elucidation of how ATMi and p53 status interact to promote cell death after radiation. We propose that ATMi and …

A Coxiella-Like Endosymbiont Is A Potential Vitamin Source For The Lone Star Tick, Todd A. Smith, Timothy Driscoll, Joseph J. Gillespie, Rahul Raghavan

Biology Faculty Publications and Presentations

Amblyomma americanum (Lone star tick) is an important disease vector in the United States. It transmits several human pathogens, including the agents of human monocytic ehrlichiosis, tularemia, and southern tick-associated rash illness. Blood-feeding insects (Class Insecta) depend on bacterial endosymbionts to provide vitamins and cofactors that are scarce in blood. It is unclear how this deficiency is compensated in ticks (Class Arachnida) that feed exclusively on mammalian blood. A bacterium related to Coxiella burnetii, the agent of human Q fever, has been observed previously within cells of A. americanum. Eliminating this bacterium (CLEAA, Coxiella-like endosymbiont of A. americanum) with antibiotics …

Regulation And Targeting Of The Fancd2 Activation In Dna Repair, Valentina Celeste Caceres

USF Tampa Graduate Theses and Dissertations

Fanconi anemia (FA) is a genome instability syndrome that is clinically manifested by bone marrow failure, congenital defects, and elevated cancer susceptibility. The FA pathway is known to regulate the repair of DNA interstrand crosslinks in part through DNA homologous recombination (HR) repair. Up to today 16 FA proteins have been discovered that may participate in the common pathway. Cells that have mutations in the FA genes are hypersensitive to DNA damaging agents and display chromosome instability. A key regulatory event in the FA pathway is monoubiquitination of FANCD2-FANCI heterodimer that is mediated by a multi-component E3 ubiquitin ligase complex …

High-Throughput Screening Of Age-Related Changes In Caenorhabditis Elegans, Neil Copes

USF Tampa Graduate Theses and Dissertations

This project was developed to identify novel methods for high-throughput culturing and screening of C. elegans to investigate age-related metabolic changes and to survey the proteomic and metabolomic factors associated with age-related changes. To accomplish these goals we developed a novel way to grow C. elegans in liquid culture in 96-well microplates for several weeks without suffering significant fluid loss due to evaporation and without needing to shake or unseal the plates for aeration. We also developed methods for assaying the total volume of live C. elegans in microplate cultures using a fluorescence microplate reader and for performing RNAi experiments …

Strategies For Preventing Age And Neurodegenerative Disease-Associated Mitochondrial Dysfunction, Vedad Delic

USF Tampa Graduate Theses and Dissertations

Mitochondrial dysfunction plays a pivotal role in the development of aging phenotypes and aging-associated neurodegenerative disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and Amyotrophic lateral sclerosis (ALS). Strategies that restore mitochondrial dysfunction may rescue the deficits of central metabolism in these disorders and improve cell survival. For example, we found that modulating the mTOR signaling pathway in a tissue culture model of aging-induced mitochondrial DNA mutation enhanced mitochondrial function as evidenced by increased oxygen consumption. Our previous melatonin studies also led us to hypothesize that caloric restriction and the hormone melatonin would reverse brain mitochondrial dysfunction in animal …

Genomic Aberrations At The 3q And 14q Loci: Investigation Of Key Players In Ovarian And Renal Cancer Biology, Punashi Dutta

USF Tampa Graduate Theses and Dissertations

Genomic aberrations are primary contributors to the pathophysiology of cancer [11]. Dysregulated expression of genes located within these aberrations are important predictors of chemoresistance, disease prognosis, and patient outcome [12]. This dissertation is focused on understanding the regulation and/or functions of specific genes located at dysregulated genomic regions such as 3q26 and 14q32 in the biology of ovarian and renal cancer, respectively.

Serous epithelial ovarian cancer (EOC) manifest amplification at the 3q26.2 locus [2], an observation consistent with the cancer genome atlas (TCGA) [13]. The most amplified gene in this region is EVI1 which has been extensively studied in hematological …