Cell and Developmental Biology Commons^™

Targeting Of Receptors For Advanced Glycation End-Products (Rage) Diminishes Acute Secondhand Smoke-Induced Inflammation In Mice, Tyler Thomas Wood

Theses and Dissertations

The receptor for advanced glycation end-products (RAGE) has increasingly been demonstrated to be an important modulator of inflammation in cases of pulmonary disease. Published reports involving tobacco smoke exposure have demonstrated increased expression of RAGE, its participation in pro-inflammatory signaling and its role in irreversible pulmonary remodeling. The current research evaluated for the first time the in vivo effects of short-term tobacco smoke exposure in RAGE null and control mice compared to identical animals exposed to room air only. Quantitative real time PCR, immunoblotting, and immunohistochemistry revealed elevated RAGE expression in controls after four weeks of exposure and an anticipated …

Caspase-Dependent Signaling Underlies Glioblastoma Cell Death In Response To The Fungal Metabolite, Fusarochromanone, Elahe Mahdavian, Monique Marshall, Patrick M. Martin, Patrice Cagle, Brian A. Salvatore, Quincy A. Quick

Biology Faculty Research

Fungal metabolites continue to show promise as a viable class of anticancer agents. In the present study, we investigated the efficacy of the fungal metabolite, fusarochromanone (FC101), for its antitumor activities in glioblastomas, which have a median survival of less than two years and a poor clinical response to surgical resection, radiation therapy and chemotherapy. Using clinically applicable doses, we demonstrated that FC101 induced glioblastoma apoptotic cell death via caspase dependent signaling, as indicated by the cleavage of poly(ADP-ribose) polymerase, glioblastoma (PARP). FC101 also induced differential reactive oxygen species (ROS) levels in glioblastoma cells, contrasting a defined role of oxidative …

Effects Of Nutritional Level Of Concentrate‐Based Diets On Meat Quality And Expression Levels Of Genes Related To Meat Quality In Hainan Black Goats, Dingfa Wang, Luli Zhou, Hanlin Zhou, Guanyu Hou, Liguang Shi, Mao Li, Xianzhou Huang, Song Guan

Faculty Publications

The present study investigated the effects of the nutritional levels of diets on meat quality and related gene expression in Hainan black goat. Twenty-four goats were divided into six dietary treatments and were fed a concentrate-based diet with two levels of crude protein (CP) (15% or 17%) and three levels of digestive energy (DE) (11.72, 12.55 or 13.39 MJ/kg DM) for 90 days. Goats fed the concentrate-based diet with 17% CP had significantly (P < 0.05) higher average daily gains (ADG) and better feed conversion rates (FCR). The pH 24h value tended to decrease (P < 0.05) with increasing DE levels. The tenderness of Longissimus dorsi muscle (LD) and Semimembranosus muscle (SM) reduced with increasing CP levels (P < 0.05). With increasing DE levels, tenderness was increased (P < 0.05). The heart fatty acid-binding protein (H-FABP) mRNA expression levels in LD and SM increased with increasing DE levels (P < 0.05), but decreased with increasing CP levels (P < 0.05). The calpastatin (CAST) and μ-calpain mRNA expressions levels in LD and SM were affected significantly (P < 0.05) by CP and DE levels in the diet. Therefore, the nutritional levels of diets affect meat quality and expression levels of genes associated with meat quality in Hainan black goats.

Bi-Directional Signaling Between Melanoma And The Microenvironment Generates A Protective Niche That Mediates Therapeutic Escape, Inna Fedorenko

USF Tampa Graduate Theses and Dissertations

Very few cancer patients are cured through drug therapy alone, with the majority exhibiting acquired resistance. To date, most studies of therapeutic escape have focused upon tumor-intrinsic mechanisms of drug resistance with little attention paid to the role of normal host cells in preventing complete tumor eradication. In the present study we implicate co-operative bi-directional signaling between melanoma cells and fibroblasts in the generation of a pro-survival niche that mediates drug resistance. Mass-spectrometry based phosphoproteomics was used to show that BRAF inhibition and chemotherapy drugs enhanced the survival of both melanoma cells and fibroblasts through the induction of fibronectin (FN)/integrin …

Regulation Of Strand-Specific Processing In Human Pre-Mir-371 And Its Mouse Homologs, Jianting Shi

Graduate School of Biomedical Sciences Theses and Dissertations

MicroRNAs (miRNAs) are small noncoding RNAs, known to regulate genes by inducing target mRNA degradation or translational repression. This regulatory function has been shown to assist developmental timing control and increasingly more evidence reveals some of the miRNAs may have tissue/cell type-specific function, showing the potential to assist cell differentiation. Mouse miR-290-295 cluster is embryonic stem cell (ESCs)-specific miRNA cluster and human miR-371-373 cluster has been verified to be its functional homolog. We have previously demonstrated that human pre-miR-371 is processed into multiple miRNA species, which represent the seeds of the mouse of miR-290-5p, miR-292-5p, miR-292-3p-iso2 and miR-293-3p. Deep sequencing …

Case Study: From Gummy Bears To Celery Stalks: Diffusion And Osmosis, Kevin M. Bonney

Publications and Research

The article describes a case study which interperses information on diffusion and osmosis with content review and knowledge application questions, as well as simple experiment that can be conducted without the use of a laboratory. Topics discussed include biological membranes, the use of gummy bears to demonstrate osmosis and osmosis in animal cells. Also mentioned is osmosis in plants. It notes that the case study was developed for use in an introductory undergraduate biology course.

Pkc-Dependent Phosphorylation Of Enos At T495 Regulates Enos Coupling And Endothelial Barrier Function In Response To G(+) -Toxins, Feng Chen, Sanjiv Kumar, Yanfang Yu, Saurabh Aggarwal, Christine Gross, Yusi Wang, Trinad Chakraborty, Alexander D. Verin, John D. Catravas, Rudolf Lucas, Stephen M. Black, David J. R. Fulton

Bioelectrics Publications

Gram positive (G(+)) infections make up similar to 50% of all acute lung injury cases which are characterized by extensive permeability edema secondary to disruption of endothelial cell (EC) barrier integrity. A primary cause of increased permeability are cholesterol-dependent cytolysins (CDCs) of G(+)-bacteria, such as pneumolysin (PLY) and listeriolysin-O (LLO) which create plasma membrane pores, promoting Ca2+-influx and activation of PKC alpha. In human lung microvascular endothelial cells (HLMVEC), pretreatment with the nitric oxide synthase (NOS) inhibitor, ETU reduced the ability of LLO to increase microvascular cell permeability suggesting an endothelial nitric oxide synthase (eNOS)-dependent mechanism. LLO stimulated superoxide production …

Evaluation Of Eight Live Attenuated Vaccine Candidates For Protection Against Challenge With Virulent Mycobacterium Avium Subspecies Paratuberclosis In Mice, John Bannantine, Jamie L. Everman, Sasha J. J.Rose, Lmar Babrak, Robab Katani, Raul G. Barletta, Adel M. Talaat, Yrjö J. Gröhn, Yung-Fu Chang, Vivek Kapur, Luiz E. Bermudez

School of Veterinary and Biomedical Sciences: Faculty Publications

Johne's disease is caused by Mycobacterium avium subsp. paratuberculosis (MAP), which results in serious economic losses worldwide in farmed livestock such as cattle, sheep, and goats. To control this disease, an effective vaccine with minimal adverse effects is needed. In order to identify a live vaccine for Johne's disease, we evaluated eight attenuated mutant strains of MAP using a C57BL/6 mouse model. The persistaence of the vaccine candidates was measured at 6, 12, and 18 weeks post vaccination. Only strains 320, 321, and 329 colonized both the liver and spleens up until the 12-week time point. The remaining five mutants …

Key Residues Of Human Cytoplasmic Protein Tyrosine Phosphatase-A And -B For Substrate Binding And Specificity, Byunghyun Park

Open Access Theses

Reversible tyrosine phosphorylation plays an important role in signaling pathways that are essential for regulating cellular growth, differentiation and metabolism. Moreover, several human diseases such as diabetes, obesity and cancers are associated with the deregulation of protein tyrosine phosphatases (PTPs). Several studies provide evidence that PTPs not only contribute to cellular differentiation, but over-expression of these molecules also leads to transformation of non-transfomed cells as well. Based on these results, designing specific PTP inhibitors may ultimately function as potential therapeutic agents to treat various diseases including cancer, diabetes, and autoimmune diseases. EphA2 is a receptor tyrosine kinase which is hypo-phosphorylated …

Ontogenetic Investigation Of Underwater Hearing Capabilities In Loggerhead Sea Turtles (Caretta Caretta) Using A Dual Testing Approach, Ashley L. Lavender, Soraya M. Bartol, Ian K. Bartol

Biological Sciences Faculty Publications

Sea turtles reside in different acoustic environments with each life history stage and may have different hearing capacity throughout ontogeny. For this study, two independent yet complementary techniques for hearing assessment, i.e. behavioral and electrophysiological audiometry, were employed to (1) measure hearing in post-hatchling and juvenile loggerhead sea turtles Caretta caretta (19-62 cm straight carapace length) to determine whether these migratory turtles exhibit an ontogenetic shift in underwater auditory detection and (2) evaluate whether hearing frequency range and threshold sensitivity are consistent in behavioral and electrophysiological tests. Behavioral trials first required training turtles to respond to known frequencies, a multi-stage, …

Lateral Line Analogue Aids Vision In Successful Predator Evasion For The Brief Squid, Lolliguncula Brevis, Carly A. York, Ian K. Bartol

Biological Sciences Faculty Publications

Cephalopods have visual and mechanoreception systems that may be employed to sense and respond to an approaching predator. While vision presumably plays the dominant role, the importance of the lateral line analogue for predator evasion has not been examined in cephalopods. To test the respective roles of vision and the lateral line analogue, brief squid, Lolliguncula brevis, were observed in the presence of summer flounder, Paralichthys dentatus, under light and dark conditions with their lateral line analogue intact and ablated. Hair cell ablation was achieved through a pharmacological technique used for the first time on a cephalopod. The …

Experimental And Computational Analysis Of The Synucleins, Agatha Munyanyi

Theses and Dissertations in Biomedical Sciences

The synuclein proteins α, β and γ which are located in the brain, have been a subject of intense research. Of particular interest is α-synuclein, which is found in misfolded forms in Lewy bodies that are associated with Parkinson's disease. Despite the efforts of researchers across the world, the physiological structure and function of the synucleins remains elusive. In recent years, highly controversial reports by some investigators indicate that in its natural form, α-synuclein exists as a tetramer instead of as an intrinsically unstructured monomer. This dissertation presents results of the experimental and computational analysis of the synucleins. First, we …

Phosphoinositides: Minor Lipids Make A Major Impact On Photoreceptor Cell Functions, Raju V. S. Rajala, Ammaji Rajala, Andrew J. Morris, Robert E. Anderson

Internal Medicine Faculty Publications

Activation of the phosphoinositide (PI) cycle generates the second messengers that control various aspects of cellular signaling. We have previously shown that two PI cycle enzymes, type II phosphatidylinositol 5-phosphate 4-kinase (PIPK IIα) and phosphoinositide 3-kinase (PI3K), are activated through light stimulation. In our earlier studies, we measured enzyme activities, instead of directly measuring the products, due to lack of sensitive analytical techniques. Cells have very low levels of PIs, compared to other lipids, so special techniques and sensitive analytical instruments are necessary for their identification and quantification. There are also other considerations, such as different responses in different cell …

Manipulating The Tumor Microenvironment For Therapeutic Benefit, Kate M. Bailey

USF Tampa Graduate Theses and Dissertations

The physical tumor microenvironment contributes significantly to carcinogenesis, cancer progression and metastatic dissemination. Two main components of the tumor microenvironment, hypoxia and acidosis, are present in nearly every solid tumor and act as powerful selection forces against the tumor. Hypoxia and acidosis promote tumor heterogeneity and contribute to chemotherapy and radiotherapy resistance. This dissertation interrogates methods to target the tumor microenvironment including two novel studies describing mechanisms of buffer therapy resistance and targeting tumor hypoxia with vasodilators to enhance the efficacy of a hypoxia activated prodrug, TH-302.

In the first study, mechanisms of buffer therapy resistance were identified and detailed. …

Fty720 (Fingolimod) Provides Insight Into The Molecular Mechanisms Of Multiple Sclerosis, Madelyn Elizabeth Crawford

Pursuit - The Journal of Undergraduate Research at The University of Tennessee

Multiple sclerosis (MS) is a neurodegenerative disorder caused by a prolonged immune- mediated inflammatory response that targets myelin. Nearly all of the drugs approved for the treatment of MS are general immunosuppressants or only function in symptom management. The oral medication fingolimod, however, is reported to have direct therapeutic effects on cells of the central nervous system in addition to immunomodulatory functions. Fingolimod is known to interact with sphingosine-1-phosphate (S1P) receptors, and the most widely- accepted theory for its mechanism of action is functional antagonism of the receptor. This review examines significant neuromodulatory effects achieved by functional antagonism of the …

Impedimetric Detection Of Mutant P53 Biomarker-Driven Metastatic Breast Cancers Under Hyposmotic Pressure, Menglu Shi, Nataly Shtraizent, Alla Polotskaia, Jill Bargonetti, Hiroshi Matsui

Publications and Research

In cancer cells, the oncogenic mutant p53 (mtp53) protein is present at high levels and gain-of-function (GOF) activities with more expression of mtp53 proteins contribute to tumor growth and metastasis. Robust analytical approaches that probe the degree of metastasis of cancer cells in connection with the mtp53 activity will be extremely useful not only for establishing a better cancer prognosis but also understanding the fundamental mechanism of mtp53 oncogenic action. Here we assessed the influence of mtp53 in breast cancers to the mechanical property of breast cancer cells. Recently, ovarian and kidney cancer cell lines have been shown to have …

Vitamin A Deficiency Causes Ovulation Abnormalities In Mice, Rebecca Ursin

DePaul Discoveries

Retinoic acid (RA) is an active metabolite of vitamin A (VA) and is involved in tissue organization, patterning, and growth. RA has been shown to regulate male reproduction, however information on its role in ovary development is limited. To investigate the functions of RA in the ovary, we examined its role in ovary development and ovulation using an in vivo dietary VA-deprivation animal model. Our preliminary results have shown that VA deficiency causes a variety of ovarian pathologies, including reduced numbers of total follicles and corpus lutea, formation of hemorrhagic and atretic follicles, and formation of bursa and follicular cysts. …

Cholinergic Signaling Exerts Protective Effects In Models Of Sympathetic Hyperactivity-Induced Cardiac Dysfunction, Mariana Gavioli, Aline Lara, Pedro W. M. Almeida, Augusto Martins Lima, Denis D. Damasceno, Cibele Rocha-Resende, Marina Ladeira, Rodrigo R. Resende, Patricia M. Martinelli, Marcos Barrouin Melo, Patricia C. Brum, Marco Antonio Peliky Fontes, Robson A. Souza Santos, Marco A. M. Prado, Silvia Guatimosim

Anatomy and Cell Biology Publications

Cholinergic control of the heart is exerted by two distinct branches; the autonomic component represented by the parasympathetic nervous system, and the recently described non-neuronal cardiomyocyte cholinergic machinery. Previous evidence has shown that reduced cholinergic function leads to deleterious effects on the myocardium. Yet, whether conditions of increased cholinergic signaling can offset the pathological remodeling induced by sympathetic hyperactivity, and its consequences for these two cholinergic axes are unknown. Here, we investigated two models of sympathetic hyperactivity: i) the chronic beta-adrenergic receptor stimulation evoked by isoproterenol (ISO), and ii) the alpha(2A)/alpha(2C)-drenergic receptor knockout (KO) mice that lack pre-synaptic adrenergic receptors. …

Identification Of Novel Small Rnas And Characterization Of The 6s Rna Of Coxiella Burnetii, Indu Warrier, Linda D. Hicks, James M. Battisti, Rahul Raghavan, Michael F. Minnick

Biology Faculty Publications and Presentations

Coxiella burnetii, an obligate intracellular bacterial pathogen that causes Q fever, undergoes a biphasic developmental cycle that alternates between a metabolically-active large cell variant (LCV) and a dormant small cell variant (SCV). As such, the bacterium undoubtedly employs complex modes of regulating its lifecycle, metabolism and pathogenesis. Small RNAs (sRNAs) have been shown to play important regulatory roles in controlling metabolism and virulence in several pathogenic bacteria. We hypothesize that sRNAs are involved in regulating growth and development of C. burnetii and its infection of host cells. To address the hypothesis and identify potential sRNAs, we subjected total RNA isolated …

Expression Of Osteoarthritis Biomarkers In Temporomandibular Joints Of Mice With And Without Receptor For Advanced Glycation End Products (Rage), Elizabeth Murayama Chavez Matias

Theses and Dissertations

This thesis will be organized into three chapters discussing the mechanism underlying the onset and progression of osteoarthritis (OA) in the temporomandibular joint (TMJ). Understanding the mechanism of OA development in the TMJ helps in understanding how OA progresses and how to treat this disease. The goal of this investigation is to examine the process of cartilage degeneration and OA biomarker expression in the TMJ to understand their role in TMJ OA onset and development.Chapter one covers mechanisms that are altered in TMJ OA during disease progression. Using animal models with different stressors such as mechanical disturbances, direct injury, and …