Cell and Developmental Biology Commons^™

Regulation Of Vcam-1 Expression By Tgfβ2 During The Formation Of The Epicardium, Margaret Elizabeth Grant Burton

MUSC Theses and Dissertations

The normal formation of the epicardium, the outer cell layer of the heart, is critical for subsequent development of the heart to proceed normally. Abnormalities in the epicardium lead to cardiac defects as shown in mice deficient in retinoid X receptor α (RXRα-/-), a model of congenital heart disease that exhibits many cardiac malformations including epicardial defects. The RXRα-/- epicardium is slower to form and once formed, it detaches from the myocardium. Previously an elevation of transforming growth factor β2 (TGFβ2) has been observed in RXRα-/- hearts at midgestation and an alteration in vascular cell adhesion molecule 1 (VCAM-1) was …

Differences In The Mechanism Of Collagen Lattice Contraction By Myofibroblasts And Smooth Muscle Cells, J. C. Dallon, H P. Ehrlich

Faculty Publications

Both rat derived vascular smooth muscle cells (SMC) and human myofibroblasts contain $\alpha$ smooth muscle actin (SMA), but they utilize different mechanisms to contract populated collagen lattices (PCLs). The difference is in how the cells generate the force that contracts the lattices. Human dermal fibroblasts transform into myofibroblasts, expressing $\alpha$-SMA within stress fibers, when cultured in lattices that remain attached to the surface of a tissue culture dish. When attached lattices are populated with rat derived vascular SMC, the cells retain their vascular SMC phenotype. Comparing the contraction of attached PCLs when they are released from the culture dish on …

Mitochondrial Physiology Of Diapausing And Developing Embryos Of The Annual Killifish Austrofundulus Limnaeus: Implications For Extreme Anoxia Tolerance, Jeffrey M. Duerr, Jason E. Podrabsky

Biology Faculty Publications and Presentations

Diapausing embryos of the annual killifish Austrofundulus limnaeus have the highest reported anoxia tolerance of any vertebrate and previous studies indicate modified mitochondrial physiology likely supports anoxic metabolism. Functional mitochondria isolated from diapausing and developing embryos of the annual killifish exhibited VO2, respiratory control ratios (RCR), and P:O ratios consistent with those obtained from other ectothermic vertebrate species. Reduced oxygen consumption associated with dormancy in whole animal respiration rates are correlated with maximal respiration rates of mitochondria isolated from diapausing versus developing embryos. P:O ratios for developing embryos were similar to those obtained from adult liver, but were diminished in …

Ornithine Decarboxylase (Odc) Regulation By Mtor: New Insights From Tsc1 Knockout Cells, Alyssa Mae Cates

Honors Program Theses

The polyamine pathway, when improperly regulated, is one central cause of skin carcinogenesis. The purpose of this project was to investigate the relationship between two biochemical signaling pathways, the mTOR (mammalian target of rapamycin) pathway and the polyamine pathway. It is known that the protein mTOR serves to regulate a key protein in the polyamine pathway, ornithine decarboxylase (ODC), but the precise mechanism remains unclear. It has been postulated that mTOR acts to regulate ODC through two RNA binding proteins, HuR (a member of the Hu family of proteins) and TIP (tristetraprolin). The project entailed characterizing that relationship using TSCl …

Formation Of The Neural Tube Epithelium Basement Membrane During Secondary Neurulation In The Chick Embryo, Leslie Ann Mataya

Honors Program Theses

Neurulation, the formation of the neural tube, is an important process in the development of vertebrates. Because this organ ultimately becomes the central nervous system of the organism, the proper development of a fully-functioning neural tube is paramount to its survival. Neural tube defects, like spina bifida and anencephaly, are among the most common congenital malformations present in live human births. The prevalence of these defects is a definite concern to medicine and human health.

A Chemical Genetics Approach To Elucidate Mechanisms Of The Fission Yeast Polo Kinase In Cell Division, Jennifer Phelan, Dawn Clifford Hart

Student Summer Scholars Manuscripts

Cell division is a fundamental biological event that underlies the growth and development of all organisms. Because human and fission yeast (Schizosaccharomyces pombe) cells divide symmetrically through constriction of the actomyosin ring, fission yeast provides an ideal model system to reveal conserved cell cycle properties. In fission yeast, an evolutionarily conserved protein, Mid1, plays a critical role in organizing the early steps of contractile ring formation. Mid1 functions as a scaffold to bridge the cell cortex with the contractile ring. Cells lacking mid1 form off-centered, highly disorganized ring structures and exhibit severe cell division defects. Our previous research …

Regulation Of Apoptotic Effects Of Erythrocarpine E, A New Cytotoxic Limonoid Extracted From Chisocheton Erythrocarpus., Norliza Shah Jehan Muttiah

Student Works (2010-2019)

The aim of this study is to determine the cytotoxic and apoptotic effects of erythrocarpine E (CEB4), a new limonoid extracted from Chisocheton erythrocarpus. MTT assay, Live/Dead® Viability/Cytotoxicity assay, cell cycle analysis, annexin V analysis, PARP cleavage analysis, DNA fragmentation assay, sandwich ELISA assay and Western blot analysis were performed on five CEB4 treated cancer cell lines; HSC4COX2- and HSC2 (oral), CaSki (cervical), HepG2 (liver), MCF7 (breast) and NHBE (normal human bronchial epithelial cell line). CEB4 treated HSC4COX2-, HSC2, CaSki, HepG2 and MCF7 cells demonstrated a cytotoxic effect and inhibited cell proliferation in a dose and time dependent manner. CEB4 …

Cytotoxic And Anti-Human Papillomavirus Activites In Selected Vegetables., Maizatul Azmah Ab. Latiff

Student Works (2010-2019)

An appropriate way to control cancer is chemoprevention as a large number of compounds have been observed to prevent the occurrence of cancer and variety of mechanisms exists for producing such protective effects. Numerous epidemiological studies have shown that diets rich in vegetables are associated with a decreased risk of cancer. Chemoprevention involves the use of natural or laboratory made substances to prevent cancer or reduce risk cancer.The E6 oncoprotein from oncogenic Human papillomaviruses (HPVs) has exhibit functions in tumorigenesis, regulation of transcriptions and apoptosis. E6 product from oncogenic viral type like HPV 16 can bind the tumor suppressor p53 …

Cytoprotective And Genoprotective Effects Of Aqueous Extracts Of Processed Pleurotus Sajor-Caju Fruiting Bodies On Hydrogen Peroxide-Induced Damage Of Human Peripheral Blood Mononuclear Cells., Mohamad Fairus Abdul Kadir

Student Works (2010-2019)

Pleurotus sajor-caju authority is one of the mushroom species that is widely grown in Malaysia. The present study was undertaken to evaluate the antioxidant, cytotoxic, cytoprotective, genotoxic and genoprotective activities of crude water extracts of this mushroom. Crude aqueous extracts were prepared from the fruiting bodies that had been processed at different temperatures such as P1: blanching (95°C ± 2°C), P2: sun drying (30°C ± 2°C), P3: freeze drying (-46°C ± 3°C) and different temperatures of oven drying (P4: 45°C, P5: 50°C, P5: 55°C and P6: 60°C ± 2°C respectively). Antioxidant capacity of all the extracts was determined using ferric …

Phosphorylation Of The Glycine Transporter 1, Javier Vargas Medrano

Open Access Theses & Dissertations

The extracellular levels of the neurotransmitter glycine in the brain are tightly regulated by the high-affinity glycine transporter 1 (GlyT1) and the clearance of glycine depends on its rate of transport and the levels of cell surface GlyT1. Over the past years, it has been shown that PKC activation diminishes the activity and promoted phosphorylation of several neurotransmitter transporters including the dopamine, serotonin and norepinephrine transporters however, its role is unknown for the glycine transporter. To get insights into the role of PKC activation on GlyT1 regulation, we used three N-terminus GlyT1 isoforms stably expressed in porcine aortic endothelial (PAE) …

Pattern Recognition In Cytopathology For Papanicolaou Screening, Jonathan Blackledge, Dmitriy Dubovitskiy

Conference papers

A unique space oriented filer is presented in order to detect and isolate the cell of a nucleus for applications in cytopathology. A classification method for nuclei is then considered based on the application of a set of features which includes certain fractal parameters. Segmentation algorithms are considered in which a self-adjustable sharpening filter is designed to enhance object location. Although the methods discussed and the algorithms developed have a range of applications, in this work we focus the engineering of a system for automating a Papanicolaou screening test using standard optical images

The Cellular And Genetic Mechanisms Underlying Morphological Diversity Of Insects, Nataliya Turchyn

Wayne State University Dissertations

The vast diversity of insect appendages provides an excellent model for examining the cellular and molecular basis of phenotypic changes in nature. One of the hallmarks of evolution of insect appendages is the differential enlargement of hind (T3) legs compared to their fore (T1) and mid (T2) counterparts. While basic information regarding the genetic mechanisms that regulate the size of the T3 legs became available in the past several years, virtually nothing is known about cellular mechanisms involved. To address this issue, we measured the relative mitotic activity (RMA) in Acheta domesticus (house cricket) and Oncopeltus fasciatus (milkweed bug), two …

Regulatory And Functional Aspects Of Foxo3a Transcription Factor And Their Implications In Prostate Cancer, Melissa Elise Dobson

Wayne State University Dissertations

The P13K/Akt pathway is a critical mediator of growth factor signaling involving many cellular functions. The deregulation of this pathway has been shown to be involved in the development of various cancers. One of the main targets of this pathway is FoxO3a, a transcription factor whose target genes are involved in important cellular processes such as apoptosis, cell cycle control, and glucose metabolism. FoxO3a is regulated by various post translational modifications including acetylation, ubiquitination and phosphorylation. The transcription factor is directly phosphorylated by Akt on 3 residues: Threonine 32, Serine 253 and Serine 315. Phosphorylation by Akt generates binding sites …

The Role Of Ledgf/P75 In Transcriptional Regulation, Jeffrey Ryan Kugelman

Open Access Theses & Dissertations

The Lens Epithelial Derived Growth Factor p75 (LEDGF/p75) is a chromatin bound protein whose cellular function is not yet clearly known. A role in transcriptional regulation had been previously proposed based on its interaction with the basal transcriptional machinery and on its effects on the expression of genes involved in the cellular response to environmental stresses. To further elucidate the function of LEDGF/p75, we conducted a global and unbiased evaluation of the role of this protein in gene expression. To that aim, we performed a microarray analysis of cellular gene expression in cells that are severely depleted of LEDGF/p75. To …

Neuroaids In Africa, Kevin Robertson, Jeff Liner, James Hakim, Jean-Louis Sankalé, Igor Grant, Scott Letendre, David Clifford, Amadou Gallo Diop, Assan Jaye, Georgette Kanmogne, Alfred Njamnshi, T. Dianne Langford, Tufa Gemechu Weyessa, Charles Wood, Mwanza Banda, Mina Hosseinipour, Ned Sacktor, Noeline Nakasuja, Paul Bangirana, Robert Paul, John Joska, Joseph Wong, Michael Boivin, Penny Holding, Betsy Kammerer, Annelies Van Rie, Prudence Ive, Avindra Nath, Kathy Lawler, Clement Adebamowo, Walter Royal Iii, Jeymohan Joseph

Nebraska Center for Virology: Faculty Publications

In July 2009, the Center for Mental Health Research on AIDS at the National Institute of Mental Health organized and supported the meeting “NeuroAIDS in Africa.” This meeting was held in Cape Town, South Africa, and was affiliated with the 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention. Presentations began with an overview of the epidemiology of HIV in sub-Saharan Africa, the molecular epidemiology of HIV, HIV-associated neurocognitive disorders (HANDs), and HAND treatment. These introductory talks were followed by presentations on HAND research and clinical care in Botswana, Cameroon, Ethiopia, The Gambia, Kenya, Malawi, Nigeria, Senegal, South Africa, Uganda, …

Functional Properties Of The Hiv-1 Subtype C Envelope Glycoprotein Associated With Mother-To-Child Transmission, Hong Zhang, Marzena Rola, John T. West, Damien C. Tully, Piotr Kubis, Jun He, Chipepo Kankasa, Charles Wood

Nebraska Center for Virology: Faculty Publications

Understanding the properties of viruses capable of establishing infection during perinatal transmission of HIV-1 is critical for designing effective means of limiting transmission. We previously demonstrated that the newly transmitted viruses (in infant) were more fit in growth, as imparted by their envelope glycoproteins, than those in their corresponding mothers. Here, we further characterized the viral envelope glycoproteins from six mother-infant transmission pairs and determined whether any specific envelope functions correlate with HIV-1 subtype C perinatal transmission. We found that most newly transmitted viruses were less susceptible to neutralization by their maternal plasma compared to contemporaneous maternal viruses. However, the …

Chronology And Evolution Of The Hiv-1 Subtype C Epidemic In Ethiopia, Damien C. Tully, Charles Wood

Nebraska Center for Virology: Faculty Publications

Objective—To reconstruct the onset date and evolutionary history of the HIV-1 subtype C epidemic in Ethiopia - one of the earliest recorded subtype C epidemics in the world.

Design—HIV-1 C env sequences with a known sampling year isolated from HIV-1 positive patients from Ethiopia between 1984 and 2003.

Methods—Evolutionary parameters including origin and demographic growth patterns were estimated using a Bayesian coalescent-based approach under either strict or relaxed molecular clock models.

Results—Bayesian evolutionary analysis indicated a most recent common ancestor date of 1965 with three distinct epidemic growth phases. Regression analysis of root-to-tip distances revealed a highly similar estimate for …

Enhancement Of Autophagy During Lytic Replication By The Kaposi’S Sarcoma-Associated Herpesvirus Replication And Transcription Activator, Hui-Ju Wen, Zhilong Yang, You Zhou, Charles Wood

Nebraska Center for Virology: Faculty Publications

Autophagy is one of two major degradation systems in eukaryotic cells. The degradation mechanism of autophagy is required to maintain the balance between the biosynthetic and catabolic processes and also contributes to defense against invading pathogens. Recent studies suggest that a number of viruses can evade or subvert the host cell autophagic pathway to enhance their own replication. Here, we investigated the effect of autophagy on the KSHV (Kaposi’s sarcoma-associated herpesvirus) life cycle. We found that the inhibition of autophagy reduces KSHV lytic reactivation from latency, and an enhancement of autophagy can be detected during KSHV lytic replication. In addition, …

Induction Of Interferon And Interferon Signaling Pathways By Replication Of Defective Interfering Particle Rna In Cells Constitutively Expressing Vesicular Stomatitis Virus Replication Proteins, Debasis Panda, Phat X. Dinh, Lalit Beura, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

We show here that replication of defective interfering (DI) particle RNA in HEK293 cells stably expressing vesicular stomatitis virus (VSV) replication proteins potently activates interferon (IFN) and IFN signaling pathways through upregulation of IFN- promoter, IFN-stimulated response element (ISRE) promoter, and NF-κB promoter activities. Replication of DI particle RNA, not mere expression of the viral replication proteins, was found to be critical for induction of IFN and IFN signaling. The stable cells supporting replication of DI RNA described in this report will be useful in further examining the innate immune signaling pathways and the host cell functions in viral genome …

Towards An Understanding Of The Herpes Simplex Virus Type 1 Latency-Reactivation Cycle, Guey-Chuen Perng, Clinton Jones

School of Veterinary and Biomedical Sciences: Faculty Publications

Infection by herpes simplex virus type 1 (HSV-1) can cause clinical symptoms in the peripheral and central nervous system. Recurrent ocular shedding can lead to corneal scarring and vision loss making HSV-1 a leading cause of corneal blindness due to an infectious agent. The primary site of HSV-1 latency is sensory neurons within trigeminal ganglia. Periodically, reactivation from latency occurs resulting in virus transmission and recurrent disease. During latency, the latency-associated transcript (LAT) is abundantly expressed. LAT expression is important for the latency-reactivation cycle in animal models, in part, because it inhibits apoptosis, viral gene expression, and productive infection. A …

Method For Identification Of Virulence Determinants, Raul G. Barletta, Beth Harris

School of Veterinary and Biomedical Sciences: Faculty Publications

Disclosed are methods for the determination of virulence determinants in bacteria and in particular bacteria of the genus Mycobacterium. Also disclosed are compositions and methods for stimulating an immune response in an animal using bacteria and virulence determinants identified by the methods of the present invention.

Expression Of Hcmv Ie1 In The U87mg Cell Line Augments Resistance To Temozolomide , Richard A. Rovin, Johnathan Lawrence, Justin J. Segula, Robert J. Winn

Journal Articles

INTRODUCTION: Human cytomegalovirus (HCMV) DNA and protein are found in gliomas but not in normal brain or other primary brain tumors. The role of HCMV infection in glioma biology is unclear. While it is unlikely that HCMV infection causes glioma, viral proteins might impart a proliferative and antiapoptotic phenotype that confers a survival advantage. Does this oncomodulation translate into a clinically relevant effect in glioma cells? To answer this question, we compared the response of the U87IE1 and U87MG malignant glioma cell lines to temozolomide. U87IE1 cells are U87MG cells that have been genetically engineered to produce HCMV IE1 protein. …

Adjacent Slice Prostate Cancer Prediction To Inform Maldi Imaging Biomarker Analysis, Shao-Hui Chuang, Xiaoyan Sun, Lisa Cazares, Julius Nyalwidhe, Dean Troyer, O. John Semmes, Jiang Li, Frederic D. Mckenzie, Nico Karssemeijer (Ed.), Ronald M. Summers (Ed.)

Electrical & Computer Engineering Faculty Publications

Prostate cancer is the second most common type of cancer among men in US [1]. Traditionally, prostate cancer diagnosis is made by the analysis of prostate-specific antigen (PSA) levels and histopathological images of biopsy samples under microscopes. Proteomic biomarkers can improve upon these methods. MALDI molecular spectra imaging is used to visualize protein/peptide concentrations across biopsy samples to search for biomarker candidates. Unfortunately, traditional processing methods require histopathological examination on one slice of a biopsy sample while the adjacent slice is subjected to the tissue destroying desorption and ionization processes of MALDI. The highest confidence tumor regions gained from the …

Matriptase/Pdgf D/Beta-Pdgfr Signaling Axis In Human Prostate Cancer: The Role Of Pten In The Regulation Of Pdgf D Expression, M. Katie Conley-Lacomb

Wayne State University Dissertations

Platelet Derived Growth Factor (PDGF) is a family of mesenchymal growth factors that regulate cell proliferation, migration, and differentiation. Unlike the classic PDGF ligands A and B, which are secreted as active dimers, PDGF D must undergo extracellular proteolytic processing to remove its N-terminal CUB domain from the C-terminal PDGF growth domain before the ligand is able to stimulate its receptor, PDGF receptor beta (?-PDGFR). Importantly, recent clinical studies have shown that ?-PDGFR is upregulated in primary prostate cancer and bone metastases. However, PDGF B, formerly thought to be the sole ligand for ?-PDGFR, is not expressed in clinical prostate …

Chapter 27 – Studying Plus-End Tracking At Single Molecule Resolution Using Tirf Microscopy, Ram Dixit, Jennifer L. Ross

Biology Faculty Research

The highly dynamic microtubule plus-ends are key sites of regulation that impact the organization and function of the microtubule cytoskeleton. Much of this regulation is performed by the microtubule plus-end tracking (+TIP) family of proteins. +TIPs are a structurally diverse group of proteins that bind to and track with growing microtubule plus-ends in cells. +TIPs regulate microtubule dynamics as well as mediate interactions between microtubule tips and other cellular structures. Most +TIPs can directly bind to microtubules in vitro; however, the mechanisms for their plus-end specificity are not fully understood. Cellular studies of +TIP activity are complicated by the fact …

Afm Study Of Structural Changes In Supported Planar Dppc Bilayers Containing General Anesthetic Isofluorane (Plus Additional Afm Experiments), Chad Mckell, Hiram Conley, David D. Busath

Faculty Publications

Atomic force microscopy (AFM) is a remarkable tool for assessing the structural properties of supported lipid planar bilayers under different physiological conditions. Previous work has shown that incorporation of anesthetics into artificial lipid bilayers results in domain formation [1], destruction of lipid aggregates and patches [2], anesthetic-lipid mixed micelle formation [2], and the development of interdigitated phases of reduced thickness compared to anesthetic-free bilayers [3]. In particular, these interdigitated phases are suspected to affect the structure and activity of membrane proteins, such as ion channels, and thus further research with proteinembedded bilayers exposed to anesthetics could reveal the mechanism responsible …

The Lyme Disease Spirochete, Borrelia Burgdorferi, In Tick Species Collected From Raccoons (Procyon Lotor) And Opossums (Didelphis Virginiana) Trapped In The Warren And Barren Counties Of South Central Kentucky, Kristina Tackett

Masters Theses & Specialist Projects

The incidence of tick-borne zoonoses such as Ehrlichiosis, Rocky Mountain Spotted Fever, and Lyme disease has steadily increased in the southeastern United States in recent years. According to the Centers for Disease Control and Prevention (CDC), the southeastern states accounted for 1,200 of the 27,000 total cases of Lyme disease reported in the U.S. in 2007. Although Ixodes scapularis is the most commonly recognized vector for the Lyme disease spirochete Borrelia burgdorferi, Dermacentor variabilis (a common vector for Rocky Mountain Spotted Fever) also has been shown to be a viable host for this pathogen. The purpose of the present …

Cloning Of "Animal Cryptochrome" Cdna From The Model Organism Chlamydomonas Reinhardtii For Functional Analysis Of Its Protein Product, Shobha Lavanya Silparasetty

Masters Theses & Specialist Projects

reinhardtii, a unicellular green alga, is a model organism to study the circadian clock. Cryptochromes are the blue light photoreceptors that entrain the clock in some organisms. The CPH1 protein of C. reinhardtii resembles the cryptochromes of the plant model Arabidopsis, but whether CPH1 entrains the circadian clock in C. reinhardtii is not yet known. Recent reports have suggested the existence of one more cryptochrome in C. reinhardtii, which resembles the cryptochromes of animals. However, the amino acid sequence of this protein shows even higher sequence similarity with the 6-4 DNA photolyase of Arabidopsis. DNA photolyases …

The Role Of Multiple Ccaat-Binding Factors In Candida Albicans Gene Expression, Lashall Lynn Bates

Graduate Theses and Dissertations

The CCAAT-binding factor is a heterooligomeric transcription factor that is evolutionarily conserved in eukaryotes. In yeast, the DNA-binding component that interacts with the CCAAT consensus sequence in promoters consists of the subunits termed Hap2p, Hap3p and Hap5p. In yeast and fungi, a fourth subunit, Hap4p, is required for regulating gene expression. The goal of this research is to understand the function of the Candida albicans CCAAT-binding factor and how it relates to virulence and pathogenicity. C. albicans is a human opportunistic pathogen responsible for a variety of mucosal and systemic infections that result in significant morbidity and mortality, particularly in …

Inhibition Of Pi 3-Kinase Signaling Contributes To Metronidazole Resistance In The Protozoan Parasite, Entamoeba Histolytica, Rhonda Powell

All Theses

Amoebiasis is defined as an intestinal infection with the human protozoan parasite, Entamoeba histolytica; approximately 100,000 deaths annually can be attributed to amoebiasis. Disease states range from asymptomatic colonization to invasive amoebiasis, characterized by abdominal pain and dysentery. Dissemination to extraintestinal sites, such as the liver and/or brain, can occur. Vesicle trafficking is critical for parasite virulence, and multiple signaling cascades within the pathogen facilitate these events.
One important regulator of signal transduction is the tightly controlled PI 3-kinase (PI3K), which phosphorylates the lipid, phosphatidylinositol bisphosphate (PIP₂), producing phosphatidylinositol trisphosphate (PIP₃). Effector proteins, such as Akt, …