Cell and Developmental Biology Commons^™

Mechanisms Of Adenovirus-Mediated Autophagy, Erin White

Dissertations & Theses (Open Access)

A patient diagnosed with a glioma, generally, has an average of 14 months year to live after implementation of conventional therapies such as surgery, chemotherapy, and radiation. Glioblastomas are highly lethal because of their aggressive nature and resistance to conventional therapies and apoptosis. Thus other avenues of cell death urgently need to be explored. Autophagy, which is also known as programmed cell death type II, has recently been identified as an alternative mechanism to kill apoptosis- resistant cancer cells. Traditionally, researchers have studied how cells undergo autophagy during viral infection as an immune response mechanism, but recently researchers have discovered …

Effects Of Lactate Dehydrogenase Haplotypes And Body Condition On Beef Cow Production, Olfat Taleb Alaamri

Graduate Theses and Dissertations

Lactate dehydrogenase (LDH) catalyzes the conversion of the pyruvate to lactate (forward) or lactate to pyruvate (reverse) in the last step of glycolysis. Objectives were to document the effects of LDH haplotypes and its SNPs, found in the promoter and coding sequence site, and body condition on beef cow production. Four single nucleotide polymorphisms (SNP) of LDH-B and Five single nucleotide polymorphisms of LDH-A were detected. Eight haplotypes of LDH-B were assigned with the same order of SNPs: G-348A, A-261G, N-222D, and C541A and four haplotypes of LDH-A were assigned with the same order of SNPs: T-327G, D-263C, G390A, A406G, …

Embryonic Development Of The Grass Shrimp, Palaemonetes Pugio, And The Influence Of Salinity On Cardiac Physiology, Amie Lynn Romney

UNLV Theses, Dissertations, Professional Papers, and Capstones

The grass shrimp, Palaemonetes pugio, inhabit the brackish waters along the Atlantic coast of North America and are a key component of the estuarine ecosystem. These decapod shrimp can tolerate large fluctuations in environmental parameters including daily and seasonal fluctuations in salinity between 0 to 55 parts per thousand (seawater at 30-32 ppt). Any observed distribution patterns of adult P. pugio in relation to salinity may be accounted for by their relative ability to tolerate a range in salinity and their ability to maintain internal water volumes and cardiac performance in the earliest life stage, the embryonic period. This thesis …

Gata-Family Transcription Factors In Magnaporthe Oryzae, Cristian F. Quispe

Department of Agronomy and Horticulture: Dissertations, Theses, and Student Research

The filamentous fungus, Magnaporthe oryzae, responsible for blast rice disease, destroys around 10-30% of the rice crop annually. Infection begins when the specialized infection structure, the appressorium, generates enormous internal turgor pressure through the accumulation of glycerol. This turgor acts on a penetration peg emerging at the base of the cell, causing it to breach the leaf surface allowing its infection.

The enzyme trehalose-6- phosphate synthase (Tps1) is a central regulator of the transition from appressorium development to infectious hyphal growth. In the first chapter we show that initiation of rice blast disease requires a regulatory mechanism involving an …

Crosstalk Between R1175 Methylation And Y1173 Phosphorylation Negatively Modulates Egfr-Mediated Erk Activation, Jung-Mao Hsu

Dissertations & Theses (Open Access)

Post-translational protein modifications are critical regulators of protein functions as they expand the signaling potentials of the modified proteins, leading to diverse physiological consequences. Currently, increasing evidence suggests that protein methylation is as important as other post-translational modifications in the regulation of various biological processes. This drives us to ask whether methylation is involved in the EGFR (epidermal growth factor receptor) signaling, a biological process extensively regulated by multiple post-translational modifications including phosphorylation, glycosylation and ubiquitination. We found that EGFR R1175 is methylated by a protein arginine methyltransferase named PRMT5. During EGFR activation, PRMT5-mediated R1175 methylation specifically enhances EGF-induced EGFR …

Combating Bioterrorism: Purification And Structural Analysis Of The E3 Proteins Of The Venezuelan Equine Encephalitis Virus And The Chikungunya Virus, Tyshia Gwin

The Journal of Purdue Undergraduate Research

Outbreaks of the Venezuelan Equine Encephalitis Virus (VEEV) and the Chikungunya Virus (CHIKV) continue to emerge in Central and South America, Africa, and Asia, but there are currently no vaccines or anti-virals for these viruses. Given their ease of transmission, debilitating symptoms, and genetic alterability, VEEV and CHIKV have great potential for development into biological weapons. Therefore, there is an urgent need to determine possible methods of treatment or prevention. One possibility of prevention lies in determining the structure and biological function of the E3 protein that plays a key role in the infectivity of the viruses. In this research, …

Na/K-Atpase Mimetic Pnaktide Peptide Inhibits The Growth Of Human Cancer Cells, Zhichuan Li, Zhongbing Zhang, Joe X. Xie, Xin Li, Jiang Tian, Ting Cai, Hongaun Cui, Hanfei Ding, Joseph I. Shapiro Md, Zijian Xie

Biochemistry and Microbiology

Cells contain a large pool of non-pumping Na/K-ATPase that participates in signal transduction. Here, we show that the expression of α1 Na/K-ATPase is significantly reduced in human prostate carcinoma as well as in several human cancer cell lines. This down-regulation impairs the ability of Na/K-ATPase to regulate Src-related signaling processes. Supplement of pNaKtide, a peptide derived from α1 Na/K-ATPase, reduces activities of Src and Src effectors. Consequently, these treatments stimulate apoptosis and inhibit growth in cultures of human cancer cells. Moreover, administration of pNaKtide inhibits angiogenesis and growth of tumor xenograft. Thus, the new findings demonstrate the in vivo effectiveness …

Comparison Of Adenoviruses As Oncolytics And Cancer Vaccines In An Immunocompetent B Cell Lymphoma Model, Eric A. Weaver, Christopher Y. Chen, Shannon M. May, Mary E. Barry, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

We have screened human adenoviruses (Ads) for oncolytic activity against a variety of mouse and hamster cell lines and have found a number that are susceptible to a variety of Ad serotypes. A20 lymphoma is derived from BALB/c mice and is susceptible to infection and killing by a variety of human Ads. A20 is also a suitable cancer vaccine model, because these cells express a unique immunoglobulin variable region that can be targeted by vaccination. To compare Ads as cancer vaccines versus Ads as oncolytics, A20 tumors were initiated in immunocompetent BALB/c mice. Mice immunized with first-generation Ad5 expressing the …

Regulation Of Cytosolic Phospholipase A2 (Cpla2) And Its Association With Cell Proliferation In Human Lens Epithelial Cells, Yin Wang, Kui-Yi Xing, Marjorie F. Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

PURPOSE. To investigate the molecular mechanism for cytosolic phospholipase A2 (cPLA2) regulation and its association to platelet-derived growth factor (PDGF)-induced cell proliferation.

METHODS. cPLA2 was examined using human lens epithelial (HLE) B3 cells. Reactive oxygen species (ROS) generation induced by PDGF was analyzed by luminescence assay. Cell proliferation was measured by cell counting and by BrdU assay. Human cPLA2 gene was cloned via RT-PCR followed by sitedirected mutagenesis to construct HLE B3 cells expressing either inactive cPLA2 enzyme with S228A mutation (S228A), or cPLA2 truncated at the calcium-binding C2 domain (C2D). Activity of cPLA2 was measured by arachidonic acid (AA) …

Metastatic Disease: Interactions Between Tumor Cells And Host Environment During Cancer Cell Spread, Jennifer M. Maclean

Electronic Thesis and Dissertation Repository

Tumor and metastasis formation are not cell autonomous phenomena, but rather an evolution of disease within and responding to the host environment. Metastatic spread from a primary tumor occurs as a result of a complex interplay between tumor cells and the host, wherein tumor cells must escape the primary tumor, enter the host vasculature, travel to and arrest in a distant tissue and survive and grow in that new organ. It is known that cells that progress through these stages must both escape and exploit host systems, yet the mechanisms used are not fully understood. Therefore, the goal of this …

The Regulation Of Cell Division And Neurogenesis By The Chromatin Remodeling Protein Atrx, Kieran L. Ritchie

Electronic Thesis and Dissertation Repository

Mutations in the ATRX gene cause alpha thalassemia mental retardation X-linked syndrome (ATR-X). Individuals with ATR-X syndrome show a broad range of developmental abnormalities including severe cognitive, behavioural, and learning deficits, seizures, and microcephaly, indicating that ATRX is essential for normal development of the central nervous system. Conditional inactivation of Atrx in the developing mouse forebrain leads to a reduction in cerebral cortical size, elevated levels of p53-dependent neuronal apoptosis, and dysgenesis of certain subcortical structures, including the hippocampus and dentate gyrus, confirming a requirement for Atrx in mammalian brain development. The mammalian ATRX gene encodes a member of the …

Calcineurin Is Required For Trpv1-Induced Ltd Of Ca1 Stratum Radiatum Interneurons, Tyron Deray Jensen

Theses and Dissertations

Learning and memory in the brain are thought to be dependent on synaptic plasticity. In response to sensory input, synapses can be strengthened or weakened, known as long-term potentiation or long-term depression (LTD), respectively. Transient receptor potential vanilloid 1 (TRPV1) has been shown to mediate a novel form of presynaptic LTD in hippocampal interneurons. TRPV1 is currently being heavily studied in the PNS and being targeted by pharmaceuticals for its anti-nociceptive and anti-inflammatory properties. However, much less is known regarding TRPV1 function in the CNS, including the signal mechanism mediating hippocampal LTD despite its obvious importance. Here we performed whole-cell …

The Effects Of Β-Amyloid On Α7 Nicotinic Acetylcholine Receptors Expressed In Xenopus Oocytes, Malia L. Anderson

Theses and Dissertations

The exact mechanism and progression of Alzheimer's disease (AD) at present is not fully understood. In patients suffering from AD, damage to the hippocampal region and impairment of learning and memory is present. It is also known that a buildup of β-amyloid plaques occur in AD patients and that β-amyloid interacts with some subtypes of neuronal nicotinic acetylcholine receptors (neuronal nAChRs). These receptors are composed of five subunits. The most prevalent nAChR subunit composition through the brain as a whole is α7. Previous data produced from our lab suggests that α7 nAChRs are also one of the most prevalent subunits …

Nod2, Rip2 And Irf5 Play A Critical Role In The Type I Interferon Response To Mycobacterium Tuberculosis, Amit K. Pandey, Yibin Yang, Zhaozhao Jiang, Sarah M. Fortune, Francois Coulombe, Marcel A. Behr, Katherine A. Fitzgerald, Christopher M. Sassetti, Michelle A. Kelliher

Katherine A. Fitzgerald

While the recognition of microbial infection often occurs at the cell surface via Toll-like receptors, the cytosol of the cell is also under surveillance for microbial products that breach the cell membrane. An important outcome of cytosolic recognition is the induction of IFNalpha and IFNbeta, which are critical mediators of immunity against both bacteria and viruses. Like many intracellular pathogens, a significant fraction of the transcriptional response to Mycobacterium tuberculosis infection depends on these type I interferons, but the recognition pathways responsible remain elusive. In this work, we demonstrate that intraphagosomal M. tuberculosis stimulates the cytosolic Nod2 pathway that responds …

Generation Of A Kupffer Cell-Evading Adenovirus For Systemic And Liver-Directed Gene Transfer, Reeti Khare, Shannon M. May, Francesco Vetrini, Eric A. Weaver, Donna Palmer, Amanda Rosewell, Nathan Grove, Philip Ng, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

As much as 90% of an intravenously (i.v.) injected dose of adenovirus serotype 5 (Ad5) is absorbed and destroyed by liver Kupffer cells. Viruses that escape these cells can then transduce hepatocytes after binding factor X (FX). Given that interactions with FX and Kupffer cells are thought to occur on the Ad5 hexon protein, we replaced its exposed hypervariable regions (HVR) with those from Ad6. When tested in vivo in BALB/c mice and in hamsters, the Ad5/6 chimera mediated >10 times higher transduction in the liver. This effect was not due to changes in FX binding. Rather, Ad5/6 appeared to …

Mechanical Test Methods For Assessing Porcine Carotid And Uterine Artery Burst Pressure Following Ex Vivo Ultrasonic Ligature Seal And Transection, Carissa M. Krane, Margaret Pinnell, Courtney Gardner, Mercedes Thompson, James Coleman, Robert Wilkens

Biology Faculty Publications

A test method was developed to identify those variables important for assessing the performance of ultrasonic surgical devices in ex vivo ligature sealing of porcine carotid and uterine arteries. Ruggedness testing using a small sample size in pilot experiments was conducted using a newly developed test method in an effort to assess the usefulness of this methodology and to identify test variables that might warrant further testing. The development of this test method included the use of a custom-designed prototypic tension device for load-controlled ex vivo vessel stretching during saline perfusion and subsequent seal and transection of porcine arteries with …

Nanosecond Pulsed Electric Field Induction Of Programmed Cell Death Is Cell Type Dependent: An In Vitro Study, Wei Ren

Theses and Dissertations in Biomedical Sciences

Nanosecond pulsed electric fields (nsPEFs) present a novel and effective method for cancer ablation by eradicating the ubiquitous cancer hallmark of apoptosis evasion and enforcing cancer programmed cell death. To develop nsPEFs as an anticancer method, a comprehensive understanding of cell death mechanisms is required. The overall objective of this dissertation is to elucidate molecular mechanisms underlying effects of nsPEFs on E4 murine squamous cell carcinoma and human T-cell Jurkat clones that are wildtype, deficient in FADD (ΔFADD) and deficient in caspase-8 (ACas-8). The overall hypothesis is that nsPEFs eliminate cancer cells through activating caspase-dependent and caspase-independent programmed cell death …

Age-Related Hamster Mitochondrial Changes And Oocyte Changes Following Autologous Platelet Mitochondrial Microinjection, Fang Li

Theses and Dissertations in Biomedical Sciences

This study's objective was to verify age-related mitochondrial changes in oocytes from old hamsters compared with those from young hamsters. We used autologous platelet mitochondrial microinjection to improve the mitochondrial quality and quantity of aged oocytes to improve their pregnancy potential. Metaphase II oocytes were collected from super-ovulated female hamsters and prepared for biochemical and morphological analysis. Adenosine triphosphate (ATP) levels, mitochondrial DNA (mtDNA) number, reactive oxygen species (ROS) level and mitochondrial membrane potential (MMP) were determined in individual oocytes from young and old hamsters. Transmission electron microscopy (TEM) allowed evaluation of oocyte ultra-structure. In oocytes from old hamsters, ATP …

Altering Nitric Oxide Bioavailability And Lipid Profiles In Endothelial Cells By Polycyclic Aromatic Hydrocarbons In Particulate Matter, Liang Yu

Theses and Dissertations in Biomedical Sciences

Epidemiologic studies have demonstrated a significant association between exposure to particulate matter (PM) and atherosclerosis. Polycyclic aromatic hydrocarbons (PAHs) present in particulate matter, are well known to induce oxidative stress and lipid peroxidation via generation of reactive oxygen species (ROS). Lipid peroxidation involves regulating endothelial nitric oxide synthase via inhibition of its activity, and as a result, mediates dilation of coronary arterioles is involved with the pathogenesis of atherosclerosis. However, data on assessment of oxidized lipid formation is limited due to low resolution of mass spectrometer methods. Taking the advantage of a Fourier Transform Ion Cyclotron Resonance Mass Spectrometer (FT-ICR-MS) …

Transcription And Translation Of Human F11r Gene Are Required For An Initial Step Of Atherogenesis Induced By Inflammatory Cytokines, Bani M. Azari, Jonathan D. Marmur, Moro O. Salifu, Yigal H. Ehrlich, Elizabeth Kornecki, Anna Babinska

Publications and Research

Background - The F11 Receptor (F11R; aka JAM-A, JAM-1) is a cell adhesion protein present constitutively on the membrane surface of circulating platelets and within tight junctions of endothelial cells (ECs). Previous reports demonstrated that exposure of ECs to pro-inflammatory cytokines causes insertion of F11R molecules into the luminal surface of ECs, ensuing with homologous interactions between F11R molecules of platelets and ECs, and a resultant adhesion of platelets to the inflamed ECs. The main new finding of the present report is that the first step in this chain of events is the de-novo transcription and translation of F11R molecules, …