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Altering Oligomerization Of Epha2 Via Mutations In The Intracellular Domain, Ryan W. Lingerak 2018 The University of Akron

Altering Oligomerization Of Epha2 Via Mutations In The Intracellular Domain, Ryan W. Lingerak

Honors Research Projects

Eph receptor tyrosine kinases (RTKs) are activated by membrane-bound ligands called ephrins. Eph RTKs are divided into two subclasses, each activated by a specific classes of the ligand ephrin. The overexpression of Eph receptors is correlated to cancer cell metastasis in several different types of cancers. Studies with the EphA2 extracellular domain (ECD) and ephrinA1 ligand have shown that upon binding of ephrin to the receptor, EphA2 undergoes increased oligomerization and activation. This indicates that oligomerization is intimately connected to kinase activity. High resolution crystal structures of the EphA2 ECD have revealed some details of these ligand bound oligomers, as ...


Superresolution Imaging Identifies That Conventional Trafficking Pathways Are Not Essential For Endoplasmic Reticulum To Outer Mitochondrial Membrane Protein Transport., Kyle Salka, Shivaprasad Bhuvanendran, Kassandra Wilson, Petros Bozidis, Mansi Mehta, Kristin Rainey, Hiromi Sesaki, George H Patterson, Jyoti K. Jaiswal, Anamaris M. Colberg-Poley 2017 George Washington University

Superresolution Imaging Identifies That Conventional Trafficking Pathways Are Not Essential For Endoplasmic Reticulum To Outer Mitochondrial Membrane Protein Transport., Kyle Salka, Shivaprasad Bhuvanendran, Kassandra Wilson, Petros Bozidis, Mansi Mehta, Kristin Rainey, Hiromi Sesaki, George H Patterson, Jyoti K. Jaiswal, Anamaris M. Colberg-Poley

Integrative Systems Biology Faculty Publications

Most nuclear-encoded mitochondrial proteins traffic from the cytosol to mitochondria. Some of these proteins localize at mitochondria-associated membranes (MAM), where mitochondria are closely apposed with the endoplasmic reticulum (ER). We have previously shown that the human cytomegalovirus signal-anchored protein known as viral mitochondria-localized inhibitor of apoptosis (vMIA) traffics from the ER to mitochondria and clusters at the outer mitochondrial membrane (OMM). Here, we have examined the host pathways by which vMIA traffics from the ER to mitochondria and clusters at the OMM. By disruption of phosphofurin acidic cluster sorting protein 2 (PACS-2), mitofusins (Mfn1/2), and dynamin related protein 1 ...


Effects Of Perceived Treatment On Quality Of Life And Medical Outcomesin A Double-Blind Placebo Surgery Trial, Cynthia McRae, Eva Cherin, T. Gayle Yamazaki, Gretchen Diem, Alexander H. Vo, Daniel W. Rusell, J. Heiner Ellgring, Stanley Fahn, Paul Greene, Sandra Dillon, Hal Winfield, Kimberly B. Bjugstad, Curt R. Freed 2017 University of Denver

Effects Of Perceived Treatment On Quality Of Life And Medical Outcomesin A Double-Blind Placebo Surgery Trial, Cynthia Mcrae, Eva Cherin, T. Gayle Yamazaki, Gretchen Diem, Alexander H. Vo, Daniel W. Rusell, J. Heiner Ellgring, Stanley Fahn, Paul Greene, Sandra Dillon, Hal Winfield, Kimberly B. Bjugstad, Curt R. Freed

Daniel W. Russell

Context This study was part of a large double-blind sham surgery–controlled trial designed to determine the effectiveness of transplantation of human embryonic dopamine neurons into the brains of persons with advanced Parkinson's disease. This portion of the study investigated the quality of life (QOL) of participants during the 1 year of double-blind follow-up. Objectives To determine whether QOL improved more in the transplant group than in the sham surgery group and to investigate outcomes at 1 year based on perceived treatment (the type of surgery patients thought they received). Design Participants were randomly assigned to receive either the ...


Engineering And Verifying Requirements For Programmable Self-Assembling Nanomachines, Robyn Lutz, Jack Lutz, James Lathrop, Titus Klinge, Eric Henderson, Davita Mathur, Dalia Abo Sheasha 2017 Iowa State University

Engineering And Verifying Requirements For Programmable Self-Assembling Nanomachines, Robyn Lutz, Jack Lutz, James Lathrop, Titus Klinge, Eric Henderson, Davita Mathur, Dalia Abo Sheasha

Robyn Lutz

We propose an extension of van Lamsweerde's goal-oriented requirements engineering to the domain of programmable DNA nanotechnology. This is a domain in which individual devices (agents) are at most a few dozen nanometers in diameter. These devices are programmed to assemble themselves from molecular components and perform their assigned tasks. The devices carry out their tasks in the probabilistic world of chemical kinetics, so they are individually error-prone. However, the number of devices deployed is roughly on the order of a nanomole (a 6 followed by fourteen 0s), and some goals are achieved when enough of these agents achieve ...


Requirements Analysis For A Product Family Of Dna Nanodevices, Robyn R. Lutz, Jack H. Lutz, James I. Lathrop, Titus H. Klinge, Divita Mathur, D. M. Stull, Taylor G. Bergquist, Eric R. Henderson 2017 Iowa State University

Requirements Analysis For A Product Family Of Dna Nanodevices, Robyn R. Lutz, Jack H. Lutz, James I. Lathrop, Titus H. Klinge, Divita Mathur, D. M. Stull, Taylor G. Bergquist, Eric R. Henderson

Robyn Lutz

DNA nanotechnology uses the information processing capabilities of nucleic acids to design self-assembling, programmable structures and devices at the nanoscale. Devices developed to date have been programmed to implement logic circuits and neural networks, capture or release specific molecules, and traverse molecular tracks and mazes. Here we investigate the use of requirements engineering methods to make DNA nanotechnology more productive, predictable, and safe. We use goal-oriented requirements modeling to identify, specify, and analyze a product family of DNA nanodevices, and we use PRISM model checking to verify both common properties across the family and properties that are specific to individual ...


Automated Requirements Analysis For A Molecular Watchdog Timer, Samuel J. Ellis, Eric R. Henderson, Titus H. Klinge, James I. Lathrop, Jack H. Lutz, Robyn R. Lutz, Divita Mathur, Andrew S. Miner 2017 Iowa State University

Automated Requirements Analysis For A Molecular Watchdog Timer, Samuel J. Ellis, Eric R. Henderson, Titus H. Klinge, James I. Lathrop, Jack H. Lutz, Robyn R. Lutz, Divita Mathur, Andrew S. Miner

Robyn Lutz

Dynamic systems in DNA nanotechnology are often programmed using a chemical reaction network (CRN) model as an intermediate level of abstraction. In this paper, we design and analyze a CRN model of a watchdog timer, a device commonly used to monitor the health of a safety critical system. Our process uses incremental design practices with goal-oriented requirements engineering, software verification tools, and custom software to help automate the software engineering process. The watchdog timer is comprised of three components: an absence detector, a threshold filter, and a signal amplifier. These components are separately designed and verified, and only then composed ...


Molecular Mechanisms Of Mycoplasma Hyopneumoniae Adherence To Swine Respiratory Epithelial Cells, Qijing Zhang 2017 Iowa State University

Molecular Mechanisms Of Mycoplasma Hyopneumoniae Adherence To Swine Respiratory Epithelial Cells, Qijing Zhang

Qijing Zhang

A microtiter plate adherence assay for Mycoplasma hyopneumoniae was established by using purified swine tracheal cilia which are the natural targets for the mycoplasma. M. hyopneumoniae bound specifically to solubilized cilia immobilized onto microtiter plates. Dextran sulfate, heparin, chondroitin sulfate, laminin, mucin, and fucoidan significantly inhibited binding of the mycoplasmas to cilia. Heparin, mucin, fucoidan, and chondroitin sulfate interacted with the adhesins on the surface of mycoplasmas, whereas laminin blocked the receptors in cilia. Treatment of cilia with neuraminidase appeared to promote adherence of the mycoplasmas; whereas, treatment of cilia with sodium metaperiodate decreased the binding. In the second study ...


Impact Of The C-Mybe308g Mutation On Mouse Myelopoiesis And Dendritic Cell Development, Peter Papathanasiou, Sawang Petvises, Ying-Ying Hey, Andrew C Perkins, Helen C O'Neill 2017 Australian National University

Impact Of The C-Mybe308g Mutation On Mouse Myelopoiesis And Dendritic Cell Development, Peter Papathanasiou, Sawang Petvises, Ying-Ying Hey, Andrew C Perkins, Helen C O'Neill

Helen O'Neill

Booreana mice carrying the c-Myb308G point mutation were analyzed to determine changes in early hematopoiesis in the bone marrow and among mature cells in the periphery. This point mutation led to increased numbers of early hematopoietic stem and progenitor cells (HSPCs), with a subsequent reduction in the development of B cells, erythroid cells, and neutrophils, and increased numbers of myeloid cells and granulocytes. Myelopoiesis was further investigated by way of particular subsets affected. A specific question addressed whether booreana mice contained increased numbers of dendritic-like cells (L-DC subset) recently identified in the spleen, since L-DCs arise in vitro by direct ...


The Glia Response After Peripheral Nerve Injury: A Comparison Between Schwann Cells And Olfactory Ensheathing Cells And Their Uses For Neural Regenerative Therapies, Matthew J Barton, James St John, Alison Wright, Jenny Ekberg 2017 Griffith University Queensland

The Glia Response After Peripheral Nerve Injury: A Comparison Between Schwann Cells And Olfactory Ensheathing Cells And Their Uses For Neural Regenerative Therapies, Matthew J Barton, James St John, Alison Wright, Jenny Ekberg

Jenny Ekberg

The peripheral nervous system (PNS) exhibits a much larger capacity for regeneration than the central nervous system (CNS). One reason for this difference is the difference in glial cell types between the two systems. PNS glia respond rapidly to nerve injury by clearing debris from the injury site, supplying essential growth factors and providing structural support; all of which enhances neuronal regeneration. Thus, transplantation of glial cells from the PNS is a very promising therapy for injuries to both the PNS and the CNS. There are two key types of PNS glia: olfactory ensheathing cells (OECs), which populate the olfactory ...


Rv0989c Encodes A Novel (E)-Geranyl Diphosphate Synthase Facilitating Decaprenyl Diphosphate Biosynthesis In Mycobacterium Tuberculosis, Francis M. Mann, Jill A. Thomas, Reuben J. Peters 2017 Iowa State University

Rv0989c Encodes A Novel (E)-Geranyl Diphosphate Synthase Facilitating Decaprenyl Diphosphate Biosynthesis In Mycobacterium Tuberculosis, Francis M. Mann, Jill A. Thomas, Reuben J. Peters

Reuben J. Peters

Mycobacterium tuberculosis (Mtb) has a highly complex cell wall, which is required for both bacterial survival and infection. Cell wall biosynthesis is dependent on decaprenyl diphosphate as a glyco-carrier, which is hence an essential metabolite in this pathogen. Previous biochemical studies indicated (E)-geranyl diphosphate (GPP) is required for the synthesis of decaprenyl diphosphate. Here we demonstrate that Rv0989c encodes the “missing” GPP synthase, representing the first such enzyme to be characterized from bacteria, and which presumably is involved in decaprenyl diphosphate biosynthesis in Mtb. Our investigation also has revealed previously unrecognized substrate plasticity of the farnesyl diphosphate synthases from ...


The Application Of Synthetic Biology To Elucidation Of Plant Mono-, Sesqui-, And Diterpenoid Metabolism, Naoki Kitaoka, Xuan Lu, Bing Yang, Reuben J. Peters 2017 Iowa State University

The Application Of Synthetic Biology To Elucidation Of Plant Mono-, Sesqui-, And Diterpenoid Metabolism, Naoki Kitaoka, Xuan Lu, Bing Yang, Reuben J. Peters

Reuben J. Peters

Plants synthesize a huge variety of terpenoid natural products, including photosynthetic pigments, signaling molecules and defensive substances. These are often produced as complex mixtures, presumably shaped by selective pressure over evolutionary timescales, some of which have been found to have pharmaceutical and other industrial uses. Elucidation of the relevant biosynthetic pathways can provide increased access (e.g., via molecular breeding or metabolic engineering), and enable reverse genetic approaches towards understanding the physiological role of these natural products in plants as well. While such information can be obtained via a variety of approaches, this review describes the emerging use of synthetic ...


Astrocyte-Derived Interleukin-6 Promotes Specific Neuronal Differentiation Of Neural Progenitor Cells From Adult Hippocampus, Jisun Oh, Michael A. McCloskey, Christopher C. Blong, Lee Bendickson, Marit Nilsen-Hamilton, Donald S. Sakaguchi 2017 Iowa State University

Astrocyte-Derived Interleukin-6 Promotes Specific Neuronal Differentiation Of Neural Progenitor Cells From Adult Hippocampus, Jisun Oh, Michael A. Mccloskey, Christopher C. Blong, Lee Bendickson, Marit Nilsen-Hamilton, Donald S. Sakaguchi

Marit Nilsen-Hamilton

The purpose of this study was to investigate the ability of astrocyte-derived factors to influence neural progenitor cell differentiation. We previously demonstrated that rat adult hippocampal progenitor cells (AHPCs) immunoreactive for the neuronal marker, class III β-tubulin (TUJ1) were significantly increased in the presence of astrocyte-derived soluble factors under non-contact co-culture conditions. Using whole cell patch clamp analysis, we observed that the co-cultured AHPCs displayed two prominent voltage-gated conductances - tetraethyl ammonium (TEA)- sensitive outward currents and fast transient inward currents. The outward and inward current densities of the co-cultured AHPCs were approximately 2.5-fold and 1.7-fold greater, respectively, than ...


Myo/Nog Cells: Targets For Preventing The Accumulation Of Skeletal Muscle-Like Cells In The Human Lens, Jacquelyn Gerhart, M. Greenbaum, V. Scheinfeld, P. Fitzgerald, M. Crawford, Arturo Bravo Nuevo, M. Pitts, Mindy George-Weinstein 2017 Philadelphia College of Osteopathic Medicine

Myo/Nog Cells: Targets For Preventing The Accumulation Of Skeletal Muscle-Like Cells In The Human Lens, Jacquelyn Gerhart, M. Greenbaum, V. Scheinfeld, P. Fitzgerald, M. Crawford, Arturo Bravo Nuevo, M. Pitts, Mindy George-Weinstein

Arturo Bravo-Nuevo

Posterior capsule opacification (PCO) is a vision impairing condition that arises in some patients following cataract surgery. The fibrotic form of PCO is caused by myofibroblasts that may emerge in the lens years after surgery. In the chick embryo lens, myofibroblasts are derived from Myo/Nog cells that are identified by their expression of the skeletal muscle specific transcription factor MyoD, the bone morphogenetic protein inhibitor Noggin, and the epitope recognized by the G8 monoclonal antibody. The goal of this study was to test the hypothesis that depletion of Myo/Nog cells will prevent the accumulation of myofibroblasts in human ...


Investigation Of The Chemical Interface In The Soybean–Aphid And Rice–Bacteria Interactions Using Maldi-Mass Spectrometry Imaging, Adam T. Klein, Gargey B. Yagnik, Jessica D. Hohenstein, Zhiyuan Ji, Jiachen Zi, Malinda D. Reichert, Gustavo C. Macintosh, Bing Yang, Reuben J. Peters, Javier Vela, Young Jin Lee 2017 Iowa State University

Investigation Of The Chemical Interface In The Soybean–Aphid And Rice–Bacteria Interactions Using Maldi-Mass Spectrometry Imaging, Adam T. Klein, Gargey B. Yagnik, Jessica D. Hohenstein, Zhiyuan Ji, Jiachen Zi, Malinda D. Reichert, Gustavo C. Macintosh, Bing Yang, Reuben J. Peters, Javier Vela, Young Jin Lee

Reuben J. Peters

Mass spectrometry imaging (MSI) is an emerging technology for high-resolution plant biology. It has been utilized to study plant–pest interactions, but limited to the surface interfaces. Here we expand the technology to explore the chemical interactions occurring inside the plant tissues. Two sample preparation methods, imprinting and fracturing, were developed and applied, for the first time, to visualize internal metabolites of leaves in matrix-assisted laser desorption ionization (MALDI)-MSI. This is also the first time nanoparticle-based ionization was implemented to ionize diterpenoid phytochemicals that were difficult to analyze with traditional organic matrices. The interactions between rice–bacterium and soybean ...


Tol2 Gene Trap Integrations In The Zebrafish Amyloid Precursor Protein Genes Appa And Aplp2 Reveal Accumulation Of Secreted App At The Embryonic Veins, Hsin-Kai Liao, Ying Wang, Kristin E. Watt, Qin Wen, Justin Breitback, Chelsy K. Kemmet, Karl J. Clark, Stephen C. Ekker, Jeffrey J. Essner, Maura McGrail 2017 Iowa State University

Tol2 Gene Trap Integrations In The Zebrafish Amyloid Precursor Protein Genes Appa And Aplp2 Reveal Accumulation Of Secreted App At The Embryonic Veins, Hsin-Kai Liao, Ying Wang, Kristin E. Watt, Qin Wen, Justin Breitback, Chelsy K. Kemmet, Karl J. Clark, Stephen C. Ekker, Jeffrey J. Essner, Maura Mcgrail

Jeffrey J. Essner

Background—The single spanning transmembrane amyloid precursor protein (APP) and its proteolytic product, amyloid-beta (Aβ) peptide, have been intensely studied due to their role in the pathogenesis of Alzheimer’s disease. However, the biological role of the secreted ectodomain of APP, which is also generated by proteolytic cleavage, is less well understood. Here, we report Tol2 red fluorescent protein (RFP) transposon gene trap integrations in the zebrafish amyloid precursor protein a (appa) and amyloid precursor-like protein 2 (aplp2) genes. The transposon integrations are predicted to disrupt the appa and aplp2 genes to primarily produce secreted ectodomains of the corresponding proteins ...


Moesin1 And Ve-Cadherin Are Required In Endothelial Cells During In Vivo Tubulogenesis, Ying Wang, Mark S. Kaiser, Jon D. Larson, Aidas Nasevicius, Karl J. Clark, Shannon A. Wadman, Sharon E. Roberg-Perez, Stephen C. Ekker, Perry B. Hackett, Maura McGrail, Jeffrey J. Essner 2017 Iowa State University

Moesin1 And Ve-Cadherin Are Required In Endothelial Cells During In Vivo Tubulogenesis, Ying Wang, Mark S. Kaiser, Jon D. Larson, Aidas Nasevicius, Karl J. Clark, Shannon A. Wadman, Sharon E. Roberg-Perez, Stephen C. Ekker, Perry B. Hackett, Maura Mcgrail, Jeffrey J. Essner

Jeffrey J. Essner

Endothelial tubulogenesis is a crucial step in the formation of functional blood vessels during angiogenesis and vasculogenesis. Here, we use in vivo imaging of living zebrafish embryos expressing fluorescent fusion proteins of β-Actin, α-Catenin, and the ERM family member Moesin1 (Moesin a), to define a novel cord hollowing process that occurs during the initial stages of tubulogenesis in intersegmental vessels (ISVs) in the embryo. We show that the primary lumen elongates along cell junctions between at least two endothelial cells during embryonic angiogenesis. Moesin1-EGFP is enriched around structures that resemble intracellular vacuoles, which fuse with the luminal membrane during expansion ...


Mutations In Tubb8 And Human Oocyte Meiotic Arrest, Ruizhi Feng, Qing Sang, Yanping Kuang, Xiaoxi Sun, Zheng Yan, Shaozhen Zhang, Juanzi Shi, Guoling Tian, Anna Luchniak, Yusuke Fukuda, Bin Li, Min Yu, Junling Chen, Yao Xu, Luo Guo, Ronggui Qu, Xueqian Wang, Zhaogui Sun, Miao Liu, Huijuan Shi, Hongyan Wang, Yi Feng, Ruijin Shao, Renjie Chai, Qiaoli Li, Qinghe Xing, Rui Zhang, Eva Nogales, Li Jin, Lin He, Mohan L. Gupta Jr., Nicholas J. Cowan, Lei Wang 2017 Fudan University

Mutations In Tubb8 And Human Oocyte Meiotic Arrest, Ruizhi Feng, Qing Sang, Yanping Kuang, Xiaoxi Sun, Zheng Yan, Shaozhen Zhang, Juanzi Shi, Guoling Tian, Anna Luchniak, Yusuke Fukuda, Bin Li, Min Yu, Junling Chen, Yao Xu, Luo Guo, Ronggui Qu, Xueqian Wang, Zhaogui Sun, Miao Liu, Huijuan Shi, Hongyan Wang, Yi Feng, Ruijin Shao, Renjie Chai, Qiaoli Li, Qinghe Xing, Rui Zhang, Eva Nogales, Li Jin, Lin He, Mohan L. Gupta Jr., Nicholas J. Cowan, Lei Wang

Mohan Gupta, Jr.

BACKGROUND Human reproduction depends on the fusion of a mature oocyte with a sperm cell to form a fertilized egg. The genetic events that lead to the arrest of human oocyte maturation are unknown.

METHODS We sequenced the exomes of five members of a four-generation family, three of whom had infertility due to oocyte meiosis I arrest. We performed Sanger sequencing of a candidate gene, TUBB8, in DNA samples from these members, additional family members, and members of 23 other affected families. The expression of TUBB8 and all other β-tubulin isotypes was assessed in human oocytes, early embryos, sperm cells ...


Diverse Stimuli Engage Different Neutrophil Extracellular Trap Pathways, Elaine F. Kenny, Alf Herzig, Renate Krüger, Aaron Muth, Santanu Mondal, Paul R. Thompson, Volker Brinkmann, Horst Von Bernuth, Arturo Zychlinsky 2017 Max Planck Institute for Infection Biology

Diverse Stimuli Engage Different Neutrophil Extracellular Trap Pathways, Elaine F. Kenny, Alf Herzig, Renate Krüger, Aaron Muth, Santanu Mondal, Paul R. Thompson, Volker Brinkmann, Horst Von Bernuth, Arturo Zychlinsky

Thompson Lab Publications

Neutrophils release neutrophil extracellular traps (NETs) which ensnare pathogens and have pathogenic functions in diverse diseases. We examined the NETosis pathways induced by five stimuli; PMA, the calcium ionophore A23187, nigericin, Candida albicans and Group B Streptococcus. We studied NET production in neutrophils from healthy donors with inhibitors of molecules crucial to PMA induced NETs including protein kinase C, calcium, reactive oxygen species, the enzymes myeloperoxidase (MPO) and neutrophil elastase. Additionally, neutrophils from chronic granulomatous disease patients, carrying mutations in the NADPH oxidase complex or a MPO-deficient patient were examined. We show that PMA, C. albicans and GBS use a ...


The P53 Independent Functions Of Estrogen-Activated Mdm2 In Cell Signaling And Mammary Architecture, Nandini Kundu 2017 The Graduate Center, City University of New York

The P53 Independent Functions Of Estrogen-Activated Mdm2 In Cell Signaling And Mammary Architecture, Nandini Kundu

All Graduate Works by Year: Dissertations, Theses, and Capstone Projects

Estrogen receptor positive (ER+) breast cancers often have MDM2 overexpression indicating a critical role for MDM2 in breast cancer tumorigenesis. The cancer genome atlas (TCGA) found that increased MDM2 expression is one of the four pathways that correlate with all breast cancer subtypes. MDM2 is mainly known as the negative regulator of wild type p53. However, aggressive breast cancers often have MDM2 overexpression and mutant p53 (mtp53). We previously reported that MDM2 provides an estrogen-mediated proliferative advantage to MCF-7 breast cancer cells (ER+, MDM2 overexpression, wild type p53), independent of wild type p53 in both 2D and 3D culture conditions ...


Body Size Regulation Via Bmp Signaling In Caenorhabditis Elegans, Uday Madaan 2017 The Graduate Center, City University of New York

Body Size Regulation Via Bmp Signaling In Caenorhabditis Elegans, Uday Madaan

All Graduate Works by Year: Dissertations, Theses, and Capstone Projects

The body size of an organism can be a crucial determinant of access to nutrition, reproductive success and overall survival in the wild. However, how body size of an individual is determined is incompletely understood. Body size is a complex trait determined by multiple pathways and genes, making it difficult to understand the role of individual genes and pathways in determining overall size. In Caenorhabditis elegans, a homolog of Bone Morphogenetic Proteins (BMP) is a major regulator of body size; functional loss of DBL-1 leads to a small body size. Due to a drastic change in body size in dbl-1 ...


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