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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 ...


Use Of Imaging Biomarkers To Assess Perfusion And Glucose Metabolism In The Skeletal Muscle Of Dystrophic Mice, Nabeel Ahmad, Ian Welch, Robert Grange, Jennifer Hadway, Savita Dhanvantari, David Hill, Ting-Yim Lee, Lisa M Hoffman 2017 The University of Western Ontario

Use Of Imaging Biomarkers To Assess Perfusion And Glucose Metabolism In The Skeletal Muscle Of Dystrophic Mice, Nabeel Ahmad, Ian Welch, Robert Grange, Jennifer Hadway, Savita Dhanvantari, David Hill, Ting-Yim Lee, Lisa M Hoffman

Lisa Hoffman

BACKGROUND: Duchenne muscular dystrophy (DMD) is a severe neuromuscular disease that affects 1 in 3500 boys. The disease is characterized by progressive muscle degeneration that results from mutations in or loss of the cytoskeletal protein, dystrophin, from the glycoprotein membrane complex, thus increasing the susceptibility of contractile muscle to injury. To date, disease progression is typically assessed using invasive techniques such as muscle biopsies, and while there are recent reports of the use of magnetic resonance, ultrasound and optical imaging technologies to address the issue of disease progression and monitoring therapeutic intervention in dystrophic mice, our study aims to validate ...


Modulation Of Cellular Energetics By Galactose And Pioglitazone., David Grimm, Leonardo Altamirano, Sudip Paudel, Leah Welker, Mary E. Konkle, Nilay Chakraborty, Michael A. Menze 2017 Eastern Illinois University

Modulation Of Cellular Energetics By Galactose And Pioglitazone., David Grimm, Leonardo Altamirano, Sudip Paudel, Leah Welker, Mary E. Konkle, Nilay Chakraborty, Michael A. Menze

Michael A. Menze

The Warburg effect is ameliorated by culturing transformed cells in the presence of galactose instead of glucose as the primary carbon source. However, metabolic consequences that are in addition to sensitizing the cells to mitochondrial toxins may occur. As such, the screening of pharmaceutical agents against transformed cells while using galactose must be carefully evaluated. Pioglitazone is used in clinical applications to treat type-2 diabetes, but clearly has other off target effects. Human hepatocellular carcinoma cells (HepG2) were cultured in glucose or galactosecontaining medium to investigate the role of pioglitazone on cellular bioenergetics employing calorimetry and respirometry. Compared to cells ...


Contribution Of Activating Transcription Factor 3 To Development Of Acinar-To-Ductal Cell Metaplasia, Jelena Toma 2017 The University of Western Ontario

Contribution Of Activating Transcription Factor 3 To Development Of Acinar-To-Ductal Cell Metaplasia, Jelena Toma

Electronic Thesis and Dissertation Repository

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death in North America. The highest risk factor for PDAC is recurrent pancreatitis. While the link between PDAC and pancreatitis is unknown, de-differentiation of acinar cells is common to both diseases. Our lab has shown that Activating Transcription Factor 3 (ATF3), a factor upregulated during pancreatic injury, contributes to the development of acinar-to-ductal cell metaplasia (ADM), a precursor phenotype of PDAC. The goal of this study was to identify how ATF3 contributes to ADM. I hypothesize that ATF3 regulates acinar gene expression promoting ADM. We observed decreased ADM development ...


Reverse-Genetic Analysis Of The Two Biotin-Containing Subunit Genes Of The Heteromeric Acetyl-Coenzyme A Carboxylase In Arabidopsis Indicates A Unidirectional Functional Redundancy, Xu Li, Hilal Ilarslan, Libuse Brachova, Hui-Rong Qian, Ling Li, Ping Che, Eve Syrkin Wurtele, Basil J. Nikolau 2017 Iowa State University

Reverse-Genetic Analysis Of The Two Biotin-Containing Subunit Genes Of The Heteromeric Acetyl-Coenzyme A Carboxylase In Arabidopsis Indicates A Unidirectional Functional Redundancy, Xu Li, Hilal Ilarslan, Libuse Brachova, Hui-Rong Qian, Ling Li, Ping Che, Eve Syrkin Wurtele, Basil J. Nikolau

Ling Li

The heteromeric acetyl-coenzyme A carboxylase catalyzes the first and committed reaction of de novo fatty acid biosynthesis in plastids. This enzyme is composed of four subunits: biotin carboxyl-carrier protein (BCCP), biotin carboxylase, α-carboxyltransferase, and β-carboxyltransferase. With the exception of BCCP, single-copy genes encode these subunits in Arabidopsis (Arabidopsis thaliana). Reverse-genetic approaches were used to individually investigate the physiological significance of the two paralogous BCCP-coding genes, CAC1A (At5g16390, codes for BCCP1) and CAC1B (At5g15530, codes for BCCP2). Transfer DNA insertional alleles that completely eliminate the accumulation of BCCP2 have no perceptible effect on plant growth, development, and fatty acid accumulation. In ...


Materials And Method For Modifying A Biochemical Component In A Plant, Ling Li, Eve Syrkin Wurtele 2017 Iowa State University

Materials And Method For Modifying A Biochemical Component In A Plant, Ling Li, Eve Syrkin Wurtele

Ling Li

A method of modifying the amount of at least one biochemical component in a plant comprising expressing Qua-Quine Starch (QQS) in the plant, the wild-type of which does not express QQS; a transgenic plant, or part thereof, which comprises and expresses QQS as a transgene and in which the amount of at least one biochemical component is modified; a tissue culture of regenerable cells of the transgenic plant; a vector comprising a nucleotide sequence, which encodes the coding sequence of QQS, operably linked to a non-native promoter, which promotes expression of the nucleotide sequence in a plant, which is other ...


Materials And Method For Increasing A Plant's Resistance To Stress, Ling Li, Eve Syrkin Wurtele 2017 Iowa State University

Materials And Method For Increasing A Plant's Resistance To Stress, Ling Li, Eve Syrkin Wurtele

Ling Li

Method of increasing resistance to a pathogen or a pest in a plant comprising introducing into the plant and expressing therein a polynucleotide comprising a nucleotide sequence encoding a Qua-Quine Starch (QQS) polypeptide; method of producing a plant with increased resistance to a pathogen or a pest comprising crossing a plant obtained in accordance with the above method with a second plant to produce progeny plants and selecting progeny plants with increased resistance to a pathogen or a pest; a plant with increased resistance to a pathogen or a pest; a seed of the plant; a hybrid of the plant ...


Genome Wide Co-Expression Among The Starch Debranching Enzyme Genes Atisa1, Atisa2, And Atisa3 In Arabidopsis Thaliana, Ling Li, Hilal Ilarslan, Martha G. James, Alan M. Myers, Eve Syrkin Wurtele 2017 Iowa State University

Genome Wide Co-Expression Among The Starch Debranching Enzyme Genes Atisa1, Atisa2, And Atisa3 In Arabidopsis Thaliana, Ling Li, Hilal Ilarslan, Martha G. James, Alan M. Myers, Eve Syrkin Wurtele

Ling Li

Each of four starch debranching enzymes (DBE) is distinct and highly conserved across the plant kingdom; however, the specific functions of these proteins in carbohydrate metabolism are not well understood. DBEs function in both biosynthesis and degradation of starch, and two have been shown to function as multimers in various quarternary structures that can contain one or more DBE proteins, i.e. ISA1 homomultimers and ISA1/ISA2 heteromultimers. This study characterizes potential functional relationships between the three isoamylase-type DBE proteins (ISA) of Arabidopsis using a comprehensive bioinformatics analysis and promoter fusion approach to determine tissue-, subcellular-, and temporal specificity of ...


Novel Species-Specific Glycoprotein On The Surface Of Mytilus Edulis And M. Trossulus Eggs, Fiona M. Harper, Kasandra J. Riley, R. D. Rawson 2017 Rollins College

Novel Species-Specific Glycoprotein On The Surface Of Mytilus Edulis And M. Trossulus Eggs, Fiona M. Harper, Kasandra J. Riley, R. D. Rawson

Faculty Publications

Protein–protein interactions play a central role in the gamete attraction, binding, and fusion stages of gamete interactions and fertilization for broadcast spawning species, such as marine mussels in the Mytilus edulis species complex. Although assortative gamete interaction has been implicated in the level of reproductive isolation among the three species in this complex, the molecular basis of these interactions has not been elucidated. Using mass spectrometry peptide sequencing, cDNA sequencing, and bioinformatics approaches, we have investigated species-level variation in the proteins expressed on the surface of mussel eggs. We herein describe an extracellular protein, MESP-1, from the surface of ...


Tumor Formation In Response To Loss Of Chromatin Remodeler Chd5 In Zebrafish, Taylor R. Sabato, Erin L. Sorlien, Dr. Joseph P. Ogas 2017 Purdue University

Tumor Formation In Response To Loss Of Chromatin Remodeler Chd5 In Zebrafish, Taylor R. Sabato, Erin L. Sorlien, Dr. Joseph P. Ogas

The Summer Undergraduate Research Fellowship (SURF) Symposium

Chromodomain helicase DNA binding protein 5 (CHD5) has been identified as a tumor suppressor in humans. Deletion or mutation of CHD5 has been observed in numerous cancers, including neuroblastoma and melanoma. We hypothesize that chd5 is also a tumor suppressor in zebrafish, a powerful model system to study tumorigenesis. Many genes involved in tumorigenesis are conserved in zebrafish, and they develop fully penetrant tumor phenotypes. We have created chd5 knock-out zebrafish using CRISPR/Cas9 and are monitoring them for tumor development. In addition to the chd5 knock-outs, we are undertaking a double-mutant approach by coupling loss of ...


Temporal Resolution Of Cell Death Signaling Events Induced By Cold Atmospheric Plasma And Electroporation In Human Cancer Cells, Danielle M. Krug, Prasoon K. Diwakar, Ahmed Hassanein 2017 Purdue University

Temporal Resolution Of Cell Death Signaling Events Induced By Cold Atmospheric Plasma And Electroporation In Human Cancer Cells, Danielle M. Krug, Prasoon K. Diwakar, Ahmed Hassanein

The Summer Undergraduate Research Fellowship (SURF) Symposium

Cancer treatment resistance and their invasive and expensive nature is propelling research towards developing alternate approaches to eradicate cancer in patients. Non-thermal, i.e., cold atmospheric plasma (CAP) and electroporation (EP) applied to the surface of cancerous tissue are new methods that are minimally invasive, safe, and selective. These approaches, both independently and synergistically, have been shown to deplete cancer cell populations, but the signaling mechanisms of death and their timelines of action are still widely unknown. To better understand the timeframe of signaling events occurring upon treatment, human cancer cell lines were treated with CAP, EP, and combined CAP ...


Modulation Of Cellular Energetics By Galactose And Pioglitazone., David Grimm, Leonardo Altamirano, Sudip Paudel, Leah Welker, Mary E. Konkle, Nilay Chakraborty, Michael A. Menze 2017 Eastern Illinois University

Modulation Of Cellular Energetics By Galactose And Pioglitazone., David Grimm, Leonardo Altamirano, Sudip Paudel, Leah Welker, Mary E. Konkle, Nilay Chakraborty, Michael A. Menze

Faculty Scholarship

The Warburg effect is ameliorated by culturing transformed cells in the presence of galactose instead of glucose as the primary carbon source. However, metabolic consequences that are in addition to sensitizing the cells to mitochondrial toxins may occur. As such, the screening of pharmaceutical agents against transformed cells while using galactose must be carefully evaluated. Pioglitazone is used in clinical applications to treat type-2 diabetes, but clearly has other off target effects. Human hepatocellular carcinoma cells (HepG2) were cultured in glucose or galactosecontaining medium to investigate the role of pioglitazone on cellular bioenergetics employing calorimetry and respirometry. Compared to cells ...


The Fossil Record Of Phenotypic Integration And Modularity: A Deep-Time Perspective On Developmental And Evolutionary Dynamics, Anjali Goswami, Wendy J. Binder, Julie Meachen, Robin O'Keefe 2017 Marshall University

The Fossil Record Of Phenotypic Integration And Modularity: A Deep-Time Perspective On Developmental And Evolutionary Dynamics, Anjali Goswami, Wendy J. Binder, Julie Meachen, Robin O'Keefe

F. Robin O’Keefe

Variation is the raw material for natural selection, but the factors shaping variation are still poorly understood. Genetic and developmental interactions can direct variation, but there has been little synthesis of these effects with the extrinsic factors that can shape biodiversity over large scales. The study of phenotypic integration and modularity has the capacity to unify these aspects of evolutionary study by estimating genetic and developmental interactions through the quantitative analysis of morphology, allowing for combined assessment of intrinsic and extrinsic effects. Data from the fossil record in particular are central to our understanding of phenotypic integration and modularity because ...


Examining The Role Of Hres On The Regulation Of Opioid Receptor Gene Expression In Neuronal Cells Undergoing Hypoxic Mimic Condition, Alberto Herrera 2017 Seton Hall University

Examining The Role Of Hres On The Regulation Of Opioid Receptor Gene Expression In Neuronal Cells Undergoing Hypoxic Mimic Condition, Alberto Herrera

Seton Hall University Dissertations and Theses (ETDs)

Hypoxia is a condition of inadequate oxygen supply, which can induce cell death. Using human neuronal cells treated with a hypoxia memetic compound, desferoxamine (DFO), a hypoxic cell model system was created. Our lab reported previously that treatment with DFO resulted in the decrease of cell viability. However, there were still surviving neurons. The surviving cells did not exhibit significant morphological changes, as compared to the control cells, under confocal microscopy analysis using annexin-V-FLUOS and propidium iodide staining, indicating that they were not at apoptotic or necrotic stages. These surviving neurons, therefore, developed adaptive responses under hypoxic challenge. Several changes ...


Acute Myeloid Leukemia, Adrianna Wayble 2017 Otterbein University

Acute Myeloid Leukemia, Adrianna Wayble

Master of Science in Nursing (MSN) Student Scholarship

The purpose of this research project is to explore the disease process of Acute Myeloid Leukemia, or AML. AML is a disease that is estimated to affect 21,380 people in the U.S., killing 10,590 this year alone according to the National Institute of Cancer (NIC, 2017). The goal of treatment for AML is complete remission, using either a combination of chemotherapy, and/or radiation, followed by stem cell transplant (Wang & Bailey, 2016). The disease is multi-faceted with many factors believed to contribute to AML, from environmental exposures to genetics (Wang & Bailey, 2016). This project discusses the treatment ...


Tumor-Targeted Delivery Of Sirna Using Fatty Acyl-Cgkrk Peptide Conjugates, Meenakshi Sharma, Naglaa Salem El-Sayed, Hung Do, Keykavous Parang, Rakesh Tiwari, Hamidreza Montazeri Aliabadi 2017 Chapman University

Tumor-Targeted Delivery Of Sirna Using Fatty Acyl-Cgkrk Peptide Conjugates, Meenakshi Sharma, Naglaa Salem El-Sayed, Hung Do, Keykavous Parang, Rakesh Tiwari, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

Tumor-targeted carriers provide efficient delivery of chemotherapeutic agents to tumor tissue. CGKRK is one of the well-known tumor targeting peptides with significant specificity for angiogenic blood vessels and tumor cells. Here, we designed fatty acyl conjugated CGKRK peptides, based on the hypothesis that hydrophobically-modified CGKRK peptide could enhance cellular permeation and delivery of siRNA targeted to tumor cells for effective silencing of selected proteins. We synthesized six fatty acyl-peptide conjugates, using a diverse chain of saturated and unsaturated fatty acids to study the efficiency of this approach. At peptide:siRNA weight/weight ratio of 10:1 (N/P ≈ 13.6 ...


Molecular Mechanisms Of C-Terminal Eps15 Homology Domain Containing (Ehd) Protein Function, Kriti Bahl 2017 University of Nebraska Medical Center

Molecular Mechanisms Of C-Terminal Eps15 Homology Domain Containing (Ehd) Protein Function, Kriti Bahl

Theses & Dissertations

Endocytic trafficking is not only an essential process for the maintenance of cellular homeostasis but also plays a vital role in regulating diverse cellular processes such as signaling, migration and cell division. The C-terminal Eps 15 Homology Domain proteins (EHD1-4) play pivotal roles in regulating distinct steps of endocytic trafficking. Among the EHDs, EHD2 is disparate both in terms of sequence homology (70%) and its subcellular localization at the caveolae. The crystal structure of EHD2 has been solved and it contains an unstructured loop consisting of two proline-phenylalanine (PF) motifs: KPFRKLNPF. However, the other paralogs EHD1, EHD3 ...


Nanosecond Electric Pulses Differentially Affect Inward And Outward Currents In Patch Clamped Adrenal Chromaffin Cells, Lisha Yang, Gale L. Craviso, P. Thomas Vernier, Indira Chatterjee, Normand Leblanc 2017 Old Dominion University

Nanosecond Electric Pulses Differentially Affect Inward And Outward Currents In Patch Clamped Adrenal Chromaffin Cells, Lisha Yang, Gale L. Craviso, P. Thomas Vernier, Indira Chatterjee, Normand Leblanc

Bioelectrics Publications

This study examined the effect of 5 ns electric pulses on macroscopic ionic currents in whole-cell voltage-clamped adrenal chromaffin cells. Current-voltage (I-V) relationships first established that the early peak inward current was primarily composed of a fast voltage-dependent Na+ current (INa), whereas the late outward current was composed of at least three ionic currents: a voltage-gated Ca2+ current (ICa), a Ca2+-activated K+ current (IK(Ca)), and a sustained voltage-dependent delayed rectifier K+ current (IKV). A constant-voltage step protocol was next used to monitor peak inward and late outward currents before and after cell ...


Ivd Formation In Monodelphis Domestica, Emma C.B. Gray, Jen Maier, Karen Sears 2017 Parkland College

Ivd Formation In Monodelphis Domestica, Emma C.B. Gray, Jen Maier, Karen Sears

Phenotypic Plasticity Research Experience for Community College Students

The research summarized on this poster supports the use of the gray short-tailed opossum (Monodelphis domestica) as a lab animal for research into invertebral disc formation and degeneration. Preliminary data suggests that some genes involved in the formation and maintenance of the notochord in mice are the same in the short-tailed opossum. Data also suggests the ossification of the vertebral column of pups proceeds anteriorly to posteriorly and that much of the maturation of the nucleus puposus happens in the first ten days.


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