An Arginine Finger Regulates The Sequential Action Of Asymmetrical Hexameric Atpase In The Double-Stranded Dna Translocation Motor,
2016
University of Kentucky
An Arginine Finger Regulates The Sequential Action Of Asymmetrical Hexameric Atpase In The Double-Stranded Dna Translocation Motor, Zhengyi Zhao, Gian Marco De-Donatis, Chad T. Schwartz, Huaming Fang, Jingyuan Li, Peixuan Guo
Pharmaceutical Sciences Faculty Publications
Biological motors are ubiquitous in living systems. Currently, how the motor components coordinate the unidirectional motion is elusive in most cases. Here, we report that the sequential action of the ATPase ring in the DNA packaging motor of bacteriophage ϕ29 is regulated by an arginine finger that extends from one ATPase subunit to the adjacent unit to promote noncovalent dimer formation. Mutation of the arginine finger resulted in the interruption of ATPase oligomerization, ATP binding/hydrolysis, and DNA translocation. Dimer formation reappeared when arginine mutants were mixed with other ATPase subunits that can offer the arginine to promote their interaction. Ultracentrifugation …
Specific Binding Affinity Of The Non-Catalytic Domain Of Eukaryotic Like Type Ib Topoisomerase Of Vaccinia Virus,
2016
CUNY Graduate Center
Specific Binding Affinity Of The Non-Catalytic Domain Of Eukaryotic Like Type Ib Topoisomerase Of Vaccinia Virus, Benjamin R. Reed
Dissertations, Theses, and Capstone Projects
Topoisomerases are ubiquitous proteins that alter supercoiling in double stranded DNA (dsDNA) during transcription and replication and. vaccinia and the closely related poxvirus variola virus, at 314 amino acids in length, encode the smallest of the type I topoisomerases(TopIB). TopIB is a two domain protein that recognizes the sequence 5’-T/CCCTT, cleaves at the 3’-end and relaxes supercoiling through rotation. The C-terminal domain (CTD) alone contains the catalytic activity and specificity. Deletion of the N-terminal domain results in a greatly reduced rate of relaxation and rapid dissociation. Biochemical data suggests that the N-terminal domain (NTD) is important for pre-cleavage binding and …
Molecular Analysis Of Ftsz-Ring Assembly In E. Coli Cytokinesis,
2016
CUNY Graduate Center
Molecular Analysis Of Ftsz-Ring Assembly In E. Coli Cytokinesis, Kuo-Hsiang Huang
Dissertations, Theses, and Capstone Projects
An essential first step in bacterial division is the assembly of a cytokinetic ring (Z-ring) formed by the tubulin-like FtsZ at midcell. The highly conserved core domain of FtsZ has been reported to mediate assembly of FtsZ polymers in vivo and in vitro. Species-specific differences in the FtsZ C-terminal domain such as the FtsZ CTV region and interactions with several modulatory proteins such as ZapC and ZapD, restricted to certain bacterial classes, also serve as key determinants of FtsZ protofilament bundling. Here, we characterize (i) the roles of the FtsZ CTV region in mediating both longitudinal and lateral interactions …
Tuning Into Toxins And Channels: The Characterizations Of Tv1 And A Human Cardiac Sodium Channel Voltage-Sensor Domain,
2016
CUNY Graduate Center
Tuning Into Toxins And Channels: The Characterizations Of Tv1 And A Human Cardiac Sodium Channel Voltage-Sensor Domain, Mohammed H. Bhuiyan
Dissertations, Theses, and Capstone Projects
In nature, peptide toxins are an abundant resource, produced both by marine and terrestrial organisms. A major target of these peptide toxins is the group of the highly important voltage-gated ion channels. Due to their high specificity and affinity, peptide toxins have been used for over a decade in discovery and characterization of voltage-gated ion channels. Although peptide toxins have been extensively characterized structurally, the structural characterization of eukaryotic voltage-gated sodium channels has seen much less progress, due to their large size and high hydrophobicity. Voltage-gated sodium channels play crucial roles in many physiological processes, and when these processes are …
Sweating The Small Stuff: Linking Plankton To Climate Change, Brian Kim '18 Makes Conncetions,
2016
Colby College
Sweating The Small Stuff: Linking Plankton To Climate Change, Brian Kim '18 Makes Conncetions, Stephen Collins
Colby Magazine
It takes an expansive mind to connect microscopic marine copepods (certain crustacean plankton) unwittingly chomping on floating microplastics with a bigger picture: the planet’s carbon pump and global climate change. But that’s what Brian Kim ’18 decided to investigate during Jan Plan, working with Bigelow Lab Senior Research Scientist David Fields.
Development Of A Novel Class Of Chemicals For Labeling Abasic Sites In Cellular Dna And Killing Cancer Cells,
2016
Wayne State University
Development Of A Novel Class Of Chemicals For Labeling Abasic Sites In Cellular Dna And Killing Cancer Cells, Shanqiao Wei
Wayne State University Dissertations
Abasic (AP) sites are the most common type of lesions in DNA. Numerous endogenous and exogenous agents and cellular processes can induce the formation of AP sites in DNA. If left unrepaired, the deleterious AP sites cause mutagenesis and cytotoxicity. Methoxyamine is known to react with AP sites and block base excision repair. Another alkoxyamine, aldehyde-reactive probe (ARP) tags AP sites with a biotin and has been widely used to quantify these sites. In this study, I have combined both these abilities into one alkoxyamine, AA3, which reacts toward AP sites with better reactivity than ARP at physiological pH. Additionally, …
Developing High-Content Screening To Assay Trans-Epithelial Transport Of Complex Proteins,
2016
Arkansas State University
Developing High-Content Screening To Assay Trans-Epithelial Transport Of Complex Proteins, Reid Allan Martin
Student Theses and Dissertations
Therapeutic proteins are becoming one of the fastest growing classes of drugs on the market. These large biologically-synthesized macromolecules are typically administered intravenously and are dependent upon cellular receptors and other active uptake mechanisms for delivery into tissues and cells. There is significant interest in developing cell-based assays to assess kinetics and mechanisms of endocytosis and transcytosis of large therapeutic proteins across various cell layers. The goal of this research was to develop a transwell “disease tissue on a chip” model to compare rates and efficiencies of different delivery systems for moving bioactive lysosomal enzymes across a human epithelial cell …
Presence Of A Prophage Determines Temperature-Dependent Capsule Production In Streptococcus Pyogenes.,
2016
George Washington University
Presence Of A Prophage Determines Temperature-Dependent Capsule Production In Streptococcus Pyogenes., Leslie Brown, Jeong-Ho Kim, Kyu Hong Cho
Biochemistry and Molecular Medicine Faculty Publications
A hyaluronic acid capsule is a major virulence factor in the pathogenesis of Streptococcus pyogenes. It acts as an anti-phagocytic agent and adhesin to keratinocytes. The expression of the capsule is primarily regulated at the transcriptional level by the two-component regulatory system CovRS, in which CovR acts as a transcriptional repressor. The covRS genes are frequently mutated in many invasive strains, and a subset of the invasive CovRS mutants does not produce a detectable level of the capsule at 37 °C, but produces a significant amount of the capsule at sub-body temperatures. Here, we report that a prophage has a …
Palmitoyl Acyltransferase Dhhc21 Mediates Endothelial Dysfunction In Systemic Inflammatory Response Syndrome,
2016
University of South Florida
Palmitoyl Acyltransferase Dhhc21 Mediates Endothelial Dysfunction In Systemic Inflammatory Response Syndrome, Richard S. Beard Jr.
Biomedical Research Institute Publications and Presentations
Endothelial dysfunction is a hallmark of systemic inflammatory response underlying multiple organ failure. Here we report a novel function of DHHC-containing palmitoyl acyltransferases (PATs) in mediating endothelial inflammation. Pharmacological inhibition of PATs attenuates barrier leakage and leucocyte adhesion induced by endothelial junction hyperpermeability and ICAM-1 expression during inflammation. Among 11 DHHCs detected in vascular endothelium, DHHC21 is required for barrier response. Mice with DHHC21 function deficiency (Zdhhc21dep/dep) exhibit marked resistance to injury, characterized by reduced plasma leakage, decreased leucocyte adhesion and ameliorated lung pathology, culminating in improved survival. Endothelial cells from Zdhhc21dep/dep display blunted barrier dysfunction and …
Isoacceptor Specific Characterization Of Trna Aminoacylation And Misacylation In Vivo,
2016
The Ohio State University
Isoacceptor Specific Characterization Of Trna Aminoacylation And Misacylation In Vivo, Kyle Mohler, Rebecca Mann, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Amino acid misincorporation during protein synthesis occurs due to misacylation of tRNAs or defects in decoding at the ribosome. While misincorporation of amino acids has been observed in a variety of contexts, less work has been done to directly assess the extent to which specific tRNAs are misacylated in vivo, and the identity of the misacylated amino acid moiety. Here we describe tRNA isoacceptor specific aminoacylation profiling (ISAP), a method to identify and quantify the amino acids attached to a tRNA species in vivo. ISAP allows compilation of aminoacylation profiles for specific isoacceptors tRNAs. To demonstrate the efficacy and …
Activation Of Nqo1 In Nqo1*2 Polymorphic Human Leukemic Hl-60 Cells By Diet-Derived Sulforaphane,
2016
New York Medical College
Activation Of Nqo1 In Nqo1*2 Polymorphic Human Leukemic Hl-60 Cells By Diet-Derived Sulforaphane, Joseph M. Wu, Ardalan Oraee, Barbara B. Doonan, John T. Pinto, Tze-Chen Hsieh
NYMC Faculty Publications
BACKGROUND: The NAD(P)H: quinone oxidoreductase (NQO1) confers protection against semiquinones and also elicits oxidative stress. The C609T polymorphism of the NQO1 gene, designated NQO1*2, significantly reduces its enzymatic activity due to rapid degradation of protein. Since down regulation of NQO1 mRNA expression correlates with increased susceptibility for developing different types of cancers, we investigated the link between leukemia and the NQO1*2 genotype by mining a web-based microarray dataset, ONCOMINE. Phytochemicals prevent DNA damage through activation of phase II detoxification enzymes including NQO1. Whether NQO1 expression/activity in leukemia cells that carry the labile NQO1*2 genotype can be induced by broccoli-derived phytochemical …
Maintenance Of Transcription-Translation Coupling By Elongation Factor P,
2016
The Ohio State University
Maintenance Of Transcription-Translation Coupling By Elongation Factor P, Sara Elgamal, Irina Artsimovitch, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Under conditions of tight coupling between translation and transcription, the ribosome enables synthesis of full-length mRNAs by preventing both formation of intrinsic terminator hairpins and loading of the transcription termination factor Rho. While previous studies have focused on transcription factors, we investigated the role of Escherichia coli elongation factor P (EF-P), an elongation factor required for efficient translation of mRNAs containing consecutive proline codons, in maintaining coupled translation and transcription. In the absence of EF-P, the presence of Rho utilization (rut) sites led to an ~30-fold decrease in translation of polyproline-encoding mRNAs. Coexpression of the Rho inhibitor Psu …
Insights Into The Molecular Roles Of Heparan Sulfate Proteoglycans (Hspgs-Syndecans) In Autocrine And Paracrine Growth Factor Signaling In The Pathogenesis Of Hodgkin's Lymphoma,
2016
CUNY Bronx Community College
Insights Into The Molecular Roles Of Heparan Sulfate Proteoglycans (Hspgs-Syndecans) In Autocrine And Paracrine Growth Factor Signaling In The Pathogenesis Of Hodgkin's Lymphoma, Rajendra Ghardbaran
Publications and Research
Syndecans (SDC, SYND) comprise a group of four structurally related type 1 transmembrane heparan sulfate proteoglycans (HSPGs) that play important roles in tumorigenic processes. SDCs exert signaling via their protein cores and their conserved transmembrane and cytoplasmic domains or by forming complexes with growth factors (GFs). In classical Hodgkin's lymphoma (cHL), a lymphoid neoplasm of predominantly B cell origin, SDC1 and SDC4 are the active SDCs, and a number of GF (vascular endothelial growth factor, fibroblast growth factor, etc.) signaling pathways have been studied. However, despite extensive pre-clinical and clinical research on SDC-mediated GF signaling in many cancer types, there …
Role Of Phosphorylation In The Regulation Of Prmt5,
2016
The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences
Role Of Phosphorylation In The Regulation Of Prmt5, Alexsandra B. Espejo
Dissertations and Theses (Open Access)
PRMT5 is a member of a group of proteins that mediate arginine methylation. It is involved in diverse cellular processes, including cell differentiation, splicing, transcription elongation and epigenetic silencing, and its expression is dysregulated in many cancers. Due to its pleiotropic functions, PRMT5 is subject to multi-level regulation. Post-translational modification (PTM) of proteins can modulate an array of cellular processes by regulating both protein interactions and protein structural changes. PRMT5 is commonly found associated with other proteins; these interactions seem to control both its catalytic activity and its substrate specificity. Recently, it became clear that PRMT5 is phosphorylated at a …
Rna2dnalign: Nucleotide Resolution Allele Asymmetries Through Quantitative Assessment Of Rna And Dna Paired Sequencing Data.,
2016
George Washington University
Rna2dnalign: Nucleotide Resolution Allele Asymmetries Through Quantitative Assessment Of Rna And Dna Paired Sequencing Data., Mercedeh Movassagh, Nawaf Alomran, Prakriti Mudvari, Merve Dede, Cem Dede, Kamran Kowsari, Paula Restrepo, Edmund Cauley, Sonali Bahl, Muzi Li, Wesley Waterhouse, Krasimira Tsaneva-Atanasova, Nathan Edwards, Anelia Horvath
Biochemistry and Molecular Medicine Faculty Publications
We introduce RNA2DNAlign, a computational framework for quantitative assessment of allele counts across paired RNA and DNA sequencing datasets. RNA2DNAlign is based on quantitation of the relative abundance of variant and reference read counts, followed by binomial tests for genotype and allelic status at SNV positions between compatible sequences. RNA2DNAlign detects positions with differential allele distribution, suggesting asymmetries due to regulatory/structural events. Based on the type of asymmetry, RNA2DNAlign outlines positions likely to be implicated in RNA editing, allele-specific expression or loss, somatic mutagenesis or loss-of-heterozygosity (the first three also in a tumor-specific setting). We applied RNA2DNAlign on 360 matching …
Epstein-Barr Viral Micrornas Target Caspase 3,
2016
Albert Einstein College of Medicine
Epstein-Barr Viral Micrornas Target Caspase 3, Cecelia Harold, Diana Cox, Kasandra J. Riley
Faculty Publications
The Epstein-Barr virus (EBV) is a ubiquitous herpesvirus that transforms B cells and causes several malignancies including Burkitt’s lymphoma. EBV differentially expresses at least 49 mature microRNAs (miRNAs) during latency in various infected epithelial and B cells. Recent high-throughput studies and functional assays have begun to reveal the function of the EBV miRNAs suggesting roles in latency, cell cycle control, and apoptosis. In particular, the central executioner of apoptosis, Caspase 3 (CASP3), was proposed as a target of select EBV miRNAs. However, whether CASP3 is truly a target of EBV miRNAs, and if so, which specific miRNAs target CASP3 is …
Regulation Of Nachrs And Stemness By Nicotine And E-Cigarettes In Nsclc,
2016
University of South Florida
Regulation Of Nachrs And Stemness By Nicotine And E-Cigarettes In Nsclc, Courtney Schaal
USF Tampa Graduate Theses and Dissertations
Lung cancer is the leading cause of cancer-related death in both men and women, nationally and internationally and kills more people each year than breast, prostate, and colon cancers combined. Non-small cell lung carcinoma (NSCLC) is the most common histological subtype of lung cancer, and accounts for 85% of all cases. Cigarette smoking is the single greatest risk factor for lung cancer, and is correlated with 80-90% of all lung cancer deaths. Nicotine, the addictive component of tobacco smoke, is not a carcinogen and cannot initiate tumors itself; however, it is known to act as a tumor promoter, by enhancing …
Study Of The Structure-Related Functions Of Eukaryotic Primase-Pol Alpha Complex During Replication,
2016
University of Nebraska Medical Center
Study Of The Structure-Related Functions Of Eukaryotic Primase-Pol Alpha Complex During Replication, Yinbo Zhang
Theses & Dissertations
During eukaryotic replication primase•polymerase α (prim•polα) complex synthesizes de novo chimeric primers composed of about 10 nt RNA and 20 nt DNA, which are subsequently extended by main replicative DNA polymerases (pol), polε and polδ, on leading and lagging strands, respectively. It is estimated that prim•polα initiates more than 10 millions of lagging strand Okazaki fragments in human genome in each replication cycle. A concerted action of the two active sites, RNA pol and DNA pol, is required to ensure the efficient priming. A remarkable feature of the prim•polα complex is the “programmed” synthesis of the chimeric primer, where the …
Role Of Ddr1 In Pancreatic Cancer,
2016
University of Nebraska Medical Center
Role Of Ddr1 In Pancreatic Cancer, Huocong Huang
Theses & Dissertations
Pancreatic ductal adenocarcinomas are highly malignant cancers, characterized by extensive invasion into surrounding tissues, metastasis to distant organs at a very early stage, and a limited response to therapy. One of the main features of pancreatic ductal adenocarcinomas is desmoplasia, which leads to extensive deposition of collagen I. We have demonstrated that collagen I can induce epithelial-mesenchymal transition (EMT) in pancreatic cancer cells. A hallmark of EMT is an increase in the expression of a mesenchymal cadherin, N-cadherin. Our previous studies have shown that up-regulation of N-cadherin can promote tumor cell invasion and that collagen I-induced EMT is through two …
Modeling And Analysis Of Germ Layer Formations Using Finite Dynamical Systems,
2016
University of Wisconsin-La Crosse
Modeling And Analysis Of Germ Layer Formations Using Finite Dynamical Systems, Alexander Garza, Megan Eberle, Eric A. Eager
Spora: A Journal of Biomathematics
The development of an embryo from a fertilised egg to a multicellular organism proceeds through numerous steps, with the formation of the three germ layers (endoderm, mesoderm, ectoderm) being one of the first. In this paper we study the mesendoderm (the tissue that collectively gives rise to both mesoderm and endoderm) gene regulatory network for two species, \textit{Xenopus laevis} and the axolotl (\textit{Ambystoma mexicanum}) using Boolean networks. We find that previously-established bistability found in these networks can be reproduced using this Boolean framework, provided that some assumptions used in previously-published differential equations models are relaxed. We conclude by discussing our …
