Mg2+-Dependent Methyl Transfer By A Knotted Protein: A Molecular Dynamics Simulation And Quantum Mechanics Study,
2020
University of Warsaw
Mg2+-Dependent Methyl Transfer By A Knotted Protein: A Molecular Dynamics Simulation And Quantum Mechanics Study, Agata P Perlinska, Marcin Kalek, Thomas Christian, Ya-Ming Hou, Joanna I Sulkowska
Department of Biochemistry and Molecular Biology Faculty Papers
Mg2+ is required for the catalytic activity of TrmD, a bacteria-specific methyltransferase that is made up of a protein topological knot-fold, to synthesize methylated m1G37-tRNA to support life. However, neither the location of Mg2+ in the structure of TrmD nor its role in the catalytic mechanism is known. Using molecular dynamics (MD) simulations, we identify a plausible Mg2+ binding pocket within the active site of the enzyme, wherein the ion is coordinated by two aspartates and a glutamate. In this position, Mg2+ additionally interacts with the carboxylate of a methyl donor cofactor S-adenosylmethionine (SAM). The computational results are validated by …
Effect Of S100b Deletion On Membrane Properties And Localization Of Ncald And Hpca,
2020
Rowan University
Effect Of S100b Deletion On Membrane Properties And Localization Of Ncald And Hpca, Natasha Hesketh
Graduate School of Biomedical Sciences Theses and Dissertations
Calcium signaling is particularly important for neuronal function. Neurons utilize a wide range of calcium-binding proteins. Dysregulation of such proteins is linked to neurodegeneration. Neurocalcin delta (NCALD), hippocalcin (HPCA), and S100B are calcium sensors that are expressed in the hippocampus, a brain region essential to memory and severely damaged in Alzheimer’s disease (AD). Despite the potential importance of these proteins, we do not fully understand the physiological significance of their relationship. Because NCALD and HPCA are known to interact with S100B, we hypothesized that the loss of S100B affects NCALD and HPCA localization, and therefore electrical properties, of hippocampal neurons. …
Epigenetic Targeting Of Mcl-1 Is Synthetically Lethal With Bcl-Xl/Bcl-2 Inhibition In Model Systems Of Glioblastoma,
2020
CUNY Bronx Community College
Epigenetic Targeting Of Mcl-1 Is Synthetically Lethal With Bcl-Xl/Bcl-2 Inhibition In Model Systems Of Glioblastoma, Enyuan Shang, Trang T. T. Nguyen, Chang Shu, Mike-Andrew Westhoff, Georg Karpel-Massler, Markus D. Siegelin
Publications and Research
Apoptotic resistance remains a hallmark of glioblastoma (GBM), the most common primary brain tumor in adults, and a better understanding of this process may result in more efficient treatments. By utilizing chromatin immunoprecipitation with next-generation sequencing (CHIP-seq), we discovered that GBMs harbor a super enhancer around the Mcl-1 locus, a gene that has been known to confer cell death resistance in GBM.We utilized THZ1, a known super-enhancer blocker, and BH3-mimetics, including ABT263, WEHI-539, and ABT199. Combined treatment with BH3-mimetics and THZ1 led to synergistic growth reduction in GBM models. Reduction in cellular viability was accompanied by significant cell death induction …
Lyssavirus Vaccine With A Chimeric Glycoprotein Protects Across Phylogroups,
2020
Thomas Jefferson University
Lyssavirus Vaccine With A Chimeric Glycoprotein Protects Across Phylogroups, Christine R Fisher, David E Lowe, Todd G Smith, Yong Yang, Christina L Hutson, Christoph Wirblich, Gino Cingolani, Matthias J. Schnell
Department of Biochemistry and Molecular Biology Faculty Papers
Rabies is nearly 100% lethal in the absence of treatment, killing an estimated 59,000 people annually. Vaccines and biologics are highly efficacious when administered properly. Sixteen rabies-related viruses (lyssaviruses) are similarly lethal, but some are divergent enough to evade protection from current vaccines and biologics, which are based only on the classical rabies virus (RABV). Here we present the development and characterization of LyssaVax, a vaccine featuring a structurally designed, functional chimeric glycoprotein (G) containing immunologically important domains from both RABV G and the highly divergent Mokola virus (MOKV) G. LyssaVax elicits high titers of antibodies specific to both RABV …
Thrombospondin-1 Plays An Essential Role In Yes-Associated Protein Nuclear Translocation During The Early Phase Of Trypanosoma Cruzi Infection In Heart Endothelial Cells,
2020
Meharry Medical College
Thrombospondin-1 Plays An Essential Role In Yes-Associated Protein Nuclear Translocation During The Early Phase Of Trypanosoma Cruzi Infection In Heart Endothelial Cells, Ashutosh Arun, Kayla J. Rayford, Ayorinde Cooley, Girish Rachakonda, Fernando Villalta, Siddharth Pratap, Maria F. Lima, Nader Sheibani, Pius N. Nde
Publications and Research
The protozoan parasite Trypanosoma cruzi is the causative agent of Chagas disease. This neglected tropical disease causes severe morbidity and mortality in endemic regions. About 30% of T. cruzi infected individuals will present with cardiac complications. Invasive trypomastigotes released from infected cells can be carried in the vascular endothelial system to infect neighboring and distant cells. During the process of cellular infection, the parasite induces host cells, to increase the levels of host thrombospondin-1 (TSP-1), to facilitate the process of infection. TSP-1 plays important roles in the functioning of vascular cells, including vascular endothelial cells with important implications in cardiovascular …
Inhibition Of Hdac1/2 Along With Trap1 Causes Synthetic Lethality In Glioblastoma Model Systems,
2020
Columbia University
Inhibition Of Hdac1/2 Along With Trap1 Causes Synthetic Lethality In Glioblastoma Model Systems, Trang T. T. Nguyen, Yiru Zhang, Enyuan Shang, Chang Shu, Catarina M. Quinzii, Mike-Andrew Westhoff, Georg Karpel-Massler, Markus D. Siegelin
Publications and Research
The heterogeneity of glioblastomas, the most common primary malignant brain tumor, remains a significant challenge for the treatment of these devastating tumors. Therefore, novel combination treatments are warranted. Here, we showed that the combined inhibition of TRAP1 by gamitrinib and histone deacetylases (HDAC1/HDAC2) through romidepsin or panobinostat caused synergistic growth reduction of established and patient-derived xenograft (PDX) glioblastoma cells. This was accompanied by enhanced cell death with features of apoptosis and activation of caspases. The combination treatment modulated the levels of pro- and anti-apoptotic Bcl-2 family members, including BIM and Noxa, Mcl-1, Bcl-2 and Bcl-xL. Silencing of Noxa, BAK and …
Molecular Mechanisms Of Manganese Porphyrin Compounds In The Prevention Of Radiation-Induced Fibrosis,
2020
University of Nebraska Medical Center
Molecular Mechanisms Of Manganese Porphyrin Compounds In The Prevention Of Radiation-Induced Fibrosis, Shashank Shrishrimal
Theses & Dissertations
Radiation therapy is frequently used as a treatment strategy for prostate cancer patients, which leads to several side effects due to damage to health tissue around the tumor and the development of radiation-induced fibrosis (RIF). Manganese (III) meso-tetrakis (N-ethylpyridinium-2-yl) porphyrin (MnTE-2-PyP or T2E or BMX-010) and other similar manganese porphyrin compounds that scavenge superoxide molecules have been demonstrated to be effective radioprotectors and prevent the development of RIF. However, understanding of the radioprotective molecular pathway associated with these compounds remains limited. Recent RNA-sequencing data from our laboratory revealed that MnTE-2-PyP treatment may activate the nuclear factor erythroid 2-related factor 2 …
The Autoimmune System: The Effect Of Physiological Stressors On Autoantibody Glycosylation And Fidelity Of Autoantibody Profiles,
2020
Rowan University
The Autoimmune System: The Effect Of Physiological Stressors On Autoantibody Glycosylation And Fidelity Of Autoantibody Profiles, Rahil Kheirkhah
Graduate School of Biomedical Sciences Theses and Dissertations
The presence of thousands of autoantibodies (aABs) in the human sera is typical, and therefore it is possible to identify an aAB profile for each individual. In the first part of this thesis, we will show the cerebrospinal fluid also exhibits an extraordinarily complex immunoglobulin G aAB profile that is composed of thousands of aABs. We show that the pattern of expression of individual aABs in CSF closely mimics that in the blood, indicative of a blood-based origin for CSF aABs. In addition, using longitudinal serum samples obtained over a span of nine years, we show remarkable stability in aAB …
Bispecific Human Il2-Ccr4 Immunotoxin Targets Human Cutaneous T-Cell Lymphoma,
2020
The Texas Medical Center Library
Bispecific Human Il2-Ccr4 Immunotoxin Targets Human Cutaneous T-Cell Lymphoma, Haoyu Wang, Zhaohui Wang, Huiping Zhang, Zeng Qi, Ariel C Johnson, David Mathes, Elizabeth A Pomfret, Erin Rubin, Christene A Huang, Zhirui Wang
Faculty, Staff and Student Publications
The majority of clinically diagnosed cutaneous T‐cell lymphomas (CTCL) highly express the cell‐surface markers CC chemokine receptor 4 (CCR4) and/or CD25. Recently, we have developed diphtheria toxin‐based recombinant Ontak®‐like human IL2 fusion toxin (IL2 fusion toxin) and anti‐human CCR4 immunotoxin (CCR4 IT). In this study, we first compared the efficacy of the CCR4 IT vs IL2 fusion toxin for targeting human CD25+CCR4+ CTCL. We demonstrated that CCR4 IT was more effective than IL2 fusion toxin. We further constructed an IL2‐CCR4 bispecific IT. The bispecific IT was significantly more effective than either IL2 fusion toxin or CCR4 IT alone. The bispecific …
The Implementation Of Exercise For Chronic Kidney Disease And Dialysis Patients,
2020
Wayne State University Division of Kinesiology, Health and Sport Studies & Honors College
The Implementation Of Exercise For Chronic Kidney Disease And Dialysis Patients, Syed Ahmad Rizvi
Honors College Theses
While commonly known to be the organ that helps with urine production within the human body, the kidney plays one of the most crucial roles in maintaining homeostasis. When establishing all of the roles the kidney has on keeping humans healthy, there is the question of how does the body cope when a patient is diagnosed with kidney failure. One of the more common treatment options that allows the body to continue to function without a kidney is by beginning a patient on a form of dialysis. However, as with any treatment, there will always be a list of side …
Utilizing Chemical Mutagenesis To Determine U21 Mechanism Of Action In Toxoplasma Gondii,
2020
University of Nebraska at Omaha
Utilizing Chemical Mutagenesis To Determine U21 Mechanism Of Action In Toxoplasma Gondii, Andrew Pham
UNO Student Research and Creative Activity Fair
The abstract has been removed to protect intellectual property of the project.
Pyrosequencing Analysis Of Irs1 Methylation Levels In Schizophrenia With Tardive Dyskinesia,
2020
Marshall University
Pyrosequencing Analysis Of Irs1 Methylation Levels In Schizophrenia With Tardive Dyskinesia, Yanli Li, Kesheng Wang, Ping Zhang, Junchao Huang, Ying Liu, Zhiren Wang, Yongke Lu, Shuping Tan, Fude Yang, Yunlong Tan
Pharmacology, Physiology and Toxicology
Tardive dyskinesia (TD) is a serious side effect of certain antipsychotic medications that are used to treat schizophrenia (SCZ) and other mental illnesses. The methylation status of the insulin receptor substrate 1 (IRS1) gene is reportedly associated with SCZ; however, no study, to the best of the authors' knowledge, has focused on the quantitative DNA methylation levels of the IRS1 gene using pyrosequencing in SCZ with or without TD. The present study aimed to quantify DNA methylation levels of 4 CpG sites in the IRS1 gene using a Chinese sample including SCZ patients with TD and without TD (NTD) and …
Generation Of In-Frame Gene Deletion Mutants In Pseudomonas Aeruginosa And Testing For Virulence Attenuation In A Simple Mouse Model Of Infection,
2020
Marshall University
Generation Of In-Frame Gene Deletion Mutants In Pseudomonas Aeruginosa And Testing For Virulence Attenuation In A Simple Mouse Model Of Infection, Meagan E. Valentine, Brandon D. Kirby, Hongwei D. Yu
Biomedical Sciences
Microorganisms are genetically versatile and diverse and have become a major source of many commercial products and biopharmaceuticals. Though some of these products are naturally produced by the organisms, other products require genetic engineering of the organism to increase the yields of production. Avirulent strains of Escherichia coli have traditionally been the preferred bacterial species for producing biopharmaceuticals; however, some products are difficult for E. coli to produce. Thus, avirulent strains of other bacterial species could provide useful alternatives for production of some commercial products. Pseudomonas eruginosa is a common and well-studied Gram-negative bacterium that could provide a suitable alternative …
Circulating Tnf-Like Protein 1a (Tl1a) Is Elevated Early In Rheumatoid Arthritis And Depends On Tnf,
2020
Zucker School of Medicine at Hofstra/Northwell
Circulating Tnf-Like Protein 1a (Tl1a) Is Elevated Early In Rheumatoid Arthritis And Depends On Tnf, Y. Song, I. A. Choi, F. Meylan, M. K. Demoruelle, T. Farley, A. C. Richard, E. Hawley, J. Botson, P. Gregersen, R. M. Siegel, +19 Additional Authors
Journal Articles
No abstract provided.
Allele-Specific Expression Changes Dynamically During T Cell Activation In Hla And Other Autoimmune Loci,
2020
Zucker School of Medicine at Hofstra/Northwell
Allele-Specific Expression Changes Dynamically During T Cell Activation In Hla And Other Autoimmune Loci, M. Gutierrez-Arcelus, Y. Baglaenko, J. Arora, S. Hannes, Y. Luo, T. Amariuta, N. Teslovich, D. A. Rao, P. K. Gregersen, S. Raychaudhuri, +8 Additional Authors
Journal Articles
© 2020, The Author(s), under exclusive licence to Springer Nature America, Inc. Genetic studies have revealed that autoimmune susceptibility variants are over-represented in memory CD4+ T cell regulatory elements1–3. Understanding how genetic variation affects gene expression in different T cell physiological states is essential for deciphering genetic mechanisms of autoimmunity4,5. Here, we characterized the dynamics of genetic regulatory effects at eight time points during memory CD4+ T cell activation with high-depth RNA-seq in healthy individuals. We discovered widespread, dynamic allele-specific expression across the genome, where the balance of alleles changes over time. These genes were enriched fourfold within autoimmune loci. …
Expression Of Concern: Redox Modification Of Cysteine Residues Regulates The Cytokine Activity Of High Mobility Group Box-1 (Hmgb1) (Molecular Medicine (2012) 18 (250-259) Doi: 10.2119/Molmed.2011.00389),
2020
Zucker School of Medicine at Hofstra/Northwell
Expression Of Concern: Redox Modification Of Cysteine Residues Regulates The Cytokine Activity Of High Mobility Group Box-1 (Hmgb1) (Molecular Medicine (2012) 18 (250-259) Doi: 10.2119/Molmed.2011.00389), H. Yang, P. Lundbäck, L. Ottosson, H. Erlandsson-Harris, E. Venereau, M. E. Bianchi, Y. Al-Abed, U. Andersson, K. J. Tracey, D. J. Antoine
Journal Articles
© The Author(s). 2020. The Editors-in-Chief would like to alert readers that this article (Yang et al. 2012) is part of an investigation being conducted by the journal following the conclusions of an institutional enquiry at the University of Liverpool with respect to the quantitative mass spectrometrygenerated results regarding acetylated and redox-modified HMGB1. Appropriate editorial action will be taken once the investigation is concluded. Huan Yang, Peter Lundbäck, Lars Ottosson, Helena Erlandsson-Harris, Emilie Venereau, Marco E. Bianchi, Yousef Al-Abed, Ulf Andersson, and Kevin J. Tracey agree to this editorial expression of concern. Daniel J. Antoine has not responded to any …
Challenges And Opportunities With Causal Discovery Algorithms: Application To Alzheimer’S Pathophysiology,
2020
Zucker School of Medicine at Hofstra/Northwell
Challenges And Opportunities With Causal Discovery Algorithms: Application To Alzheimer’S Pathophysiology, X. Shen, S. Ma, P. Vemuri, G. Simon, M. W. Weiner, P. Aisen, R. Petersen, C. R. Jack, P. Davies, V. Shibley, +90 Additional Authors
Journal Articles
© 2020, The Author(s). Causal Structure Discovery (CSD) is the problem of identifying causal relationships from large quantities of data through computational methods. With the limited ability of traditional association-based computational methods to discover causal relationships, CSD methodologies are gaining popularity. The goal of the study was to systematically examine whether (i) CSD methods can discover the known causal relationships from observational clinical data and (ii) to offer guidance to accurately discover known causal relationships. We used Alzheimer’s disease (AD), a complex progressive disease, as a model because the well-established evidence provides a “gold-standard” causal graph for evaluation. We evaluated …
Celebrating 20 Years Of Ighv Mutation Analysis In Cll.,
2020
Zucker School of Medicine at Hofstra/Northwell
Celebrating 20 Years Of Ighv Mutation Analysis In Cll., N. Chiorazzi, F. K. Stevenson
Journal Articles
The division of CLL into 2 broad subsets with highly significant differences in clinical behavior was reported in 2 landmark papers in Blood in 1999.1,2 The simple analysis of the mutational status of the IGV regions provided both a prognostic indicator and an insight into the cellular origins. Derivation from B cells with very low or no IGV mutations generally leads to a more aggressive disease course than derivation from B cells with higher levels. This finding focused attention on surface Ig (sIg), the major B-cell receptor, and revealed dynamic antigen engagement in vivo as a tumor driver. It has …
Key Role Of Mif-Related Neuroinflammation In Neurodegeneration And Cognitive Impairment In Alzheimer's Disease,
2020
Zucker School of Medicine at Hofstra/Northwell
Key Role Of Mif-Related Neuroinflammation In Neurodegeneration And Cognitive Impairment In Alzheimer's Disease, E. Nasiri, R. Sankowski, H. Dietrich, A. Oikonomidi, P. T. Huerta, J. Popp, Y. Al-Abed, M. Bacher
Journal Articles
No abstract provided.
Design And Application Of Single-Cell Rna Sequencing To Study Kidney Immune Cells In Lupus Nephritis,
2020
Zucker School of Medicine at Hofstra/Northwell
Design And Application Of Single-Cell Rna Sequencing To Study Kidney Immune Cells In Lupus Nephritis, D. A. Rao, A. Arazi, D. Wofsy, B. Diamond
Journal Articles
No abstract provided.
