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The Autoimmune System: The Effect Of Physiological Stressors On Autoantibody Glycosylation And Fidelity Of Autoantibody Profiles, Rahil Kheirkhah 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, Haoyu Wang, Zhaohui Wang, Huiping Zhang, Zeng Qi, Ariel C Johnson, David Mathes, Elizabeth A Pomfret, Erin Rubin, Christene A Huang, Zhirui Wang 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, Syed Ahmad Rizvi 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, Andrew Pham 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, Yanli Li, Kesheng Wang, Ping Zhang, Junchao Huang, Ying Liu, Zhiren Wang, Yongke Lu, Shuping Tan, Fude Yang, Yunlong Tan 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, Meagan E. Valentine, Brandon D. Kirby, Hongwei D. Yu 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, 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 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, 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 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), 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 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, 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 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., N. Chiorazzi, F. K. Stevenson 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, E. Nasiri, R. Sankowski, H. Dietrich, A. Oikonomidi, P. T. Huerta, J. Popp, Y. Al-Abed, M. Bacher 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, D. A. Rao, A. Arazi, D. Wofsy, B. Diamond 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.


Unique White Matter Structural Connectivity In Early-Stage Drug-Naive Parkinson Disease, V. R. Mishra, K. R. Sreenivasan, Z. Yang, X. Zhuang, D. Cordes, Z. Mari, I. Litvan, H. H. Fernandez, D. Eidelberg, R. R. Walsh, +2 additional authors 2020 Zucker School of Medicine at Hofstra/Northwell

Unique White Matter Structural Connectivity In Early-Stage Drug-Naive Parkinson Disease, V. R. Mishra, K. R. Sreenivasan, Z. Yang, X. Zhuang, D. Cordes, Z. Mari, I. Litvan, H. H. Fernandez, D. Eidelberg, R. R. Walsh, +2 Additional Authors

Journal Articles

© 2019 American Academy of Neurology. OBJECTIVE: To investigate the topographic arrangement and strength of whole-brain white matter (WM) structural connectivity in patients with early-stage drug-naive Parkinson disease (PD). METHODS: We employed a model-free data-driven approach for computing whole-brain WM topologic arrangement and connectivity strength between brain regions by utilizing diffusion MRI of 70 participants with early-stage drug-naive PD and 41 healthy controls. Subsequently, we generated a novel group-specific WM anatomical network by minimizing variance in anatomical connectivity of each group. Global WM connectivity strength and network measures were computed on this group-specific WM anatomical network and were compared between …


Creatinine Fluctuation In Patients With Lupus Nephritis: Considerations For Clinical Trial Endpoints, S. Almaani, U. Bhatt, C. Arriens, E. Bonfa, M. Dall'Era, F. Houssiau, K. Kalunian, M. Mackay, J. Sanchez-Guerrero, B. H. Rovin, +1 additional author 2020 Zucker School of Medicine at Hofstra/Northwell

Creatinine Fluctuation In Patients With Lupus Nephritis: Considerations For Clinical Trial Endpoints, S. Almaani, U. Bhatt, C. Arriens, E. Bonfa, M. Dall'era, F. Houssiau, K. Kalunian, M. Mackay, J. Sanchez-Guerrero, B. H. Rovin, +1 Additional Author

Journal Articles

No abstract provided.


Identification Of Unusual Phospholipids From Bovine Heart Mitochondria By Hplc-Ms/Ms., J. Kim, C. L. Hoppel 2020 Zucker School of Medicine at Hofstra/Northwell

Identification Of Unusual Phospholipids From Bovine Heart Mitochondria By Hplc-Ms/Ms., J. Kim, C. L. Hoppel

Journal Articles

Phospholipids, including ether phospholipids, are composed of numerous isomeric and isobaric species that have the same backbone and acyl chains. This structural resemblance results in similar fragmentation patterns by collision-induced dissociation of phospholipids regardless of class, yielding complicated tandem mass spectrometry (MS/MS) spectra when isobaric species are analyzed together. Furthermore, the presence of isobaric species can lead to misassignment of species when made solely based on their molecular weights. In this study, we used normal-phase HPLC for ESI-MS/MS analysis of phospholipids from bovine heart mitochondria. Class separation by HPLC eliminates chances for misidentification of isobaric species from different classes of …


Radiomics And Supervised Machine Learning In The Diagnosis Of Parkinsonism With Fdg Pet: Promises And Challenges., S. Peng, P. G. Spetsieris, D. Eidelberg, Y. Ma 2020 Zucker School of Medicine at Hofstra/Northwell

Radiomics And Supervised Machine Learning In The Diagnosis Of Parkinsonism With Fdg Pet: Promises And Challenges., S. Peng, P. G. Spetsieris, D. Eidelberg, Y. Ma

Journal Articles

No abstract provided.


Apol1 Polymorphism Modulates Sphingolipid Profile Of Human Podocytes, M. Valsecchi, V. Cazzetta, F. Oriolo, X. Lan, R. Piazza, M. A. Saleem, P. C. Singhal, D. Mavilio, J. Mikulak, M. Aureli 2020 Zucker School of Medicine at Hofstra/Northwell

Apol1 Polymorphism Modulates Sphingolipid Profile Of Human Podocytes, M. Valsecchi, V. Cazzetta, F. Oriolo, X. Lan, R. Piazza, M. A. Saleem, P. C. Singhal, D. Mavilio, J. Mikulak, M. Aureli

Journal Articles

No abstract provided.


T Cell-Intrinsic Irf5 Regulates T Cell Signaling, Migration, And Differentiation And Promotes Intestinal Inflammation, J. Yan, S. P. Pandey, B. J. Barnes, J. R. Turner, C. Abraham 2020 Zucker School of Medicine at Hofstra/Northwell

T Cell-Intrinsic Irf5 Regulates T Cell Signaling, Migration, And Differentiation And Promotes Intestinal Inflammation, J. Yan, S. P. Pandey, B. J. Barnes, J. R. Turner, C. Abraham

Journal Articles

© 2020 The Author(s) IRF5 polymorphisms are associated with multiple immune-mediated diseases, including ulcerative colitis. IRF5 contributions are attributed to its role in myeloid lineages. How T cell-intrinsic IRF5 contributes to inflammatory outcomes is not well understood. We identify a previously undefined key role for T cell-intrinsic IRF5. In mice, IRF5 in CD4+ T cells promotes Th1- and Th17-associated cytokines and decreases Th2-associated cytokines. IRF5 is required for the optimal assembly of the TCR-initiated signaling complex and downstream signaling at early times, and at later times binds to promoters of Th1- and Th17-associated transcription factors and cytokines. IRF5 also regulates …


Prolonged Targeted Cardiovascular Epidural Stimulation Improves Immunological Molecular Profile: A Case Report In Chronic Severe Spinal Cord Injury, O. Bloom, J. M. Wecht, B. E. Ditterline, S. Wang, A. Ovechkin, C. A. Angeli, A. A. Arcese, S. J. Harkema 2020 Zucker School of Medicine at Hofstra/Northwell

Prolonged Targeted Cardiovascular Epidural Stimulation Improves Immunological Molecular Profile: A Case Report In Chronic Severe Spinal Cord Injury, O. Bloom, J. M. Wecht, B. E. Ditterline, S. Wang, A. Ovechkin, C. A. Angeli, A. A. Arcese, S. J. Harkema

Journal Articles

No abstract provided.


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