Medicine and Health Sciences Commons^™

Tubular Cell And Keratinocyte Single-Cell Transcriptomics Applied To Lupus Nephritis Reveal Type I Ifn And Fibrosis Relevant Pathways, E. Der, H. Suryawanshi, P. Morozov, M. Kustagi, Goilav, Ranabathou, P. Izmirly, A. Davidson, R. Furie, F. Zhang, +57 Additional Authors

Journal Articles

© 2019, The Author(s), under exclusive licence to Springer Nature America, Inc. The molecular and cellular processes that lead to renal damage and to the heterogeneity of lupus nephritis (LN) are not well understood. We applied single-cell RNA sequencing (scRNA-seq) to renal biopsies from patients with LN and evaluated skin biopsies as a potential source of diagnostic and prognostic markers of renal disease. Type I interferon (IFN)-response signatures in tubular cells and keratinocytes distinguished patients with LN from healthy control subjects. Moreover, a high IFN-response signature and fibrotic signature in tubular cells were each associated with failure to respond to …

Defining Inflammatory Cell States In Rheumatoid Arthritis Joint Synovial Tissues By Integrating Single-Cell Transcriptomics And Mass Cytometry, F. Zhang, K. Wei, K. Slowikowski, C. Y. Fonseka, A. Rao, Kelly, S. M. Goodman, D. Tabechian, P. K. Gregersen, S. Raychaudhuri, +55 Additional Authors

Journal Articles

© 2019, The Author(s), under exclusive licence to Springer Nature America, Inc. To define the cell populations that drive joint inflammation in rheumatoid arthritis (RA), we applied single-cell RNA sequencing (scRNA-seq), mass cytometry, bulk RNA sequencing (RNA-seq) and flow cytometry to T cells, B cells, monocytes, and fibroblasts from 51 samples of synovial tissue from patients with RA or osteoarthritis (OA). Utilizing an integrated strategy based on canonical correlation analysis of 5,265 scRNA-seq profiles, we identified 18 unique cell populations. Combining mass cytometry and transcriptomics revealed cell states expanded in RA synovia: THY1(CD90) + HLA-DRA hi sublining fibroblasts, IL1B + …

Metabolic And Microstructural Alterations In The Sle Brain Correlate With Cognitive Impairment, M. Mackay, A. Vo, C. C. Tang, W. Anderson, N. J. Ploran, C. Aranow, P. Watson, B. T. Volpe, B. Diamond, D. Eidelberg, +5 Additional Authors

Journal Articles

No abstract provided.

Forebrain Cholinergic Signaling Regulates Innate Immune Responses And Inflammation, K. R. Lehner, H. A. Silverman, M. E. Adorissio, A. Roy, A. Al-Onaizi, S. S. Chavan, Y. Al-Abed, C. N. Metz, K. J. Tracey, V. A. Paviov, +6 Additional Authors

Journal Articles

No abstract provided.

Influence Of Genetic Copy Number Variants Of The Human Glut3 Glucose Transporter Gene Slc2a3 On Protein Expression, Glycolysis And Rheumatoid Arthritis Risk: A Genetic Replication Study, K. R. Simpfendorfer, W. Li, A. Shih, H. Wen, N. P. Kothari, A. Einsidler, A. Wuster, J. Hunkapiller, T. W. Behrens, P. K. Gregersen, +5 Additional Authors

Journal Articles

No abstract provided.

Assessment Of Pain Symptoms And Quality Of Life Using The International Spinal Cord Injury Data Sets In Persons With Chronic Spinal Cord Injury, K. Gibbs, A. Beaufort, A. Stein, T. M. Leung, N. Sison, Z. Bloom

Journal Articles

Introduction: Traumatic spinal cord injury (SCI) triggers complex changes that can negatively impact health and quality of life. The International SCI Data Sets were developed to enable more comparable data collection on the complex sequelae of SCI across studies. This should facilitate progress in mechanistic understanding and improving treatments of SCI. Study design: Prospective observational pilot study. Objectives: To collect data on pain symptoms and quality of life (QoL) in adults living with chronic SCI. Setting: Academic medical center, New York, USA. Methods: The International SCI Basic Pain and Qol Data Sets were used to collect data from participants with …

Fc Receptor-Like 2 (Fcrl2) Is A Novel Marker Of Low-Risk Cll And Refines Prognostication Based On Ighv Mutation Status, L. K. Shea, K. Honjo, D. T. Redden, E. Tabengwa, Li, J. Li, M. Shakhmatov, N. Chiorazzi, R. S. Davis

Journal Articles

No abstract provided.

Erratum: Distinct Hla Associations With Rheumatoid Arthritis Subsets Defined By Serological Subphenotype (The American Journal Of Human Genetics (2019) 105(3) (616–624), (S0002929719303052), (10.1016/J.Ajhg.2019.08.002)), C. Terao, B. Brynedal, Z. Chen, X. Jiang, Westerlind, Hansson, P. J. Jakobsson, K. Lundberg, P. K. Gregersen, S. Raychaudhuri, +10 Additional Authors

Journal Articles

© 2019 The Author(s) (The American Journal of Human Genetics 105, 616–624; September 5, 2019) In the originally published version of this article, the first author, Chikashi Tereo, had footnotes indicating affiliations with the first seven institutions. The correct affiliations are the first six plus footnote 17, indicating equal contribution. This error has been corrected here and online, and the authors and copyeditor express their regret for the mistake.

Patterns Of Ana(+) B Cells For Sle Patient Stratification, J. Suurmond, Y. Atisha-Fregoso, A. N. Barlev, S. A. Calderon, C. Mackay, Z. Aranow, B. Diamond

Journal Articles

No abstract provided.

Challenges And Inconsistencies In Using Lysophosphatidic Acid As A Biomarker For Ovarian Cancer, T. Yagi, M. Shoaib, C. E. Kuschner, M. Nishikimi, B. Becker, Z. T. Lee, J. Kim

Journal Articles

No abstract provided.

Tissue-Specific Metabolic Profiles After Prolonged Cardiac Arrest Reveal Brain Metabolome Dysfunction Predominantly After Resuscitation, J. Choi, M. Shoaib, T. Yin, G. Nayyar, Shinozaki, G. F. Stevens, L. B. Becker, J. Kim

Journal Articles

No abstract provided.

Effect Of Vitamin D On Serum Markers Of Bone Turnover In Sle In A Randomised Controlled Trial, S. K. Tedeschi, C. Aranow, D. L. Kamen, M. Leboff, Diamond, H. Costenbader

Journal Articles

© 2019 Author(s). Objective Bone health in SLE is adversely affected by vitamin D deficiency, inflammatory cytokines and glucocorticoid use. We hypothesised that vitamin D supplementation would increase markers of bone formation and decrease markers of bone resorption in SLE subjects. Methods We studied 43 vitamin D-deficient SLE subjects who participated in a 12-week randomised controlled trial of 2000-4000 IU/day vitamin D supplementation versus placebo. Subjects had inactive SLE (SLE Disease Activity Index ≤4) and were taking D, N-terminal propeptide of type 1 collagen (P1NP) and C-telopeptide (CTX). We tested the effect of vitamin D versus placebo on change (δ) …

Aquaporin-4 Water Channel In The Brain And Its Implication For Health And Disease., S. Mader, L. Brimberg

Journal Articles

Aquaporin-4 (AQP4) is a water channel expressed on astrocytic endfeet in the brain. The role of AQP4 has been studied in health and in a range of pathological conditions. Interest in AQP4 has increased since it was discovered to be the target antigen in the inflammatory autoimmune disease neuromyelitis optica spectrum disorder (NMOSD). Emerging data suggest that AQP4 may also be implicated in the glymphatic system and may be involved in the clearance of beta-amyloid in Alzheimer's disease (AD). In this review, we will describe the role of AQP4 in the adult and developing brain as well as its implication …

Clinically Significant Gains In Skillful Grasp Coordination By An Individual With Tetraplegia Using An Implanted Brain-Computer Interface With Forearm Transcutaneous Muscle Stimulation, M. Bockbrader, N. Annetta, D. Friedenberg, M. Schwemmer, Skomrock, Colachis, M. Zhang, C. Bouton, A. Rezai, W. J. Mysiw, +1 Additional Author

Journal Articles

© 2019 American Congress of Rehabilitation Medicine Objective: To demonstrate naturalistic motor control speed, coordinated grasp, and carryover from trained to novel objects by an individual with tetraplegia using a brain-computer interface (BCI)-controlled neuroprosthetic. Design: Phase I trial for an intracortical BCI integrated with forearm functional electrical stimulation (FES). Data reported span postimplant days 137 to 1478. Setting: Tertiary care outpatient rehabilitation center. Participant: A 27-year-old man with C5 class A (on the American Spinal Injury Association Impairment Scale) traumatic spinal cord injury Interventions: After array implantation in his left (dominant) motor cortex, the participant trained with BCI-FES to control …

Human B-1 Cells And B-1 Cell Antibodies Change With Advancing Age, N. Rodriguez-Zhurbenko, T. D. Quach, T. J. Hopkins, T. L. Rothstein, Z. M. Hernandez

Journal Articles

© 2019 Rodriguez-Zhurbenko, Quach, Hopkins, Rothstein and Hernandez. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Age-related deficits in the immune system have been associated with an increased incidence of infections, autoimmune diseases, and cancer. Human B cell populations change quantitatively …

Mus Musculus Deficient For Secretory Antibodies Show Delayed Growth With An Altered Urinary Metabolome, K. R. Simpfendorfer, N. Wang, D. L. Tull, D. P. De Souza, A. Nahid, A. Mu, D. M. Hocking, J. S. Pedersen, O. L. Wijburg, R. A. Strugnell, +1 Additional Author

Journal Articles

© 2019 The Author(s). Background: The polymeric immunoglobulin receptor (pIgR) maintains the integrity of epithelial barriers by transporting polymeric antibodies and antigens through the epithelial mucosa into the lumen. In this study, we examined the role of pIgR in maintaining gut barrier integrity, which is important for the normal development in mice. Methods: Cohorts of pIgR -/- mice and their wildtype controls were housed under Specific Pathogen Free (SPF) conditions and monitored for weight gain as an indicator of development over time. The general physiology of the gastrointestinal tract was analysed using immunohistochemistry in young (8-12 weeks of age) and …

Rnai Transfection Optimized In Primary Naïve B Cells For The Targeted Analysis Of Human Plasma Cell Differentiation, T. Shih, S. De, B. J. Barnes

Journal Articles

Upon antigen recognition, naïve B cells undergo rapid proliferation followed by differentiation to specialized antibody secreting cells (ASCs), called plasma cells. Increased circulating plasma cells are reported in patients with B cell-associated malignancies, chronic graft-vs.-host disease, and autoimmune disorders. Our aim was to optimize an RNAi-based method that efficiently and reproducibly knocks-down genes of interest in human primary peripheral B cells for the targeted analysis of ASC differentiation. The unique contributions of transcriptional diversity in species-specific regulatory networks and the mechanisms of gene function need to be approached directly in human B cells with tools to hone our basic inferences …

Large-Scale Validation Of The Paddling Pool Task In The Clockmaze For Studying Hippocampus-Based Spatial Cognition In Mice, R. Sankowski, T. S. Huerta, R. Kalra, T. J. Klein, J. Strohl, A. Al-Abed, S. Robbiati, P. T. Huerta

Journal Articles

No abstract provided.

Focused Hla Analysis In Caucasians With Myositis Identifies Significant Associations With Autoantibody Subgroups., S. Rothwell, H. Chinoy, J. A. Lamb, F. W. Miller, L. G. Rider, L. R. Wedderburn, N. J. Mchugh, A. T. Lee, P. K. Gregersen, I. E. Lundberg, +23 Additional Authors

Journal Articles

OBJECTIVES: Idiopathic inflammatory myopathies (IIM) are a spectrum of rare autoimmune diseases characterised clinically by muscle weakness and heterogeneous systemic organ involvement. The strongest genetic risk is within the major histocompatibility complex (MHC). Since autoantibody presence defines specific clinical subgroups of IIM, we aimed to correlate serotype and genotype, to identify novel risk variants in the MHC region that co-occur with IIM autoantibodies.

METHODS: We collected available autoantibody data in our cohort of 2582 Caucasian patients with IIM. High resolution human leucocyte antigen (HLA) alleles and corresponding amino acid sequences were imputed using SNP2HLA from existing genotyping data and tested …

The Bin1 Rs744373 Snp Is Associated With Increased Tau-Pet Levels And Impaired Memory, N. Franzmeier, A. Rubinski, J. Neitzel, M. Ewers, W. Weiner, Aisen, R. Petersen, C. R. Jack, P. Davies, B. Ances, +90 Additional Authors

Journal Articles

© 2019, The Author(s). The single nucleotide polymorphism (SNP) rs744373 in the bridging integrator-1 gene (BIN1) is a risk factor for Alzheimer’s disease (AD). In the brain, BIN1 is involved in endocytosis and sustaining cytoskeleton integrity. Post-mortem and in vitro studies suggest that BIN1-associated AD risk is mediated by increased tau pathology but whether rs744373 is associated with increased tau pathology in vivo is unknown. Here we find in 89 older individuals without dementia, that BIN1 rs744373 risk-allele carriers show higher AV1451 tau-PET across brain regions corresponding to Braak stages II–VI. In contrast, the BIN1 rs744373 SNP was not associated …