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Biogeographic Study Of Human Gut-Associated Crassphage Suggests Impacts From Industrialization And Recent Expansion, Tanvi P/ Honap, Krithivasan Sankaranarayanan, Stephanie L. Schnorr, Andrew T. Ozga, Christina Warinner, Cecil M. Lewis Jr.

Anthropology Faculty Research

CrAssphage (cross-assembly phage) is a bacteriophage that was first discovered in human gut metagenomic data. CrAssphage belongs to a diverse family of crAss-like bacteriophages thought to infect gut commensal bacteria belonging to Bacteroides species. However, not much is known about the biogeography of crAssphage and whether certain strains are associated with specific human populations. In this study, we screened publicly available human gut metagenomic data from 3,341 samples for the presence of crAssphage sensu stricto (NC_024711.1). We found that crAssphage prevalence is low in traditional, hunter-gatherer populations, such as the Hadza from Tanzania and Matses from Peru, as compared to …

Expression Of Cytokines And Chemokines As Predictors Of Stroke Outcomes In Acute Ischemic Stroke, Sarah R. Martha, Qiang Cheng, Justin F. Fraser, Liyu Gong, Lisa A. Collier, Stephanie M. Davis, Doug Lukins, Abdulnasser Alhajeri, Stephen Grupke, Keith R. Pennypacker

Institute for Biomedical Informatics Faculty Publications

Introduction: Ischemic stroke remains one of the most debilitating diseases and is the fifth leading cause of death in the US. The ability to predict stroke outcomes within the acute period of stroke would be essential for care planning and rehabilitation. The Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC; clinicaltrials.gov NCT03153683) study collects arterial blood immediately distal and proximal to the intracranial thrombus at the time of mechanical thrombectomy. These blood samples are an innovative resource in evaluating acute gene expression changes at the time of ischemic stroke. The purpose of this study was to identify inflammatory genes and …

Week Of January 13, 2020, New York Medical College

InTouch

• Ira J. Bedzow, Ph.D., is Named UNESCO Chair of Bioethics
• Department of Surgery Hosts Sixteenth Annual Louis R.M. Del Guercio, M.D., Distinguished Visiting Professorship and Research Day
• Graduate Student Association Aims to Enhance Student Life
• Center for Disaster Medicine Hosts Pediatric Focused Disaster Response Training

Brief Communication: Long-Term Absence Of Langerhans Cells Alters The Gene Expression Profile Of Keratinocytes And Dendritic Epidermal T Cells., Qingtai Su, Aurélie Bouteau, Jacob Cardenas, Balaji Uthra, Yuanyaun Wang, Cynthia Smitherman, Jinghua Gu, Botond Z. Igyártó

Department of Microbiology and Immunology Faculty Papers

Tissue-resident and infiltrating immune cells are continuously exposed to molecules derived from the local cells that often come in form of secreted factors, such as cytokines. These factors are known to impact the immune cells' biology. However, very little is known about whether the tissue resident immune cells in return also affect the local environment. In this study, with the help of RNA-sequencing, we show for the first time that long-term absence of epidermal resident Langerhans cells led to significant gene expression changes in the local keratinocytes and resident dendritic epidermal T cells. Thus, immune cells might play an active …

Frontotemporal Dementia Nonsense Mutation Of Progranulin Rescued By Aminoglycosides, Lisha Kuang, Kei Hashimoto, Eric J. Huang, Matthew S. Gentry, Haining Zhu

Molecular and Cellular Biochemistry Faculty Publications

Frontotemporal dementia (FTD) is an early onset dementia and is characterized by progressive atrophy of the frontal and/or temporal lobes. FTD is highly heritable with mutations in progranulin accounting for 5-26% of cases in different populations. Progranulin is involved in endocytosis, secretion and lysosomal processes, but its function under physiological and pathological conditions remains to be defined. Many FTD-causing nonsense progranulin mutations contain a premature termination codon (PTC), thus progranulin haploinsufficiency has been proposed as a major disease mechanism. Currently, there is no effective FTD treatment or therapy.

Aminoglycosides are a class of antibiotics that possess a less known function …

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 …

Investigating The Potential And Pitfalls Of Ev-Encapsulated Micrornas As Circulating Biomarkers Of Breast Cancer, Brian M. Moloney, Katie E. Gilligan, Doireann P. Joyce, Clodagh P. O'Neill, Killian P. O'Brien, Sonja Khan, Claire L. Glynn, Ronan M. Waldron, Ciarán M. Maguire, Emma Holian, Erin Naughton, Mohamed Elhadi, Andrea B. Grealish, Carmel Malone, Emma Mcdermott, Peter Dockery, Thomas Ritter, Adriele Prina-Mello, Michael J. Kerin, Róisín M. Dwyer

Forensic Science Publications

Extracellular vesicles (EVs) shuttle microRNA (miRNA) throughout the circulation and are believed to represent a fingerprint of the releasing cell. We isolated and characterized serum EVs of breast tumour-bearing animals, breast cancer (BC) patients, and healthy controls. EVs were characterized using transmission electron microscopy (TEM), protein quantification, western blotting, and nanoparticle tracking analysis (NTA). Absolute quantitative (AQ)-PCR was employed to analyse EV-miR-451a expression. Isolated EVs had the appropriate morphology and size. Patient sera contained significantly more EVs than did healthy controls. In tumour-bearing animals, a correlation between serum EV number and tumour burden was observed. There was no significant relationship …

Dopamine-Dependent Transcriptional Dynamics In Striatal Physiology And Cocaine Reward, Morgan Elizabeth Zipperly

All ETDs from UAB

Exposure to drugs of abuse alters transcriptional programs and neuronal activity, leading to long-lasting cellular and behavioral adaptations that may contribute to addiction. The nucleus accumbens (NAc), part of the mesocorticolimbic dopamine pathway, plays a central role in motivation, reward, and reward-related learning, and this brain region is highly implicated in the development and maintenance of addiction. However, the specific contributions of defined cell populations in the NAc to drug reward processes is still poorly understood. Here, we used electrophysiological, optogenetic, and single-nucleus RNA-sequencing (snRNA-seq) approaches in a rodent model system to define the acute physiological and transcriptional responses of …

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

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

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

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

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

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

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

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

Journal Articles

No abstract provided.

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

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

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

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

Journal Articles

No abstract provided.

Plasma Metabolomics Supports The Use Of Long-Duration Cardiac Arrest Rodent Model To Study Human Disease By Demonstrating Similar Metabolic Alterations., M. Shoaib, R. C. Choudhary, J. Choi, N. Kim, K. Hayashida, T. Yagi, T. Yin, M. Nishikimi, L. B. Becker, J. Kim, +1 Additional Author

Journal Articles

Cardiac arrest (CA) is a leading cause of death and there is a necessity for animal models that accurately represent human injury severity. We evaluated a rat model of severe CA injury by comparing plasma metabolic alterations to human patients. Plasma was obtained from adult human control and CA patients post-resuscitation, and from male Sprague-Dawley rats at baseline and after 20 min CA followed by 30 min cardiopulmonary bypass resuscitation. An untargeted metabolomics evaluation using UPLC-QTOF-MS/MS was performed for plasma metabolome comparison. Here we show the metabolic commonality between humans and our severe injury rat model, highlighting significant metabolic dysfunction …

A Double-Blind, Placebo-Controlled, Phase Ii, Randomized Study Of Lovastatin Therapy In The Treatment Of Mildly Active Rheumatoid Arthritis, C. Aranow, J. Cush, M. B. Bolster, C. C. Striebich, M. Dall'era, M. Mackay, E. Olech, T. Frech, B. Diamond, A. Davidson Mbbs, +14 Additional Authors

Journal Articles

© 2019 The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. 3-hydroxy-3-methylglutaryl coenzyme-A (HMG Co-A) reductase inhibitors (statins) are standard treatment for hyperlipidaemia. In addition to lipid-lowering abilities, statins exhibit multiple anti-inflammatory effects. The objectives of this study were to determine whether treatment of patients with RA with lovastatin decreased CRP or reduced disease activity. Methods: We conducted a randomized double-blind placebo-controlled 12 week trial of lovastatin vs placebo in 64 RA patients with mild clinical disease activity but an elevated CRP. The primary efficacy end point was the reduction …

Peripheral Nervous System Disease In Systemic Lupus Erythematosus: Results From An International Inception Cohort Study, J. G. Hanly, Q. Li, L. Su, M. B. Urowitz, C. Gordon, S. C. Bae, J. Romero-Diaz, C. Aranow, M. Mackay, V. Farewell, +33 Additional Authors

Journal Articles

© 2019, American College of Rheumatology Objective: To determine the frequency, clinical characteristics, associations, and outcomes of different types of peripheral nervous system (PNS) disease in a multiethnic/multiracial, prospective inception cohort of systemic lupus erythematosus (SLE) patients. Methods: Patients were evaluated annually for 19 neuropsychiatric (NP) events including 7 types of PNS disease. SLE disease activity, organ damage, autoantibodies, and patient and physician assessment of outcome were measured. Time to event and linear regressions were used as appropriate. Results: Of 1,827 SLE patients, 88.8% were female, and 48.8% were white. The mean ± SD age was 35.1 ± 13.3 years, …

Fusion, 2020, George Washington University, William H. Beaumont Medical Research Honor Society

Fusion

No abstract provided.

Effect Of Sleep Deprivation And Sleep Recovery On Heart Rate And Heart Rate Variability In Males Versus Females, Abrianna Lochner Spt, Elena Crooks Pt, Dpt, Phd, Myles Gordon Finlay Ba, Julie A. Erwin Ms, Kimberly Honn Phd

2020 Symposium Posters

Introduction

Elevated heart rate (HR) and low HR variability (HRV) are indicators of increased sympathetic tone and cardiovascular risk. Here, we assess the effect of one night of sleep deprivation and a subsequent night of recovery sleep on HR and HRV in healthy males versus females.

Methods

Fifty-nine subjects (29.5±8.5y, n=35 female) completed a 4-day/3-night laboratory study. Subjects had a baseline sleep opportunity (22:00–08:00), followed by 38h of sleep deprivation, and a recovery sleep opportunity (22:00–08:00). EKG was monitored via Holter monitors to measure HR and the pNN50 and rMMSD variables of HRV. Time points used for analyses included 09:00–09:20 …

Targeting Potential Drivers Of Covid-19: Neutrophil Extracellular Traps., Bj Barnes, Jm Adrover, A Baxter-Stoltzfus, A Borczuk, J Cools-Lartigue, Jm Crawford, J Daßler-Plenker, P Guerci, A Weber, M Egeblad, +13 Additional Authors

Journal Articles

No abstract provided.

Iglv3-21∗01 Is An Inherited Risk Factor For Cll Through The Acquisition Of A Single-Point Mutation Enabling Autonomous Bcr Signaling, P. C. Maity, M. Bilal, M. T. Koning, M. Young, C. A. Van Bergen, V. Renna, A. Nicolò, A. N. Mazzarello, N. Chiorazzi, H. Jumaa, +28 Additional Authors

Journal Articles

© 2020 National Academy of Sciences. All rights reserved. The prognosis of chronic lymphocytic leukemia (CLL) depends on different markers, including cytogenetic aberrations, oncogenic mutations, and mutational status of the immunoglobulin (Ig) heavy-chain variable (IGHV) gene. The number of IGHV mutations distinguishes mutated (M) CLL with a markedly superior prognosis from unmutated (UM) CLL cases. In addition, B cell antigen receptor (BCR) stereotypes as defined by IGHV usage and complementaritydetermining regions (CDRs) classify ∼30% of CLL cases into prognostically important subsets. Subset 2 expresses a BCR with the combination of IGHV3-21-derived heavy chains (HCs) with IGLV3- 21-derived light chains (LCs), …

Integrated Urine Proteomics And Renal Single-Cell Genomics Identify An Interferon-Γ Response Gradient In Lupus Nephritis., A. Fava, J. P. Buyon, C. Mohan, T. Zhang, H. M. Belmont, P. Izmirly, A. Arazi, A. Davidson, B. Diamond, M. Petri, +12 Additional Authors

Journal Articles

Lupus nephritis, one of the most serious manifestations of systemic lupus erythematosus (SLE), has both a heterogeneous clinical and pathological presentation. For example, proliferative nephritis identifies a more aggressive disease class that requires immunosuppression. However, the current classification system relies on the static appearance of histopathological morphology which does not capture differences in the inflammatory response. Therefore, a biomarker grounded in the disease biology is needed to understand the molecular heterogeneity of lupus nephritis and identify immunologic mechanism and pathways. Here, we analyzed the patterns of 1000 urine protein biomarkers in 30 patients with active lupus nephritis. We found that …