Digital Commons Network^™

Comprehensive Analysis Of Phospholipids In The Brain, Heart, Kidney, And Liver: Brain Phospholipids Are Least Enriched With Polyunsaturated Fatty Acids, J. Choi, T. Yin, K. Shinozaki, J. W. Lampe, J. F. Stevens, L. B. Becker, J. Kim

Journal Articles

No abstract provided.

High-Mobility Group Box 1-Induced Complement Activation Causes Sterile Inflammation, S. Y. Kim, M. Son, S. E. Lee, I. H. Park, M. S. Kwak, M. Han, H. S. Lee, E. S. Kim, B. Diamond, J. S. Shin, +3 Additional Authors

Journal Articles

© 2018 Kim, Son, Lee, Kwak, Han, Lee, Park, Kim, Kim, Lee, Choi, Diamond and Shin. High-mobility group box 1 (HMGB1), a well-known danger-associated molecular pattern molecule, acts as a pro-inflammatory molecule when secreted by activated immune cells or released after necrotic cell damage. HMGB1 binds to immunogenic bacterial components and augments septic inflammation. In this study, we show how HMGB1 mediates complement activation, promoting sterile inflammation. We show that HMGB1 activates the classical pathway of complement system in an antibody-independent manner after binding to C1q. The C3a complement activation product in human plasma and C5b-9 membrane attack complexes on …

Immunization Elicits Antigen-Specific Antibody Sequestration In Dorsal Root Ganglia Sensory Neurons, M. Gunasekaran, P. K. Chatterjee, A. Shih, G. H. Imperato, G. Kumar, A. Lee, C. Bouton, B. Sherry, B. Diamond, T. R. Coleman, C. N. Metz, K. J. Tracey, S. S. Chavan, +9 Additional Authors

Journal Articles

No abstract provided.

Erythropoiesis: Insights Into Pathophysiology And Treatments In 2017, A. Zivot, J. M. Lipton, A. Narla, L. Blanc

Journal Articles

No abstract provided.

Lineage-Specific Functionality Of An Interferon Regulatory Factor 5 Lupus Risk Haplotype: Lack Of B Cell Intrinsic Effects, J. Calise, S. M. Renteria, P. K. Gregersen, B. Diamond

Journal Articles

No abstract provided.

Myosin Iia Interacts With The Spectrin-Actin Membrane Skeleton To Control Red Blood Cell Membrane Curvature And Deformability, A. S. Smith, R. B. Nowak, S. Zhou, M. Giannetto, D. S. Gokhin, J. Papoin, I. C. Ghiran, L. Blanc, J. Wan, V. M. Fowler

Journal Articles

No abstract provided.

Highly Conserved Molecular Pathways, Including Wnt Signaling, Promote Functional Recovery From Spinal Cord Injury In Lampreys, P. E. Herman, A. Papatheodorou, S. A. Bryant, C. K. Waterbury, J. R. Herdy, A. A. Arcese, J. D. Buxbaum, J. J. Smith, J. R. Morgan, O. Bloom

Journal Articles

No abstract provided.

Reproducible Network And Regional Topographies Of Abnormal Glucose Metabolism Associated With Progressive Supranuclear Palsy: Multivariate And Univariate Analyses In American And Chinese Patient Cohorts, J. Ge, J. Wu, S. Peng, P. Wu, J. Wang, H. Zhang, Y. Guan, D. Eidelberg, C. Zuo, Y. Ma

Journal Articles

No abstract provided.

Mutations Of Recombinant Aquaporin-4 Antibody In The Fc Domain Can Impair Complement-Dependent Cellular Cytotoxicity And Transplacental Transport, S. Mader, L. Brimberg, J. N. Soltys, J. L. Bennett, B. Diamond

Journal Articles

© 2018 Mader, Brimberg, Soltys, Bennett and Diamond. Maternal antibodies provide protection for the developing fetus. Transplacental transport of pathogenic autoantibodies might pose a risk for the developing fetus. The transport of antibodies across the placenta to the fetal circulation occurs through the neonatal Fc salvage receptor (FcRn). During gestation, maternal autoantibodies are able to penetrate the embryonic brain before a functional intact blood-brain barrier is established. Brain-reactive antibodies to the water channel protein aquaporin-4 (AQP4) are a hallmark finding in neuromyelitis optica (NMO), a neurological disease that predominantly affects women, many of whom are of childbearing age. AQP4-IgG mediate …

Follicular Helper T Cells In Systemic Lupus Erythematosus, S. J. Kim, K. Lee, B. Diamond

Journal Articles

© 2018 Kim, Lee and Diamond. CD4+ follicular helper T (Tfh) cells constitute a subset of effector T cells that participate in the generation of high-affinity humoral responses. They express the chemokine receptor CXCR5 and produce the cytokine IL-21, both of which are required for their contribution to germinal center formation. Uncontrolled expansion of Tfh cells is observed in various mouse models of systemic autoimmune diseases and in patients with these diseases. In particular, the frequency of circulating Tfh is correlated with disease activity and anti-DNA antibody titer in patients with systemic lupus erythematosus. Recent studies reveal functional diversity within …

Mutant Klf1 In Adult Anemic Nan Mice Leads To Profound Transcriptome Changes And Disordered Erythropoiesis, D. Nébor, J. H. Graber, S. L. Ciciotte, R. F. Robledo, J. Papoin, E. Hartman, K. R. Gillinder, A. C. Perkins, L. Blanc, L. L. Peters, +1 Additional Author

Journal Articles

© 2018, The Author(s). Anemic Nan mice carry a mutation (E339D) in the second zinc finger of erythroid transcription factor KLF1. Nan-KLF1 fails to bind a subset of normal KLF1 targets and ectopically binds a large set of genes not normally engaged by KLF1, resulting in a corrupted fetal liver transcriptome. Here, we performed RNAseq using flow cytometric-sorted spleen erythroid precursors from adult Nan and WT littermates rendered anemic by phlebotomy to identify global transcriptome changes specific to the Nan Klf1 mutation as opposed to anemia generally. Mutant Nan-KLF1 leads to extensive and progressive transcriptome corruption in adult spleen erythroid …

Constitutive Vagus Nerve Activation Modulates Immune Suppression In Sepsis Survivors, M. Rana, Y. Fei-Bloom, M. Son, A. L. Bella, M. Ochani, Y. A. Levine, P. Y. Chiu, P. Wang, S. S. Chavan, B. T. Volpe, B. Sherry, B. Diamond

Journal Articles

© 2018 Rana, Fei-Bloom, Son, La Bella, Ochani, Levine, Chiu, Wang, Chavan, Volpe, Sherry and Diamond. Patients surviving a septic episode exhibit persistent immune impairment and increased mortality due to enhanced vulnerability to infections. In the present study, using the cecal ligation and puncture (CLP) model of polymicrobial sepsis, we addressed the hypothesis that altered vagus nerve activity contributes to immune impairment in sepsis survivors. CLP-surviving mice exhibited less TNFα in serum following administration of LPS, a surrogate for an infectious challenge, than control-operated (control) mice. To evaluate the role of the vagus nerve in the diminished response to LPS, …

Correction To: Exploring The Biological Functional Mechanism Of The Hmgb1/Tlr4/Md-2 Complex By Surface Plasmon Resonance., M. He, M. E. Bianchi, T. R. Coleman, K. J. Tracey, Y. Al-Abed

Journal Articles

After publication of this article (He et al., 2018), the corresponding authors recognised an error in Scheme 1, in particular to section "A. HMGB1/TLR4/MD-2 complex formation". Above "Step 2: B box binding to MD-2", the text incorrectly read: "Low affinity / extremely slow off". In addition, some text was omitted below "TLR4/MD-2". The correct version of Scheme 1 is included in this Correction article. The original article (He et al., 2018) has been corrected.

Exploring The Biological Functional Mechanism Of The Hmgb1/Tlr4/Md-2 Complex By Surface Plasmon Resonance., M. He, M. E. Bianchi, T. R. Coleman, K. J. Tracey, Y. Al-Abed

Journal Articles

High Mobility Group Box 1 (HMGB1) was first identified as a nonhistone chromatin-binding protein that functions as a pro-inflammatory cytokine and a Damage-Associated Molecular Pattern molecule when released from necrotic cells or activated leukocytes. HMGB1 consists of two structurally similar HMG boxes that comprise the pro-inflammatory (B-box) and the anti-inflammatory (A-box) domains. Paradoxically, the A-box also contains the epitope for the well-characterized anti-HMGB1 monoclonal antibody "2G7", which also potently inhibits HMGB1-mediated inflammation in a wide variety of in vivo models. The molecular mechanisms through which the A-box domain inhibits the inflammatory activity of HMGB1 and 2G7 exerts anti-inflammatory activity after …

Belimumab Promotes Negative Selection Of Activated Autoreactive B Cells In Systemic Lupus Erythematosus Patients., W. Huang, T. D. Quach, C. Dascalu, Z. Liu, T. Leung, M. Lesser, R. Furie, M. Mackay, C. Aranow Md, A. Davidson Md, +5 Additional Authors

Journal Articles

Belimumab has therapeutic benefit in active systemic lupus erythematosus (SLE), especially in patients with high-titer anti-dsDNA antibodies. We asked whether the profound B cell loss in belimumab-treated SLE patients is accompanied by shifts in the immunoglobulin repertoire. We enrolled 15 patients who had been continuously treated with belimumab for more than 7 years, 17 matched controls, and 5 patients who were studied before and after drug initiation. VH genes of sort-purified mature B cells and plasmablasts were subjected to next-generation sequencing. We found that B cell-activating factor (BAFF) regulates the transitional B cell checkpoint, with conservation of transitional 1 (T1) …

Serologic Features Of Cohorts With Variable Genetic Risk For Systemic Lupus Erythematosus., J. Bhattacharya, K. Pappas, B. Toz, C. Aranow, M. Mackay, P. K. Gregersen, O. Doumbo, A. K. Traore, M. L. Lesser, B. Diamond, +9 Additional Authors

Journal Articles

Systemic lupus erythematosus (SLE) is an autoimmune disease with genetic, hormonal, and environmental influences. In Western Europe and North America, individuals of West African descent have a 3-4 fold greater incidence of SLE than Caucasians. Paradoxically, West Africans in sub-Saharan Africa appear to have a low incidence of SLE, and some studies suggest a milder disease with less nephritis. In this study, we analyzed sera from African American female SLE patients and four other cohorts, one with SLE and others with varying degrees of risk for SLE in order to identify serologic factors that might correlate with risk of or …

Dissociated Oxygen Consumption And Carbon Dioxide Production In The Post-Cardiac Arrest Rat: A Novel Metabolic Phenotype., K. Shinozaki, L. Becker, Kota Saeki, J. Kim, T. Yin, Tong Da, J. W. Lampe

Journal Articles

BACKGROUND: The concept that resuscitation from cardiac arrest (CA) results in a metabolic injury is broadly accepted, yet patients never receive this diagnosis. We sought to find evidence of metabolic injuries after CA by measuring O

METHODS AND RESULTS: Rats were anesthetized and randomized into 3 groups: resuscitation from 10-minute asphyxia with inhaled 100% O

CONCLUSIONS: CA altered cellular metabolism resulting in increased VO

Plasma Cell Differentiation Pathways In Systemic Lupus Erythematosus, S. Malkiel, A. N. Barlev, Y. Atisha-Fregoso, J. Suurmond, B. Diamond

Journal Articles

No abstract provided.

Identification Of Cytokine-Specific Sensory Neural Signals By Decoding Murine Vagus Nerve Activity, T. P. Zanos, H. A. Silverman, T. Levy, T. Tsaava, E. Battinelli, P. W. Lorraine, J. M. Ashe, S. S. Chavan, K. J. Tracey, C. E. Bouton

Journal Articles

© 2018 National Academy of Sciences. All Rights Reserved. The nervous system maintains physiological homeostasis through reflex pathways that modulate organ function. This process begins when changes in the internal milieu (e.g., blood pressure, temperature, or pH) activate visceral sensory neurons that transmit action potentials along the vagus nerve to the brainstem. IL-1β and TNF, inflammatory cytokines produced by immune cells during infection and injury, and other inflammatory mediators have been implicated in activating sensory action potentials in the vagus nerve. However, it remains unclear whether neural responses encode cytokine-specific information. Here we develop methods to isolate and decode specific …

Increased Reactive Oxygen Species And Cell Cycle Defects Contribute To Anemia In The Rasa3 Mutant Mouse Model Scat, E. S. Hartman, E. C. Brindley, J. Papoin, S. L. Ciciotte, Y. Zhao, L. L. Peters, L. Blanc

Journal Articles

No abstract provided.

Analysis Of Menstrual Effluent: Diagnostic Potential For Endometriosis, L. A. Warren, A. Shih, S. M. Renteira, T. Seckin, B. Blau, K. Simpfendorfer, C. N. Metz, P. K. Gregersen

Journal Articles

No abstract provided.

Biosocial Criminology Versus The Constitution, Karen E. Balter

Regis University Student Publications (comprehensive collection)

The continually emerging field of biosocial criminology provides a basis for productively merging biology with sociological reasonings for criminal behavior. Mainstream research in criminology focuses on environmental factors as the sole reason individuals exhibit antisocial behavior patterns and may ultimately commit crimes. Criminological research has travelled in this direction for decades. The current climate within this community subscribes heavily to the notion that biology has very little to do with why people behave the way they do, and if it did, government control would be the norm. The nature of biocriminology opens a door through which constitutional issues may enter. …

Novel Caries Loci In Children And Adults Implicated By Genome-Wide Analysis Of Families, Manika Govil, Nandita Mukhopadhyay, Daniel E. Weeks, Eleanor Feingold, John R. Shaffer, Steven M. Levy, Alexandre R. Vieira, Rebecca L. Slayton, Daniel W. Mcneil, Robert J. Weyant, Richard J. Crout, Mary L. Marazita

Faculty & Staff Scholarship

Background: Dental caries is a common chronic disease among children and adults alike, posing a substantial health burden. Caries is affected by multiple genetic and environmental factors, and prior studies have found that a substantial proportion of caries susceptibility is genetically inherited.

Methods: To identify such genetic factors, we conducted a genome-wide linkage scan in 464 extended families with 2616 individuals from Iowa, Pennsylvania and West Virginia for three dental caries phenotypes: (1) PRIM: dichotomized as zero versus one or more affected primary teeth, (2) QTOT1: age-adjusted quantitative caries measure for both primary and permanent dentitions including pre-cavitated lesions, and …

Metabolic And Transcriptional Modules Independently Diversify Plasma Cell Lifespan And Function, Wing Y. Lam, Arijita Jash, Cong-Hui Yao, Lucas D'Souza, Rachel Wong, Ryan M. Nunley, Gordon P. Meares, Gary J. Patti, Deepta Bhattacharya

Faculty & Staff Scholarship

Plasma cell survival and the consequent duration of immunity vary widely with infection or vaccination. Using fluorescent glucose analog uptake, we defined multiple developmentally independent mouse plasma cell populations with varying life- spans. Long-lived plasma cells imported more fluo- rescent glucose analog, expressed higher surface levels of the amino acid transporter CD98, and had more autophagosome mass than did short-lived cells. Low amino acid concentrations triggered re- ductions in both antibody secretion and mitochon- drial respiration, especially by short-lived plasma cells. To explain these observations, we found that glutamine was used for both mitochondrial respira- tion and anaplerotic reactions, yielding …

Study Of Flare Assessment In Systemic Lupus Erythematosus Based On Paper Patients, D. Isenberg, J. Sturgess, E. Allen, C. Aranow, A. Askanase, B. Sang-Cheol, S. Bernatsky, I. Bruce, J. Buyon, C. Gordon, +29 Additional Authors

Journal Articles

© 2017, The Authors. Arthritis Care & Research published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology. Objective: To determine the level of agreement of disease flare severity (distinguishing severe, moderate, and mild flare and persistent disease activity) in a large paper-patient exercise involving 988 individual cases of systemic lupus erythematosus. Methods: A total of 988 individual lupus case histories were assessed by 3 individual physicians. Complete agreement about the degree of flare (or persistent disease activity) was obtained in 451 cases (46%), and these provided the reference standard for the second part of the study. This …

Lifelong Behavioral And Neuropathological Consequences Of Repetitive Mild Traumatic Brain Injury, B. C. Mouzon, C. Bachmeier, J. O. Ojo, C. M. Acker, S. Ferguson, D. Paris, G. Ait-Ghezala, G. Crynen, P. Davies, F. Crawford, +2 Additional Authors

Journal Articles

© 2017 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association. Objective: Exposure to repetitive concussion, or mild traumatic brain injury (mTBI), has been linked with increased risk of long-term neurodegenerative changes, specifically chronic traumatic encephalopathy (CTE). To date, preclinical studies largely have focused on the immediate aftermath of mTBI, with no literature on the lifelong consequences of mTBI in these models. This study provides the first account of lifelong neurobehavioral and histological consequences of repetitive mTBI providing unique insight into the constellation of evolving and ongoing pathologies with late …

On Statistical Modeling Of Sequencing Noise In High Depth Data To Assess Tumor Evolution, R. Rabadan, G. Bhanot, S. Marsilio, N. Chiorazzi, L. Pasqualucci, H. Khiabanian

Journal Articles

© 2017, Springer Science+Business Media, LLC, part of Springer Nature. One cause of cancer mortality is tumor evolution to therapy-resistant disease. First line therapy often targets the dominant clone, and drug resistance can emerge from preexisting clones that gain fitness through therapy-induced natural selection. Such mutations may be identified using targeted sequencing assays by analysis of noise in high-depth data. Here, we develop a comprehensive, unbiased model for sequencing error background. We find that noise in sufficiently deep DNA sequencing data can be approximated by aggregating negative binomial distributions. Mutations with frequencies above noise may have prognostic value. We evaluate …

Neuro-Immune Interactions In Inflammation And Host Defense: Implications For Transplantation, S. S. Chavan, P. Ma, I. M. Chiu

Journal Articles

© 2017 The American Society of Transplantation and the American Society of Transplant Surgeons Sensory and autonomic neurons of the peripheral nervous system (PNS) play a critical role in regulating the immune system during tissue inflammation and host defense. Recent studies have identified the molecular mechanisms underlying the bidirectional communication between the nervous system and the immune system. Here, we highlight the studies that demonstrate the importance of the neuro-immune interactions in health and disease. Nociceptor sensory neurons detect immune mediators to produce pain, and release neuropeptides that act on the immune system to regulate inflammation. In parallel, neural reflex …

Design And Mechanism Of (S)-3-Amino-4-(Difluoromethylenyl)Cyclopent-1-Ene-1-Carboxylic Acid, A Highly Potent Γ-Aminobutyric Acid Aminotransferase Inactivator For The Treatment Of Addiction, J. I. Juncosa, K. Takaya, H. V. Le, M. J. Moschitto, P. M. Weerawarna, R. Mascarenhas, D. Liu, S. L. Dewey, R. B. Silverman

Journal Articles

© 2018 American Chemical Society. γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system. Inhibition of GABA aminotransferase (GABA-AT), a pyridoxal 5′-phosphate (PLP)-dependent enzyme that degrades GABA, has been established as a possible strategy for the treatment of substance abuse. The raised GABA levels that occur as a consequence of this inhibition have been found to antagonize the rapid release of dopamine in the ventral striatum (nucleus accumbens) that follows an acute challenge by an addictive substance. In addition, increased GABA levels are also known to elicit an anticonvulsant effect in patients with epilepsy. We previously …

Glucocorticoid Use And Factors Associated With Variability In This Use In The Systemic Lupus International Collaborating Clinics Inception Cohort, J. Little, B. Parker, M. Lunt, J. G. Hanly, M. B. Urowitz, A. E. Clarke, J. Romero-Diaz, C. Aranow, M. Mackay, I. N. Bruce, +32 Additional Authors

Journal Articles

© The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. Objectives. To describe glucocorticoid (GC) use in the SLICC inception cohort and to explore factors associated with GC use. In particular we aimed to assess temporal trends in GC use and to what extent physician-related factors may influence use. Methods. Patients were recruited within 15 months of diagnosis of SLE from 33 centres between 1999 and 2011 and continue to be reviewed annually. Descriptive statistics were used to detail oral and parenteral GC use. Cross sectional and longitudinal analyses were …