Organisms Commons^™

Iiv-6 Inhibits Nf-Kappab Responses In Drosophila, Cara C. West, Florentina Rus, Ying Chen, Anni Kleino, Monique Gangloff, Don B. Gammon, Neal S. Silverman

Neal Silverman

The host immune response and virus-encoded immune evasion proteins pose constant, mutual selective pressure on each other. Virally encoded immune evasion proteins also indicate which host pathways must be inhibited to allow for viral replication. Here, we show that IIV-6 is capable of inhibiting the two Drosophila NF-kappaB signaling pathways, Imd and Toll. Antimicrobial peptide (AMP) gene induction downstream of either pathway is suppressed when cells infected with IIV-6 are also stimulated with Toll or Imd ligands. We find that cleavage of both Imd and Relish, as well as Relish nuclear translocation, three key points in Imd signal transduction, occur …

Control Of Antiviral Innate Immune Response By Protein Geranylgeranylation, Shigao Yang, Zhaozhao Jiang, Katherine A. Fitzgerald, Donghai Wang

Katherine A. Fitzgerald

The mitochondrial antiviral signaling protein (MAVS) orchestrates host antiviral innate immune response to RNA virus infection. However, how MAVS signaling is controlled to eradicate virus while preventing self-destructive inflammation remains obscure. Here, we show that protein geranylgeranylation, a posttranslational lipid modification of proteins, limits MAVS-mediated immune signaling by targeting Rho family small guanosine triphosphatase Rac1 into the mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) at the mitochondria-ER junction. Protein geranylgeranylation and subsequent palmitoylation promote Rac1 translocation into MAMs upon viral infection. MAM-localized Rac1 limits MAVS' interaction with E3 ligase Trim31 and hence inhibits MAVS ubiquitination, aggregation, and activation. Rac1 also facilitates …

Use Of Urine Antigen Testing For Blastomyces In An Integrated Health System, Dennis J. Baumgardner

Dennis J. Baumgardner, MD

Purpose: Blastomycosis, an endemic fungal infection, mimics many other diseases. We explored the use of Blastomyces urine antigen (BuAg), reportedly the most sensitive noninvasive test, in clinical practice and compared it to other noninvasive tests.

Methods: A total of 836 BuAg tests performed on unique patients (first test only) at one large integrated health system from June 2013 to May 2016 were retrospectively reviewed to examine test characteristics and demographic features. Of these, 100 cases from 2015, a year containing a large local blastomycosis outbreak, were randomly selected for detailed analysis.

Results: Demographics for the BuAg-tested population: mean age 54.9 …

Blastomyces: Why Be Dimorphic?, Dennis J. Baumgardner

Dennis J. Baumgardner, MD

In introducing the infectious disease focus for this edition of the Journal of Patient-Centered Research and Reviews, the author describes the unsolved mysteries surrounding the dimorphic fungus Blastomyces and the related pathogenesis of pulmonary blastomycosis.

Geodemographic Features Of Human Blastomycosis In Eastern Wisconsin, Megan E. Huber, Dennis J. Baumgardner, Jessica J. F. Kram, Melissa A. Lemke

Dennis J. Baumgardner, MD

Purpose

Blastomycosis is an endemic fungal infection. In rural northern Wisconsin, blastomycosis cases are associated with certain environmental features including close proximity to waterways. Other studies have associated blastomycosis with particular soil chemicals. However, blastomycosis also occurs in urban and suburban regions. We explored the geodemographic associations of blastomycosis cases in the more urban/suburban landscape of eastern Wisconsin.

Methods

We conducted a retrospective study of 193 laboratory-identified blastomycosis cases in a single eastern Wisconsin health system, 2007–2015. Controls were 250 randomly selected cases of community-diagnosed pneumonia from a similar time period. Geographic features of home addresses were explored using Google …

Geographic Distribution Of Infant Death During Birth Hospitalization And Maternal Group B Streptococcus Colonization: Eastern Wisconsin, Jessica J.F. Kram, Dennis J. Baumgardner, Kiley A. Bernhard, Melissa A. Lemke

Dennis J. Baumgardner, MD

Background: Neonatal death rate in the United States is 4/1,000 live births; infant death rate is 6/1,000. Group B Streptococcus (GBS) may be transmitted from a colonized mother (rates vary from 15% to 35%) to the newborn during a vaginal delivery, and may contribute to neonatal death.

Purpose: To explore the geographic distribution and associated risk factors for maternal GBS colonization and infant death prior to discharge in eastern Wisconsin births.

Methods: Retrospective study of institutional data from PeriData.net, a comprehensive birth registry, utilizing data from 2007 through 2013 at all Aurora medical centers. Categorical variables were analyzed with chi-square …

The Spatial Dynamics Of Dengue Virus In Kamphaeng Phet, Thailand, Piraya Bhoomiboonchoo, Robert V. Gibbons, Angkana Huang, In-Kyu Yoon, Darunee Buddhari, Ananda Nisalak, Natkamol Chansatiporn, Mathuros Thipayamongkolgul, Siripen Kalanarooj, Timothy Endy, Alan L. Rothman, Anon Srikiatkhachorn, Sharone Green, Mammen P. Mammen, Derek A. Cummings, Henrik Salje

Sharone Green

BACKGROUND: Dengue is endemic to the rural province of Kamphaeng Phet, Northern Thailand. A decade of prospective cohort studies has provided important insights into the dengue viruses and their generated disease. However, as elsewhere, spatial dynamics of the pathogen remain poorly understood. In particular, the spatial scale of transmission and the scale of clustering are poorly characterized. This information is critical for effective deployment of spatially targeted interventions and for understanding the mechanisms that drive the dispersal of the virus.

METHODOLOGY/PRINCIPAL FINDINGS: We geocoded the home locations of 4,768 confirmed dengue cases admitted to the main hospital in Kamphaeng Phet …

Malaria-Induced Nlrp12/Nlrp3-Dependent Caspase-1 Activation Mediates Inflammation And Hypersensitivity To Bacterial Superinfection, Marco A. Ataide, Warrison A. Andrade, Dario S. Zamboni, Donghai Wang, Maria Do Carmo Souza, Bernardo S. Franklin, Samir Elian, Flaviano S. Martins, Dhelio Pereira, George W. Reed, Katherine A. Fitzgerald, Douglas T. Golenbock, Ricardo T. Gazzinelli

Katherine A. Fitzgerald

Cyclic paroxysm and high fever are hallmarks of malaria and are associated with high levels of pyrogenic cytokines, including IL-1beta. In this report, we describe a signature for the expression of inflammasome-related genes and caspase-1 activation in malaria. Indeed, when we infected mice, Plasmodium infection was sufficient to promote MyD88-mediated caspase-1 activation, dependent on IFN-gamma-priming and the expression of inflammasome components ASC, P2X7R, NLRP3 and/or NLRP12. Pro-IL-1beta expression required a second stimulation with LPS and was also dependent on IFN-gamma-priming and functional TNFR1. As a consequence of Plasmodium-induced caspase-1 activation, mice produced extremely high levels of IL-1beta upon a second …

The Validity Of Animal Experiments In Medical Research, Gill Langley

Gill Langley, PhD

Other animals, such as mice, rats, rabbits, dogs and monkeys, are widely used as surrogates for humans in fundamental medical research. This involves creating disorders in animals by chemical, surgical or genetic means, with the aim of mimicking selected aspects of human illnesses. It is a truism that any model or surrogate is not identical to the target being modelled. So, in medical research, experiments using animals or cell cultures or even healthy volunteers instead of patients (being the target population with the target illness) will inevitably have limitations, although these will be greater or lesser depending on the model.

Their Bugs Are Worse Than Their Bite: Emerging Infectious Disease And The Human-Animal Interface, Michael Greger

Michael Greger, MD, FACLM

In the twenty-five years since that announcement, what we now know as AIDS has killed 20 million people (National AIDS Trust 2005). Where did the AIDS virus— and other emerging diseases, such as severe acute respiratory syndrome (SARS), Ebola, mad cow— come from?

Welcome To The Journal Of Evolution And Health, Aaron Blaisdell, Paul Jaminet, David C. Pendergrass

Aaron P Blaisdell

Welcome to the first issue of the Journal of Evolution and Health! The Journal of Evolution and Health is the peer-reviewed, open-access journal of the Ancestral Health Society, a community of scientists, healthcare professionals, and laypersons who collaborate to understand health challenges from an evolutionary perspective.