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X-F Su, L Sun, B-L Liu, X-J Tao, H-Q Li, F-F Li, L Ye, K-O Lee, J-H Ma, S-L Chen
Aim: Patients with cardiac diseases, especially ischemic heart disease, are known to have a high prevalence of diabetes mellitus (DM). They are at risk of having inadequate glucose control. An intensive diabetes screening and treatment program was developed to identify and treat DM in patients admitted with cardiac diseases. Methods: Adult inpatients of 2 cardiac wards, namely Ward-A and Ward-B, at Nanjing Hospital, Nanjing, China, were studied. Patients were randomly assigned into either ward. In addition to routine examination and treatment, an intensive screening and treatment program to identify and treat patients with DM or impaired glucose regulation (IGR) was only applied in Ward-A patients...
October 17, 2016: Experimental and Clinical Endocrinology & Diabetes
Robert W Hoffman, Joan T Merrill, Marta M E Alarcón-Riquelme, Michelle Petri, Ernst R Dow, Eric Nantz, Laura K Nisenbaum, Krista M Schroeder, Wendy J Komocsar, Narayanan B Perumal, Matthew D Linnik, David C Airey, Yushi Liu, Guilherme V Rocha, Richard E Higgs
OBJECTIVE: Systemic lupus erythematosus (SLE) has substantial unmet medical need and its pathogenesis is incompletely understood. This study characterized baseline gene expression and pharmacodynamic (PD)-induced changes in whole blood gene expression from two phase III, 52-week (W), randomized, placebo-controlled, double-blind studies of 1,760 SLE patients treated with the B cell activating factor (BAFF)-blocking IgG4 monoclonal antibody, tabalumab. METHODS: Patient samples were obtained from ILLUMINATE-1 and -2 while control samples were from healthy donors...
October 9, 2016: Arthritis & Rheumatology
Eyal Reinstein, Ana Gutierrez-Fernandez, Shay Tzur, Concetta Bormans, Shai Marcu, Einav Tayeb-Fligelman, Chana Vinkler, Annick Raas-Rothschild, Dana Irge, Meytal Landau, Mordechai Shohat, Xose S Puente, Doron M Behar, Carlos Lopez-Otın
In the vast majority of pediatric patients with dilated cardiomyopathy, the specific etiology is unknown. Studies on families with dilated cardiomyopathy have exemplified the role of genetic factors in cardiomyopathy etiology. In this study, we applied whole-exome sequencing to members of a non-consanguineous family affected by a previously unreported congenital dilated cardiomyopathy syndrome necessitating early-onset heart transplant. Exome analysis identified compound heterozygous variants in the FLNC gene...
September 7, 2016: European Journal of Human Genetics: EJHG
Umit Arslan Nayki, Cenk Nayki, Nihal Cetin, Ferda Keskin Cimen, Abdulkadir Coban, Renad Mammadov, Ismail Hakkı Tas, Ismail Malkoc
AIM: To investigate the effect of Kineret® on ischemia reperfusion (IR) injury in rat ovaries. METHODS: Rats were divided into four groups: ovarian IR (IRG); 50 mg/kg Kineret® + ovarian IR (KIR-50); 100 mg/kg Kineret® + ovarian IR (KIR-100); and sham operation (SOC). KIR-50 (n = 10) and KIR-100 (n = 10) groups received an intraperitoneal injection of Kineret® at doses of 50 and 100 mg/kg, respectively. IRG and SOC (n = 10) rat groups were given distilled water as solvent using the same method...
August 24, 2016: Journal of Obstetrics and Gynaecology Research
Tamarah D de Jong, Joyce Lübbers, Samina Turk, Saskia Vosslamber, Elise Mantel, Hetty J Bontkes, Conny J van der Laken, Johannes W Bijlsma, Dirkjan van Schaardenburg, Cornelis L Verweij
BACKGROUND: The type I interferon (IFN) signature in rheumatoid arthritis (RA) has shown clinical relevance in relation to disease onset and therapeutic response. Identification of the cell type(s) contributing to this IFN signature could provide insight into the signature's functional consequences. The aim of this study was to investigate the contribution of peripheral leukocyte subsets to the IFN signature in early arthritis. METHODS: Blood was collected from 26 patients with early arthritis and lysed directly or separated into peripheral blood mononuclear cells (PBMCs) and polymorphonuclear granulocytes (PMNs)...
2016: Arthritis Research & Therapy
Catherine Simpson, Nathaniel G Jones, Emily A Hull-Ryde, Dmitri Kireev, Michael Stashko, Keliang Tang, Jim Janetka, Scott A Wildman, William J Zuercher, Matthieu Schapira, Raymond Hui, William Janzen, L David Sibley
The protozoan parasite Toxoplasma gondii secretes a family of serine-threonine protein kinases into its host cell in order to disrupt signaling and alter immune responses. One prominent secretory effector is the rhoptry protein 18 (ROP18), a serine-threonine kinase that phosphorylates immunity related GTPases (IRGs) and hence blocks interferon gamma-mediated responses in rodent cells. Previous genetic studies show that ROP18 is a major virulence component of T. gondii strains from North and South America. Here, we implemented a high throughput screen to identify small molecule inhibitors of ROP18 in vitro and subsequently validated their specificity within infected cells...
March 11, 2016: ACS Infectious Diseases
Jerod A Merkle, Kevin L Monteith, Ellen O Aikens, Matthew M Hayes, Kent R Hersey, Arthur D Middleton, Brendan A Oates, Hall Sawyer, Brandon M Scurlock, Matthew J Kauffman
The green wave hypothesis (GWH) states that migrating animals should track or 'surf' high-quality forage at the leading edge of spring green-up. To index such high-quality forage, recent work proposed the instantaneous rate of green-up (IRG), i.e. rate of change in the normalized difference vegetation index over time. Despite this important advancement, no study has tested the assumption that herbivores select habitat patches at peak IRG. We evaluated this assumption using step selection functions parametrized with movement data during the green-up period from two populations each of bighorn sheep, mule deer, elk, moose and bison, totalling 463 individuals monitored 1-3 years from 2004 to 2014...
June 29, 2016: Proceedings. Biological Sciences
Kelly A Grussendorf, Christopher J Trezza, Alexander T Salem, Hikmat Al-Hashimi, Brendan C Mattingly, Drew E Kampmeyer, Liakot A Khan, David H Hall, Verena Göbel, Brian D Ackley, Matthew Buechner
Determination of luminal diameter is critical to the function of small single-celled tubes. A series of EXC proteins, including EXC-1, prevent swelling of the tubular excretory canals in Caenorhabditis elegans In this study, cloning of exc-1 reveals it to encode a homolog of mammalian IRG proteins, which play roles in immune response and autophagy and are associated with Crohn's disease. Mutants in exc-1 accumulate early endosomes, lack recycling endosomes, and exhibit abnormal apical cytoskeletal structure in regions of enlarged tubules...
August 2016: Genetics
Maninjay K Atianand, Wenqian Hu, Ansuman T Satpathy, Ying Shen, Emiliano P Ricci, Juan R Alvarez-Dominguez, Ankit Bhatta, Stefan A Schattgen, Jason D McGowan, Juliana Blin, Joerg E Braun, Pallavi Gandhi, Melissa J Moore, Howard Y Chang, Harvey F Lodish, Daniel R Caffrey, Katherine A Fitzgerald
Long intergenic noncoding RNAs (lincRNAs) are important regulators of gene expression. Although lincRNAs are expressed in immune cells, their functions in immunity are largely unexplored. Here, we identify an immunoregulatory lincRNA, lincRNA-EPS, that is precisely regulated in macrophages to control the expression of immune response genes (IRGs). Transcriptome analysis of macrophages from lincRNA-EPS-deficient mice, combined with gain-of-function and rescue experiments, revealed a specific role for this lincRNA in restraining IRG expression...
June 16, 2016: Cell
Ke Ren, Yuanzi Lv, Yujie Zhuo, Changmai Chen, Hengfei Shi, Lin Guo, Guang Yang, Yayi Hou, Ren Xiang Tan, Erguang Li
UNLABELLED: Respiratory syncytial virus (RSV) infection is a common cause of lower respiratory tract illness in infants and children. RSV is a negative-sense, single-strand RNA (ssRNA) virus that mainly infects airway epithelial cells. Accumulating evidence indicates that reactive oxygen species (ROS) production is a major factor for pulmonary inflammation and tissue damage of RSV disease. We investigated immune-responsive gene-1 (IRG1) expression during RSV infection, since IRG1 has been shown to mediate innate immune response to intracellular bacterial pathogens by modulating ROS and itaconic acid production...
August 15, 2016: Journal of Virology
Danielle Pilla-Moffett, Matthew F Barber, Gregory A Taylor, Jörn Coers
Cell-autonomous immunity is essential for host organisms to defend themselves against invasive microbes. In vertebrates, both the adaptive and the innate branches of the immune system operate cell-autonomous defenses as key effector mechanisms that are induced by pro-inflammatory interferons (IFNs). IFNs can activate cell-intrinsic host defenses in virtually any cell type ranging from professional phagocytes to mucosal epithelial cells. Much of this IFN-induced host resistance program is dependent on four families of IFN-inducible GTPases: the myxovirus resistance proteins, the immunity-related GTPases, the guanylate-binding proteins (GBPs), and the very large IFN-inducible GTPases...
August 28, 2016: Journal of Molecular Biology
Barbara A Fox, Leah M Rommereim, Rebekah B Guevara, Alejandra Falla, Miryam Andrea Hortua Triana, Yanbo Sun, David J Bzik
UNLABELLED: Ingestion of the obligate intracellular protozoan parasite Toxoplasma gondii causes an acute infection that leads to chronic infection of the host. To facilitate the acute phase of the infection, T. gondii manipulates the host response by secreting rhoptry organelle proteins (ROPs) into host cells during its invasion. A few key ROP proteins with signatures of kinases or pseudokinases (ROPKs) act as virulence factors that enhance parasite survival against host gamma interferon-stimulated innate immunity...
2016: MBio
Urs B Müller, Jonathan C Howard
Nobody doubts that infections have imposed specialisations on the mammalian genome. However sufficient information is usually missing to attribute a specific genomic modification to pressure from a specific pathogen. Recent studies on mechanisms of mammalian resistance against the ubiquitous protozoan parasite, Toxoplasma gondii, have shown that the small rodents presumed to be largely responsible for transmission of the parasite to its definitive host, the domestic cat, possess distinctive recognition proteins, and interferon-inducible effector proteins (IRG proteins) that limit the potential virulence of the parasite...
August 2016: Current Opinion in Microbiology
M O Taha, J V de Oliveira, M Dias Borges, F de Lucca Melo, F G Gualtieri, A L E Silva Aidar, R L Pacheco, T de Melo Alexandre E Silva, R K Klajner, L R Iuamoto, L Munhoz Torres, B J Morais Mendes de Paula, K de Campos, I Souza de Oliveira, D J Fagundes
BACKGROUND: The goal of this study was to investigate whether exogenous offer of L-arginine (LARG) modulates the gene expression of intestinal dysfunction caused by ischemia and reperfusion. METHODS: Eighteen Wistar-EPM1 male rats (250-300 g) were anesthetized and subjected to laparotomy. The superior mesenteric vessels were exposed, and the rats were randomized into 3 groups (n = 6): the control group (CG), with no superior mesenteric artery interruption; the ischemia/reperfusion group (IRG), with 60 minutes of ischemia and 120 minutes of reperfusion and saline injections; and the L-arginine group (IRG + LARG), with L-arginine injected in the femoral vein 5 minutes before ischemia, 5 minutes after reperfusion, and after 55 minutes of reperfusion...
March 2016: Transplantation Proceedings
Jelena Maric-Biresev, Julia P Hunn, Oleg Krut, J Bernd Helms, Sascha Martens, Jonathan C Howard
BACKGROUND: The interferon-γ (IFN-γ)-inducible immunity-related GTPase (IRG), Irgm1, plays an essential role in restraining activation of the IRG pathogen resistance system. However, the loss of Irgm1 in mice also causes a dramatic but unexplained susceptibility phenotype upon infection with a variety of pathogens, including many not normally controlled by the IRG system. This phenotype is associated with lymphopenia, hemopoietic collapse, and death of the mouse. RESULTS: We show that the three regulatory IRG proteins (GMS sub-family), including Irgm1, each of which localizes to distinct sets of endocellular membranes, play an important role during the cellular response to IFN-γ, each protecting specific membranes from off-target activation of effector IRG proteins (GKS sub-family)...
2016: BMC Biology
Jörn Coers, Arun K Haldar
Many intracellular bacterial and protozoan pathogens reside within host cell vacuoles customized by the microbial invaders to fit their needs. Within such pathogen-containing vacuoles (PVs) microbes procure nutrients and simultaneously hide from cytosolic host defense systems. Among the many PV-resident human pathogens are the bacterium Chlamydia trachomatis and the protozoan Toxoplasma gondii. Immune responses directed against their PVs are poorly characterized. We reported that activation of host cells with IFNγ triggers the attachment of polyubiquitin chains to Toxoplasma- and Chlamydia-containing vacuoles and thereby marks PVs for destruction...
November 2015: Communicative & Integrative Biology
Renuka Choudhary, Sudarshan Kumar, Sohan V Singh, Anil K Sharma, Talla Sridhar Goud, Amrendra K Srivastava, Anil Kumar, Ashok K Mohanty, Ramesh C Upadhyay
Normalization of cellular mRNA data using internal reference gene (IRG) is an essential step in expression analysis studies. MIQE guidelines ensure that the choice and appropriateness of IRG should be validated for particular tissues or cell types and specific experimental designs. The objective of the present study was to assess 15 IRGs from different functional classes that could serve as best IRGs for Bos indicus (Tharparkar cattle) melanocyte cells under heat stress and hormonal treatment. We implemented the use of geNorm, NormFinder and BestKeeper algorithm to measure the stability of the gene transcript...
June 2016: Molecular and Cellular Probes
Kathrin Schulte, Nikolaus Pawlowski, Katja Faelber, Chris Fröhlich, Jonathan Howard, Oliver Daumke
BACKGROUND: The immunity-related GTPases (IRGs) constitute a powerful cell-autonomous resistance system against several intracellular pathogens. Irga6 is a dynamin-like protein that oligomerizes at the parasitophorous vacuolar membrane (PVM) of Toxoplasma gondii leading to its vesiculation. Based on a previous biochemical analysis, it has been proposed that the GTPase domains of Irga6 dimerize in an antiparallel fashion during oligomerization. RESULTS: We determined the crystal structure of an oligomerization-impaired Irga6 mutant bound to a non-hydrolyzable GTP analog...
2016: BMC Biology
Tamarah D de Jong, Saskia Vosslamber, Elise Mantel, Sander de Ridder, John G Wesseling, Tineke C T M van der Pouw Kraan, Cyra Leurs, Harald Hegen, Florian Deisenhammer, Joep Killestein, Ingrid E Lundberg, Jiri Vencovsky, Mike T Nurmohamed, Dirkjan van Schaardenburg, Irene E M Bultink, Alexandre E Voskuyl, D Michiel Pegtel, Conny J van der Laken, Johannes W J Bijlsma, Cornelis L Verweij
BACKGROUND: Activation of the type I interferon (IFN) response program is described for several autoimmune diseases, including systemic lupus erythematosus (SLE), multiple sclerosis (MS), myositis (IIM) and rheumatoid arthritis (RA). While IFNα contributes to SLE pathology, IFNβ therapy is often beneficial in MS, implying different immunoregulatory roles for these IFNs. This study was aimed to investigate potential diversification of IFNα-and IFNβ-mediated response programs in autoimmune diseases...
2016: Arthritis Research & Therapy
Jan Naujoks, Christoph Tabeling, Brian D Dill, Christine Hoffmann, Andrew S Brown, Mareike Kunze, Stefan Kempa, Andrea Peter, Hans-Joachim Mollenkopf, Anca Dorhoi, Olivia Kershaw, Achim D Gruber, Leif E Sander, Martin Witzenrath, Susanne Herold, Andreas Nerlich, Andreas C Hocke, Ian van Driel, Norbert Suttorp, Sammy Bedoui, Hubert Hilbi, Matthias Trost, Bastian Opitz
Macrophages can be niches for bacterial pathogens or antibacterial effector cells depending on the pathogen and signals from the immune system. Here we show that type I and II IFNs are master regulators of gene expression during Legionella pneumophila infection, and activators of an alveolar macrophage-intrinsic immune response that restricts bacterial growth during pneumonia. Quantitative mass spectrometry revealed that both IFNs substantially modify Legionella-containing vacuoles, and comparative analyses reveal distinct subsets of transcriptionally and spatially IFN-regulated proteins...
February 2016: PLoS Pathogens
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