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Sample records for ifn barrier illustrating

  1. Contaminant fluxes through site containment barriers: Performance assessment and illustrative results

    International Nuclear Information System (INIS)

    Vita, C.L.

    1994-01-01

    Contaminant mass flux by advective and diffusive transport is predicted for five containment barriers that use one or more clay liners, flexible membrane liners (FMLs), or liquid collection and removal systems (LCRS)s. Barriers are engineered systems intended to contain and isolate site contaminants from the environment. Barriers include liners, caps, and cutoff walls. Barriers may be used in contaminated-site cleanups (including CERCLA and RCRA), RCRA landfills, or other RCRA TSDFs. Concepts are provided for barrier performance assessment, including analysis and optimization, for meeting performance requirements and controlling risk at minimum cost. Concepts and results can help in planning, designing, or evaluating and communicating, the use or effectiveness of proposed or existing barriers for site cleanups or waste containment. 15 refs., 6 figs., 5 tabs

  2. Exposure to bacterial DNA before hemorrhagic shock strongly aggravates systemic inflammation and gut barrier loss via an IFN-gamma-dependent route

    NARCIS (Netherlands)

    Luyer, Misha D.; Buurman, Wim A.; Hadfoune, M.'hamed; Wolfs, T.; van't Veer, Cornelis; Jacobs, Jan A.; Dejong, Cornelis H.; Greve, Jan Willem M.

    2007-01-01

    OBJECTIVE: To investigate the role of bacterial DNA in development of an excessive inflammatory response and loss of gut barrier loss following systemic hypotension. SUMMARY BACKGROUND DATA: Bacterial infection may contribute to development of inflammatory complications following major surgery;

  3. Medical Illustration

    Science.gov (United States)

    ... as medical books, journals, magazines, pharma or biotech marketing, films, online video, exhibits, posters, wall charts, educational ... of the health career profession with strong communication skills, medical illustrators work closely with clients to interpret ...

  4. Lambda Interferon (IFN-gamma), a Type III IFN, is induced by viruses and IFNs and displays potent antiviral activity against select virus infections in vivo

    DEFF Research Database (Denmark)

    Ank, Nina; West, Hans; Bartholdy, C.

    2006-01-01

    Type III interferons (IFNs) (interleukin-28/29 or lambda interferon [IFN-lambda]) are cytokines with IFN-like activities. Here we show that several classes of viruses induce expression of IFN-lambda1 and -lambda2/3 in similar patterns. The IFN-lambdas were-unlike alpha/beta interferon (IFN......-alpha/beta)-induced directly by stimulation with IFN-alpha or -lambda, thus identifying type III IFNs as IFN-stimulated genes. In vitro assays revealed that IFN-lambdas have appreciable antiviral activity against encephalomyocarditis virus (EMCV) but limited activity against herpes simplex virus type 2 (HSV-2), whereas IFN......-alpha potently restricted both viruses. Using three murine models for generalized virus infections, we found that while recombinant IFN-alpha reduced the viral load after infection with EMCV, lymphocytic choriomeningitis virus (LCMV), and HSV-2, treatment with recombinant IFN-lambda in vivo did not affect viral...

  5. Lambda interferon (IFN-lambda), a type III IFN, is induced by viruses and IFNs and displays potent antiviral activity against select virus infections in vivo

    DEFF Research Database (Denmark)

    Ank, Nina; West, Hans; Bartholdy, Christina

    2006-01-01

    Type III interferons (IFNs) (interleukin-28/29 or lambda interferon [IFN-lambda]) are cytokines with IFN-like activities. Here we show that several classes of viruses induce expression of IFN-lambda1 and -lambda2/3 in similar patterns. The IFN-lambdas were-unlike alpha/beta interferon (IFN......-alpha/beta)-induced directly by stimulation with IFN-alpha or -lambda, thus identifying type III IFNs as IFN-stimulated genes. In vitro assays revealed that IFN-lambdas have appreciable antiviral activity against encephalomyocarditis virus (EMCV) but limited activity against herpes simplex virus type 2 (HSV-2), whereas IFN......-alpha potently restricted both viruses. Using three murine models for generalized virus infections, we found that while recombinant IFN-alpha reduced the viral load after infection with EMCV, lymphocytic choriomeningitis virus (LCMV), and HSV-2, treatment with recombinant IFN-lambda in vivo did not affect viral...

  6. Illustrator CC digital classroom

    CERN Document Server

    Smith, Jennifer

    2013-01-01

    A complete training package lets you learn Adobe Illustrator CC at your own speed Adobe Illustrator is the leading drawing and illustration software used to create artwork for a variety of media. This book-and-DVD package provides 13 self-paced lessons that get you up to speed on the latest version of Illustrator (Creative Cloud). Step-by-step instructions in the full-color book are supported by video tutorials on the DVD. Together, these tools will help you learn Adobe Illustrator basics, essential skills, and all the new capabilities in Illustrator CC-in no time.  Includes step-by-step in

  7. IFN-γ signaling to astrocytes protects from autoimmune mediated neurological disability.

    Directory of Open Access Journals (Sweden)

    Claudia Hindinger

    Full Text Available Demyelination and axonal degeneration are determinants of progressive neurological disability in patients with multiple sclerosis (MS. Cells resident within the central nervous system (CNS are active participants in development, progression and subsequent control of autoimmune disease; however, their individual contributions are not well understood. Astrocytes, the most abundant CNS cell type, are highly sensitive to environmental cues and are implicated in both detrimental and protective outcomes during autoimmune demyelination. Experimental autoimmune encephalomyelitis (EAE was induced in transgenic mice expressing signaling defective dominant-negative interferon gamma (IFN-γ receptors on astrocytes to determine the influence of inflammation on astrocyte activity. Inhibition of IFN-γ signaling to astrocytes did not influence disease incidence, onset, initial progression of symptoms, blood brain barrier (BBB integrity or the composition of the acute CNS inflammatory response. Nevertheless, increased demyelination at peak acute disease in the absence of IFN-γ signaling to astrocytes correlated with sustained clinical symptoms. Following peak disease, diminished clinical remission, increased mortality and sustained astrocyte activation within the gray matter demonstrate a critical role of IFN-γ signaling to astrocytes in neuroprotection. Diminished disease remission was associated with escalating demyelination, axonal degeneration and sustained inflammation. The CNS infiltrating leukocyte composition was not altered; however, decreased IL-10 and IL-27 correlated with sustained disease. These data indicate that astrocytes play a critical role in limiting CNS autoimmune disease dependent upon a neuroprotective signaling pathway mediated by engagement of IFN-γ receptors.

  8. Getting “Inside” Type I IFNs: Type I IFNs in Intracellular Bacterial Infections

    Directory of Open Access Journals (Sweden)

    Deann T. Snyder

    2017-01-01

    Full Text Available Type I interferons represent a unique and complex group of cytokines, serving many purposes during innate and adaptive immunity. Discovered in the context of viral infections, type I IFNs are now known to have myriad effects in infectious and autoimmune disease settings. Type I IFN signaling during bacterial infections is dependent on many factors including whether the infecting bacterium is intracellular or extracellular, as different signaling pathways are activated. As such, the repercussions of type I IFN induction can positively or negatively impact the disease outcome. This review focuses on type I IFN induction and downstream consequences during infection with the following intracellular bacteria: Chlamydia trachomatis, Listeria monocytogenes, Mycobacterium tuberculosis, Salmonella enterica serovar Typhimurium, Francisella tularensis, Brucella abortus, Legionella pneumophila, and Coxiella burnetii. Intracellular bacterial infections are unique because the bacteria must avoid, circumvent, and even co-opt microbial “sensing” mechanisms in order to reside and replicate within a host cell. Furthermore, life inside a host cell makes intracellular bacteria more difficult to target with antibiotics. Because type I IFNs are important immune effectors, modulating this pathway may improve disease outcomes. But first, it is critical to understand the context-dependent effects of the type I IFN pathway in intracellular bacterial infections.

  9. A Promising IFN-Deficient System to Manufacture IFN-Sensitive Influenza Vaccine Virus.

    Science.gov (United States)

    Chen, Can; Fan, Wenhui; Li, Jing; Zheng, Weinan; Zhang, Shuang; Yang, Limin; Liu, Di; Liu, Wenjun; Sun, Lei

    2018-01-01

    Interferon (IFN)-sensitive and replication-incompetent influenza viruses are likely to be the alternatives to inactivated and attenuated virus vaccines. Some IFN-sensitive influenza vaccine candidates with modified non-structural protein 1 (NS1) are highly attenuated in IFN-competent hosts but induce robust antiviral immune responses. However, little research has been done on the manufacturability of these IFN-sensitive vaccine viruses. Here, RIG-I-knockout 293T cells were used to package the IFN-sensitive influenza A/WSN/33 (H1N1) virus expressing the mutant NS1 R38A/K41A. We found that the packaging efficiency of the NS1 R38A/K41A virus in RIG-I-knockout 293T cells was much higher than that in 293T cells. Moreover, the NS1 R38A/K41A virus almost lost its IFN antagonist activity and could no longer replicate in A549, MDCK, and Vero cells after 3-6 passages. This indicated that the replication of NS1 R38A/K41A virus is limited in conventional cells. Therefore, we further established a stable Vero cell line expressing the wild-type (WT) NS1 of the WSN virus, based on the Tet-On 3G system. The NS1 R38A/K41A virus was able to steadily propagate in this IFN-deficient cell line for at least 20 passages. In a mouse model, the NS1 R38A/K41A virus showed more than a 4-log reduction in lung virus titers compared to the WT virus at 3 and 5 days post infection. Furthermore, we observed that the NS1 R38A/K41A virus triggered high-level of IFN-α/β production in lung tissues and was eliminated from the host in a relatively short period of time. Additionally, this virus induced high-titer neutralizing antibodies against the WT WSN, A/Puerto Rico/8/1934 (PR8), or A/California/04/2009 (CA04) viruses and provided 100% protection against the WT WSN virus. Thus, we found that the replication of the NS1 R38A/K41A virus was limited in IFN-competent cells and mice. We also presented a promising IFN-deficient system, involving a RIG-I-knockout 293T cell line to package the IFN

  10. Textile Art as Illustration.

    Science.gov (United States)

    Dickman, Floyd C.

    1998-01-01

    Used in picture-book illustration, such techniques as embroidery, applique, wood-block printing, batik, and quilting reflect cultural heritages and add richly textured images to this annotated list of titles for children from preschool through junior high. (Author)

  11. Exogenous HIV-1 Nef upsets the IFN-γ-induced impairment of human intestinal epithelial integrity.

    Directory of Open Access Journals (Sweden)

    Maria Giovanna Quaranta

    Full Text Available The mucosal tissues play a central role in the transmission of HIV-1 infection as well as in the pathogenesis of AIDS. Despite several clinical studies reported intestinal dysfunction during HIV infection, the mechanisms underlying HIV-induced impairments of mucosal epithelial barrier are still unclear. It has been postulated that HIV-1 alters enterocytic function and HIV-1 proteins have been detected in several cell types of the intestinal mucosa. In the present study, we analyzed the effect of the accessory HIV-1 Nef protein on human epithelial cell line.We used unstimulated or IFN-γ-stimulated Caco-2 cells, as a model for homeostatic and inflamed gastrointestinal tracts, respectively. We investigated the effect of exogenous recombinant Nef on monolayer integrity analyzing its uptake, transepithelial electrical resistance, permeability to FITC-dextran and the expression of tight junction proteins. Moreover, we measured the induction of proinflammatory mediators. Exogenous Nef was taken up by Caco-2 cells, increased intestinal epithelial permeability and upset the IFN-γ-induced reduction of transepithelial resistance, interfering with tight junction protein expression. Moreover, Nef inhibited IFN-γ-induced apoptosis and up-regulated TNF-α, IL-6 and MIP-3α production by Caco-2 cells while down-regulated IL-10 production. The simultaneous exposure of Caco-2 cells to Nef and IFN-γ did not affect cytokine secretion respect to untreated cells. Finally, we found that Nef counteracted the IFN-γ induced arachidonic acid cascade.Our findings suggest that exogenous Nef, perturbing the IFN-γ-induced impairment of intestinal epithelial cells, could prolong cell survival, thus allowing for accumulation of viral particles. Our results may improve the understanding of AIDS pathogenesis, supporting the discovery of new therapeutic interventions.

  12. Radiology illustrated. Gastrointestinal tract

    International Nuclear Information System (INIS)

    Choi, Byung Ihn

    2015-01-01

    Radiology Illustrated: Gastrointestinal Tract is the second of two volumes designed to provide clear and practical guidance on the diagnostic imaging of abdominal diseases. The book presents approximately 300 cases with 1500 carefully selected and categorized illustrations of gastrointestinal tract diseases, along with key text messages and tables that will help the reader easily to recall the relevant images as an aid to differential diagnosis., Essential points are summarized at the end of each text message to facilitate rapid review and learning. Additionally, brief descriptions of each clinical problem are provided, followed by case studies of both common and uncommon pathologies that illustrate the roles of the different imaging modalities, including ultrasound, radiography, computed tomography, and magnetic resonance imaging.

  13. Radiology illustrated. Gastrointestinal tract

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Byung Ihn (ed.) [Seoul National University Hospital (Korea, Republic of). Dept. of Radiology

    2015-02-01

    Radiology Illustrated: Gastrointestinal Tract is the second of two volumes designed to provide clear and practical guidance on the diagnostic imaging of abdominal diseases. The book presents approximately 300 cases with 1500 carefully selected and categorized illustrations of gastrointestinal tract diseases, along with key text messages and tables that will help the reader easily to recall the relevant images as an aid to differential diagnosis., Essential points are summarized at the end of each text message to facilitate rapid review and learning. Additionally, brief descriptions of each clinical problem are provided, followed by case studies of both common and uncommon pathologies that illustrate the roles of the different imaging modalities, including ultrasound, radiography, computed tomography, and magnetic resonance imaging.

  14. Adaptation illustrations: Chapter 4

    Science.gov (United States)

    Maria Janowiak; Patricia Butler; Chris Swanston; Matt St. Pierre; Linda. Parker

    2012-01-01

    In this chapter, we demonstrate how the Adaptation Workbook (Chapter 3) can be used with the Adaptation Strategies and Approaches (Chapter 2) to develop adaptation tactics for two real-world management issues. The two illustrations in this chapter are intended to provide helpful tips to managers completing the Adaptation Workbook, as well as to show how the anticipated...

  15. Radiology illustrated. Spine

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Heung Sik; Lee, Joon Woo [Seoul National Univ. Bundang Hospital, Seongnam, Kyonggi-do (Korea, Republic of). Dept. of Radiology; Kwon, Jong Won [Samsung Medical Center, Seoul (Korea, Republic of). Dept. of Radiology

    2014-04-01

    Offers a practical approach to image interpretation for spinal disorders. Includes numerous high-quality radiographic images and schematic illustrations. Will serve as a self-learning book covering daily routine cases from the basic to the advanced. Radiology Illustrated: Spine is an up-to-date, superbly illustrated reference in the style of a teaching file that has been designed specifically to be of value in clinical practice. Common, critical, and rare but distinctive spinal disorders are described succinctly with the aid of images highlighting important features and informative schematic illustrations. The first part of the book, on common spinal disorders, is for radiology residents and other clinicians who are embarking on the interpretation of spinal images. A range of key disorders are then presented, including infectious spondylitis, cervical trauma, spinal cord disorders, spinal tumors, congenital disorders, uncommon degenerative disorders, inflammatory arthritides, and vascular malformations. The third part is devoted to rare but clinically significant spinal disorders with characteristic imaging features, and the book closes by presenting practical tips that will assist in the interpretation of confusing cases.

  16. Highly Pathogenic H5N1 Influenza A Virus Strains Provoke Heterogeneous IFN-α/β Responses That Distinctively Affect Viral Propagation in Human Cells

    Science.gov (United States)

    Matthaei, Markus; Budt, Matthias; Wolff, Thorsten

    2013-01-01

    The fatal transmissions of highly pathogenic avian influenza A viruses (IAV) of the H5N1 subtype to humans and high titer replication in the respiratory tract indicate that these pathogens can overcome the bird-to-human species barrier. While type I interferons (IFN-α/β) are well described to contribute to the species barrier of many zoonotic viruses, current data to the role of these antiviral cytokines during human H5N1 IAV infections is limited and contradictory. We hypothesized an important role for the IFN system in limiting productive infection of avian H5N1 strains in human cells. Hence, we examined IFN-α/β gene activation by different avian and human H5N1 isolates, if the IFN-α/β response restricts H5N1 growth and whether the different strains were equally capable to regulate the IFN-α/β system via their IFN-antagonistic NS1 proteins. Two human H5N1 isolates and a seasonal H3N2 strain propagated efficiently in human respiratory cells and induced little IFN-β, whereas three purely avian H5N1 strains were attenuated for replication and provoked higher IFN secretion. Replication of avian viruses was significantly enhanced on interferon-deficient cells, and exogenous IFN potently limited the growth of all strains in human cells. Moreover, IFN-α/β activation by all strains depended on retinoic acid-inducible gene I excluding principal differences in receptor activation between the different viruses. Interestingly, all H5N1 NS1 proteins suppressed IFN-α/β induction comparably well to the NS1 of seasonal IAV. Thus, our study shows that H5N1 strains are heterogeneous in their capacity to activate human cells in an NS1-independent manner. Our findings also suggest that H5N1 viruses need to acquire adaptive changes to circumvent strong IFN-α/β activation in human host cells. Since no single amino acid polymorphism could be associated with a respective high- or low induction phenotype we propose that the necessary adaptations to overcome the human IFN

  17. Highly pathogenic H5N1 influenza A virus strains provoke heterogeneous IFN-α/β responses that distinctively affect viral propagation in human cells.

    Directory of Open Access Journals (Sweden)

    Markus Matthaei

    Full Text Available The fatal transmissions of highly pathogenic avian influenza A viruses (IAV of the H5N1 subtype to humans and high titer replication in the respiratory tract indicate that these pathogens can overcome the bird-to-human species barrier. While type I interferons (IFN-α/β are well described to contribute to the species barrier of many zoonotic viruses, current data to the role of these antiviral cytokines during human H5N1 IAV infections is limited and contradictory. We hypothesized an important role for the IFN system in limiting productive infection of avian H5N1 strains in human cells. Hence, we examined IFN-α/β gene activation by different avian and human H5N1 isolates, if the IFN-α/β response restricts H5N1 growth and whether the different strains were equally capable to regulate the IFN-α/β system via their IFN-antagonistic NS1 proteins. Two human H5N1 isolates and a seasonal H3N2 strain propagated efficiently in human respiratory cells and induced little IFN-β, whereas three purely avian H5N1 strains were attenuated for replication and provoked higher IFN secretion. Replication of avian viruses was significantly enhanced on interferon-deficient cells, and exogenous IFN potently limited the growth of all strains in human cells. Moreover, IFN-α/β activation by all strains depended on retinoic acid-inducible gene I excluding principal differences in receptor activation between the different viruses. Interestingly, all H5N1 NS1 proteins suppressed IFN-α/β induction comparably well to the NS1 of seasonal IAV. Thus, our study shows that H5N1 strains are heterogeneous in their capacity to activate human cells in an NS1-independent manner. Our findings also suggest that H5N1 viruses need to acquire adaptive changes to circumvent strong IFN-α/β activation in human host cells. Since no single amino acid polymorphism could be associated with a respective high- or low induction phenotype we propose that the necessary adaptations to

  18. The Scientist as Illustrator.

    Science.gov (United States)

    Iwasa, Janet H

    2016-04-01

    Proficiency in art and illustration was once considered an essential skill for biologists, because text alone often could not suffice to describe observations of biological systems. With modern imaging technology, it is no longer necessary to illustrate what we can see by eye. However, in molecular and cellular biology, our understanding of biological processes is dependent on our ability to synthesize diverse data to generate a hypothesis. Creating visual models of these hypotheses is important for generating new ideas and for communicating to our peers and to the public. Here, I discuss the benefits of creating visual models in molecular and cellular biology and consider steps to enable researchers to become more effective visual communicators. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. A grieving process illustrated?

    Science.gov (United States)

    Hutchinson, Rory

    2018-03-01

    The sudden death of Pablo Picasso's closest friend Carlos Casagemas in 1901 came as a great shock to the young Picasso. From a young age, Picasso had ruminated on life and death; however, this was his first experience of bereavement. Following the death of Casagemas, Picasso's paintings can be seen as a diary of his grieving process and clearly illustrate the five stages of the grieving process as outlined by Kubler-Ross in ' On Death and Dying ' (1969). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  20. Radiology illustrated. Pediatric radiology

    Energy Technology Data Exchange (ETDEWEB)

    Kim, In-One (ed.) [Seoul National Univ. College of Medicine (Korea, Republic of). Dept. of Radiology

    2014-11-01

    Depicts characteristic imaging findings of common and uncommon diseases in the pediatric age group. Will serve as an ideal diagnostic reference in daily practice. Offers an excellent teaching aid, with numerous high-quality illustrations. This case-based atlas presents images depicting the findings typically observed when imaging a variety of common and uncommon diseases in the pediatric age group. The cases are organized according to anatomic region, covering disorders of the brain, spinal cord, head and neck, chest, cardiovascular system, gastrointestinal system, genitourinary system, and musculoskeletal system. Cases are presented in a form resembling teaching files, and the images are accompanied by concise informative text. The goal is to provide a diagnostic reference suitable for use in daily routine by both practicing radiologists and radiology residents or fellows. The atlas will also serve as a teaching aide and a study resource, and will offer pediatricians and surgeons guidance on the clinical applications of pediatric imaging.

  1. Melanoma NOS1 expression promotes dysfunctional IFN signaling.

    Science.gov (United States)

    Liu, Qiuzhen; Tomei, Sara; Ascierto, Maria Libera; De Giorgi, Valeria; Bedognetti, Davide; Dai, Cuilian; Uccellini, Lorenzo; Spivey, Tara; Pos, Zoltan; Thomas, Jaime; Reinboth, Jennifer; Murtas, Daniela; Zhang, Qianbing; Chouchane, Lotfi; Weiss, Geoffrey R; Slingluff, Craig L; Lee, Peter P; Rosenberg, Steven A; Alter, Harvey; Yao, Kaitai; Wang, Ena; Marincola, Francesco M

    2014-05-01

    In multiple forms of cancer, constitutive activation of type I IFN signaling is a critical consequence of immune surveillance against cancer; however, PBMCs isolated from cancer patients exhibit depressed STAT1 phosphorylation in response to IFN-α, suggesting IFN signaling dysfunction. Here, we demonstrated in a coculture system that melanoma cells differentially impairs the IFN-α response in PBMCs and that the inhibitory potential of a particular melanoma cell correlates with NOS1 expression. Comparison of gene transcription and array comparative genomic hybridization (aCGH) between melanoma cells from different patients indicated that suppression of IFN-α signaling correlates with an amplification of the NOS1 locus within segment 12q22-24. Evaluation of NOS1 levels in melanomas and IFN responsiveness of purified PBMCs from patients indicated a negative correlation between NOS1 expression in melanomas and the responsiveness of PBMCs to IFN-α. Furthermore, in an explorative study, NOS1 expression in melanoma metastases was negatively associated with patient response to adoptive T cell therapy. This study provides a link between cancer cell phenotype and IFN signal dysfunction in circulating immune cells.

  2. Systemic Activation of the IFN System by Exposure of Natural Epithelia to Physiologic (Low Dose) Levels of IFN

    Science.gov (United States)

    1990-06-20

    possibility that epithelial surfaces of the upper alimentary and/or respiratory mucosa exposed to lymphocytes treated with low concentrations of IFN or with IFN... Biotechnology Program Office of Naval Research Office of Naval Research 800 N. Quincy Street Code 1213 Arlington, VA 22217-5000 800 N. Quincy Street Arlington

  3. Radiology illustrated. Chest radiology

    International Nuclear Information System (INIS)

    Lee, Kyung Soo; Han, Joungho; Chung, Man Pyo; Jeong, Yeon Joo

    2014-01-01

    Pattern approach to the diagnosis of lung diseases based on CT scan appearances. Guide to quick and reliable differential diagnosis. CT-pathology correlation. Emphasis on state-of-the-art MDCT. The purpose of this atlas is to illustrate how to achieve reliable diagnoses when confronted by the different abnormalities, or ''disease patterns'', that may be visualized on CT scans of the chest. The task of pattern recognition has been greatly facilitated by the advent of multidetector CT (MDCT), and the focus of the book is very much on the role of state-of-the-art MDCT. A wide range of disease patterns and distributions are covered, with emphasis on the typical imaging characteristics of the various focal and diffuse lung diseases. In addition, clinical information relevant to differential diagnosis is provided and the underlying gross and microscopic pathology is depicted, permitting CT-pathology correlation. The entire information relevant to each disease pattern is also tabulated for ease of reference. This book will be an invaluable handy tool that will enable the reader to quickly and easily reach a diagnosis appropriate to the pattern of lung abnormality identified on CT scans.

  4. IFN signaling: how a non-canonical model led to the development of IFN mimetics

    Directory of Open Access Journals (Sweden)

    Howard M Johnson

    2013-07-01

    Full Text Available The classical model of cytokine signaling dominates our view of specific gene activation by cytokines such as the interferons (IFNs. The importance of the model extends beyond cytokines and applies to hormones such as growth hormone (GH and insulin, and growth factors such as epidermal growth factor (EGF and fibroblast growth factor (FGF. According to this model, ligand activates the cell via interaction with the extracellular domain of the receptor. This results in activation of receptor or receptor-associated tyrosine kinases, primarily of the Janus kinase (JAK family, phosphorylation and dimerization of the STAT transcription factors, which dissociate from the receptor cytoplasmic domain and translocate to the nucleus. This view ascribes no further role to the ligand, JAK kinase, or receptor in either specific gene activation or the associated epigenetic events. The presence of dimeric STATs in the nucleus essentially explains it all. Our studies have resulted in the development of a non-canonical, more complex model of IFNγ signaling that is akin to that of steroid hormone/steroid receptor signaling. We have shown that ligand, receptor, activated JAKs and STATs are associated with specific gene activation, where the receptor subunit IFNGR1 functions as a co-transcription factor and the JAKs are involved in associated epigenetic events. We found that the type I IFN system functions similarly. The fact that GH receptor, insulin receptor, EGF receptor, and FGF receptor undergo nuclear translocation upon ligand binding suggests that they may also function similarly. The steroid hormone/steroid receptor nature of type I and II IFN signaling provides insight into the specificity of signaling by members of cytokine families. The non-canonical model could also provide better understanding to more complex cytokine families such as those of IL-2 and IL-12, whose members often use the same JAKs and STATs, but also have different functions and

  5. Contact inhibition and interferon (IFN)-modulated gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Kulesh, D.A.

    1986-01-01

    The relationship between cell morphology, proliferation and contact inhibition was studied in normal and malignant human cells which varied in their sensitivity to contact inhibition. Their ability to proliferate was examined under conditions where the cells were constrained into different shapes. Cell proliferation was quantitated by labeling indices, which were inferred by autoradiography, and by total cell counts. The normal cells (JHU-1, IMR-90) were dependent on cell shape for proliferation capability while the transformed cells (RT4, HT1080) were shape-dependent for proliferation. Interferon (IFN) induced shape-dependent proliferation and contact inhibition in the transformed cells when used at subantiproliferative concentrations. This ability of B-IFN to confer a level of proliferation control which is characteristic of normal fibroblasts suggests a possible relationship between gene expression mediated by IFN and those genes involved in the maintenance of regulated cell proliferation. To evaluate this possibility, cDNA libraries were constructed from IFN-treated and untreated HT1080 cells. The resulting 10 IFN-induced and 11 IFN-repressed sequences were then differentially rescreened using /sup 32/P-cDNA probes. This screening resulted in the identification of at least four cDNA sequences which appeared to be proliferation regulated as well as IFN-modulated. These cloned, regulated cDNA sequences were then used as /sup 32/P-labeled probes to study both the gene expression at the mRNA level employing Northern blotting and slot blotting techniques.

  6. The IFN Response in Bats Displays Distinctive IFN-Stimulated Gene Expression Kinetics with Atypical RNASEL Induction.

    Science.gov (United States)

    De La Cruz-Rivera, Pamela C; Kanchwala, Mohammed; Liang, Hanquan; Kumar, Ashwani; Wang, Lin-Fa; Xing, Chao; Schoggins, John W

    2018-01-01

    Bats host a large number of zoonotic viruses, including several viruses that are highly pathogenic to other mammals. The mechanisms underlying this rich viral diversity are unknown, but they may be linked to unique immunological features that allow bats to act as asymptomatic viral reservoirs. Vertebrates respond to viral infection by inducing IFNs, which trigger antiviral defenses through IFN-stimulated gene (ISG) expression. Although the IFN system of several bats is characterized at the genomic level, less is known about bat IFN-mediated transcriptional responses. In this article, we show that IFN signaling in bat cells from the black flying fox ( Pteropus alecto ) consists of conserved and unique ISG expression profiles. In IFN-stimulated cells, bat ISGs comprise two unique temporal subclusters with similar early induction kinetics but distinct late-phase declines. In contrast, human ISGs lack this decline phase and remained elevated for longer periods. Notably, in unstimulated cells, bat ISGs were expressed more highly than their human counterparts. We also found that the antiviral effector 2-5A-dependent endoribonuclease, which is not an ISG in humans, is highly IFN inducible in black flying fox cells and contributes to cell-intrinsic control of viral infection. These studies reveal distinctive innate immune features that may underlie a unique virus-host relationship in bats. Copyright © 2017 by The American Association of Immunologists, Inc.

  7. A functional IFN-λ4-generating DNA polymorphism could protect older asthmatic women from aeroallergen sensitization and associate with clinical features of asthma

    DEFF Research Database (Denmark)

    Chinnaswamy, Sreedhar; Wardzynska, Aleksandra; Pawelczyk, Malgorzata

    2017-01-01

    Lambda interferons (IFNLs) have immunomodulatory functions at epithelial barrier surfaces. IFN-λ4, a recent member of this family is expressed only in a subset of the population due to a frameshift-causing DNA polymorphism rs368234815. We examined the association of this polymorphism with atopy (...

  8. Barrier Island Activity to Illustrate Hands-On Science

    Science.gov (United States)

    Griffin, Suzanne H.

    The department of Physics of the University of Glasgow was concerned about losing students after the end of the level 1 Physics course. The current research project started as an attempt to find out the reasons for this, but moved to investigate attitudes towards Physics at several stages during secondary school and attitudes towards science with primary pupils. Analyses of factors, which influence students' intentions towards studying Physics, were performed against the background of the Theory of Planned Behaviour, which interprets people's behaviour by considering three factors: attitude towards behaviour (advantages or disadvantages of being involved in the behaviour, e.g. studying Physics for Honours); subjective norm (approval or disapproval of important people towards engaging in the behaviour, e.g. parents, teacher, general norms of the society); perceived behavioural control (skills, knowledge, cooperation of others, abilities, efforts required to perform the behaviour). Analysis of these factors revealed some reasons for students' withdrawal from Physics after level 1 and pointed to factors which may facilitate students' persistence in the subject. A general analysis of level 1 and level 2 students' attitudes towards different aspects of the university Physics course revealed that the level 1 students' attitudes towards their university course of lectures and course of laboratories tended to be negatively polarised. Recommendations were suggested on the basis of the gathered evidence about how to make students' experience in university Physics more satisfactory for them. The data obtained from the separate analyses of females' and males' attitudes towards university Physics course have showed that attitudes of females and males were similar. The only significant difference between level 1 females and males was found to be the perceived behavioural control factor (students' attitudes towards course difficulty, attitudes towards work load in the course), which was significantly lower for females than for males. Special attention in this work was given to the problem of university Physics laboratory practice. Possibilities to improve students' attitudes towards laboratory work were discussed. This could be done through introduction of pre-lab (aimed to consolidate students' grasp of the necessary background for performing the experiment) and post-lab (aimed to provide students with opportunity to apply the theory they have learned and skills they have obtained from doing laboratory work to solve everyday problems). Examples of pre- and post-labs that were designed for the first term of the level 1 university Physics laboratory practice are given in the Appendix T. The project was extended from the university to the school area where cross-age analyses (measurements at one time with pupils of different age) of pupils' attitudes towards Science/Physics lessons were performed. Pupils from upper Primary P6/P7 up to Higher S5/S6 were involved in the research. These analyses have shown that patterns of Scottish pupils' attitudes towards Science/Physics lessons are not linear with age: attitudes of pupils who were self-selected towards the subject were not always more positive than attitudes of lower level pupils: primary school pupils' attitudes towards science lessons were significantly more positive than attitudes of secondary S2 pupils; pupils doing Standard Grade Physics course were similar in their evaluations of Physics lessons at both S3 and S4 levels; at Higher Grade Physics pupils' attitudes towards science lessons were significantly less positive than attitudes of Standard Grade Physics pupils. Pupils' attitudes towards Science/Physics lessons can be considered as a good indicator of pupils' reactions towards existing syllabuses in Science and Physics. Special attention in this study was devoted to the so-called "problem of girls in Physics". Separate analyses of boys' and girls' interests towards Physics topics revealed that although boys and girls are equally interested in certain areas of the subject, there are areas in Physics where boys and girls interests are significantly different. No differences were found in intensity of boys' and girls' interests towards suggested Physics topics at primary P6/P7 level, S3 and S5/S6 levels. At S2 and S4 levels a significant decline of girls' interests relative to boys interests was observed. S2 and S4 stages are decision making ones when pupils have the opportunity to select courses for the future. It was also revealed that the ratio of boys to girls in Physics once established at S2 level remains unchanged through the years of Standard Grade and Higher Grade Physics courses. This may indicate that if the number of girls in Physics is an issue for concern then attention should be paid to the primary and, especially early secondary years to attract girls to Physics. School Physics courses in Scotland revealed a high retention rate of girls in Physics. Analyses of preferred activities revealed that practical work is the most enjoyable activity in Science/Physics lessons for both girls and boys at every stage of schooling and studying the theory was found to be the least enjoyable activity at school for both genders at every age. The picture was almost the reverse with university Physics students.

  9. Trends in Illustration: A digital approach to large format illustrations ...

    African Journals Online (AJOL)

    In view of this, this study uses Adobe Photoshop CS4, a digital draw and paint tool, to illustrate some of the notable folktales in Igbo oral tradition. Vector and Raster techniques of computer graphics will be employed and discussed. Basic information on digital illustration will also be enumerated in the project. This piece of ...

  10. Illustrations

    OpenAIRE

    2014-01-01

    Facettes multiples de la mangrove Divers faciès végétaux de la mangrove Rhizophora et Avicennia. © Cormier. Avicennia et Laguncularia. © Cormier. Mangrove : un écosystème forestier parcouru de bolons. © Cormier. Écosystème à mangrove (du rebord de plateau au bolon, y compris rizières de mangrove et tannes). Cormier © Orstom. Faune typique de la mangrove Monodactylus (Psettia sebae). Vidy © Orstom. Crabes violonistes (Uca spp.) Intès © Orstom. Les Rivières du Sud : des mangroves densémen...

  11. Illustrations

    OpenAIRE

    2015-01-01

    Fig. 5 – Détail de la carte des formations superficielles du plateau insulaire de la Guadeloupe(Augris et al., 1992) Fig. 6 – Détail de la carte des formations superficielles du plateau insulaire de la Martinique(Augris et al., 2000) Baie échancrée, récif frangeant, récif barrière, et mangrove sur la côte est de la Martinique.© Ifremer/A. Guillou Mangrove à Rhizophora mangle dans le Grand Cul-de-Sac Marin (Gùadeloupe).© M. Louis Pente externe d'un récif corallien en bon état de santé (Mar...

  12. Illustrations

    OpenAIRE

    2016-01-01

    Fig. 1 : Nicolas Poussin, Ravissement de saint Paul (version Scarron), Paris, musée du Louvre. Fig. 4 : Nicolas Poussin, Ravissement de saint Paul (version Scarron), restitution du format d’origine : environ 128 x 96 cm (détail de la fig. 1). Fig. 5 : Giovanni Lanfranco, Ravissement de la Madeleine, Naples, museo nazionale Capodimonte. Fig. 6 : Nicolas Poussin, Ravissement de saint Paul (version Chantelou), Sarasota, Ringling Museum of Art. Fig. 7 : Nicolas Poussin, Assomption, Paris, mus...

  13. Illustrations

    OpenAIRE

    2015-01-01

    1/ Atelier de Neri di Bici (attr.), Saint Yves rendant la justice, XVe siècle (Florence, Opera del Duomo) 2/ Le Sodoma,Saint Yves rendant la justice, 1507 (San Gimignano, fresque du Palais communal) 3/ Jacopo da Empoli, Saint Yves entre la veuve et l’orphelin, 1616 (Florence, galerie Pitti) 4/ Jacopo da Empoli, Saint Luc recommandant saint Yves à la Vierge, v. 1630 (Paris, Musée du Louvre) 5/ Giacomo Triga, La Vierge et les saints Yves, Gilles et Gimnesius, 1723 (Rome, église Santa Lucia ...

  14. Creating a digital medical illustration.

    Science.gov (United States)

    Culley, Joanna

    2016-01-01

    This paper covers the steps required to complete a medical illustration in a digital format using Adobe Illustrator and Photoshop. The project example is the surgical procedure for the release of the glenohumeral joint for the condition known as 'frozen shoulder'. The purpose is to demonstrate one method which an artist can use within digital media to create a colour illustration such as the release of the glenohumeral joint. Included is a general overview as how to deal with the administration of a medical illustration commission through the experience of a professional freelance artist.

  15. Wild type measles virus attenuation independent of type I IFN

    Directory of Open Access Journals (Sweden)

    Horvat Branka

    2008-02-01

    Full Text Available Abstract Background Measles virus attenuation has been historically performed by adaptation to cell culture. The current dogma is that attenuated virus strains induce more type I IFN and are more resistant to IFN-induced protection than wild type (wt. Results The adaptation of a measles virus isolate (G954-PBL by 13 passages in Vero cells induced a strong attenuation of this strain in vivo. The adapted virus (G954-V13 differs from its parental strain by only 5 amino acids (4 in P/V/C and 1 in the M gene. While a vaccine strain, Edmonston Zagreb, could replicate equally well in various primate cells, both G954 strains exhibited restriction to the specific cell type used initially for their propagation. Surprisingly, we observed that both G954 strains induced type I IFN, the wt strain inducing even more than the attenuated ones, particularly in human plasmacytoid Dendritic Cells. Type I IFN-induced protection from the infection of both G954 strains depended on the cell type analyzed, being less efficient in the cells used to grow the viral strain. Conclusion Thus, mutations in M and P/V/C proteins can critically affect MV pathogenicity, cellular tropism and lead to virus attenuation without interfering with the α/β IFN system.

  16. Biologic consequences of Stat1-independent IFN signaling

    Science.gov (United States)

    Gil, M. Pilar; Bohn, Erwin; O'Guin, Andrew K.; Ramana, Chilakamarti V.; Levine, Beth; Stark, George R.; Virgin, Herbert W.; Schreiber, Robert D.

    2001-01-01

    Although Stat1 is required for many IFN-dependent responses, recent work has shown that IFNγ functions independently of Stat1 to affect the growth of tumor cells or immortalized fibroblasts. We now demonstrate that both IFNγ and IFNα/β regulate proliferative responses in cells of the mononuclear phagocyte lineage derived from Stat1-null mice. Using both representational difference analysis and gene arrays, we show that IFNγ exerts its Stat1-independent actions on mononuclear phagocytes by regulating the expression of many genes. This result was confirmed by monitoring changes in expression and function of the corresponding gene products. Regulation of the expression of these genes requires the IFNγ receptor and Jak1. The physiologic relevance of IFN-dependent, Stat1-independent signaling was demonstrated by monitoring antiviral responses in Stat1-null mice. Thus, the IFN receptors engage alternative Stat1-independent signaling pathways that have important physiological consequences. PMID:11390995

  17. Retrospective analysis of drug utilization, health care resource use, and costs associated with IFN therapy for adjuvant treatment of malignant melanoma

    Directory of Open Access Journals (Sweden)

    Zhang Y

    2015-07-01

    demonstrated the largest difference between IFN-treated and observation patients. Outpatient service costs for IFN-treated patients were $32,414±$2,498, over three times greater than those for observation patients ($10,556±$1,128; P<0.0001.Conclusion: The majority of adjuvant melanoma patients in this study was treated with observation versus IFN treatment. Among those who attempted IFN treatment, most could not complete the recommended course of therapy. Health care costs were significantly greater for patients treated with IFN, with the greatest differences being for melanoma-related medical cost components. These findings illustrate the significant economic burden borne by adjuvant melanoma patients and their health insurers.Keywords: adjuvant melanoma, interferon, claims data, cost analysis

  18. IFN-alpha antibodies in patients with age-related macular degeneration treated with recombinant human IFN-alpha2a

    DEFF Research Database (Denmark)

    Ross, Christian; Engler, Claus Bødker; Sander, Birgit

    2002-01-01

    We tested for development of binding and neutralizing antibodies to interferon-alpha (IFN-alpha) during IFN-alpha2a therapy of patients with age-related macular degeneration (AMD) of the eyes. Antibodies were investigated retrospectively in sera of 34 patients treated with 3 x 10(6) IU IFN-alpha2...

  19. Interferons and interferon (IFN)-inducible protein 10 during highly active anti-retroviral therapy (HAART)-possible immunosuppressive role of IFN-alpha in HIV infection

    DEFF Research Database (Denmark)

    Stylianou, E; Aukrust, P; Bendtzen, K

    2000-01-01

    -infected patients had raised levels of both IP-10 and IFN-alpha compared with healthy controls (n = 19), with particularly high levels in advanced disease. HAART induced a marked decrease in levels of both IFN-alpha, neopterin and IP-10, though not to normal concentrations. In contrast, IFN-gamma levels were low...

  20. IFN-alpha antibodies in patients with age-related macular degeneration treated with recombinant human IFN-alpha2a

    DEFF Research Database (Denmark)

    Ross, Christian; Engler, Claus Bødker; Sander, Birgit

    2002-01-01

    We tested for development of binding and neutralizing antibodies to interferon-alpha (IFN-alpha) during IFN-alpha2a therapy of patients with age-related macular degeneration (AMD) of the eyes. Antibodies were investigated retrospectively in sera of 34 patients treated with 3 x 10(6) IU IFN-alpha2a...

  1. IFN regulatory factor 1 restricts hepatitis E virus replication by activating STAT1 to induce antiviral IFN-stimulated genes.

    Science.gov (United States)

    Xu, Lei; Zhou, Xinying; Wang, Wenshi; Wang, Yijin; Yin, Yuebang; Laan, Luc J W van der; Sprengers, Dave; Metselaar, Herold J; Peppelenbosch, Maikel P; Pan, Qiuwei

    2016-10-01

    IFN regulatory factor 1 (IRF1) is one of the most important IFN-stimulated genes (ISGs) in cellular antiviral immunity. Although hepatitis E virus (HEV) is a leading cause of acute hepatitis worldwide, how ISGs counteract HEV infection is largely unknown. This study was conducted to investigate the effect of IRF1 on HEV replication. Multiple cell lines were used in 2 models that harbor HEV. In different HEV cell culture systems, IRF1 effectively inhibited HEV replication. IRF1 did not trigger IFN production, and chromatin immunoprecipitation sequencing data analysis revealed that IRF1 bound to the promoter region of signal transducers and activators of transcription 1 (STAT1). Functional assay confirmed that IRF1 could drive the transcription of STAT1, resulting in elevation of total and phosphorylated STAT1 proteins and further activating the transcription of a panel of downstream antiviral ISGs. By pharmacological inhibitors and RNAi-mediated gene-silencing approaches, we revealed that antiviral function of IRF1 is dependent on the JAK-STAT cascade. Furthermore, induction of ISGs and the anti-HEV effect of IRF1 overlapped that of IFNα, but was potentiated by ribavirin. We demonstrated that IRF1 effectively inhibits HEV replication through the activation of the JAK-STAT pathway, and the subsequent transcription of antiviral ISGs, but independent of IFN production.-Xu, L., Zhou, X., Wang, W., Wang, Y., Yin, Y., van der Laan, L. J. W., Sprengers, D., Metselaar, H. J., Peppelenbosch, M. P., Pan, Q. IFN regulatory factor 1 restricts hepatitis E virus replication by activating STAT1 to induce antiviral IFN-stimulated genes. © FASEB.

  2. Illustrations of the twin paradox

    International Nuclear Information System (INIS)

    Rebhan, E.

    1985-01-01

    In order to provide a more intuitive understanding of the twin paradox, several illustrations of this are presented. In one of these, each of the twins is equipped with a lamp whose monochromatic light can be observed by the other. In other illustrations the travelling twin uses an Einstein train instead of a space ship, all the cars of the train and all stations along the route of the train being equipped with clocks. (author)

  3. Research Article Polymorphism detection of promoter region of IFN ...

    Indian Academy of Sciences (India)

    MRT Pack 24 DVDs

    Improving animal health is considered to be the basic goal of the animal breeding ..... Additionally, cytokines including TGF-β, IFN-y and TNF-α, IL-1α, IL- .... of lipopolysaccharide-binding protein in protection of mice against a ... Humoral Immune Response to Killed H5N1 HPAI Vaccine in a Red Jungle fowl Population.

  4. Anti-inflammatory mechanisms of IFN-γ studied in experimental autoimmune encephalomyelitis reveal neutrophils as a potential target in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Nichole M Miller

    2015-08-01

    Full Text Available Multiple sclerosis (MS is an autoimmune disease of the central nervous system (CNS mediated by T helper (h1 and/or Th17 CD4 T cells that drive inflammatory lesion development along with demyelination and neuronal damage. Defects in immune regulatory mechanisms are thought to play a role in the pathogenesis of MS. While an early clinical trial indicated that IFN-γ administration was detrimental to MS, studies in the mouse model of MS, experimental autoimmune encephalomyelitis (EAE, indicated that IFN-γ exhibits a number of anti-inflammatory properties within the CNS. These mechanisms include inhibition of IL-17 production, induction of regulatory T cells, T cell apoptosis and regulation of chemokine production. Mice deficient in IFN-γ or its receptor were instrumental in deciphering the anti-inflammatory properties of IFN-γ in the CNS. In particular, they revealed that IFN-γ is a major regulator of neutrophil recruitment into the CNS, which by a variety of mechanisms including disruption of the blood-brain-barrier (BBB and production of reactive oxygen species are thought to contribute to the onset and progression of EAE. Neutrophils were also shown to be instrumental in EAE relapses. To date neutrophils have not been appreciated as a driver of MS, but more recently based largely on the strong EAE data this view is being reevaluated by some investigators in the field.

  5. Radiology illustrated. Uroradiology. 2. ed.

    International Nuclear Information System (INIS)

    Kim, Seung Hyup

    2012-01-01

    Uroradiology is an up-to-date, image-oriented reference in the style of a teaching file that has been designed specifically to be of value in clinical practice. All aspects of the imaging of urologic diseases are covered, and case studies illustrate the findings obtained with the relevant imaging modalities in both common and uncommon conditions. Most chapters focus on a particular clinical problem, but normal findings, congenital anomalies, and interventions are also discussed and illustrated. In this second edition, the range and quality of the illustrations have been enhanced, and many schematic drawings have been added to help readers memorize characteristic imaging findings through pattern recognition. The accompanying text is concise and informative. Besides serving as an outstanding aid to differential diagnosis, this book will provide a user-friendly review tool for certification or recertification in radiology. (orig.)

  6. Illustrating and Designing Quranic Imagery

    Science.gov (United States)

    Almenoar, Lubna

    2009-01-01

    Selected verses from Abdullah Yusuf Ali's English language translation of the meaning of the Quran have been used as a literary text to teach both descriptive and figurative imagery (including similes, metaphors and symbols) to students at the undergraduate level in an Islamic institution. The technique--Illustrating and Designing for teaching…

  7. Local IFN-gamma therapy of HPV16-associated tumours

    Czech Academy of Sciences Publication Activity Database

    Mikyšková, Romana; Bieblová, Jana; Šímová, Jana; Indrová, Marie; Jandlová, Táňa; Vonka, V.; Šmahel, M.; Bubeník, Jan; Mendoza, Luis

    2003-01-01

    Roč. 49, č. 1 (2003), s. 26-32 ISSN 0015-5500 R&D Projects: GA MZd NC7148; GA MZd NC5900; GA ČR GA301/01/0985 Grant - others:GA CZ(CZ) Liga proti rakovině Institutional research plan: CEZ:AV0Z5052915 Keywords : MHC class I * IFN-gamma * HPV16 Subject RIV: FD - Oncology ; Hematology Impact factor: 0.527, year: 2003

  8. Gene expression in IFN-g-activated murine macrophages

    Directory of Open Access Journals (Sweden)

    Pereira C.A.

    2004-01-01

    Full Text Available Macrophages are critical for natural immunity and play a central role in specific acquired immunity. The IFN-gamma activation of macrophages derived from A/J or BALB/c mice yielded two different patterns of antiviral state in murine hepatitis virus 3 infection, which were related to a down-regulation of the main virus receptor. Using cDNA hybridization to evaluate mRNA accumulation in the cells, we were able to identify several genes that are differently up- or down-regulated by IFN-gamma in A/J (267 and 266 genes, respectively, up- and down-regulated or BALB/c (297 and 58 genes, respectively, up- and down-regulated mouse macrophages. Macrophages from mice with different genetic backgrounds behave differently at the molecular level and comparison of the patterns of non-activated and IFN-gamma-activated A/J or BALB/c mouse macrophages revealed, for instance, an up-regulation and a down-regulation of genes coding for biological functions such as enzymatic reactions, nucleic acid synthesis and transport, protein synthesis, transport and metabolism, cytoskeleton arrangement and extracellular matrix, phagocytosis, resistance and susceptibility to infection and tumors, inflammation, and cell differentiation or activation. The present data are reported in order to facilitate future correlation of proteomic/transcriptomic findings as well as of results obtained from a classical approach for the understanding of biological phenomena. The possible implication of the role of some of the gene products relevant to macrophage biology can now be further scrutinized. In this respect, a down-regulation of the main murine hepatitis virus 3 receptor gene was detected only in IFN-gamma-activated macrophages of resistant mice.

  9. Biologic consequences of Stat1-independent IFN signaling

    OpenAIRE

    Gil, M. Pilar; Bohn, Erwin; O'Guin, Andrew K.; Ramana, Chilakamarti V.; Levine, Beth; Stark, George R.; Virgin, Herbert W.; Schreiber, Robert D.

    2001-01-01

    Although Stat1 is required for many IFN-dependent responses, recent work has shown that IFNγ functions independently of Stat1 to affect the growth of tumor cells or immortalized fibroblasts. We now demonstrate that both IFNγ and IFNα/β regulate proliferative responses in cells of the mononuclear phagocyte lineage derived from Stat1-null mice. Using both representational difference analysis and gene arrays, we show that IFNγ exerts its Stat1-independent actions on m...

  10. Converse Barrier Certificate Theorem

    DEFF Research Database (Denmark)

    Wisniewski, Rafael; Sloth, Christoffer

    2013-01-01

    This paper presents a converse barrier certificate theorem for a generic dynamical system.We show that a barrier certificate exists for any safe dynamical system defined on a compact manifold. Other authors have developed a related result, by assuming that the dynamical system has no singular...... points in the considered subset of the state space. In this paper, we redefine the standard notion of safety to comply with generic dynamical systems with multiple singularities. Afterwards, we prove the converse barrier certificate theorem and illustrate the differences between ours and previous work...

  11. DMPD: What is disrupting IFN-alpha's antiviral activity? [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 15283983 What is disrupting IFN-alpha's antiviral activity? Mbow ML, Sarisky RT. Tr...ends Biotechnol. 2004 Aug;22(8):395-9. (.png) (.svg) (.html) (.csml) Show What is disrupting IFN-alpha's ant...iviral activity? PubmedID 15283983 Title What is disrupting IFN-alpha's antiviral activity? Authors Mbow ML,

  12. Autophagy Facilitates IFN-γ-induced Jak2-STAT1 Activation and Cellular Inflammation*

    Science.gov (United States)

    Chang, Yu-Ping; Tsai, Cheng-Chieh; Huang, Wei-Ching; Wang, Chi-Yun; Chen, Chia-Ling; Lin, Yee-Shin; Kai, Jui-In; Hsieh, Chia-Yuan; Cheng, Yi-Lin; Choi, Pui-Ching; Chen, Shun-Hua; Chang, Shih-Ping; Liu, Hsiao-Sheng; Lin, Chiou-Feng

    2010-01-01

    Autophagy is regulated for IFN-γ-mediated antimicrobial efficacy; however, its molecular effects for IFN-γ signaling are largely unknown. Here, we show that autophagy facilitates IFN-γ-activated Jak2-STAT1. IFN-γ induces autophagy in wild-type but not in autophagy protein 5 (Atg5−/−)-deficient mouse embryonic fibroblasts (MEFs), and, autophagy-dependently, IFN-γ induces IFN regulatory factor 1 and cellular inflammatory responses. Pharmacologically inhibiting autophagy using 3-methyladenine, a known inhibitor of class III phosphatidylinositol 3-kinase, confirms these effects. Either Atg5−/− or Atg7−/− MEFs are, independent of changes in IFN-γ receptor expression, resistant to IFN-γ-activated Jak2-STAT1, which suggests that autophagy is important for IFN-γ signal transduction. Lentivirus-based short hairpin RNA for Atg5 knockdown confirmed the importance of autophagy for IFN-γ-activated STAT1. Without autophagy, reactive oxygen species increase and cause SHP2 (Src homology-2 domain-containing phosphatase 2)-regulated STAT1 inactivation. Inhibiting SHP2 reversed both cellular inflammation and the IFN-γ-induced activation of STAT1 in Atg5−/− MEFs. Our study provides evidence that there is a link between autophagy and both IFN-γ signaling and cellular inflammation and that autophagy, because it inhibits the expression of reactive oxygen species and SHP2, is pivotal for Jak2-STAT1 activation. PMID:20592027

  13. Exogenous IFN-beta regulates the RANKL-c-Fos-IFN-beta signaling pathway in the collagen antibody-induced arthritis model.

    Science.gov (United States)

    Zhao, Rong; Chen, Ni-Nan; Zhou, Xiao-Wei; Miao, Ping; Hu, Chao-Ying; Qian, Liu; Yu, Qi-Wen; Zhang, Ji-Ying; Nie, Hong; Chen, Xue-hua; Li, Pu; Xu, Rong; Xiao, Lian-Bo; Zhang, Xin; Liu, Jian-Ren; Zhang, Dong-Qing

    2014-12-10

    Although a variety of drugs have been used to treat the symptoms of rheumatoid arthritis (RA), none of them are able to cure the disease. Interferon β (IFN-β) has pleiotropic effects on RA, but whether it can be used to treat RA remains globally controversial. Thus, in this study we tested the effects of IFN-β on RA patients and on collagen antibody-induced arthritis (CAIA) model mice. The cytokine and auto-antibody expression profiles in the serum and synovial fluid (SF) from RA patients were assessed using enzyme-linked immunosorbent assay (ELISA) and compared with the results from osteoarthritis (OA) patients. Exogenous IFN-β was administered to RA patients and CAIA model mice, and the therapeutic effects were evaluated. Endogenous IFN-β expression in the joint bones of CAIA model mice was evaluated by quantitative real-time PCR (qRT-PCR). The effects of exogenous IFN-β on CAIA model mice were assessed using a clinical scoring system, hematoxylin eosin and safranin-O with fast green counterstain histology, molybdenum target X-ray, and tartrate-resistant acid phosphatase (TRAP) staining. The RANKL-RANK signaling pathway was analyzed using qRT-PCR. The RAW 264.7 cell line was differentiated into osteoclasts with RANKL stimulation and then treated with exogenous IFN-β. The expression of inflammatory cytokines (IFN-γ, IL-17, MMP-3, and RANKL) and auto-antibodies (CII antibodies, RF-IgM, and anti-CCP/GPI) were significantly higher in RA compared with OA patients. After IFN-β intervention, some clinical symptoms in RA patients were partially alleviated, and the expression of IFN-γ, IL-17, MMP-3, and OPG) returned to normal levels. In the CAIA model, the expression of endogenous IFN-β in the joint bones was decreased. After IFN-β administration, the arthritis scores were decreased; synovial inflammation, cartilage, and bone destruction were clearly attenuated; and the expression of c-Fos and NFATc1 were reduced, while RANKL and TRAF6 expression was

  14. Cellular sources and targets of IFN-γ-mediated protection against viral demyelination and neurological deficits

    Science.gov (United States)

    Murray, Paul D.; McGavern, Dorian B.; Pease, Larry R.; Rodriguez, Moses

    2017-01-01

    IFN-γ is an anti-viral and immunomodulatory cytokine critical for resistance to multiple pathogens. Using mice with targeted disruption of the gene for IFN-γ, we previously demonstrated that this cytokine is critical for resistance to viral persistence and demyelination in the Theiler’s virus model of multiple sclerosis. During viral infections, IFN-γ is produced by natural killer (NK) cells, CD4+ and CD8+ T cells; however, the proportions of lymphocyte subsets responding to virus infection influences the contributions to IFN-γ-mediated protection. To determine the lymphocyte subsets that produce IFN-γ to maintain resistance, we used adoptive transfer strategies to generate mice with lymphocyte-specific deficiencies in IFN-γ-production. We demonstrate that IFN-γ production by both CD4+ and CD8+ T cell subsets is critical for resistance to Theiler’s murine encephalomyelitis virus (TMEV)-induced demyelination and neurological disease, and that CD4+ T cells make a greater contribution to IFN-γ-mediated protection. To determine the cellular targets of IFN-γ-mediated responses, we used adoptive transfer studies and bone marrow chimerism to generate mice in which either hematopoietic or somatic cells lacked the ability to express IFN-γ receptor. We demonstrate that IFN-γ receptor must be present on central nervous system glia, but not bone marrow-derived lymphocytes, in order to maintain resistance to TMEV-induced demyelination. PMID:11857334

  15. Experimental Evaluation of the Transport Mechanisms of PoIFN-α in Caco-2 Cells

    Directory of Open Access Journals (Sweden)

    Xin Liu

    2017-11-01

    Full Text Available For the development of an efficient intestinal delivery system for Porcine interferon-α (PoIFN-α, the understanding of transport mechanisms of which in the intestinal cell is essential. In this study, we investigated the absorption mechanisms of PoIFN-α in intestine cells. Caco-2 cells and fluorescein isothiocyanate-labeled (FITC-PoIFN-α were used to explore the whole transport process, including endocytosis, intracellular trafficking, exocytosis, and transcytosis. Via various techniques, the transport pathways of PoIFN-α in Caco-2 cells and the mechanisms were clarified. Firstly, the endocytosis of PoIFN-α by Caco-2 cells was time, concentration and temperature dependence. And the lipid raft/caveolae endocytosis was the most likely endocytic pathway for PoIFN-α. Secondly, both Golgi apparatus and lysosome were involved in the intracellular trafficking of PoIFN-α. Thirdly, the treatment of indomethacin resulted in a significant decrease of exocytosis of PoIFN-α, indicating the participation of cyclooxygenase. Finally, to evaluate the efficiency of PoIFN-α transport, the transepithelial electrical resistance (TEER value was measured to investigate the tight junctional integrity of the cell monolayers. The fluorescence microscope results revealed that the transport of PoIFN-α across the Caco-2 cell monolayers was restricted. In conclusion, this study depicts a probable picture of PoIFN-α transport in Caco-2 cells characterized by non-specificity, partial energy-dependency and low transcytosis.

  16. The CXC chemokines gamma interferon (IFN-gamma)-inducible protein 10 and monokine induced by IFN-gamma are released during severe melioidosis

    NARCIS (Netherlands)

    Lauw, F. N.; Simpson, A. J.; Prins, J. M.; van Deventer, S. J.; Chaowagul, W.; White, N. J.; van der Poll, T.

    2000-01-01

    Gamma interferon (IFN-gamma)-inducible protein 10 (IP-10) and monokine induced by IFN-gamma (Mig) are related CXC chemokines which bind to the CXCR3 receptor and specifically target activated T lymphocytes and natural killer (NK) cells. The production of IP-10 and Mig by various cell types in vitro

  17. Loss of PTEN causes SHP2 activation, making lung cancer cells unresponsive to IFN

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Chia-Ling [Translational Research Center, Taipei Medical University, Taipei 110, Taiwan (China); Chiang, Tzu-Hui; Tseng, Po-Chun [Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan (China); Wang, Yu-Chih [Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan (China); Lin, Chiou-Feng, E-mail: cflin2014@tmu.edu.tw [Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan (China); Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan (China)

    2015-10-23

    Src homology-2 domain-containing phosphatase (SHP) 2, an oncogenic phosphatase, inhibits type II immune interferon (IFN)-γ signaling by subverting signal transducers and activators of transcription 1 tyrosine phosphorylation and activation. For cancer immunoediting, this study aimed to investigate the decrease of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a tumor suppressor protein, leading to cellular impairment of IFN-γ signaling. In comparison with human lung adenocarcinoma A549 cells, the natural PTEN loss in another human lung adenocarcinoma line, PC14PE6/AS2 cells, presents reduced responsiveness in IFN-γ-induced IFN regulatory factor 1 activation and CD54 expression. Artificially silencing PTEN expression in A549 cells also caused cells to be unresponsive to IFN-γ without affecting IFN-γ receptor expression. IFN-γ-induced inhibition of cell proliferation and cytotoxicity were demonstrated in A549 cells but were defective in PC14PE6/AS2 cells and in PTEN-deficient A549 cells. Aberrant activation of SHP2 by ROS was specifically shown in PC14PE6/AS2 cells and PTEN-deficient A549 cells. Inhibiting ROS and SHP2 rescued cellular responses to IFN-γ-induced cytotoxicity and inhibition of cell proliferation in PC14PE6/AS2 cells. These results demonstrate that a decrease in PTEN facilitates ROS/SHP2 signaling, causing lung cancer cells to become unresponsive to IFN-γ. - Highlights: • This study demonstrates that PTEN decrease causes cellular unresponsive to IFN-γ. • Lung cancer cells with PTEN deficiency show unresponsive to IFN-γ signaling. • PTEN decrease inhibits IFN-γ-induced CD54, cell proliferation inhibition, and cytotoxicity. • ROS-mediated SHP2 activation makes PTEN-deficient cells unresponsive to IFN-γ.

  18. An illustration of whole systems thinking.

    Science.gov (United States)

    Kalim, Kanwal; Carson, Ewart; Cramp, Derek

    2006-08-01

    The complexity of policy-making in the NHS is such that systemic, holistic thinking is needed if the current government's plans are to be realized. This paper describes systems thinking and illustrates its value in understanding the complexity of the diabetes National Service Framework (NSF); its role in identifying problems and barriers previously not predicted; and in reaching conclusions as to how it should be implemented. The approach adopted makes use of soft systems methodology (SSM) devised by Peter Checkland. This analysis reveals issues relating to human communication, information provision and resource allocation needing to be addressed. From this, desirable and feasible changes are explored as means of achieving a more effective NSF, examining possible changes from technical, organizational, economic and cultural perspectives. As well as testing current health policies and plans, SSM can be used to test the feasibility of new health policies. This is achieved by providing a greater understanding and appreciation of what is happening in the real world and how people work. Soft systems thinking is the best approach, given the complexity of health care. It is a flexible, cost-effective solution, which should be a prerequisite before any new health policy is launched.

  19. Identification of Two Subgroups of Type I IFNs in Perciforme Fish Large Yellow Croaker Larimichthys crocea Provides Novel Insights into Function and Regulation of Fish Type I IFNs

    Directory of Open Access Journals (Sweden)

    Yang Ding

    2016-09-01

    Full Text Available Like mammals, fish possess an interferon regulatory factor 3 (IRF3/IRF7-dependent type I IFN responses, but the exact mechanism by which IRF3/IRF7 regulate the type I IFNs remains largely unknown. In this study, we identified two type I IFNs in the Perciforme fish large yellow croaker Larimichthys crocea, one of which belongs to the fish IFNd subgroup, and the other is assigned to a novel subgroup of group I IFNs in fish, tentatively termed IFNh. The two IFN genes are constitutively expressed in all examined tissues, but with varied expression levels. Both IFN genes can be rapidly induced in head kidney and spleen tissues by polyinosinic-polycytidylic acid. The recombinant IFNh was shown to be more potent to trigger a rapid induction of the antiviral genes MxA and PKR than the IFNd, suggesting that they may play distinct roles in regulating early antiviral immunity. Strikingly, IFNd, but not IFNh, could induce the gene expression of itself and IFNh through a positive feedback loop mediated by the IFNd-dependent activation of IRF3 and IRF7. Furthermore, our data demonstrate that the induction of IFNd can be enhanced by the dimeric formation of IRF3 and IRF7, while the IFNh expression mainly involves IRF3. Taken together, our findings demonstrate that the IFN responses are diverse in fish and are likely to be regulated by distinct mechanisms.

  20. IFN-beta inhibits T cell activation capacity of central nervous system APCs

    DEFF Research Database (Denmark)

    Teige, Ingrid; Liu, Yawei; Issazadeh-Navikas, Shohreh

    2006-01-01

    We have previously investigated the physiological effects of IFN-beta on chronic CNS inflammation and shown that IFN-beta(-/-) mice develop a more severe experimental autoimmune encephalomyelitis than their IFN-beta(+/-) littermates. This result was shown to be associated with a higher activation...... state of the glial cells and a higher T cell cytokine production in the CNS. Because this state suggested a down-regulatory effect of IFN-beta on CNS-specific APCs, these results were investigated further. We report that IFN-beta pretreatment of astrocytes and microglia (glial cells) indeed down......-modulate their capacity to activate autoreactive Th1 cells. First, we investigated the intrinsic ability of glial cells as APCs and report that glial cells prevent autoreactive Th1 cells expansion while maintaining Ag-specific T cell effector functions. However, when the glial cells are treated with IFN-beta before...

  1. Endogenous IFN-β signaling exerts anti-inflammatory actions in experimentally induced focal cerebral ischemia

    DEFF Research Database (Denmark)

    Inácio, Ana R; Liu, Yawei; Clausen, Bettina H

    2015-01-01

    of infiltrating leukocytes in the brain 2 days after stroke. Concomitantly, in the blood of IFN-βKO mice, we found a higher percentage of total B cells but a similar percentage of mature and activated B cells, collectively indicating a higher proliferation rate. The additional differential regulation......BACKGROUND: Interferon (IFN)-β exerts anti-inflammatory effects, coupled to remarkable neurological improvements in multiple sclerosis, a neuroinflammatory condition of the central nervous system. Analogously, it has been hypothesized that IFN-β, by limiting inflammation, decreases neuronal death...... strength tests, and cerebral infarct volumes were given by lack of neuronal nuclei immunoreactivity. RESULTS: Here, we report alterations in local and systemic inflammation in IFN-β knockout (IFN-βKO) mice over 8 days after induction of focal cerebral ischemia. Notably, IFN-βKO mice showed a higher number...

  2. Control of HIV infection by IFN-α: implications for latency and a cure.

    Science.gov (United States)

    Bourke, Nollaig M; Napoletano, Silvia; Bannan, Ciaran; Ahmed, Suaad; Bergin, Colm; McKnight, Áine; Stevenson, Nigel J

    2018-03-01

    Viral infections, including HIV, trigger the production of type I interferons (IFNs), which in turn, activate a signalling cascade that ultimately culminates with the expression of anti-viral proteins. Mounting evidence suggests that type I IFNs, in particular IFN-α, play a pivotal role in limiting acute HIV infection. Highly active anti-retroviral treatment reduces viral load and increases life expectancy in HIV positive patients; however, it fails to fully eliminate latent HIV reservoirs. To revisit HIV as a curable disease, this article reviews a body of literature that highlights type I IFNs as mediators in the control of HIV infection, with particular focus on the anti-HIV restriction factors induced and/or activated by IFN-α. In addition, we discuss the relevance of type I IFN treatment in the context of HIV latency reversal, novel therapeutic intervention strategies and the potential for full HIV clearance.

  3. We Can Still Be Friends: IFN-γ Breaks Up Macrophage Enhancers.

    Science.gov (United States)

    Novakovic, Boris; Wang, Cheng; Logie, Colin

    2017-08-15

    Interferon (IFN)-γ can prime macrophages for inflammatory responses by several mechanisms, including enhancer establishment and gene activation. In this issue of Immunity, Kang et al. (2017) provide insight into the mechanisms of IFN-γ-mediated gene repression as they show that IFN-γ promotes the disassembly of select active enhancers by interfering with enhancer-binding transcription factor MAF. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. PAI-1 and IFN-γ in the regulation of innate immune homeostasis during sublethal yersiniosis.

    Science.gov (United States)

    Wang, Zheng; Zhao, Qi; Han, Yuxia; Zhang, Dongxia; Zhang, Liangyan; Luo, Deyan

    2013-03-01

    Plasminogen activator inhibitor type 1 (PAI-l), a key part of the fibrinolytic system, plays a critical host protective role during the acute phase of infection by regulating interferon(IFN)-γ release. IFN-γ regulates PAI-1 expression, which suggests an intricate interplay between PAI-1 and IFN-γ. Here, using the notion of a feedback loop, we report the complicated regulatory relationship between PAI-1 and IFN-γ. Mice were inoculated intravenously with 1×10(3) colony forming units of Yersinia enterocolitica; PAI-1 deficiency enhanced lethality (pimmune homeostasis. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. IFN-induced modulation of histocompatibility antigens on human cells. Background, mechanisms and perspectives

    DEFF Research Database (Denmark)

    Hokland, M; Basse, P; Justesen, J

    1989-01-01

    IFN proteins are a family of lymphokines with anti-viral effects. Several other effects of IFNs have also been described, including enhancement of natural killer (NK) cell activity, enhancement of cytotoxic T-lymphocyte activity, and enhancement of the expression of major histocompatibility compl...... to the classical anti-viral mechanism. This concept proposes that the MHC-enhancing effect of IFNs is a vital part of the immunological defense against virus infections and an integral part of the anti-viral effects of IFN proteins. Udgivelsesdato: 1988-Nov...

  6. Reconstruction of gene regulatory modules from RNA silencing of IFN-α modulators: experimental set-up and inference method.

    Science.gov (United States)

    Grassi, Angela; Di Camillo, Barbara; Ciccarese, Francesco; Agnusdei, Valentina; Zanovello, Paola; Amadori, Alberto; Finesso, Lorenzo; Indraccolo, Stefano; Toffolo, Gianna Maria

    2016-03-12

    Inference of gene regulation from expression data may help to unravel regulatory mechanisms involved in complex diseases or in the action of specific drugs. A challenging task for many researchers working in the field of systems biology is to build up an experiment with a limited budget and produce a dataset suitable to reconstruct putative regulatory modules worth of biological validation. Here, we focus on small-scale gene expression screens and we introduce a novel experimental set-up and a customized method of analysis to make inference on regulatory modules starting from genetic perturbation data, e.g. knockdown and overexpression data. To illustrate the utility of our strategy, it was applied to produce and analyze a dataset of quantitative real-time RT-PCR data, in which interferon-α (IFN-α) transcriptional response in endothelial cells is investigated by RNA silencing of two candidate IFN-α modulators, STAT1 and IFIH1. A putative regulatory module was reconstructed by our method, revealing an intriguing feed-forward loop, in which STAT1 regulates IFIH1 and they both negatively regulate IFNAR1. STAT1 regulation on IFNAR1 was object of experimental validation at the protein level. Detailed description of the experimental set-up and of the analysis procedure is reported, with the intent to be of inspiration for other scientists who want to realize similar experiments to reconstruct gene regulatory modules starting from perturbations of possible regulators. Application of our approach to the study of IFN-α transcriptional response modulators in endothelial cells has led to many interesting novel findings and new biological hypotheses worth of validation.

  7. Energy barrier to decoherence

    International Nuclear Information System (INIS)

    Mizel, Ari; Mitchell, M. W.; Cohen, Marvin L.

    2001-01-01

    We propose a ground-state approach to realizing quantum computers. This scheme is time-independent and inherently defends against decoherence by possessing an energy barrier to excitation. We prove that our time-independent qubits can perform the same algorithms as their time-dependent counterparts. Advantages and disadvantages of the time-independent approach are described. A model involving quantum dots is provided for illustration

  8. IFN-γ-producing Th1-like regulatory T cells may limit acute cellular renal allograft rejection: Paradoxical post-transplantation effects of IFN-γ.

    Science.gov (United States)

    Xu, Xiaoguang; Huang, Haiyan; Wang, Qiang; Cai, Ming; Qian, Yeyong; Han, Yong; Wang, Xinying; Gao, Yu; Yuan, Ming; Xu, Liang; Yao, Chen; Xiao, Li; Shi, Bingyi

    2017-02-01

    IFN-γ is a protypical proinflammatory cytokine that plays a central role in inflammation and acute graft rejection. Accumulating evidence indicates that IFN-γ can exert previously unexpected immunoregulatory activities. However, little is known about the role of IFN-γ secreted by Th1-like regulatory T cells in human kidney transplantation. To determine the function of IFN-γ in acute T cell-mediated renal allograft rejection (ACR), we examined serum cytokine expression profiles in ACR patients by human cytokine multiplex immunoassay and analyzed the cellular origins of IFN-γ in peripheral blood and renal allograft biopsies from ACR cases and controls by flow cytometry and immunohistochemistry, respectively. The results showed significant reduction in serum concentrations of Th1-inducing cytokines IL-12p70 and IFN-γ as well as Th2-related cytokine IL-4 in ACR patients compared with stable controls. However, levels of several Th1-, Th2- and Th17-related cytokines, such as IL-2, TNF-α, TNF-β, IL-12 (p40), IL-10, IL-15, IL-17, IL-21, and IL-23, as well as the frequencies of Th1 and Th17 cell, did not differ between ACR cases and stable controls. Moreover, we found the levels of IFN-γ were correlated with those of the anti-inflammatory factor, IL-1 receptor antagonist (IL-1Ra) in ACR. Notably, the Th1-like Treg cell-to-Foxp3 - Th1 cell ratio was significantly lower in ACR patients compared with that in stable controls. In graft biopsies from ACR patients, Treg cells and Th1-like Treg cells were less abundant than those without ACR. Our study indicates that IFN-γ secreted from Th1-like Treg cells negatively modulates ACR. Copyright © 2016 Elsevier GmbH. All rights reserved.

  9. IFN-Alpha receptor-1 upregulation in PBMC from HCV naïve patients carrying cc genotype. possible role of IFN-lambda.

    Directory of Open Access Journals (Sweden)

    Eleonora Lalle

    Full Text Available IL-28B gene polymorphisms predict better therapeutic response and spontaneous clearance of HCV. Moreover, higher expression of IFN-lambda has been reported in patients with the rs12979860 CC favourable genotype. The study aim was to establish possible relationships between IL-28B rs12979860 genotypes and expression of IFN-alpha receptor-1 (IFNAR-1 in naïve HCV patients, and to explore the possible role of IFN-lambda.IFNAR-1 mRNA levels were measured in PBMC from naïve patients with chronic hepatitis C with different IL-28 genotypes. The ability of IFN-lambda to up-regulate the expression of IFNAR-1 was established in PBMC from healthy donors carrying different IL-28B genotypes.Lower IFNAR-1 mRNA levels were observed in PBMC from HCV-infected naïve patients as compared to healthy donors. In healthy donors, IFNAR-1 mRNA levels were independent from IL-28B genotype, while in HCV patients, an increasing gradient was observed in TT vs CT vs CC carriers. In the latter group, a direct correlation between IFNAR-1 and endogenous IL-28B expression was observed. Moreover, IFN-lambda up-regulated IFNAR-1 expression in normal PBMC in a time-and dose-dependent manner, with a more effective response in CC vs TT carriers.Endogenous levels of IFN-lambda may be responsible for partial restoration of IFNAR-1 expression in HCV patients with favourable IL-28 genotype. This, in turn, may confer to CC carriers a response advantage to either endogenous or exogenous IFN-alpha, representing the biological basis for the observed association between CC genotype and favourable outcome of either natural infection (clearance vs chronicization or IFN therapy.

  10. Biodistribution analysis of 125I-albumin-IFN-alpha2b fusion protein in rats

    International Nuclear Information System (INIS)

    Zhou Yaoyuan; Zhang Rongjun; Cai Gangming; Gu Xiaobo; Jiang Mengjun; Zhang Bo; Yang Min; Cao Guoxian; Yang Jianliang

    2009-01-01

    125 I-albumin-IFN-alpha2b was prepared with the methods of Ch-T and purified with PD-10 column. The radiochemical purity was measured with TCA (trichloroacetic acid) precipitation. The antiviral activities of 125 I-albumin-IFN-alpha2b and albumin-IFN-alpha2b were compared with WISH/VSV system in vitro. SD rats were injected with 125 I-albumin-IFN-alpha2b subcutaneously and sacrificed at 0.5, 2, 6, 24, 48, 90, 180 and 300 h post-injection. Selected organs were dissected, weighed and their radioactivity was measured using γ-counter. The accumulated radioactivity in the tissues was calculated in terms of percentage of injected dose per gram organ (%ID·g -1 ). The labeling yield was 82.72%. The radiochemical purity of 125 I-albumin-IFN-alpha2b was 95.53%, and its radioactivity was 0.26 MBq/μg. The antiviral bioactivities of albumin-IFN-alpha2b and 125 I-albumin- IFN-alpha2b did not change. Biodistribution analysis of 125 I-albumin-IFN-alpha2b in rats showed that concentrated 125 I-albumin-IFN-alpha2b in blood reached maximum at 6 h post injection, and eliminated slowly. No specific accumulation was seen in other tissues. 125 I-albumin-IFN-alpha2b could maintain in peripheral blood for a long time and it meant albumin-IFN-alpha2b would be an effective long-term interferon. (authors)

  11. 45 CFR 1170.13 - Illustrative examples.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Illustrative examples. 1170.13 Section 1170.13... ASSISTED PROGRAMS OR ACTIVITIES Discrimination Prohibited § 1170.13 Illustrative examples. (a) The following examples will illustrate the application of the foregoing provisions to some of the activities...

  12. Resolution of PMA-Induced Skin Inflammation Involves Interaction of IFN-γ and ALOX15

    Directory of Open Access Journals (Sweden)

    Guojun Zhang

    2013-01-01

    Full Text Available Background. Acute inflammation and its timely resolution play important roles in the body’s responses to the environmental stimulation. Although IFN-γ is well known for the induction of inflammation, its role in the inflammation resolution is still poorly understood. Methodology and Principal Findings. In this study, we investigated the function of interferon gamma (IFN-γ during the resolution of PMA-induced skin inflammation in vivo. The results revealed that the expression levels of IL-6, TNF-α, and monocyte chemoattractant protein 1 (MCP-1 in skin decreased during the resolution stage of PMA-induced inflammation, while IFN-γ is still maintained at a relatively high level. Neutralization of endogenous IFN-γ led to accelerated reduction of epidermal thickness and decreased epithelial cell proliferation. Similarly, decreased infiltration of inflammatory cells (Gr1+ or CD11b+ cells and a significant reduction of proinflammatory cytokines were also observed upon the blockade of IFN-γ. Furthermore, neutralization of IFN-γ boosted ALOX15 expression of the skin during inflammation resolution. In accordance, application of lipoxin A4 (LXA4, a product of ALOX15 obtained a proresolution effect similar to neutralization of IFN-γ. These results demonstrated that through upregulating ALOX15-LXA4 pathway, blockage of IFN-γ can promote the resolution of PMA-induced skin inflammation.

  13. Pharmacogenomics of IFN-beta in multiple sclerosis: towards a personalized medicine approach

    NARCIS (Netherlands)

    Vosslamber, Saskia; van Baarsen, Lisa G. M.; Verweij, Cornelis L.

    2009-01-01

    Multiple sclerosis (MS) is an inflammatory disease of the CNS. The clinical presentation of MS is heterogeneous. Interferons (IFNs) were the first agents to show clinical efficacy in the treatment of MS and prolonged treatment is still the best available therapy. Although IFN treatment ameliorates

  14. Stat1-independent regulation of gene expression in response to IFN

    Science.gov (United States)

    Ramana, Chilakamarti V.; Gil, M. Pilar; Han, Yulong; Ransohoff, Richard M.; Schreiber, Robert D.; Stark, George R.

    2001-01-01

    Although Stat1 is essential for cells to respond fully to IFN-γ, there is substantial evidence that, in the absence of Stat1, IFN-γ can still regulate the expression of some genes, induce an antiviral state and affect cell growth. We have now identified many genes that are regulated by IFN-γ in serum-starved Stat1-null mouse fibroblasts. The proteins induced by IFN-γ in Stat1-null cells can account for the substantial biological responses that remain. Some genes are induced in both wild-type and Stat1-null cells and thus are truly Stat1-independent. Others are subject to more complex regulation in response to IFN-γ, repressed by Stat1 in wild-type cells and activated in Stat1-null cells. Many genes induced by IFN-γ in Stat1-null fibroblasts also are induced by platelet-derived growth factor in wild-type cells and thus are likely to be involved in cell proliferation. In mouse cells expressing the docking site mutant Y440F of human IFN-γ receptor subunit 1, the mouse Stat1 is not phosphorylated in response to human IFN-γ, but c-myc and c-jun are still induced, showing that the Stat1 docking site is not required for Stat1-independent signaling. PMID:11390994

  15. The cost of successful antiviral therapy in hepatitis C patients: a comparison of IFN-free versus IFN-based regimens at an individual patient level in Australia

    Directory of Open Access Journals (Sweden)

    Lee AS

    2017-10-01

    Full Text Available Allister Sebastian Lee,1 Mieke L van Driel,2 Darrell HG Crawford3,4 1Faculty of Medicine, 2Primary Care Clinical Unit, Faculty of Medicine, 3School of Clinical Medicine, Faculty of Medicine, University of Queensland, 4Gallipoli Medical Research Foundation, Greenslopes Private Hospital, Brisbane, Australia Background: Chronic hepatitis C remains a major global health burden with serious long-term consequences if left untreated. Recently the treatment standard of care has shifted to new interferon (IFN-free drug regimens, which have been shown to be safe and effective. The aim of our study was to assess and compare medical resource utilization and costs of successfully treating patients with IFN-based and IFN-free therapies in Australia. Methods: We performed a retrospective chart review of 30 HCV-infected patients successfully treated with IFN-based therapy between 2013 and 2015. We also generated a model for a virtual group of 100 genotype 1 (GT1 and 100 genotype 3 (GT3 patients treated with IFN-free therapy derived from national guidelines and clinical trial data. Results: In comparison to virtual patients receiving IFN-free therapy, our IFN-treated patients on average had distinctively more liver clinic visits and blood tests. However, mean total cost per patient was $19,164 and $85,300 (AUD more for GT1 and GT3 patients receiving IFN-free therapy, respectively. This difference was largely accounted for by higher antiviral drug costs. Of our 30 patients treated with IFN, total mean cost per patient during the study period was $33,595. Conclusion: Resource utilization is lower with IFN-free treatment, which reflects the reduced need for patient monitoring and improved side-effect profile of these new drugs. However, total costs are still largely dominated by antiviral drug costs, representing a huge burden on national budgets. Our insight into resource utilization and costs associated with both types of treatment can serve as a reference for

  16. Characterization of the bovine type I IFN locus: rearrangements, expansions, and novel subfamilies

    Directory of Open Access Journals (Sweden)

    Walker Angela M

    2009-04-01

    Full Text Available Abstract Background The Type I interferons (IFN have major roles in the innate immune response to viruses, a function that is believed to have led to expansion in the number and complexity of their genes, although these genes have remained confined to single chromosomal region in all mammals so far examined. IFNB and IFNE define the limits of the locus, with all other Type I IFN genes except IFNK distributed between these boundaries, strongly suggesting that the locus has broadened as IFN genes duplicated and then evolved into a series of distinct families. Results The Type I IFN locus in Bos taurus has undergone significant rearrangement and expansion compared to mouse and human, however, with the constituent genes separated into two sub-loci separated by >700 kb. The IFNW family is greatly expanded, comprising 24 potentially functional genes and at least 8 pseudogenes. The IFNB (n = 6, represented in human and mouse by one copy, are also present as multiple copies in Bos taurus. The IFNT, which encode a non-virally inducible, ruminant-specific IFN secreted by the pre-implantation conceptus, are represented by three genes and two pseudogenes. The latter have sequences intermediate between IFNT and IFNW. A new Type I IFN family (IFNX of four members, one of which is a pseudogene, appears to have diverged from the IFNA lineage at least 83 million years ago, but is absent in all other sequenced genomes with the possible exception of the horse, a non-ruminant herbivore. Conclusion In summary, we have provided the first comprehensive annotation of the Type I IFN locus in Bos taurus, thereby providing an insight into the functional evolution of the Type I IFN in ruminants. The diversity and global spread of the ruminant species may have required an expansion of the Type I IFN locus and its constituent genes to provide broad anti-viral protection required for foraging and foregut fermentation.

  17. SH2 modified STAT1 induces HLA-I expression and improves IFN-γ signaling in IFN-α resistant HCV replicon cells.

    Directory of Open Access Journals (Sweden)

    Bret Poat

    2010-09-01

    Full Text Available We have developed multiple stable cell lines containing subgenomic HCV RNA that are resistant to treatment with interferon alpha (IFN-α. Characterization of these IFN-α resistant replicon cells showed defects in the phosphorylation and nuclear translocation of STAT1 and STAT2 proteins due to a defective Jak-STAT pathway.In this study, we have developed an alternative strategy to overcome interferon resistance in a cell culture model by improving intracellular STAT1 signaling. An engineered STAT1-CC molecule with double cysteine substitutions in the Src-homology 2 (SH2 domains of STAT1 (at Ala-656 and Asn-658 efficiently phosphorylates and translocates to the nucleus of IFN-resistant cells in an IFN-γ dependent manner. Transfection of a plasmid clone containing STAT1-CC significantly activated the GAS promoter compared to wild type STAT1 and STAT3. The activity of the engineered STAT1-CC is dependent upon the phosphorylation of tyrosine residue 701, since the construct with a substituted phenylalanine residue at position 701 (STAT1-CC-Y701F failed to activate GAS promoter in the replicon cells. Intracellular expression of STAT1-CC protein showed phosphorylation and nuclear translocation in the resistant cell line after IFN-γ treatment. Transient transfection of STAT1-CC plasmid clone into an interferon resistant cell line resulted in inhibition of viral replication and viral clearance in an IFN-γ dependent manner. Furthermore, the resistant replicon cells transfected with STAT1-CC constructs significantly up regulated surface HLA-1 expression when compared to the wild type and Y to F mutant controls.These results suggest that modification of the SH2 domain of the STAT1 molecule allows for improved IFN-γ signaling through increased STAT1 phosphorylation, nuclear translocation, HLA-1 surface expression, and prolonged interferon antiviral gene activation.

  18. IFN-gamma-induced chemokines synergize with pertussis toxin to promote T cell entry to the central nervous system

    DEFF Research Database (Denmark)

    Millward, Jason M; Caruso, Maria; Campbell, Iain L

    2007-01-01

    Inflammation of the CNS, which occurs during multiple sclerosis and experimental autoimmune encephalomyelitis, is characterized by increased levels of IFN-gamma, a cytokine not normally expressed in the CNS. To investigate the role of IFN-gamma in CNS, we used intrathecal injection of a replication......-defective adenovirus encoding murine IFN-gamma (AdIFNgamma) to IFN-gamma-deficient (GKO) mice. This method resulted in stable, long-lived expression of IFN-gamma that could be detected in cerebrospinal fluid using ELISA and Luminex bead immunoassay. IFN-gamma induced expression in the CNS of message and protein...... was predominantly localized to meningeal and ependymal cells, and was also seen in astrocytes and microglia. IFN-gamma-induced chemokine expression did not lead to inflammation. However, when pertussis toxin was given i.p. to mice infected with the IFN-gamma vector, there was a dramatic increase in the number of T...

  19. Ribavirin enhances IFN-α signalling and MxA expression: a novel immune modulation mechanism during treatment of HCV.

    Directory of Open Access Journals (Sweden)

    Nigel J Stevenson

    Full Text Available The nucleoside analogue Ribavirin significantly increases patient response to IFN-α treatment of HCV, by directly inhibiting viral replication. Recent studies indicate that Ribavirin also regulates immunity and we propose that Ribavirin enhances specific interferon sensitive gene (ISG expression by amplifying the IFN-α-JAK/STAT pathway. We found that IFN-α-induced STAT1 and STAT3 phosphorylation was increased in hepatocytes co-treated with Ribavirin and IFN-α, compared to IFN-α alone. Ribavirin specifically enhanced IFN-α induced mRNA and protein of the anti-viral mediator MxA, which co-localised with HCV core protein. These novel findings indicate for the first time that Ribavirin, in addition to its viral incorporation, also enhances IFN-α-JAK/STAT signalling, leading to a novel MxA-mediated immuno-modulatory mechanism that may enhance IFN-α anti-viral activity against HCV.

  20. ISG15 Inhibits IFN-α-Resistant Liver Cancer Cell Growth

    Directory of Open Access Journals (Sweden)

    Xin-xing Wan

    2013-01-01

    Full Text Available Hepatocellular carcinoma (HCC is one of the most prevalent tumors worldwide. Interferon-α (IFN-α has been widely used in the treatment of HCC, but patients eventually develop resistance. ISG15 ubiquitin-like modifier (ISG15 is a ubiquitin-like protein transcriptionally regulated by IFN-α which shows antivirus and antitumor activities. However, the exact role of ISG15 is unknown. In the present study, we showed that IFN-α significantly induced ISG15 expression but failed to induce HepG2 cell apoptosis, whereas transient overexpression of ISG15 dramatically increased HepG2 cell apoptosis. ISG15 overexpression increased overall protein ubiquitination, which was not observed in cells with IFN-α-induced ISG15 expression, suggesting that IFN-α treatment not only induced the expression of ISG15 but also inhibited ISG15-mediated ubiquitination. The tumor suppressor p53 and p21 proteins are the key regulators of cell survival and death in response to stress signals such as DNA damage. We showed that p53 or p21 is only up regulated in HepG2 cells ectopically expressing ISG15, but not in the presence of IFN-α-induced ISG15. Our results suggest that ISG15 overexpression could be developed into a powerful gene-therapeutic tool for treating IFN-α-resistant HCC.

  1. Post-transcriptional regulation of macrophage ABCA1, an early response gene to IFN

    International Nuclear Information System (INIS)

    Alfaro Leon, Martha Leticia; Evans, Glenn F.; Farmen, Mark W.; Zuckerman, Steven H.

    2005-01-01

    Interferon-γ (IFN-γ) down-regulates receptors associated with reverse cholesterol transport including ABCA1. In the present study, the kinetics and mechanism of ABCA1 down-regulation were determined in mouse peritoneal macrophages. IFN-γ decreased ABCA1 mRNA 1 h following IFN-γ addition and was maximally reduced by 3 h. Down-regulation was protein synthesis dependent and involved post-transcriptional processes. ABCA1 message had a T 1/2 of 115 min in actinomycin treated cells that was reduced to a T 1/2 of 37 min by IFN-γ. The decrease in message stability was also associated with a rapid loss of ABCA1 protein, significant 3 h following IFN-γ addition. The kinetics of ABCA1 message and protein decrease was consistent with the early IFN-γ-induced changes in Stat1 phosphorylation and nuclear translocation observed in these cells. Therefore, ABCA1 can be considered as an early response gene to macrophage activation by IFN-γ with down-regulation occurring by message destabilization

  2. Interferon lambda (IFN-λ) efficiently blocks norovirus transmission in a mouse model.

    Science.gov (United States)

    Rocha-Pereira, Joana; Jacobs, Sophie; Noppen, Sam; Verbeken, Eric; Michiels, Thomas; Neyts, Johan

    2018-01-01

    Human noroviruses are highly efficient in person to person transmission thus associated with explosive outbreaks of acute gastroenteritis. Outbreak control is limited to disinfection and isolation measures. Strategies to control the spread of noroviruses should be developed and models to study norovirus transmission will greatly facilitate this. Here, a mouse-to-mouse transmission model, in which mice develop acute murine norovirus (MNV)-induced diarrhea, was used to explore the role of interferon lambda (IFN-λ) in the control of a norovirus infection. Sentinel AG129 mice [deficient in IFN-α/β and IFN-γ receptors] that were co-housed with MNV-infected mice shedding high amounts of virus in their stool, developed a MNV-infection with associated diarrhea. Inoculation of such sentinel mice with an IFN-λ expression plasmid resulted in the production of circulating IFN-λ and upregulation of the expression of IFN-stimulated genes (ISGs) of the gut. Injection of the IFN-λ-expressing plasmid to sentinels prevents MNV-induced disease upon exposure to MNV-infected mice, as well as MNV replication in the small intestine, the associated signs of inflammation and the mounting of a specific IgG-based immune response. This demonstrates that IFN-λ can alone mediate protection against transmission of norovirus. The development of a simple delivery method for IFN-λ could be explored as a strategy to control norovirus outbreaks and protect vulnerable populations such as the elderly and immunocompromised. Copyright © 2017. Published by Elsevier B.V.

  3. Thermostability of IFN-γ and IP-10 release assays for latent infection with Mycobacterium tuberculosis

    DEFF Research Database (Denmark)

    Blauenfeldt, Thomas; Wagner, Dirk; Aabye, Martine Grosos

    2016-01-01

    accuracy of IP-10 release assay and IGRAs. RESULTS: We included 65 patients with confirmed pulmonary tuberculosis and 160 healthy controls from 6 European centres collaborating in the TBnet. In patients, IP-10 responses increased 1.07 (IQR 0.90-1.36) fold and IFN-γ responses decreased 0.88 (IQR 0......INTRODUCTION: Interferon-γ (IFN-γ) inducible protein 10kD (IP-10) and IFN-γ release assays (IGRAs) are immunodiagnostic tests aiming to identify the presence of specific cellular immune responses, interpreted as markers for latent infection with Mycobacterium tuberculosis. Incubation at higher...

  4. "Illustrating the Machinery of Life": Viruses

    Science.gov (United States)

    Goodsell, David S.

    2012-01-01

    Data from electron microscopy, X-ray crystallography, and biophysical analysis are used to create illustrations of viruses in their cellular context. This report describes the scientific data and artistic methods used to create three illustrations: a depiction of the poliovirus lifecycle, budding of influenza virus from a cell surface, and a…

  5. 48 CFR 9904.401-60 - Illustrations.

    Science.gov (United States)

    2010-10-01

    ... Section 9904.401-60 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.401-60 Illustrations. (a) The following examples are illustrative...

  6. 48 CFR 9904.404-60 - Illustrations.

    Science.gov (United States)

    2010-10-01

    ... Section 9904.404-60 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.404-60 Illustrations. (a) Illustrations of costs which must be...

  7. 48 CFR 9904.409-60 - Illustrations.

    Science.gov (United States)

    2010-10-01

    ... Section 9904.409-60 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.409-60 Illustrations. The following examples are illustrative of...

  8. 48 CFR 9904.402-60 - Illustrations.

    Science.gov (United States)

    2010-10-01

    ... Section 9904.402-60 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.402-60 Illustrations. (a) Illustrations of costs which are incurred...

  9. Mullerian Inhibiting Substances (MIS) Augments IFN-gamma Mediated Inhibition of Breast Cancer Cell Growth

    National Research Council Canada - National Science Library

    Gupta, Vandana

    2006-01-01

    MIS is a member of the TGF family. The purpose of this study is to test the hypothesis that MIS and IFN-gamma might be more effective in the inhibition of breast cancer cell growth than either agent alone...

  10. Gliovascular and cytokine interactions modulate brain endothelial barrier in vitro.

    Science.gov (United States)

    Chaitanya, Ganta V; Cromer, Walter E; Wells, Shannon R; Jennings, Merilyn H; Couraud, P Olivier; Romero, Ignacio A; Weksler, Babette; Erdreich-Epstein, Anat; Mathis, J Michael; Minagar, Alireza; Alexander, J Steven

    2011-11-23

    The glio-vascular unit (G-unit) plays a prominent role in maintaining homeostasis of the blood-brain barrier (BBB) and disturbances in cells forming this unit may seriously dysregulate BBB. The direct and indirect effects of cytokines on cellular components of the BBB are not yet unclear. The present study compares the effects of cytokines and cytokine-treated astrocytes on brain endothelial barrier. 3-dimensional transwell co-cultures of brain endothelium and related-barrier forming cells with astrocytes were used to investigate gliovascular barrier responses to cytokines during pathological stresses. Gliovascular barrier was measured using trans-endothelial electrical resistance (TEER), a sensitive index of in vitro barrier integrity. We found that neither TNF-α, IL-1β or IFN-γ directly reduced barrier in human or mouse brain endothelial cells or ECV-304 barrier (independent of cell viability/metabolism), but found that astrocyte exposure to cytokines in co-culture significantly reduced endothelial (and ECV-304) barrier. These results indicate that the barrier established by human and mouse brain endothelial cells (and other cells) may respond positively to cytokines alone, but that during pathological conditions, cytokines dysregulate the barrier forming cells indirectly through astrocyte activation involving reorganization of junctions, matrix, focal adhesion or release of barrier modulating factors (e.g. oxidants, MMPs). © 2011 Chaitanya et al; licensee BioMed Central Ltd.

  11. White adipose tissue IFN-γ expression and signalling along the progression of rodent cancer cachexia.

    Science.gov (United States)

    Yamashita, Alex Shimura; das Neves, Rodrigo Xavier; Rosa-Neto, José Cesar; Lira, Fábio Dos Santos; Batista, Miguel Luís; Alcantara, Paulo Sérgio; Otoch, José Pinhata; Seelaender, Marília

    2017-01-01

    Cachexia is associated with increased morbidity and mortality in cancer. The White adipose tissue (WAT) synthesizes and releases several pro-inflammatory cytokines that play a role in cancer cachexia-related systemic inflammation. IFN-γ is a pleiotropic cytokine that regulates several immune and metabolic functions. To assess whether IFN-γ signalling in different WAT pads is modified along cancer-cachexia progression, we evaluated IFN-γ receptors expression (IFNGR1 and IFNGR2) and IFN-γ protein expression in a rodent model of cachexia (7, 10, and 14days after tumour implantation). IFN-γ protein expression was heterogeneously modulated in WAT, with increases in the mesenteric pad and decreased levels in the retroperitoneal depot along cachexia progression. Ifngr1 was up-regulated 7days after tumour cell injection in mesenteric and epididymal WAT, but the retroperitoneal depot showed reduced Ifngr1 gene expression. Ifngr2 gene expression was increased 7 and 14days after tumour inoculation in mesenteric WAT. The results provide evidence that changes in IFN-γ expression and signalling may be perceived at stages preceding refractory cachexia, and therefore, might be employed as a means to assess the early stage of the syndrome. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Intracellular fate of recombinant human interferon-gamma (rIFN) in U937 cells

    International Nuclear Information System (INIS)

    Finbloom, D.S.

    1986-01-01

    After IFN binds to specific receptors on macrophages, both modulation of surface molecules and induction of microbicidal and tumoricidal activity occurs 24-48 hr later. Since the intracellular events required to insure these responses are poorly defined, the fate of radiolabeled rIFN in U937 cells was examined. Endocytosis was determined by exposing cells to pH 2.5 to allow rIFN to dissociate leaving only intracellular ligand. Degradation was measured as trichloroacetic acid soluble radioactivity in the media. Of the 4-5000 molecules of rIFN that specifically and saturably (at 300 U/ml) bound at 4 0 C, 40% dissociated during 15-30 min after cells were warmed to 37 0 C. However, if cells were continuously exposed at 37 0 C to lower levels of rIFN (60-100 U/ml), 30-40% of those molecules capable of binding to the cell at that concentration were internalized. Furthermore, 60% of the molecules were degraded during 3-4 hr of additional culture. Since exposure of cells to chloroquine and monensin resulted in only partial inhibition of degradation (75% and 43%, respectively), there may also be degradation within endosomes or on the cell following binding to its receptor. Soon thereafter, degradation products are measurable. Since many biological responses require prolonged incubation with the molecule, intracellular processing of IFN may be important for expression of these effects

  13. Immune cell-poor melanomas benefit from PD-1 blockade after targeted type I IFN activation.

    Science.gov (United States)

    Bald, Tobias; Landsberg, Jennifer; Lopez-Ramos, Dorys; Renn, Marcel; Glodde, Nicole; Jansen, Philipp; Gaffal, Evelyn; Steitz, Julia; Tolba, Rene; Kalinke, Ulrich; Limmer, Andreas; Jönsson, Göran; Hölzel, Michael; Tüting, Thomas

    2014-06-01

    Infiltration of human melanomas with cytotoxic immune cells correlates with spontaneous type I IFN activation and a favorable prognosis. Therapeutic blockade of immune-inhibitory receptors in patients with preexisting lymphocytic infiltrates prolongs survival, but new complementary strategies are needed to activate cellular antitumor immunity in immune cell-poor melanomas. Here, we show that primary melanomas in Hgf-Cdk4(R24C) mice, which imitate human immune cell-poor melanomas with a poor outcome, escape IFN-induced immune surveillance and editing. Peritumoral injections of immunostimulatory RNA initiated a cytotoxic inflammatory response in the tumor microenvironment and significantly impaired tumor growth. This critically required the coordinated induction of type I IFN responses by dendritic, myeloid, natural killer, and T cells. Importantly, antibody-mediated blockade of the IFN-induced immune-inhibitory interaction between PD-L1 and PD-1 receptors further prolonged the survival. These results highlight important interconnections between type I IFNs and immune-inhibitory receptors in melanoma pathogenesis, which serve as targets for combination immunotherapies. Using a genetically engineered mouse melanoma model, we demonstrate that targeted activation of the type I IFN system with immunostimulatory RNA in combination with blockade of immune-inhibitory receptors is a rational strategy to expose immune cell-poor tumors to cellular immune surveillance. ©2014 American Association for Cancer Research.

  14. Apoptotic-cell-derived membrane microparticles and IFN-α induce an inflammatory immune response.

    Science.gov (United States)

    Niessen, Anna; Heyder, Petra; Krienke, Stefan; Blank, Norbert; Tykocinski, Lars-Oliver; Lorenz, Hanns-Martin; Schiller, Martin

    2015-07-15

    A dysregulation in the clearance of apoptotic material is considered a major pathogenetic factor for the emergence of autoimmune diseases. Apoptotic-cell-derived membrane microparticles (AdMPs), which are released from the cell surface during apoptosis, have been implicated in the pathogenesis of autoimmunity. Also of importance are cytokines, such as interferon-α (IFN-α), which is known to be a major player in patients with systemic lupus erythematosus (SLE). This study investigates the combined effect of AdMPs and IFN-α on professional phagocytes. In the presence of IFN-α, phagocytosis of AdMPs by human monocytes was significantly increased in a dose-dependent manner. The combination of AdMPs and raised IFN-α concentrations resulted in an increase in the secretion of pro-inflammatory cytokines and an upregulation of surface molecule expression involved in antigen uptake. In addition, macrophage polarisation was shifted towards a more inflammatory type of cell. The synergism between IFN-α and AdMPs seemed to be mediated by an upregulation of phosphorylated STAT1. Our results indicate that IFN-α, together with AdMPs, amplify the initiation and maintenance of inflammation. This mechanism might especially play a crucial role in disorders with a defective clearance of apoptotic material. © 2015. Published by The Company of Biologists Ltd.

  15. Construction of recombinant plasmid pIRESEgr-IFN γ and its expression in Lewis lung carcinoma induced by irradiation

    International Nuclear Information System (INIS)

    Yang Wei; Li Xiuyi; Gong Shouliang; Sun Ting; Gong Pingsheng

    2007-01-01

    Objective: To construct the recombinant plasmid pIRESEgr-IFN γ and detect its expression in Lewis lung carcinoma induced by irradiation in vitro. Methods: The recombinant plasmid pIRESEgr-IFN γ containing Egr-1 promoter and IFN γ gene was constructed with gene recombinant technique. The plasmid was transferred into Lewis lung carcinoma by liposome in vitro. The correlations of dose- and time-effects in the expression of IFN γ gene induced by X-ray were detected by ELISA. Results: The identification with enzymes proved that Egr-1 promoter and IFN γ gene were inserted into vector pIRESlneo correctly. After X-ray irradiation with different doses, the expression of IFN γ in the supernatant of Lewis lung carcinoma transfected by pIRESEgr-IFN γ was significantly higher than that in 0 Gy group (P<0.001). After 5 Gy X-ray irradiation, the expression of IFN γ was the highest, being 4.39 times as much as that in 0 Gy group. The expression of IFN γ in the supernatant increased after 5 Gy X-ray irradiation, being 6.27 times as much as that in 0 h group 36 h after irradiation. Conclusion: The recombinant plasmid pIRESEgr-IFN γ is constructed successfully, and it has the property of enhancing the expression of IFN γ gene induced by irradiation. (authors)

  16. Targeted Recombinant Fusion Proteins of IFN gamma and Mimetic IFN gamma with PDGF beta R Bicyclic Peptide Inhibits Liver Fibrogenesis In Vivo

    NARCIS (Netherlands)

    Bansal, Ruchi; Prakash, Jai; De Ruiter, Marieke; Poelstra, Klaas

    2014-01-01

    Hepatic stellate cells (HSCs), following transdifferentiation to myofibroblasts plays a key role in liver fibrosis. Therefore, attempts to attenuate this myofibroblastic phenotype would be a promising therapeutic approach. Interferon gamma (IFN gamma) is a potent anti-fibrotic cytokine, but its

  17. Unique nonstructural proteins of Pneumonia Virus of Mice (PVM) promote degradation of interferon (IFN) pathway components and IFN-stimulated gene proteins.

    Science.gov (United States)

    Dhar, Jayeeta; Barik, Sailen

    2016-12-01

    Pneumonia Virus of Mice (PVM) is the only virus that shares the Pneumovirus genus of the Paramyxoviridae family with Respiratory Syncytial Virus (RSV). A deadly mouse pathogen, PVM has the potential to serve as a robust animal model of RSV infection, since human RSV does not fully replicate the human pathology in mice. Like RSV, PVM also encodes two nonstructural proteins that have been implicated to suppress the IFN pathway, but surprisingly, they exhibit no sequence similarity with their RSV equivalents. The molecular mechanism of PVM NS function, therefore, remains unknown. Here, we show that recombinant PVM NS proteins degrade the mouse counterparts of the IFN pathway components. Proteasomal degradation appears to be mediated by ubiquitination promoted by PVM NS proteins. Interestingly, NS proteins of PVM lowered the levels of several ISG (IFN-stimulated gene) proteins as well. These results provide a molecular foundation for the mechanisms by which PVM efficiently subverts the IFN response of the murine cell. They also reveal that in spite of their high sequence dissimilarity, the two pneumoviral NS proteins are functionally and mechanistically similar.

  18. Illustrations of vacuum polarization by solitons

    International Nuclear Information System (INIS)

    MacKenzie, R.; Wilczek, F.

    1984-01-01

    The value and limitations of the adiabatic method for calculating induced charges are discussed in a general way and illustrated in some simple models in 1+1 dimensions. The relevance of the size of solitons is emphasized

  19. Illustrations in Text: A Retentional Role.

    Science.gov (United States)

    Duchastel, Philippe C.

    1981-01-01

    Describes the results of a study of the retentional role of illustrations in a text and their effect on enhancing long-term memory with 15-year-old secondary school students. Seven references are listed. (CHC)

  20. Cell-specific type I IFN signatures in autoimmunity and viral infection: what makes the difference?

    Directory of Open Access Journals (Sweden)

    Chieko Kyogoku

    Full Text Available Gene expression profiling of peripheral blood mononuclear cells (PBMCs has revealed a crucial role for type I interferon (IFN in the pathogenesis of systemic lupus erythematosus (SLE. However, it is unclear how particular leucocyte subsets contribute to the overall type I IFN signature of PBMCs and whole blood samples.Furthermore, a detailed analysis describing the differences in the IFN signature in autoimmune diseases from that observed after viral infection has not been performed to date. Therefore, in this study, the transcriptional responses in peripheral T helper cells (CD4(+ and monocyte subsets (CD16(- inflammatory and CD16(+ resident monocytes isolated from patients with SLE, healthy donors (ND immunised with the yellow fever vaccine YFV-17Dand untreated controls were compared by global gene expression profiling.It was striking that all of the transcripts that were regulated in response to viral exposure were also found to be differentially regulated in SLE, albeit with markedly lower fold-change values. In addition to this common IFN signature, a pathogenic IFN-associated gene signature was detected in the CD4(+ T cells and monocytes from the lupus patients. IL-10, IL-9 and IL-15-mediated JAK/STAT signalling was shown to be involved in the pathological amplification of IFN responses observed in SLE. Type I IFN signatures identified were successfully applied for the monitoring of interferon responses in PBMCs of an independent cohort of SLE patients and virus-infected individuals. Moreover, these cell-type specific gene signatures allowed a correct classification of PBMCs independent from their heterogenic cellular composition. In conclusion, our data show for the first time that monocytes and CD4 cells are sensitive biosensors to monitor type I interferon response signatures in autoimmunity and viral infection and how these transriptional responses are modulated in a cell- and disease-specific manner.

  1. IFN-β: A Contentious Player in Host–Pathogen Interaction in Tuberculosis

    Science.gov (United States)

    Sabir, Naveed; Hussain, Tariq; Shah, Syed Zahid Ali; Zhao, Deming; Zhou, Xiangmei

    2017-01-01

    Tuberculosis (TB) is a major health threat to the human population worldwide. The etiology of the disease is Mycobacterium tuberculosis (Mtb), a highly successful intracellular pathogen. It has the ability to manipulate the host immune response and to make the intracellular environment suitable for its survival. Many studies have addressed the interactions between the bacteria and the host immune cells as involving many immune mediators and other cellular players. Interferon-β (IFN-β) signaling is crucial for inducing the host innate immune response and it is an important determinant in the fate of mycobacterial infection. The role of IFN-β in protection against viral infections is well established and has been studied for decades, but its role in mycobacterial infections remains much more complicated and debatable. The involvement of IFN-β in immune evasion mechanisms adopted by Mtb has been an important area of investigation in recent years. These advances have widened our understanding of the pro-bacterial role of IFN-β in host–pathogen interactions. This pro-bacterial activity of IFN-β appears to be correlated with its anti-inflammatory characteristics, primarily by antagonizing the production and function of interleukin 1β (IL-1β) and interleukin 18 (IL-18) through increased interleukin 10 (IL-10) production and by inhibiting the nucleotide-binding domain and leucine-rich repeat protein-3 (NLRP3) inflammasome. Furthermore, it also fails to provoke a proper T helper 1 (Th1) response and reduces the expression of major histocompatibility complex II (MHC-II) and interferon-γ receptors (IFNGRs). Here we will review some studies to provide a paradigm for the induction, regulation, and role of IFN-β in mycobacterial infection. Indeed, recent studies suggest that IFN-β plays a role in Mtb survival in host cells and its downregulation may be a useful therapeutic strategy to control Mtb infection. PMID:29258190

  2. The Scaffolding Protein IQGAP1 Interacts with NLRC3 and Inhibits Type I IFN Production.

    Science.gov (United States)

    Tocker, Aaron M; Durocher, Emily; Jacob, Kimberly D; Trieschman, Kate E; Talento, Suzanna M; Rechnitzer, Alma A; Roberts, David M; Davis, Beckley K

    2017-10-15

    Sensing of cytosolic nucleotides is a critical initial step in the elaboration of type I IFN. One of several upstream receptors, cyclic GMP-AMP synthase, binds to cytosolic DNA and generates dicyclic nucleotides that act as secondary messengers. These secondary messengers bind directly to stimulator of IFN genes (STING). STING recruits TNFR-associated NF-κB kinase-binding kinase 1 which acts as a critical node that allows for efficient activation of IFN regulatory factors to drive the antiviral transcriptome. NLRC3 is a recently characterized nucleotide-binding domain, leucine-rich repeat containing protein (NLR) that negatively regulates the type I IFN pathway by inhibiting subcellular redistribution and effective signaling of STING, thus blunting the transcription of type I IFNs. NLRC3 is predominantly expressed in lymphoid and myeloid cells. IQGAP1 was identified as a putative interacting partner of NLRC3 through yeast two-hybrid screening. In this article, we show that IQGAP1 associates with NLRC3 and can disrupt the NLRC3-STING interaction in the cytosol of human epithelial cells. Furthermore, knockdown of IQGAP1 in THP1 and HeLa cells causes significantly more IFN-β production in response to cytosolic nucleic acids. This result phenocopies NLRC3-deficient macrophages and fibroblasts and short hairpin RNA knockdown of NLRC3 in THP1 cells. Our findings suggest that IQGAP1 is a novel regulator of type I IFN production, possibly via interacting with NLRC3 in human monocytic and epithelial cells. Copyright © 2017 by The American Association of Immunologists, Inc.

  3. Evaluating pleural ADA, ADA2, IFN-γ and IGRA for diagnosing tuberculous pleurisy.

    Science.gov (United States)

    Keng, Li-Ta; Shu, Chin-Chung; Chen, Jason Yao-Ping; Liang, Sheng-Kai; Lin, Ching-Kai; Chang, Lih-Yu; Chang, Chia-Hao; Wang, Jann-Yuan; Yu, Chong-Jen; Lee, Li-Na

    2013-10-01

    Conventional methods for diagnosing tuberculous pleurisy (TB pleurisy) are either invasive or have a long turn-around-time. Performances of pleural adenosine deaminase (ADA), ADA2, interferon-gamma (IFN-γ), and interferon-gamma release assays (IGRA) as diagnostic tools for TB pleurisy were evaluated. Eighty-eight patients with lymphocyte-predominant pleural exudates between June 2010 and March 2011, including 31 with clinically diagnosed TB pleurisy, were prospectively studied. Pleural ADA and ADA2 activity were measured by colorimetric method, IFN-γ levels by enzyme-linked immuno-sorbent assay, and IGRA by enzyme-linked immuno-spot (T-SPOT.TB) assay. Pleural ADA, ADA2, and IFN-γ levels, but not the proportion of positive T-SPOT.TB assay, were significantly higher in patients with TB pleurisy than in those without TB pleurisy. The area under the receiver-operating-characteristic (ROC) curve was 0.920, 0.893, 0.875, and 0.544 for IFN-γ, ADA2, ADA, and T-SPOT.TB assay, respectively. The combination of ADA ≥ 40 IU/L and IFN-γ ≥ 75 pg/mL yielded a specificity of 100%. Pleural ADA, ADA2 and IFN-γ, but not T-SPOT.TB assay, are all sensitive and specific for TB pleurisy. In patients with lymphocyte-predominant pleural exudates, ADA ≥ 40 IU/L and IFN-γ ≥ 75 pg/mL in pleural effusion imply a very high probability of TB pleurisy. Copyright © 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  4. Barrier Systems

    NARCIS (Netherlands)

    Heteren, S. van

    2015-01-01

    Barrier-system dynamics are a function of antecedent topography and substrate lithology, Relative sea-level (RSL) changes, sediment availability and type, climate, vegetation type and cover, and various aero- and hydrodynamic processes during fair-weather conditions and extreme events. Global change

  5. Preparing Colorful Astronomical Images and Illustrations

    Science.gov (United States)

    Levay, Z. G.; Frattare, L. M.

    2001-12-01

    We present techniques for using mainstream graphics software, specifically Adobe Photoshop and Illustrator, for producing composite color images and illustrations from astronomical data. These techniques have been used with numerous images from the Hubble Space Telescope to produce printed and web-based news, education and public presentation products as well as illustrations for technical publication. While Photoshop is not intended for quantitative analysis of full dynamic range data (as are IRAF or IDL, for example), we have had much success applying Photoshop's numerous, versatile tools to work with scaled images, masks, text and graphics in multiple semi-transparent layers and channels. These features, along with its user-oriented, visual interface, provide convenient tools to produce high-quality, full-color images and graphics for printed and on-line publication and presentation.

  6. Collaborative study for the validation of an improved HPLC assay for recombinant IFN-alfa-2.

    Science.gov (United States)

    Jönsson, K H; Daas, A; Buchheit, K H; Terao, E

    2016-01-01

    The current European Pharmacopoeia (Ph. Eur.) texts for Interferon (IFN)-alfa-2 include a nonspecific photometric protein assay using albumin as calibrator and a highly variable cell-based assay for the potency determination of the protective effects. A request was expressed by the Official Medicines Control Laboratories (OMCLs) for improved methods for the batch control of recombinant interferon alfa-2 bulk and market surveillance testing of finished products, including those formulated with Human Serum Albumin (HSA). A HPLC method was developed at the Medical Products Agency (MPA, Sweden) for the testing of IFN-alfa-2 products. An initial collaborative study run under the Biological Standardisation Programme (BSP; study code BSP039) revealed the need for minor changes to improve linearity of the calibration curves, assay reproducibility and robustness. The goal of the collaborative study, coded BSP071, was to transfer and further validate this improved HPLC method. Ten laboratories participated in the study. Four marketed IFN-alfa-2 preparations (one containing HSA) together with the Ph. Eur. Chemical Reference Substance (CRS) for IFN-alfa-2a and IFN-alfa-2b, and in-house reference standards from two manufacturers were used for the quantitative assay. The modified method was successfully transferred to all laboratories despite local variation in equipment. The resolution between the main and the oxidised forms of IFN-alfa-2 was improved compared to the results from the BSP039 study. The improved method even allowed partial resolution of an extra peak after the principal peak. Symmetry of the main IFN peak was acceptable for all samples in all laboratories. Calibration curves established with the Ph. Eur. IFN-alfa-2a and IFN-alfa-2b CRSs showed excellent linearity with intercepts close to the origin and coefficients of determination greater than 0.9995. Assay repeatability, intermediate precision and reproducibility varied with the tested sample within acceptable

  7. Thyroid epithelial cell hyperplasia in IFN-gamma deficient NOD.H-2h4 mice.

    Science.gov (United States)

    Yu, Shiguang; Sharp, Gordon C; Braley-Mullen, Helen

    2006-01-01

    The role of inflammatory cells in thyroid epithelial cell (thyrocyte) hyperplasia is unknown. Here, we demonstrate that thyrocyte hyperplasia in IFN-gamma-/- NOD.H-2h4 mice has an autoimmune basis. After chronic exposure to increased dietary iodine, 60% of IFN-gamma-/- mice had severe thyrocyte hyperplasia with minimal or moderate lymphocyte infiltration, and thyroid dysfunction with reduced serum T4. All mice produced anti-thyroglobulin autoantibody. Some wild-type NOD.H-2h4 mice had isolated areas of thyrocyte hyperplasia with predominantly lymphocytic infiltration, whereas IL-4-/- and 50% of wild-type NOD.H-2h4 mice developed lymphocytic thyroiditis but no thyrocyte hyperplasia. Both thyroid infiltrating inflammatory cells and environmental factors (iodine) were required to induce thyrocyte hyperplasia. Splenocytes from IFN-gamma-/- mice with thyrocyte hyperplasia, but not splenocytes from naïve IFN-gamma-/- mice, induced hyperplasia in IFN-gamma-/- NOD.H-2h4.SCID mice. These results may provide clues for understanding the mechanisms underlying development of epithelial cell hyperplasia not only in thyroids but also in other tissues and organs.

  8. Nuclear export signal of PRRSV NSP1α is necessary for type I IFN inhibition

    International Nuclear Information System (INIS)

    Chen, Zhi; Liu, Shaoning; Sun, Wenbo; Chen, Lei; Yoo, Dongwan; Li, Feng; Ren, Sufang; Guo, Lihui; Cong, Xiaoyan; Li, Jun; Zhou, Shun; Wu, Jiaqiang

    2016-01-01

    The nonstructural protein 1α (NSP1α) of porcine reproductive and respiratory syndrome virus (PRRSV) is a nucleo-cytoplasmic protein that suppresses the production of type I interferon (IFN). In this study, we investigated the relationship between the subcellular distribution of NSP1α and its inhibition of type I IFN. NSP1α was found to contain the classical nuclear export signal (NES) and NSP1α nuclear export was CRM-1-mediated. NSP1α was shuttling between the nucleus and cytoplasm. We also showed that the nuclear export of NSP1α was necessary for its ability for type I IFN inhibition. NSP1α was also found to interact with CBP, which implies a possible mechanism of CBP degradation by NSP1α. Taken together, our results describe a novel mechanism of PRRSV NSP1α for type I IFN inhibition and suppression of the host innate antiviral response. - Highlights: •NSP1α contains the NES and NSP1α nuclear export was CRM-1-mediated. •NSP1α was shuttling between the nucleus and cytoplasm continuously. •The nuclear export of NSP1α was necessary for its ability for type I IFN inhibition. •NSP1α interacts with CBP, which implies the mechanism of CBP degradation by NSP1α.

  9. Impaired IFN-α-mediated signal in dendritic cells differentiates active from latent tuberculosis.

    Directory of Open Access Journals (Sweden)

    Stefania Parlato

    Full Text Available Individuals exposed to Mycobacterium tuberculosis (Mtb may be infected and remain for the entire life in this condition defined as latent tuberculosis infection (LTBI or develop active tuberculosis (TB. Among the multiple factors governing the outcome of the infection, dendritic cells (DCs play a major role in dictating antibacterial immunity. However, current knowledge on the role of the diverse components of human DCs in shaping specific T-cell response during Mtb infection is limited. In this study, we performed a comparative evaluation of peripheral blood circulating DC subsets as well as of monocyte-derived Interferon-α DCs (IFN-DCs from patients with active TB, subjects with LTBI and healthy donors (HD. The proportion of circulating myeloid BDCA3+ DCs (mDC2 and plasmacytoid CD123+ DCs (pDCs declined significantly in active TB patients compared to HD, whereas the same subsets displayed a remarkable activation in LTBI subjects. Simultaneously, the differentiation of IFN-DCs from active TB patients resulted profoundly impaired compared to those from LTBI and HD individuals. Importantly, the altered developmental trait of IFN-DCs from active TB patients was associated with down-modulation of IFN-linked genes, marked changes in molecular signaling conveying antigen (Ag presentation and full inability to induce Ag-specific T cell response. Thus, these data reveal an important role of IFN-α in determining the induction of Mtb-specific immunity.

  10. Nuclear export signal of PRRSV NSP1α is necessary for type I IFN inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Zhi [Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Sangyuan Road No. 8, Jinan 250100 (China); Liu, Shaoning [Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Sangyuan Road No. 8, Jinan 250100 (China); Shandong Institute of Veterinary Drug Quality Inspection, Shandong Key Laboratory for Quality Safety Monitoring and Risk Assessment of Animal Products, Huaicun Street No. 68, Jinan 250722, Shandong Province (China); Sun, Wenbo; Chen, Lei [Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Sangyuan Road No. 8, Jinan 250100 (China); Yoo, Dongwan [Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Ave, Urbana, IL 61802 (United States); Li, Feng [Department of Biology and Microbiology, Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, SD 57007 (United States); Ren, Sufang; Guo, Lihui; Cong, Xiaoyan; Li, Jun [Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Sangyuan Road No. 8, Jinan 250100 (China); Zhou, Shun [College of marine science and engineering, Qingdao Agricultural University, Changcheng Road No. 700, Qingdao 266109 (China); Wu, Jiaqiang, E-mail: wujiaqiang2000@sina.com [Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Sangyuan Road No. 8, Jinan 250100 (China); and others

    2016-12-15

    The nonstructural protein 1α (NSP1α) of porcine reproductive and respiratory syndrome virus (PRRSV) is a nucleo-cytoplasmic protein that suppresses the production of type I interferon (IFN). In this study, we investigated the relationship between the subcellular distribution of NSP1α and its inhibition of type I IFN. NSP1α was found to contain the classical nuclear export signal (NES) and NSP1α nuclear export was CRM-1-mediated. NSP1α was shuttling between the nucleus and cytoplasm. We also showed that the nuclear export of NSP1α was necessary for its ability for type I IFN inhibition. NSP1α was also found to interact with CBP, which implies a possible mechanism of CBP degradation by NSP1α. Taken together, our results describe a novel mechanism of PRRSV NSP1α for type I IFN inhibition and suppression of the host innate antiviral response. - Highlights: •NSP1α contains the NES and NSP1α nuclear export was CRM-1-mediated. •NSP1α was shuttling between the nucleus and cytoplasm continuously. •The nuclear export of NSP1α was necessary for its ability for type I IFN inhibition. •NSP1α interacts with CBP, which implies the mechanism of CBP degradation by NSP1α.

  11. The illustrated A brief history of time

    CERN Document Server

    Hawking, Stephen

    1996-01-01

    This is Stephen Hawking's updated, expanded and illustrated edition of his celebrated work which includes the most recent developments in the field, many of which were forecast by him. At the same time, he explains his complex theories through a fresh visual dimension. Over one hunded and fifty stunning colour illustrations have been specially commissioned for this purpose to help the reader understand what have become popular mythic images of our century, but which nonetheless remain difficult, abstract ideas to grasp. It includes a new introduction written specially for this edition.

  12. Suppression of EAE by oral tolerance is independent of endogenous IFN-beta whereas treatment with recombinant IFN-beta ameliorates EAE

    DEFF Research Database (Denmark)

    Liu, Yawei; Teige, Ingrid; Ericsson, Ida

    2010-01-01

    IFN-beta is anticipated to have an important function in mucosal tolerance, as it is one of the major cytokines produced by plasmacytoid dendritic cells, and has recently been suggested as central to the maintenance of mucosal homeostasis. Here, we have investigated whether oral tolerance is depe......, however this was not a prerequisite for establishment of oral tolerance.Immunology and Cell Biology advance online publication, 12 January 2010; doi:10.1038/icb.2009.111....

  13. IFN-λ: A New Class of Interferon with Distinct Functions-Implications for Hepatitis C Virus Research

    Directory of Open Access Journals (Sweden)

    Bing Liu

    2015-01-01

    Full Text Available Pegylated interferon-α and ribavirin (PEG-IFN/RBV is widely used to treat chronic hepatitis C virus infection with notorious adverse reactions since the broad expression of IFN-α receptors on all nucleated cells. Accordingly, a Type III IFN with restricted receptors distribution is much safer as an alternative for HCV therapy. In addition, single nucleotide polymorphisms (SNPs near the human IFN-λ3 gene, IL-28B, correlate strongly with the ability to achieve a sustained virological response (SVR to therapy with pegylated IFN-α plus ribavirin in patients infected with chronic hepatitis C. Furthermore, we also discuss the most recent findings: IFN-λ4 predicts treatment outcomes of HCV infection. In consideration of the apparent limitations of current HCV therapy, especially high failure rate and universal side effects, prediction of treatment outcomes prior to the initiation of treatment and developing new alternative drugs are two important goals in HCV research.

  14. A Segmentation Analysis of an Illustrator's Quilt

    Science.gov (United States)

    Bonnici, Joseph; Scherban, Dwight M.

    2007-01-01

    Jerry Pinkney's pencils and watercolors have created an indelible niche in African American children's literature, celebrating a magical world where children's thoughts flow freely back in time and across space. His illustrations have been repeatedly recognized by multiple awards and honor book citations (Brodie, 1998), including the Coretta Scott…

  15. Illustrating the disassembly of 3D models

    KAUST Repository

    Guo, Jianwei; Yan, Dongming; Li, Er; Dong, Weiming; Wonka, Peter; Zhang, Xiaopeng

    2013-01-01

    We present a framework for the automatic disassembly of 3D man-made models and the illustration of the disassembly process. Given an assembled 3D model, we first analyze the individual parts using sharp edge loops and extract the contact faces

  16. Radiology illustrated. Hepatobiliary and pancreatic radiology

    International Nuclear Information System (INIS)

    Choi, Byung Ihn

    2014-01-01

    Clear, practical guide to the diagnostic imaging of diseases of the liver, biliary tree, gallbladder, pancreas, and spleen. A wealth of carefully selected and categorized illustrations. Highlighted key points to facilitate rapid review. Aid to differential diagnosis. Radiology Illustrated: Hepatobiliary and Pancreatic Radiology is the first of two volumes that will serve as a clear, practical guide to the diagnostic imaging of abdominal diseases. This volume, devoted to diseases of the liver, biliary tree, gallbladder, pancreas, and spleen, covers congenital disorders, vascular diseases, benign and malignant tumors, and infectious conditions. Liver transplantation, evaluation of the therapeutic response of hepatocellular carcinoma, trauma, and post-treatment complications are also addressed. The book presents approximately 560 cases with more than 2100 carefully selected and categorized illustrations, along with key text messages and tables, that will allow the reader easily to recall the relevant images as an aid to differential diagnosis. At the end of each text message, key points are summarized to facilitate rapid review and learning. In addition, brief descriptions of each clinical problem are provided, followed by both common and uncommon case studies that illustrate the role of different imaging modalities, such as ultrasound, radiography, CT, and MRI.

  17. Illustrative Line Styles for Flow Visualization

    NARCIS (Netherlands)

    Everts, Maarten H.; Bekker, Hendrik; Roerdink, Jos B. T. M.; Isenberg, Tobias

    2011-01-01

    We present a flexible illustrative line style model for the visualization of streamline data. Our model partitions view-oriented line strips into parallel bands whose basic visual properties can be controlled independently. We thus extend previous line stylization techniques specifically for

  18. Flow Visualization using Illustrative Line Styles

    NARCIS (Netherlands)

    Everts, Maarten H.; Bekker, Hendrik; Roerdink, Jos B. T. M.; Isenberg, Tobias; Bekker, Paulus

    2011-01-01

    We present a flexible illustrative line style model for the visualization of streamline data. Our model partitions view- oriented line strips into parallel bands whose basic visual properties can be controlled independently. We thus extend previous line stylization techniques specifically for

  19. Radiology illustrated. Hepatobiliary and pancreatic radiology

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Byung Ihn (ed.) [Seoul National Univ. Hospital (Korea, Republic of). Dept. of Radiology

    2014-04-01

    Clear, practical guide to the diagnostic imaging of diseases of the liver, biliary tree, gallbladder, pancreas, and spleen. A wealth of carefully selected and categorized illustrations. Highlighted key points to facilitate rapid review. Aid to differential diagnosis. Radiology Illustrated: Hepatobiliary and Pancreatic Radiology is the first of two volumes that will serve as a clear, practical guide to the diagnostic imaging of abdominal diseases. This volume, devoted to diseases of the liver, biliary tree, gallbladder, pancreas, and spleen, covers congenital disorders, vascular diseases, benign and malignant tumors, and infectious conditions. Liver transplantation, evaluation of the therapeutic response of hepatocellular carcinoma, trauma, and post-treatment complications are also addressed. The book presents approximately 560 cases with more than 2100 carefully selected and categorized illustrations, along with key text messages and tables, that will allow the reader easily to recall the relevant images as an aid to differential diagnosis. At the end of each text message, key points are summarized to facilitate rapid review and learning. In addition, brief descriptions of each clinical problem are provided, followed by both common and uncommon case studies that illustrate the role of different imaging modalities, such as ultrasound, radiography, CT, and MRI.

  20. Simple Laboratory Experiment for Illustrating Soil Respiration.

    Science.gov (United States)

    Hattey, J. A.; Johnson, G. V.

    1997-01-01

    Describes an experiment to illustrate the effect of food source and added nutrients (N) on microbial activity in the soil. Supplies include air-dried soil, dried plant material, sources of carbon and nitrogen, a trap such as KOH, colored water, and a 500-mL Erlenmeyer flask. Includes a diagram of an incubation chamber to demonstrate microbial…

  1. Straussian Grounded-Theory Method: An Illustration

    Science.gov (United States)

    Thai, Mai Thi Thanh; Chong, Li Choy; Agrawal, Narendra M.

    2012-01-01

    This paper demonstrates the benefits and application of Straussian Grounded Theory method in conducting research in complex settings where parameters are poorly defined. It provides a detailed illustration on how this method can be used to build an internationalization theory. To be specific, this paper exposes readers to the behind-the-scene work…

  2. 48 CFR 9904.408-60 - Illustrations.

    Science.gov (United States)

    2010-10-01

    ... Section 9904.408-60 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.408-60 Illustrations. (a) Company A's vacation plan provides that...

  3. 48 CFR 9904.403-60 - Illustrations.

    Science.gov (United States)

    2010-10-01

    ... Section 9904.403-60 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.403-60 Illustrations. (a) The following table lists some typical...

  4. 48 CFR 9904.407-60 - Illustrations.

    Science.gov (United States)

    2010-10-01

    ... Section 9904.407-60 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.407-60 Illustrations. (a) Contractor A's written practice is to set...

  5. 48 CFR 9904.406-60 - Illustrations.

    Science.gov (United States)

    2010-10-01

    ... Section 9904.406-60 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.406-60 Illustrations. (a) A contractor allocates general management...

  6. 48 CFR 9904.410-60 - Illustrations.

    Science.gov (United States)

    2010-10-01

    ... Section 9904.410-60 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.410-60 Illustrations. (a) Business Unit A has been including the...

  7. 48 CFR 9904.405-60 - Illustrations.

    Science.gov (United States)

    2010-10-01

    ... Section 9904.405-60 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.405-60 Illustrations. (a) An auditor recommends disallowance of...

  8. 13 CFR 112.7 - Illustrative applications.

    Science.gov (United States)

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Illustrative applications. 112.7 Section 112.7 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION NONDISCRIMINATION IN FEDERALLY... or recruitment advertising, employment, layoff or termination, upgrading, demotion, or transfer...

  9. Viral infection causes rapid sensitization to lipopolysaccharide: central role of IFN-alpha beta

    DEFF Research Database (Denmark)

    Nansen, A; Randrup Thomsen, A

    2001-01-01

    LPS is the major active agent in the pathogenesis of Gram-negative septic shock. In this report we have studied the influence of concurrent viral infection on the outcome of LPS-induced shock. We find that infection with vesicular stomatitis virus sensitizes mice to LPS at an early time point...... following infection. Treatment of mice with the chemical IFN inducer, polyinosinic:polycytidylic acid, has a similar effect. This hypersensitivity to LPS correlated with hyperproduction of TNF-alpha in vivo. The cellular and molecular mechanisms underlying this phenomenon were investigated using Ab......-depleted and gene-targeted mice. Our results revealed that while NK cell depletion and elimination of IFN-gamma partially protected against the sensitizing effects of vesicular stomatitis virus and polyinosinic:polycytidylic acid, the most striking effect was observed in IFN-alphabetaR-deficient mice. Thus...

  10. Influence of type I IFN signaling on anti-MOG antibody-mediated demyelination

    DEFF Research Database (Denmark)

    Berg, Carsten Tue; Khorooshi, Reza M. H.; Asgari, Nasrin

    2017-01-01

    Background Antibodies with specificity for myelin oligodendrocyte glycoprotein (MOG) are implicated in multiple sclerosis and related diseases. The pathogenic importance of anti-MOG antibody in primary demyelinating pathology remains poorly characterized. Objective The objective of this study...... is to investigate whether administration of anti-MOG antibody would be sufficient for demyelination and to determine if type I interferon (IFN) signaling plays a similar role in anti-MOG antibody-mediated pathology, as has been shown for neuromyelitis optica-like pathology. Methods Purified IgG2a monoclonal anti...... demyelination in wild-type and IFNAR1-KO mice. Conclusions Anti-MOG antibody and complement was sufficient to induce callosal demyelination, and pathology was dependent on type I IFN. Induction of EAE in IFNAR1-KO mice overcame the dependence on type I IFN for anti-MOG and complement-mediated demyelination....

  11. IFN-gamma shapes immune invasion of the central nervous system via regulation of chemokines

    DEFF Research Database (Denmark)

    Tran, E H; Prince, E N; Owens, T

    2000-01-01

    Dynamic interplay between cytokines and chemokines directs trafficking of leukocyte subpopulations to tissues in autoimmune inflammation. We have examined the role of IFN-gamma in directing chemokine production and leukocyte infiltration to the CNS in experimental autoimmune encephalomyelitis (EA......-gamma in EAE, acting on T cell proliferation and directing chemokine production, with profound implications for the onset and progression of disease.......). BALB/c and C57BL/6 mice are resistant to induction of EAE by immunization with myelin basic protein. However, IFN-gamma-deficient (BALB/c) and IFN-gammaR-deficient (C57BL/6) mice developed rapidly progressing lethal disease. Widespread demyelination and disseminated leukocytic infiltration of spinal...

  12. Information barriers

    International Nuclear Information System (INIS)

    Fuller, J.L.; Wolford, J.

    2001-01-01

    Full text: An information barrier (IB) consists of procedures and technology that prevent the release of sensitive information during a joint inspection of a sensitive nuclear item, and provides confidence that the measurement system into which it has been integrated functions exactly as designed and constructed. Work in the U.S. on radiation detection system information barriers dates back at least to 1990, even though the terminology is more recent. In January 1999 the Joint DoD-DOE Information Barrier Working Group was formed in the United States to help coordinate technical efforts related to information barrier R and D. This paper presents an overview of the efforts of this group, by its Chairs, as well as recommendations for further information barrier R and D. Progress on the demonstration of monitoring systems containing IBs is also provided. From the U.S. perspective, the basic, top-level functional requirements for the information barrier portion of an integrated radiation signature-information barrier inspection system are twofold: The host must be assured that his classified information is protected from disclosure to the inspecting party; and The inspecting party must be confident that the integrated inspection system measures, processes, and presents the radiation-signature-based measurement conclusion in an accurate and reproducible manner. It is the position of the United States that in the absence of any agreement to share classified nuclear weapons design information in the conduct of an inspection regime, the requirement to protect host country classified warhead design information is paramount and admits no tradeoff versus the confidence provided to the inspecting party in the accuracy and reproducibility of the measurements. The U.S. has reached an internal consensus on several critical design elements that define a general standard for radiation signature information barrier design. These criteria have stood the test of time under intense

  13. Bioinformatics analysis of the factors controlling type I IFN gene expression in autoimmune disease and virus-induced immunity

    Directory of Open Access Journals (Sweden)

    Di eFeng

    2013-09-01

    Full Text Available Patients with systemic lupus erythematosus (SLE and Sjögren's syndrome (SS display increased levels of type I IFN-induced genes. Plasmacytoid dendritic cells (PDCs are natural interferon producing cells and considered to be a primary source of IFN-α in these two diseases. Differential expression patterns of type I IFN inducible transcripts can be found in different immune cell subsets and in patients with both active and inactive autoimmune disease. A type I IFN gene signature generally consists of three groups of IFN-induced genes - those regulated in response to virus-induced type I IFN, those regulated by the IFN-induced mitogen-activated protein kinase/extracellular-regulated kinase (MAPK/ERK pathway, and those by the IFN-induced phosphoinositide-3 kinase (PI-3K pathway. These three groups of type I IFN-regulated genes control important cellular processes such as apoptosis, survival, adhesion, and chemotaxis, that when dysregulated, contribute to autoimmunity. With the recent generation of large datasets in the public domain from next-generation sequencing and DNA microarray experiments, one can perform detailed analyses of cell type-specific gene signatures as well as identify distinct transcription factors that differentially regulate these gene signatures. We have performed bioinformatics analysis of data in the public domain and experimental data from our lab to gain insight into the regulation of type I IFN gene expression. We have found that the genetic landscape of the IFNA and IFNB genes are occupied by transcription factors, such as insulators CTCF and cohesin, that negatively regulate transcription, as well as IRF5 and IRF7, that positively and distinctly regulate IFNA subtypes. A detailed understanding of the factors controlling type I IFN gene transcription will significantly aid in the identification and development of new therapeutic strategies targeting the IFN pathway in autoimmune disease.

  14. Type I IFN-related NETosis in ataxia telangiectasia and Artemis deficiency.

    Science.gov (United States)

    Gul, Ersin; Sayar, Esra Hazar; Gungor, Bilgi; Eroglu, Fehime Kara; Surucu, Naz; Keles, Sevgi; Guner, Sukru Nail; Findik, Siddika; Alpdundar, Esin; Ayanoglu, Ihsan Cihan; Kayaoglu, Basak; Geckin, Busra Nur; Sanli, Hatice Asena; Kahraman, Tamer; Yakicier, Cengiz; Muftuoglu, Meltem; Oguz, Berna; Cagdas Ayvaz, Deniz Nazire; Gursel, Ihsan; Ozen, Seza; Reisli, Ismail; Gursel, Mayda

    2017-11-16

    Pathological inflammatory syndromes of unknown etiology are commonly observed in ataxia telangiectasia (AT) and Artemis deficiency. Similar inflammatory manifestations also exist in patients with STING-associated vasculopathy in infancy (SAVI). We sought to test the hypothesis that the inflammation-associated manifestations observed in patients with AT and Artemis deficiency stem from increased type I IFN signature leading to neutrophil-mediated pathological damage. Cytokine/protein signatures were determined by ELISA, cytometric bead array, or quantitative PCR. Stat1 phosphorylation levels were determined by flow cytometry. DNA species accumulating in the cytosol of patients' cells were quantified microscopically and flow cytometrically. Propensity of isolated polymorhonuclear granulocytes to form neutrophil extracellular traps (NETs) was determined using fluorescence microscopy and picogreen assay. Neutrophil reactive oxygen species levels and mitochondrial stress were assayed using fluorogenic probes, microscopy, and flow cytometry. Type I and III IFN signatures were elevated in plasma and peripheral blood cells of patients with AT, Artemis deficiency, and SAVI. Chronic IFN production stemmed from the accumulation of DNA in the cytoplasm of AT and Artemis-deficient cells. Neutrophils isolated from patients spontaneously produced NETs and displayed indicators of oxidative and mitochondrial stress, supportive of their NETotic tendencies. A similar phenomenon was also observed in neutrophils from healthy controls exposed to patient plasma samples or exogeneous IFN-α. Type I IFN-mediated neutrophil activation and NET formation may contribute to inflammatory manifestations observed in patients with AT, Artemis deficiency, and SAVI. Thus, neutrophils represent a promising target to manage inflammatory syndromes in diseases with active type I IFN signature. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights

  15. Floating barrier

    Energy Technology Data Exchange (ETDEWEB)

    1968-05-06

    This floating barrier consists of relatively long elements which can be connected to form a practically continuous assembly. Each element consists of an inflatable tube with an apron of certain height, made of impregnated fabric which is resistant to ocean water and also to hydrocarbons. Means for connecting one element to the following one, and means for attaching ballast to the apron are also provided.

  16. Characterization of monocyte-derived dendritic cells maturated with IFN-alpha

    DEFF Research Database (Denmark)

    Svane, I M; Nikolajsen, K; Walter, M R

    2006-01-01

    Dendritic cells (DC) are promising candidates for cancer immunotherapy. These cells can be generated from peripheral blood monocytes cultured with granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin-4 (IL-4). In order to obtain full functional capacity, maturation is required......, maturation with IFN-alpha has only a small effect on induction of autologous T-cell stimulatory capacity of the DC. However, an increase in DC allogeneic T-cell stimulatory capacity was observed. These data suggest that IFN-alpha has a potential as a maturation agent used in DC-based cancer vaccine trials...

  17. Lion (Panthera leo) and cheetah (Acinonyx jubatus) IFN-gamma sequences.

    Science.gov (United States)

    Maas, Miriam; Van Rhijn, Ildiko; Allsopp, Maria T E P; Rutten, Victor P M G

    2010-04-15

    Cloning and sequencing of the full length lion and cheetah interferon-gamma (IFN-gamma) transcript will enable the expression of the recombinant cytokine, to be used for production of monoclonal antibodies and to set up lion and cheetah-specific IFN-gamma ELISAs. These are relevant in blood-based diagnosis of bovine tuberculosis, an important threat to lions in the Kruger National Park. Alignment of nucleotide and amino acid sequences of lion and cheetah and that of domestic cats showed homologies of 97-100%. Copyright 2009 Elsevier B.V. All rights reserved.

  18. Distinct mechanisms of loss of IFN-gamma mediated HLA class I inducibility in two melanoma cell lines

    International Nuclear Information System (INIS)

    Rodríguez, Teresa; Méndez, Rosa; Del Campo, Ana; Jiménez, Pilar; Aptsiauri, Natalia; Garrido, Federico; Ruiz-Cabello, Francisco

    2007-01-01

    The inability of cancer cells to present antigen on the cell surface via MHC class I molecules is one of the mechanisms by which tumor cells evade anti-tumor immunity. Alterations of Jak-STAT components of interferon (IFN)-mediated signaling can contribute to the mechanism of cell resistance to IFN, leading to lack of MHC class I inducibility. Hence, the identification of IFN-γ-resistant tumors may have prognostic and/or therapeutic relevance. In the present study, we investigated a mechanism of MHC class I inducibility in response to IFN-γ treatment in human melanoma cell lines. Basal and IFN-induced expression of HLA class I antigens was analyzed by means of indirect immunofluorescence flow cytometry, Western Blot, RT-PCR, and quantitative real-time RT-PCR (TaqMan ® Gene Expression Assays). In demethylation studies cells were cultured with 5-aza-2'-deoxycytidine. Electrophoretic Mobility Shift Assay (EMSA) was used to assay whether IRF-1 promoter binding activity is induced in IFN-γ-treated cells. Altered IFN-γ mediated HLA-class I induction was observed in two melanoma cells lines (ESTDAB-004 and ESTDAB-159) out of 57 studied, while treatment of these two cell lines with IFN-α led to normal induction of HLA class I antigen expression. Examination of STAT-1 in ESTDAB-004 after IFN-γ treatment demonstrated that the STAT-1 protein was expressed but not phosphorylated. Interestingly, IFN-α treatment induced normal STAT-1 phosphorylation and HLA class I expression. In contrast, the absence of response to IFN-γ in ESTDAB-159 was found to be associated with alterations in downstream components of the IFN-γ signaling pathway. We observed two distinct mechanisms of loss of IFN-γ inducibility of HLA class I antigens in two melanoma cell lines. Our findings suggest that loss of HLA class I induction in ESTDAB-004 cells results from a defect in the earliest steps of the IFN-γ signaling pathway due to absence of STAT-1 tyrosine-phosphorylation, while absence

  19. IFN-γ Induces Mimic Extracellular Trap Cell Death in Lung Epithelial Cells Through Autophagy-Regulated DNA Damage.

    Science.gov (United States)

    Lin, Chiou-Feng; Chien, Shun-Yi; Chen, Chia-Ling; Hsieh, Chia-Yuan; Tseng, Po-Chun; Wang, Yu-Chih

    2016-02-01

    Treatment of interferon-γ (IFN-γ) causes cell growth inhibition and cytotoxicity in lung epithelial malignancies. Regarding the induction of autophagy related to IFN-γ signaling, this study investigated the link between autophagy and IFN-γ cytotoxicity. In A549 human lung cancer cells, IFN-γ treatment induced concurrent apoptotic and nonapoptotic events. Unexpectedly, the nonapoptotic cells present mimic extracellular trap cell death (ETosis), which was regulated by caspase-3 and by autophagy induction through immunity-related GTPase family M protein 1 and activating transcription factor 6. Furthermore, IFN-γ signaling controlled mimic ETosis through a mechanism involving an autophagy- and Fas-associated protein with death domain-controlled caspase-8/-3 activation. Following caspase-mediated lamin degradation, IFN-γ caused DNA damage-associated ataxia telangiectasia and Rad3-related protein (ATR)/ataxia telangiectasia mutated (ATM)-regulated mimic ETosis. Upon ATR/ATM signaling, peptidyl arginine deiminase 4 (PAD4)-mediated histone 3 citrullination promoted mimic ETosis. Such IFN-γ-induced effects were defective in PC14PE6/AS2 human lung cancer cells, which were unsusceptible to IFN-γ-induced autophagy. Due to autophagy-based caspase cascade activation, IFN-γ triggers unconventional caspase-mediated DNA damage, followed by ATR/ATM-regulated PAD4-mediated histone citrullination during mimic ETosis in lung epithelial malignancy.

  20. Illustrating answers: an evaluation of automatically retrieved illustrations of answers to medical questions

    NARCIS (Netherlands)

    Bosma, W.E.; Theune, Mariet; van Hooijdonk, C.M.J.; Krahmer, E.; Maes, F.

    In this paper we discuss and evaluate a method for automatic text illustration, applied to answers to medical questions. Our method for selecting illustrations is based on the idea that similarities between the answers and picture-related text (the picture’s caption or the section/paragraph that

  1. T cell-derived IFN-γ downregulates protective group 2 innate lymphoid cells in murine lupus erythematosus.

    Science.gov (United States)

    Düster, Mathis; Becker, Martina; Gnirck, Ann-Christin; Wunderlich, Malte; Panzer, Ulf; Turner, Jan-Eric

    2018-04-19

    Innate lymphoid cells (ILCs) are important regulators of the immune response and play a crucial role in the restoration of tissue homeostasis after injury. GATA-3 + IL-13- and IL-5-producing group 2 innate lymphoid cells (ILC2s) have been shown to promote tissue repair in barrier organs, but despite extensive research on ILCs in the recent years, their potential role in autoimmune diseases is still incompletely understood. In the present study, we investigate the role of ILC2s in the MRL/MpJ-Fas lpr (MRL-lpr) mouse model for severe organ manifestation of systemic lupus erythematosus (SLE). We show that in these MRL-lpr mice, progression of lupus nephritis is accompanied with a reduction of ILC2 abundance in the inflamed renal tissue. Proliferation/survival and cytokine production of kidney-residing ILC2s was suppressed by IFN-γ and, to a lesser extent, by IL-27 which were produced by activated T cells and myeloid cells in the nephritic kidney, respectively. Most importantly, restoration of ILC2 numbers by IL-33-mediated expansion ameliorated lupus nephritis and prevented mortality in MRL-lpr mice. In summary, we show here that development of SLE-like kidney inflammation leads to a downregulation of the renal ILC2 response and identify an ILC2-expanding therapy as a promising treatment approach for autoimmune diseases. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Selling pictures: the illustrated auction catalogue

    Directory of Open Access Journals (Sweden)

    Elizabeth Pergam

    2014-12-01

    Full Text Available This essay is based upon a survey of reproductions in auction catalogues – from their first appearance in the early eighteenth century until their more consistent use in the second decade of the twentieth century. Examining the role of these illustrations sheds light on how auctions functioned; it was not just the works of art that were traded, but knowledge about those works of art became currency to be exchanged. In contrast to the high end engravings and photographs of luxury illustrated art books, reproductions in auction catalogues – publications produced as ephemeral marketing tools – were of noticeably lower quality. This study of the status of reproductions, therefore, investigates the evolving understanding of art knowledge, both aesthetic and economic, and the interdependence of the market and connoisseurship.

  3. Crédit des illustrations

    OpenAIRE

    2017-01-01

    Illustration de couverture : Lyon, cathédrale Saint-Jean, culée de l’arc-boutant 2/3 : David (XIIIe siècle) surgissant de l’échafaudage (XXIe siècle). Photo Jean-Pierre Gobillot. Illustration de la quatrième de couverture : Lyon, cathédrale Saint-Jean, arcature extérieure de l’abside, chapiteau central. Dessin Ghislaine Macabéo. Photos Jean-Pierre Gobillot : fig. 1, 2, 10, 13, 14, 16, 23, 28, 29, 34, 35, 36, 37, 40, 41, 46, 54, 55, 56, 59, 60, 67, 76a, 78, 80, 82, 83, 88, 90, 97, 105, 106, 11...

  4. The Cambridge Illustrated History of Astronomy

    Science.gov (United States)

    Hoskin, Michael

    Expertly written and lavishly illustrated, The Cambridge Illustrated History of Astronomy offers a unique account of astronomical theory and practice from antiquity to the present day. How did Moslems of the Middle Ages use astronomy to calculate the direction of Mecca from far-flung corners of the Islamic world? Who was the only ancient Greek to suspect that the earth might revolve around the sun? How did Christopher Columbus abuse his knowledge of a lunar eclipse predicted by an astronomical almanac? Packed with anecdotes and intriguing detail, this book describes how we observed the sky and interpreted what we saw at different periods of history; how this influenced our beliefs and mythology; and how great astronomers contributed to what we now know. The result is a lively and highly visual history of astronomy - a compelling read for specialists and non-specialists alike.

  5. Illustrative visualization of 3D city models

    Science.gov (United States)

    Doellner, Juergen; Buchholz, Henrik; Nienhaus, Marc; Kirsch, Florian

    2005-03-01

    This paper presents an illustrative visualization technique that provides expressive representations of large-scale 3D city models, inspired by the tradition of artistic and cartographic visualizations typically found in bird"s-eye view and panoramic maps. We define a collection of city model components and a real-time multi-pass rendering algorithm that achieves comprehensible, abstract 3D city model depictions based on edge enhancement, color-based and shadow-based depth cues, and procedural facade texturing. Illustrative visualization provides an effective visual interface to urban spatial information and associated thematic information complementing visual interfaces based on the Virtual Reality paradigm, offering a huge potential for graphics design. Primary application areas include city and landscape planning, cartoon worlds in computer games, and tourist information systems.

  6. Mechanisms in ancient Chinese books with illustrations

    CERN Document Server

    Hsiao, Kuo-Hung

    2014-01-01

    This book presents a unique approach for studying mechanisms and machines with drawings that were depicted unclearly in ancient Chinese books. The historical, cultural and technical backgrounds of the mechanisms are explained, and various mechanisms described and illustrated in ancient books are introduced. By utilizing the idea for the conceptual design of modern mechanisms, all feasible designs of ancient mechanisms with uncertain members and joints that meet the technical standards of the subjects’ time periods are synthesized systematically. Ancient Chinese crossbows (the original crossbow and repeating crossbows), textile mechanisms (silk-reeling mechanism, spinning mechanisms, and looms), and many other artisan's tool mechanisms are used as illustrated examples.  Such an approach provides a logical method for the reconstruction designs of ancient mechanisms with uncertain structures. It also provides an innovative direction for researchers to further identify the original structures of mechanisms...

  7. Astronomical knowledge transmission through illustrated Aratea manuscripts

    CERN Document Server

    Dolan, Marion

    2017-01-01

    This carefully researched monograph is a historical investigation of the illustrated Aratea astronomical manuscript and its many interpretations over the centuries. Aratus' 270 B.C.E. Greek poem describing the constellations and astrological phenomena was translated and copied over 800 years into illuminated manuscripts that preserved and illustrated these ancient stories about the constellations. The Aratea survives in its entirety due to multiple translations from Greek to Latin and even to Arabic, with many illuminated versions being commissioned over the ages. The survey encompasses four interrelated disciplines: history of literature, history of myth, history of science, and history of art. Aratea manuscripts by their nature are a meeting place of these distinct branches, and the culling of information from historical literature and from the manuscripts themselves focuses on a wider, holistic view; a narrow approach could not provide a proper prospective. What is most essential to know about this work is...

  8. Some illustrative examples of model uncertainty

    International Nuclear Information System (INIS)

    Bier, V.M.

    1994-01-01

    In this paper, we first discuss the view of model uncertainty proposed by Apostolakis. We then present several illustrative examples related to model uncertainty, some of which are not well handled by this formalism. Thus, Apostolakis' approach seems to be well suited to describing some types of model uncertainty, but not all. Since a comprehensive approach for characterizing and quantifying model uncertainty is not yet available, it is hoped that the examples presented here will service as a springboard for further discussion

  9. Atlas of Illustrative Cases of Tattoo Complications.

    Science.gov (United States)

    Serup, Jørgen

    2017-01-01

    Tattoos, and tattoo complications as well, are colorful and visually flashy. A clinical outlook provides important clues to diagnosis by pattern recognition. This atlas,which is a report of 79 case illustrations, is made as a practical tool and vade mecum for the clinician. The atlas can be used in the office and as a bedside tool. It includes characteristic photos, and each case is accompanied with a brief medical history, a comment with learning points, the final diagnosis, and a review of therapeutic options. This spectrum of cases illustrates the different diagnostic entities according to the newly proposed Bispebjerg University Hospital ('Tattoo Clinic') diagnostic system of tattoo complications, a system reported to the 11th revision of the WHO disease classification system. Cases include allergies predominantly seen in red tattoos manifesting the characteristic patterns of plaque elevation, excessive hyperkeratosis, ulcerating reactions, urticaria, and generalized skin rash. Each type of reaction has typical clues to diagnosis and a typical disease course. 'Cross-sensitivity' allergic reactions in old tattoos of the same color as the trigger tattoo are also illustrated. Reactions in black tattoos are dominated by a pattern with papulonodular reactions, which are nonallergic anddue to pigment agglomeration in the skin. Reactions may be granulomatous and a marker of systemic sarcoidosis, sometimes associated with a general outbreak in the skin in black tattoos, e.g. 'rush phenomenon'. Bacterial infections are also illustrated. The technical hazards of tattooing and sequels as well as unwanted effects of tattoo removal by lasers are shown along with severe scarring following tattoo removal by caustics. This atlas is a tutorial in modern medical and surgical treatments of tattoo complications. © 2017 S. Karger AG, Basel.

  10. IEE wiring regulations explained and illustrated

    CERN Document Server

    Scaddan, Brian

    2013-01-01

    The IEE Wiring Regulations Explained and Illustrated, Second Edition discusses the recommendations of the IEE Regulations for the Electrical Equipment of Buildings for the safe selection or erection of wiring installations. The book emphasizes earthing, bonding, protection, and circuit design of electrical wirings. The text reviews the fundamental requirements for safety, earthing systems, the earth fault loop impedance, and supplementary bonding. The book also describes the different types of protection, such as protection against mechanical damage, overcurrent, under voltage (which prevents

  11. Barrier experiment: Shock initiation under complex loading

    Energy Technology Data Exchange (ETDEWEB)

    Menikoff, Ralph [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-01-12

    The barrier experiments are a variant of the gap test; a detonation wave in a donor HE impacts a barrier and drives a shock wave into an acceptor HE. The question we ask is: What is the trade-off between the barrier material and threshold barrier thickness to prevent the acceptor from detonating. This can be viewed from the perspective of shock initiation of the acceptor subject to a complex pressure drive condition. Here we consider key factors which affect whether or not the acceptor undergoes a shock-to-detonation transition. These include the following: shock impedance matches for the donor detonation wave into the barrier and then the barrier shock into the acceptor, the pressure gradient behind the donor detonation wave, and the curvature of detonation front in the donor. Numerical simulations are used to illustrate how these factors affect the reaction in the acceptor.

  12. IFN-ε is constitutively expressed by cells of the reproductive tract and is inefficiently secreted by fibroblasts and cell lines.

    Directory of Open Access Journals (Sweden)

    Pascale Hermant

    Full Text Available Type-I interferons (IFNs form a large family of cytokines that primarily act to control the early development of viral infections. Typical type-I IFN genes, such as those encoding IFN-α or IFN-β are upregulated by viral infection in many cell types. In contrast, the gene encoding IFN-ε was reported to be constitutively expressed by cells of the female reproductive tract and to contribute to the protection against vaginal infections with herpes simplex virus 2 and Chlamydia muridarum. Our data confirm the lack of induction of IFN-ε expression after viral infection and the constitutive expression of IFN-ε by cells of the female but also of the male reproductive organs. Interestingly, when expressed from transfected expression plasmids in 293T, HeLa or Neuro2A cells, the mouse and human IFN-ε precursors were inefficiently processed and secretion of IFN-ε was minimal. Analysis of chimeric constructs produced between IFN-ε and limitin (IFN-ζ showed that both the signal peptide and the mature moiety of IFN-ε contribute to poor processing of the precursor. Immunofluorescent detection of FLAG-tagged IFN-ε in transfected cells suggested that IFN-ε and chimeric proteins were defective for progression through the secretory pathway. IFN-ε did not, however, act intracellularly and impart an antiviral state to producing cells. Given the constitutive expression of IFN-ε in specialized cells and the poor processing of IFN-ε precursor in fibroblasts and cell lines, we hypothesize that IFN-ε secretion may require a co-factor specifically expressed in cells of the reproductive organs, that might secure the system against aberrant release of this IFN.

  13. Characterization of the binding of radioiodinated hybrid recombinant IFN-alpha A/D to murine and human lymphoid cell lines

    International Nuclear Information System (INIS)

    Faltynek, C.R.; Princler, G.L.; Schwabe, M.; Shata, M.T.; Lewis, G.K.; Kamin-Lewis, R.M.

    1990-01-01

    The hybrid recombinant human interferon (IFN) rIFN-alpha A/D was radioiodinated. Specific binding of [125I]rIFN-alpha A/D was observed with both human and murine cell lines. The binding of [125I]rIFN-alpha A/D to human Daudi cells had similar characteristics to the previously described binding of [125I]rIFN-alpha A or -alpha 2. The following lines of evidence demonstrated that [125I]rIFN-alpha A/D bound with high affinity to the same receptor on murine cells as murine IFN-alpha and -beta: (i) the binding of [125I]rIFN-alpha A/D to murine LBRM cells was inhibited to a similar extent by natural murine IFN-alpha, natural murine IFN-beta, and rIFN-A/D; (ii) the Kd (approximately 2 X 10(-10) M) obtained from both competition experiments and saturation binding experiments with [125I]rIFN-alpha A/D was comparable to the previously reported Kd for the binding of natural murine IFN-alpha and -beta to other murine cell lines; (iii) the size of the cross-linked [125I]rIFN-alpha A/D receptor complex formed on murine LBRM cells was similar to the previously reported cross-linked complex formed after binding radioiodinated natural murine IFN-beta to other murine cell lines. Due to the current lack of readily available recombinant murine IFN-alpha or -beta for radiolabeling and the previously demonstrated biological activity of rIFN-alpha A/D on murine cells, [125I]rIFN-alpha A/D should prove to be a useful reagent for further studies of murine IFN receptors

  14. Smart parking barrier

    KAUST Repository

    Alharbi, Abdulrazaq M.

    2016-01-01

    positioning of the movable parking barrier, and a parking controller configured to initiate movement of the parking barrier, via the barrier drive. The movable parking barrier can be positioned between a first position that restricts access to the parking

  15. Deficiency of the AIM2-ASC Signal Uncovers the STING-Driven Overreactive Response of Type I IFN and Reciprocal Depression of Protective IFN-γ Immunity in Mycobacterial Infection.

    Science.gov (United States)

    Yan, Shanshan; Shen, Hongbo; Lian, Qiaoshi; Jin, Wenlong; Zhang, Ronghua; Lin, Xuan; Gu, Wangpeng; Sun, Xiaoyu; Meng, Guangxun; Tian, Zhigang; Chen, Zheng W; Sun, Bing

    2018-02-01

    The nucleic acids of Mycobacterium tuberculosis can be detected by intracellular DNA sensors, such as cyclic GMP-AMP synthase and absent in melanoma 2 (AIM2), which results in the release of type I IFN and the proinflammatory cytokine IL-1β. However, whether cross-talk occurs between AIM2-IL-1β and cyclic GMP-AMP synthase-type I IFN signaling upon M. tuberculosis infection in vivo is unclear. In this article, we demonstrate that mycobacterial infection of AIM2 -/- mice reciprocally induces overreactive IFN-β and depressive IFN-γ responses, leading to higher infection burdens and more severe pathology. We also describe the underlying mechanism whereby activated apoptosis-associated speck-like protein interacts with a key adaptor, known as stimulator of IFN genes (STING), and inhibits the interaction between STING and downstream TANK-binding kinase 1 in bone marrow-derived macrophages and bone marrow-derived dendritic cells, consequently reducing the induction of type I IFN. Of note, apoptosis-associated speck-like protein expression is inversely correlated with IFN-β levels in PBMCs from tuberculosis patients. These data demonstrate that the AIM2-IL-1β signaling pathway negatively regulates the STING-type I IFN signaling pathway by impeding the association between STING and TANK-binding kinase 1, which protects the host from M. tuberculosis infection. This finding has potential clinical significance. Copyright © 2018 by The American Association of Immunologists, Inc.

  16. Programmed death-1 receptor suppresses γ-IFN producing NKT cells in human tuberculosis.

    Science.gov (United States)

    Singh, Amar; Dey, Aparajit Ballav; Mohan, Anant; Mitra, Dipendra Kumar

    2014-05-01

    IFN-γ biased Th1 effector immune response is crucial for containment of Mycobacterium tuberculosis infection. Various T cell subsets with regulatory function dictate the generation of Th1 like cells. NKT cells are a specialized T cell subset known to be activated early in immune response and control T cell response via release of immunoregulatory cytokines like IFN-γ, IL-4 and IL-10. M. tuberculosis, with abundance of its cell wall lipids may potently activate NKT cells resulting in cytokine production and PD-1 expression. In this study, among 49 treatment naive active pulmonary tuberculosis patients, we found a higher percentage of PD1(+) NKT cells correlating with sputum bacillary load. Furthermore, blocking PD-1 increased the number of IFN-γ producing NKT cells by inhibiting their apoptosis. Moreover, peripheral frequency of NKT cells declined with therapy suggesting their role in host T cell response. In this study, we concluded that PD-1 preferentially induces apoptosis of IFN-γ producing NKT cells while sparing NKT cells that produce IL-4. Such a polarized NKT cell function may impose a Th2 bias on the ensuing effector T cell response leading to inefficient clearance of M. tuberculosis. Inhibiting PD-1 may therefore alter the T cell response in favor of the host by rescuing type 1 NKT cells from apoptosis and boosting Th1 effector T cell functions against M. tuberculosis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Quantitative detection of fusion protein rIFN-β-HSA by a sandwich ...

    African Journals Online (AJOL)

    user

    2011-02-14

    Feb 14, 2011 ... (Corning-Costar, NY, USA), urine microalbumin kits were purchased from ... regarded as the standard of rIFN-β-HSA and was stored at −80°C. ... and antibody concentration, sample incubating time and detecting. Zhu et al.

  18. Interleukin-4 (IL-4) and Interferon-Gamma (IFN-gamma) in pregnant ...

    African Journals Online (AJOL)

    Background and Objective:- To assess if gestational factors affect the resistance of C57BL/6 mice to L. major infection, this study determined the levels of IL-4 and IFN-gamma in popliteal lymph node cells of pregnant C57BL/6 mice infected with L. major at 16 hours, 5 days-, 10 days- and 15 days- post plug by PCR, ELISA ...

  19. Lack of Neuronal IFN-β-IFNAR Causes Lewy Body- and Parkinson's Disease-like Dementia

    DEFF Research Database (Denmark)

    Ejlerskov, Patrick; Hultberg, Jeanette Göransdotter; Wang, JunYang

    2015-01-01

    -causing mutant proteins. Mice lacking Ifnb function exhibited motor and cognitive learning impairments with accompanying α-synuclein-containing Lewy bodies in the brain, as well as a reduction in dopaminergic neurons and defective dopamine signaling in the nigrostriatal region. Lack of IFN-β signaling caused...

  20. Ceramide formation is involved in Lactobacillus acidophilus-induced IFN-beta response in dendritic cells

    DEFF Research Database (Denmark)

    Fuglsang, Eva; Henningsen, Louise; Frøkiær, Hanne

    of sphingomyelin to ceramide by acid sphingomyelinase (ASMase) at the outer leaflet of the PM is a key event in endocytosis of gram-positive Lactobacillus acidophilus (L. acidophilus) and the subsequent induction of IFN-beta in DCs and, as the gram-negative Escherichia coli (E. coli) does not induce appreciable...

  1. Injury-Induced Type I IFN Signaling Regulates Inflammatory Responses in the Central Nervous System

    DEFF Research Database (Denmark)

    Khorooshi, Reza; Owens, Trevor

    2010-01-01

    Innate glial response is critical for the induction of inflammatory mediators and recruitment of leukocytes to sites of the injury in the CNS. We have examined the involvement of type I IFN signaling in the mouse hippocampus following sterile injury (transection of entorhinal afferents). Type I I...

  2. Ubiquilin 1 Promotes IFN-γ-Induced Xenophagy of Mycobacterium tuberculosis.

    Directory of Open Access Journals (Sweden)

    Erik T Sakowski

    2015-07-01

    Full Text Available The success of Mycobacterium tuberculosis (Mtb as a pathogen rests upon its ability to grow intracellularly in macrophages. Interferon-gamma (IFN-γ is critical in host defense against Mtb and stimulates macrophage clearance of Mtb through an autophagy pathway. Here we show that the host protein ubiquilin 1 (UBQLN1 promotes IFN-γ-mediated autophagic clearance of Mtb. Ubiquilin family members have previously been shown to recognize proteins that aggregate in neurodegenerative disorders. We find that UBQLN1 can interact with Mtb surface proteins and associates with the bacilli in vitro. In IFN-γ activated macrophages, UBQLN1 co-localizes with Mtb and promotes the anti-mycobacterial activity of IFN-γ. The association of UBQLN1 with Mtb depends upon the secreted bacterial protein, EsxA, which is involved in permeabilizing host phagosomes. In autophagy-deficient macrophages, UBQLN1 accumulates around Mtb, consistent with the idea that it marks bacilli that traffic through the autophagy pathway. Moreover, UBQLN1 promotes ubiquitin, p62, and LC3 accumulation around Mtb, acting independently of the E3 ligase parkin. In summary, we propose a model in which UBQLN1 recognizes Mtb and in turn recruits the autophagy machinery thereby promoting intracellular control of Mtb. Thus, polymorphisms in ubiquilins, which are known to influence susceptibility to neurodegenerative illnesses, might also play a role in host defense against Mtb.

  3. Nuclear reorganization barriers to electron transfer

    International Nuclear Information System (INIS)

    Sutin, N.; Brunschwig, B.S.; Creutz, C.; Winkler, J.R.

    1988-01-01

    The nuclear barrier to electron transfer arises from the need for reorganization of intramolecular and solvent internuclear distances prior to electron transfer. For reactions with relatively small driving force (''normal'' free-energy region) the nuclear factors and rates increase as intrinsic inner-shell and outer-shell barriers decrease; this is illustrated by data for transition metal complexes in their ground electronic states. By contrast, in the inverted free-energy region, rates and nuclear factors decrease with decreasing ''intrinsic'' barriers; this is illustrated by data for the decay of charge-transfer excited states. Several approaches to the evaluation of the outer-shell barrier are explored in an investigation of the distance dependence of the nuclear factor in intramolecular electron-transfer processes. 39 refs., 14 figs., 3 tabs

  4. The MEK1/2-ERK Pathway Inhibits Type I IFN Production in Plasmacytoid Dendritic Cells

    Directory of Open Access Journals (Sweden)

    Vaclav Janovec

    2018-02-01

    Full Text Available Recent studies have reported that the crosslinking of regulatory receptors (RRs, such as blood dendritic cell antigen 2 (BDCA-2 (CD303 or ILT7 (CD85g, of plasmacytoid dendritic cells (pDCs efficiently suppresses the production of type I interferons (IFN-I, α/β/ω and other cytokines in response to toll-like receptor 7 and 9 (TLR7/9 ligands. The exact mechanism of how this B cell receptor (BCR-like signaling blocks TLR7/9-mediated IFN-I production is unknown. Here, we stimulated BCR-like signaling by ligation of RRs with BDCA-2 and ILT7 mAbs, hepatitis C virus particles, or BST2 expressing cells. We compared BCR-like signaling in proliferating pDC cell line GEN2.2 and in primary pDCs from healthy donors, and addressed the question of whether pharmacological targeting of BCR-like signaling can antagonize RR-induced pDC inhibition. To this end, we tested the TLR9-mediated production of IFN-I and proinflammatory cytokines in pDCs exposed to a panel of inhibitors of signaling molecules involved in BCR-like, MAPK, NF-ĸB, and calcium signaling pathways. We found that MEK1/2 inhibitors, PD0325901 and U0126 potentiated TLR9-mediated production of IFN-I in GEN2.2 cells. More importantly, MEK1/2 inhibitors significantly increased the TLR9-mediated IFN-I production blocked in both GEN2.2 cells and primary pDCs upon stimulation of BCR-like or phorbol 12-myristate 13-acetate-induced protein kinase C (PKC signaling. Triggering of BCR-like and PKC signaling in pDCs resulted in an upregulation of the expression and phoshorylation of c-FOS, a downstream gene product of the MEK1/2-ERK pathway. We found that the total level of c-FOS was higher in proliferating GEN2.2 cells than in the resting primary pDCs. The PD0325901-facilitated restoration of the TLR9-mediated IFN-I production correlated with the abrogation of MEK1/2-ERK-c-FOS signaling. These results indicate that the MEK1/2-ERK pathway inhibits TLR9-mediated type I IFN production in pDCs and that

  5. IFN-γ protects from lethal IL-17 mediated viral encephalomyelitis independent of neutrophils

    Directory of Open Access Journals (Sweden)

    Savarin Carine

    2012-05-01

    Full Text Available Abstract Background The interplay between IFN-γ, IL-17 and neutrophils during CNS inflammatory disease is complex due to cross-regulatory factors affecting both positive and negative feedback loops. These interactions have hindered the ability to distinguish the relative contributions of neutrophils, Th1 and Th17 cell-derived effector molecules from secondary mediators to tissue damage and morbidity. Methods Encephalitis induced by a gliatropic murine coronavirus was used as a model to assess the direct contributions of neutrophils, IFN-γ and IL-17 to virus-induced mortality. CNS inflammatory conditions were selectively manipulated by adoptive transfer of virus-primed wild-type (WT or IFN-γ deficient (GKO memory CD4+ T cells into infected SCID mice, coupled with antibody-mediated neutrophil depletion and cytokine blockade. Results Transfer of GKO memory CD4+ T cells into infected SCID mice induced rapid mortality compared to recipients of WT memory CD4+ T cells, despite similar virus control and demyelination. In contrast to recipients of WT CD4+ T cells, extensive neutrophil infiltration and IL-17 expression within the CNS in recipients of GKO CD4+ T cells provided a model to directly assess their contribution(s to disease. Recipients of WT CD4+ T cells depleted of IFN-γ did not express IL-17 and were spared from mortality despite abundant CNS neutrophil infiltration, indicating that mortality was not mediated by excessive CNS neutrophil accumulation. By contrast, IL-17 depletion rescued recipients of GKO CD4+ T cells from rapid mortality without diminishing neutrophils or reducing GM-CSF, associated with pathogenic Th17 cells in CNS autoimmune models. Furthermore, co-transfer of WT and GKO CD4+ T cells prolonged survival in an IFN-γ dependent manner, although IL-17 transcription was not reduced. Conclusions These data demonstrate that IL-17 mediates detrimental clinical consequences in an IFN-γ-deprived environment, independent of

  6. IFN-γ and IP-10 in tracheal aspirates from premature infants: relationship with bronchopulmonary dysplasia.

    Science.gov (United States)

    Aghai, Zubair H; Saslow, Judy G; Mody, Kartik; Eydelman, Riva; Bhat, Vishwanath; Stahl, Gary; Pyon, Kee; Bhandari, Vineet

    2013-01-01

    Interferon-gamma (IFN-γ) and interferon-inducible protein of 10 kDa (IP-10) are potent inflammatory mediators and contribute to acute lung injury in adults. Recently, a potential role for IFN-γ and IP-10 in the pathogenesis of bronchopulmonary dysplasia (BPD) has been reported in animal models. To study the association between IFN-γ and IP-10 in tracheal aspirate (TA) and the development of BPD in premature infants. TA samples collected within 48 hr after birth from 79 mechanically ventilated premature neonates [gestational age (GA) IP-10 was determined using a commercially available ELISA kit. Total protein in TA was measured by Bradford assay to correct for sampling related dilution. BPD was defined as the need of supplemental oxygen at 36 weeks postmenstrual age (PMA). Twenty infants (GA 26.4 ± 1.9w, BW 860 ± 201 g) survived without BPD at 36 weeks PMA and 59 infants (GA 25.5 ± 1.5w, BW 751 ± 163 g) died before 36 weeks PMA or developed BPD. The mean IFN-γ level was higher in infants who died or developed BPD (9.7 ± 2.8 vs. 3.1 ± 1.1 pg/ml, P = 0.03). Similarly, the mean IP-10 level was higher in infants who died or developed BPD (63.4 ± 17.5 pg/ml) compared to those who survived without BPD (18.5 ± 7.5 pg/ml, P = 0.02). Higher IFN-γ and IP-10 levels in TA samples are associated with the development of BPD or death in premature infants. Copyright © 2012 Wiley Periodicals, Inc.

  7. Atlas of Illustrative Cases of Tattoo Complications

    DEFF Research Database (Denmark)

    Serup, Jørgen

    2017-01-01

    proposed Bispebjerg University Hospital ('Tattoo Clinic') diagnostic system of tattoo complications, a system reported to the 11th revision of the WHO disease classification system. Cases include allergies predominantly seen in red tattoos manifesting the characteristic patterns of plaque elevation......'. Bacterial infections are also illustrated. The technical hazards of tattooing and sequels as well as unwanted effects of tattoo removal by lasers are shown along with severe scarring following tattoo removal by caustics. This atlas is a tutorial in modern medical and surgical treatments of tattoo...

  8. Illustrated & Dissected: Professor Richard Sawdon Smith.

    Science.gov (United States)

    2015-06-01

    This Alternative Gallery feature introduces the photographic artist Professor Richard Sawdon Smith. Professor Sawdon Smith's work stems around a fascination with representations of anatomy that have been fuelled by his experience as a hospital patient. The work has allowed him to explore ideas through the use of medical illustrations which include early anatomical drawings, personal medical photography and facial modelling. The work highlights how such imagery can be used in the context of a patient seeking understanding and acceptance of ill health and disease using the body as a canvas on which to translate the experience.

  9. Illustrating Mathematics using 3D Printers

    OpenAIRE

    Knill, Oliver; Slavkovsky, Elizabeth

    2013-01-01

    3D printing technology can help to visualize proofs in mathematics. In this document we aim to illustrate how 3D printing can help to visualize concepts and mathematical proofs. As already known to educators in ancient Greece, models allow to bring mathematics closer to the public. The new 3D printing technology makes the realization of such tools more accessible than ever. This is an updated version of a paper included in book Low-Cost 3D Printing for science, education and Sustainable Devel...

  10. Concanavalin A/IFN-gamma triggers autophagy-related necrotic hepatocyte death through IRGM1-mediated lysosomal membrane disruption.

    Directory of Open Access Journals (Sweden)

    Chih-Peng Chang

    Full Text Available Interferon-gamma (IFN-γ, a potent Th1 cytokine with multiple biological functions, can induce autophagy to enhance the clearance of the invading microorganism or cause cell death. We have reported that Concanavalin A (Con A can cause autophagic cell death in hepatocytes and induce both T cell-dependent and -independent acute hepatitis in immunocompetent and immunodeficient mice, respectively. Although IFN-γ is known to enhance liver injury in Con A-induced hepatitis, its role in autophagy-related hepatocyte death is not clear. In this study we report that IFN-γ can enhance Con A-induced autophagic flux and cell death in hepatoma cell lines. A necrotic cell death with increased lysosomal membrane permeabilization (LMP is observed in Con A-treated hepatoma cells in the presence of IFN-γ. Cathepsin B and L were released from lysosomes to cause cell death. Furthermore, IFN-γ induces immunity related GTPase family M member 1(IRGM1 translocation to lysosomes and prolongs its activity in Con A-treated hepatoma cells. Knockdown of IRGM1 inhibits the IFN-γ/Con A-induced LMP change and cell death. Furthermore, IFN-γ(-/- mice are resistant to Con A-induced autophagy-associated necrotic hepatocyte death. We conclude that IFN-γ enhances Con A-induced autophagic flux and causes an IRGM1-dependent lysosome-mediated necrotic cell death in hepatocytes.

  11. Immunostimulatory effects of natural human interferon-alpha (huIFN-alpha) on carps Cyprinus carpio L.

    Science.gov (United States)

    Watanuki, Hironobu; Chakraborty, Gunimala; Korenaga, Hiroki; Kono, Tomoya; Shivappa, R B; Sakai, Masahiro

    2009-10-15

    Human interferon-alpha (huIFN-alpha) is an important immunomodulatory substance used in the treatment and prevention of numerous infectious and immune-related diseases in animals. However, the immunostimulatory effects of huIFN-alpha in fish remain to be investigated. In the current study, the immune responses of the carp species Cyprinus carpio L. to treatment with huIFN-alpha were analyzed via measurement of superoxide anion production, phagocytic activity and the expression of cytokine genes including interleukin-1beta, tumor necrosis factor-alpha and interleukin 10. Low doses of huIFN-alpha were administered orally once a day for 3 days, and sampling was carried out at 1, 3 and 5 days post-treatment. Our results indicate that a low dose of huIFN-alpha significantly increased phagocytic activity and superoxide anion production in the carp kidney. The huIFN-alpha-treated fish also displayed a significant upregulation in cytokine gene expression. The current study demonstrates the stimulatory effects of huIFN-alpha on the carp immune system and highlights the immunomodulatory role of huIFN-alpha in fish.

  12. The essential role of the sialic acid residues for IFN-β1a activity determined in vivo

    DEFF Research Database (Denmark)

    Olesen, Lasse Dissing; Andersen, Morten Thaysen

      Recombinant human interferon-beta (rhIFN-β) is the leading therapeutic intervention shown to change the cause of relapsing remitting multiple sclerosis and both a non-glycosylated and a significantly more active glycosylated variant of rhIFN-β are used in treatment. This study investigates the ...

  13. Autoimmune pancreatitis: An illustrated guide to diagnosis

    International Nuclear Information System (INIS)

    Proctor, R.D.; Rofe, C.J.; Bryant, T.J.C.; Hacking, C.N.; Stedman, B.

    2013-01-01

    Autoimmune pancreatitis (AIP) remains one of the rarer forms of pancreatitis but has become increasingly well recognized and widely diagnosed as it is an important differential, particularly due to the dramatic response to appropriate therapy. It is now best considered as part of a multisystem disease and the notion of “IgG4-related systemic sclerosing disease” has become widely recognized as the number of extra-pancreatic associations of AIP grows. More recently AIP has been classified into two subtypes: lymphoplasmacytic sclerosing pancreatitis (LPSP) and idiopathic duct-centric pancreatitis (IDCP) with distinct geographical, age and sex distributions for the two subtypes, in addition to different pathological characteristics. The role of imaging is crucial in AIP and should be considered in conjunction with clinical, serological, and histopathological findings to make the diagnosis. Radiologists are uniquely placed to raise the possibility of AIP and aid the exclusion of significant differentials to allow the initiation of appropriate management and avoidance of unnecessary intervention. Radiological investigation may reveal a number of characteristic imaging findings in AIP but appearances can vary considerably and the focal form of AIP may appear as a pancreatic mass, imitating pancreatic carcinoma. This review will illustrate typical and atypical appearances of AIP on all imaging modes. Emphasis will be placed on the imaging features that are likely to prove useful in discriminating AIP from other causes prior to histopathological confirmation. In addition, examples of relevant differential diagnoses are discussed and illustrated

  14. The DNA sensor, cyclic GMP-AMP synthase, is essential for induction of IFN-β during Chlamydia trachomatis infection.

    Science.gov (United States)

    Zhang, Yugen; Yeruva, Laxmi; Marinov, Anthony; Prantner, Daniel; Wyrick, Priscilla B; Lupashin, Vladimir; Nagarajan, Uma M

    2014-09-01

    IFN-β has been implicated as an effector of oviduct pathology resulting from genital chlamydial infection in the mouse model. In this study, we investigated the role of cytosolic DNA and engagement of DNA sensors in IFN-β expression during chlamydial infection. We determined that three-prime repair exonuclease-1, a host 3' to 5' exonuclease, reduced IFN-β expression significantly during chlamydial infection using small interfering RNA and gene knockout fibroblasts, implicating cytosolic DNA as a ligand for this response. The DNA sensor cyclic GMP-AMP synthase (cGAS) has been shown to bind cytosolic DNA to generate cyclic GMP-AMP, which binds to the signaling adaptor stimulator of IFN genes (STING) to induce IFN-β expression. We determined that cGAS is required for IFN-β expression during chlamydial infection in multiple cell types. Interestingly, although infected cells deficient for STING or cGAS alone failed to induce IFN-β, coculture of cells depleted for either STING or cGAS rescued IFN-β expression. These data demonstrate that cyclic GMP-AMP produced in infected cGAS(+)STING(-) cells can migrate into adjacent cells via gap junctions to function in trans in cGAS(-)STING(+) cells. Furthermore, we observed cGAS localized in punctate regions on the cytosolic side of the chlamydial inclusion membrane in association with STING, indicating that chlamydial DNA is most likely recognized outside the inclusion as infection progresses. These novel findings provide evidence that cGAS-mediated DNA sensing directs IFN-β expression during Chlamydia trachomatis infection and suggest that effectors from infected cells can directly upregulate IFN-β expression in adjacent uninfected cells during in vivo infection, contributing to pathogenesis. Copyright © 2014 by The American Association of Immunologists, Inc.

  15. Illustrating the disassembly of 3D models

    KAUST Repository

    Guo, Jianwei

    2013-06-11

    We present a framework for the automatic disassembly of 3D man-made models and the illustration of the disassembly process. Given an assembled 3D model, we first analyze the individual parts using sharp edge loops and extract the contact faces between each pair of neighboring parts. The contact faces are then used to compute the possible moving directions of each part. We then present a simple algorithm for clustering the sets of the individual parts into meaningful sub-assemblies, which can be used for a hierarchical decomposition. We take the stability of sub-assemblies into account during the decomposition process by considering the upright orientation of the input models. Our framework also provides a user-friendly interface to enable the superimposition of the constraints for the decomposition. Finally, we visualize the disassembly process by generating an animated sequence. The experiments demonstrate that our framework works well for a variety of complex models. © 2013 Elsevier Ltd.

  16. Chemical constituents from Aspidosperma illustre (Apocynaceae)

    International Nuclear Information System (INIS)

    Barbosa, Lara F.; Mathias, Leda; Braz-Filho, Raimundo; Vieira, Ivo J. Curcino

    2010-01-01

    A new natural product oleanane-type triterpene, olean-12-ene-11α-methoxy-3β-acetate (10) was isolated from Aspidosperma illustre, together with β-amyrin (3), lupeol (4), β-amyrin acetate (5), lupeol acetate (6), olean-12-ene-28-hydroxy-3α-tetradecanoate (7), olean-12-ene-28-carboxy-3α-hexadecanoate (8), ursolic acid (9) triterpenes, and two monoterpenic indole alkaloids, b-yoimbine (1) and 1,2-dehydroaspidospermidine (2). These compounds were characterized on their spectral data basis, mainly one- ( 1 H, 13 C, APT) and two-dimensional ( 1 H- 1 H-COSY, 1 H- 1 HNOESY, HMQC and HMBC) NMR, and mass spectra, involving also comparison with data from the literature. (author)

  17. Uncertainty relation and probability. Numerical illustration

    International Nuclear Information System (INIS)

    Fujikawa, Kazuo; Umetsu, Koichiro

    2011-01-01

    The uncertainty relation and the probability interpretation of quantum mechanics are intrinsically connected, as is evidenced by the evaluation of standard deviations. It is thus natural to ask if one can associate a very small uncertainty product of suitably sampled events with a very small probability. We have shown elsewhere that some examples of the evasion of the uncertainty relation noted in the past are in fact understood in this way. We here numerically illustrate that a very small uncertainty product is realized if one performs a suitable sampling of measured data that occur with a very small probability. We introduce a notion of cyclic measurements. It is also shown that our analysis is consistent with the Landau-Pollak-type uncertainty relation. It is suggested that the present analysis may help reconcile the contradicting views about the 'standard quantum limit' in the detection of gravitational waves. (author)

  18. Adobe Illustrator CS2 crash course

    OpenAIRE

    Pedro Amado

    2007-01-01

    Introdução ao Adobe Illustrator.Compilação de informações, links e tutorial passo-a-passo para a iniciação a este softwarelt;p>FBAUP, Pedro Amado, 2007-01-22Versão 0.1 (alfa). Actualizada em 2007-01-22.Este trabalho está licenciado sob uma Licença Creative Commons Atribuição-Uso Não-Comercial-Partilha nos termos da mesma Licença 2.5 Portugal. Para ver uma cópia destalicença, visite http://creativecommons.org/licenses/by-nc-sa/2.5/pt/ ou envie uma cartapara Creative Commons, 559 Nathan Abbott ...

  19. Effects of IFN-β1a and IFN-β1b treatment on the expression of cytokines, inducible NOS (NOS type II), and myelin proteins in animal model of multiple sclerosis.

    Science.gov (United States)

    Lubina-Dąbrowska, Natalia; Stepień, Adam; Sulkowski, Grzegorz; Dąbrowska-Bouta, Beata; Langfort, Józef; Chalimoniuk, Małgorzata

    2017-08-01

    The aim of this study was to investigate the effects of interferon (IFN)-β1a and IFN-β1b treatment on inflammatory factors and myelin protein levels in the brain cortex of the Lewis rat experimental autoimmune encephalomyelitis (EAE), animal model of multiple sclerosis. To induce EAE, rat were immunized with inoculums containing spinal cord guinea pig homogenized in phosphate-buffered saline and emulsified in Freund's complete adjuvant containing 110 µg of the appropriate antigen in 100 µl of an emulsion and additionally 4-mg/ml Mycobacterium tuberculosis (H37Ra). The rats were treated three times per week with subcutaneous applications of 300,000 units IFN-β1a or IFN-β1b. The treatments were started 8 days prior to immunization and continued until day 14 after immunization. The rats were killed on the 14th day of the experiment. EAE induced dramatic increase in interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-concentrations and inducible nitric oxide synthase (iNOS) expression in the brain, which closely corresponded to the course of neurological symptoms and the loss of weight. Both IFN-β1b and IFN-β1a treatments inhibited the pro-inflammatory cytokines (IL-6, IL-1β, TNF-α and IFN-γ), decreased the activation of astrocytes, increased the myelin protein level in the brain cortex, and improved the neurological status of EAE rats by different mechanisms; IFN-β1a reduced iNOS expression, at least in part, by the enhancement of IL-10, while IFN-β1b diminished IL-10 concentration and did not decrease EAE-induced iNOS expression.

  20. Mucus as a Barrier to Drug Delivery

    DEFF Research Database (Denmark)

    Bøgh, Marie; Nielsen, Hanne Mørck

    2015-01-01

    Viscoelastic mucus lines all mucosal surfaces of the body and forms a potential barrier to mucosal drug delivery. Mucus is mainly composed of water and mucins; high-molecular weight glycoproteins forming an entangled network. Consequently, mucus forms a steric barrier and due to its negative charge...... barrier to drug delivery. Current knowledge of mucus characteristics and barrier properties, as achieved by state-of-the-art methodologies, is the topic of this MiniReview emphasizing the gastrointestinal mucus and an overall focus on oral drug delivery. Cell culture-based in vitro models are well......, studies of peptide and protein drug diffusion in and through mucus and studies of mucus-penetrating nanoparticles are included to illustrate the mucus as a potentially important barrier to obtain sufficient bioavailability of orally administered drugs, and thus an important parameter to address...

  1. Identification of IFN-gamma-producing CD4+ T cells following PMA stimulation

    DEFF Research Database (Denmark)

    Kemp, K; Bruunsgaard, H

    2001-01-01

    Treatment of T cells with phorbol esters, such as phorbol myristate acetate (PMA), induces downregulation of CD4, making unambiguous identification of this subset difficult. In this study, the kinetics of intracellular expression of interferon-gamma (IFN-gamma) and downmodulation of surface CD4...... were measured in peripheral blood mononuclear cells (PBMC) after PMA stimulation. The number of IFN-gamma-producing cells increased within a 4-h period while the fluorescence intensity of the CD4(+) cell population decreased, and the two phenomena were correlated (n = 9; p = 0.01). Our data suggest...... that intracellular staining of CD4 together with cytokine staining will make identification of CD4(+) cells possible and facilitate the procedure of intracellular staining of cytokines....

  2. IFN-γ regulates human dental pulp stem cells behavior via NF-κB and MAPK signaling

    Science.gov (United States)

    He, Xinyao; Jiang, Wenkai; Luo, Zhirong; Qu, Tiejun; Wang, Zhihua; Liu, Ningning; Zhang, Yaqing; Cooper, Paul R.; He, Wenxi

    2017-01-01

    During caries, dental pulp expresses a range of pro-inflammatory cytokines in response to the infectious challenge. Interferon gamma (IFN-γ) is a dimerized soluble cytokine, which is critical for immune responses. Previous study has demonstrated that IFN-γ at relative high concentration (100 ng/mL) treatment improved the impaired dentinogenic and immunosuppressive regulatory functions of disease-derived dental pulp stem cells (DPSCs). However, little is known about the regulatory effects of IFN-γ at relative low concentration on healthy DPSC behavior (including proliferation, migration, and multiple-potential differentiation). Here we demonstrate that IFN-γ at relatively low concentrations (0.5 ng/mL) promoted the proliferation and migration of DPSCs, but abrogated odonto/osteogenic differentiation. Additionally, we identified that NF-κB and MAPK signaling pathways are both involved in the process of IFN-γ-regulated odonto/osteogenic differentiation of DPSCs. DPSCs treated with IFN-γ and supplemented with pyrrolidine dithiocarbamate (PDTC, an NF-κB inhibitor) or SB203580 (a MAPK inhibitor) showed significantly improved potential for odonto/osteogenic differentiation of DPSCs both in vivo and in vitro. These data provide important insight into the regulatory effects of IFN-γ on the biological behavior of DPSCs and indicate a promising therapeutic strategy for dentin/pulp tissue engineering in future endodontic treatment. PMID:28098169

  3. Activation of IFN pathways and plasmacytoid dendritic cell recruitment in target organs of primary Sjögren's syndrome.

    Science.gov (United States)

    Gottenberg, Jacques-Eric; Cagnard, Nicolas; Lucchesi, Carlo; Letourneur, Franck; Mistou, Sylvie; Lazure, Thierry; Jacques, Sebastien; Ba, Nathalie; Ittah, Marc; Lepajolec, Christine; Labetoulle, Marc; Ardizzone, Marc; Sibilia, Jean; Fournier, Catherine; Chiocchia, Gilles; Mariette, Xavier

    2006-02-21

    Gene expression analysis of target organs might help provide new insights into the pathogenesis of autoimmune diseases. We used global gene expression profiling of minor salivary glands to identify patterns of gene expression in patients with primary Sjögren's syndrome (pSS), a common and prototypic systemic autoimmune disease. Gene expression analysis allowed for differentiating most patients with pSS from controls. The expression of 23 genes in the IFN pathways, including two Toll-like receptors (TLR8 and TLR9), was significantly different between patients and controls. Furthermore, the increased expression of IFN-inducible genes, BAFF and IFN-induced transmembrane protein 1, was also demonstrated in ocular epithelial cells by quantitative RT-PCR. In vitro activation showed that these genes were effectively modulated by IFNs in salivary gland epithelial cells, the target cells of autoimmunity in pSS. The activation of IFN pathways led us to investigate whether plasmacytoid dendritic cells were recruited in salivary glands. These IFN-producing cells were detected by immunohistochemistry in all patients with pSS, whereas none was observed in controls. In conclusion, our results support the pathogenic interaction between the innate and adaptive immune system in pSS. The persistence of the IFN signature might be related to a vicious circle, in which the environment interacts with genetic factors to drive the stimulation of salivary TLRs.

  4. Activation of IFN pathways and plasmacytoid dendritic cell recruitment in target organs of primary Sjögren’s syndrome

    Science.gov (United States)

    Gottenberg, Jacques-Eric; Cagnard, Nicolas; Lucchesi, Carlo; Letourneur, Franck; Mistou, Sylvie; Lazure, Thierry; Jacques, Sebastien; Ba, Nathalie; Ittah, Marc; Lepajolec, Christine; Labetoulle, Marc; Ardizzone, Marc; Sibilia, Jean; Fournier, Catherine; Chiocchia, Gilles; Mariette, Xavier

    2006-01-01

    Gene expression analysis of target organs might help provide new insights into the pathogenesis of autoimmune diseases. We used global gene expression profiling of minor salivary glands to identify patterns of gene expression in patients with primary Sjögren’s syndrome (pSS), a common and prototypic systemic autoimmune disease. Gene expression analysis allowed for differentiating most patients with pSS from controls. The expression of 23 genes in the IFN pathways, including two Toll-like receptors (TLR8 and TLR9), was significantly different between patients and controls. Furthermore, the increased expression of IFN-inducible genes, BAFF and IFN-induced transmembrane protein 1, was also demonstrated in ocular epithelial cells by quantitative RT-PCR. In vitro activation showed that these genes were effectively modulated by IFNs in salivary gland epithelial cells, the target cells of autoimmunity in pSS. The activation of IFN pathways led us to investigate whether plasmacytoid dendritic cells were recruited in salivary glands. These IFN-producing cells were detected by immunohistochemistry in all patients with pSS, whereas none was observed in controls. In conclusion, our results support the pathogenic interaction between the innate and adaptive immune system in pSS. The persistence of the IFN signature might be related to a vicious circle, in which the environment interacts with genetic factors to drive the stimulation of salivary TLRs. PMID:16477017

  5. IFN-γ regulates human dental pulp stem cells behavior via NF-κB and MAPK signaling.

    Science.gov (United States)

    He, Xinyao; Jiang, Wenkai; Luo, Zhirong; Qu, Tiejun; Wang, Zhihua; Liu, Ningning; Zhang, Yaqing; Cooper, Paul R; He, Wenxi

    2017-01-18

    During caries, dental pulp expresses a range of pro-inflammatory cytokines in response to the infectious challenge. Interferon gamma (IFN-γ) is a dimerized soluble cytokine, which is critical for immune responses. Previous study has demonstrated that IFN-γ at relative high concentration (100 ng/mL) treatment improved the impaired dentinogenic and immunosuppressive regulatory functions of disease-derived dental pulp stem cells (DPSCs). However, little is known about the regulatory effects of IFN-γ at relative low concentration on healthy DPSC behavior (including proliferation, migration, and multiple-potential differentiation). Here we demonstrate that IFN-γ at relatively low concentrations (0.5 ng/mL) promoted the proliferation and migration of DPSCs, but abrogated odonto/osteogenic differentiation. Additionally, we identified that NF-κB and MAPK signaling pathways are both involved in the process of IFN-γ-regulated odonto/osteogenic differentiation of DPSCs. DPSCs treated with IFN-γ and supplemented with pyrrolidine dithiocarbamate (PDTC, an NF-κB inhibitor) or SB203580 (a MAPK inhibitor) showed significantly improved potential for odonto/osteogenic differentiation of DPSCs both in vivo and in vitro. These data provide important insight into the regulatory effects of IFN-γ on the biological behavior of DPSCs and indicate a promising therapeutic strategy for dentin/pulp tissue engineering in future endodontic treatment.

  6. Role of IL-12 and IFN-γ in immune response to toxoplasma gondii infection

    International Nuclear Information System (INIS)

    Moawad, M.A.F.; ElGawish, M.A.M.

    2004-01-01

    Interlenkin 12 (IL-12) is a potent immunoregulatory molecule that is critically involved in a wide range of diseases. In several murine models of intracellular infection, endogenous IL-12 has been shown to be crucial for the generation of a protective Th1 response in a primary infection for a intracellular pathogens. Interferon-gamma (IFN-γ) is also an important mediator of cellular immunity against microbial pathogens and tumor cells due to its potent capacity to activate macrophages for enhanced cytotoxicity. The aim of the present study is to evaluate the immune response to toxoplasma gondii after primary inflection (infected groups and secondary infection (re-infected groups for over 19 weeks (the time of the experiment). the evaluation was assessed by measurements of levels of IL-12 and IFN-γ using ELISA technique in the sera of these infected rats. The results demonstrated that the primary immune response induced a fluctuation in the levels of IL-12 in the sera of infected rats, which reached maximum value of 122.6 ±1.4 pg/ml after 15 weeks of primary infection. While, in the challenged groups (secondary immune response, re-infected groups) the levels of IL-12 were generally lower than that of the primary immune response. On the other hand, IFN-γ levels increased significantly in the secondary immune response (re-infected groups) as compared to primary immune response 9 infected groups) In conclusion, the results suggest that IL-12 might have a role in the defense mechanism against intracellular infection with T-gondii especially in primary immune response than in the secondary immune response. This is in contrast to IFN-γ that takes the up-hand in secondary immune response to T-gondii infection

  7. Intracranial AAV-IFN-β gene therapy eliminates invasive xenograft glioblastoma and improves survival in orthotopic syngeneic murine model.

    Science.gov (United States)

    GuhaSarkar, Dwijit; Neiswender, James; Su, Qin; Gao, Guangping; Sena-Esteves, Miguel

    2017-02-01

    The highly invasive property of glioblastoma (GBM) cells and genetic heterogeneity are largely responsible for tumor recurrence after the current standard-of-care treatment and thus a direct cause of death. Previously, we have shown that intracranial interferon-beta (IFN-β) gene therapy by locally administered adeno-associated viral vectors (AAV) successfully treats noninvasive orthotopic glioblastoma models. Here, we extend these findings by testing this approach in invasive human GBM xenograft and syngeneic mouse models. First, we show that a single intracranial injection of AAV encoding human IFN-β eliminates invasive human GBM8 tumors and promotes long-term survival. Next, we screened five AAV-IFN-β vectors with different promoters to drive safe expression of mouse IFN-β in the brain in the context of syngeneic GL261 tumors. Two AAV-IFN-β vectors were excluded due to safety concerns, but therapeutic studies with the other three vectors showed extensive tumor cell death, activation of microglia surrounding the tumors, and a 56% increase in median survival of the animals treated with AAV/P2-Int-mIFN-β vector. We also assessed the therapeutic effect of combining AAV-IFN-β therapy with temozolomide (TMZ). As TMZ affects DNA replication, an event that is crucial for second-strand DNA synthesis of single-stranded AAV vectors before active transcription, we tested two TMZ treatment regimens. Treatment with TMZ prior to AAV-IFN-β abrogated any benefit from the latter, while the reverse order of treatment doubled the median survival compared to controls. These studies demonstrate the therapeutic potential of intracranial AAV-IFN-β therapy in a highly migratory GBM model as well as in a syngeneic mouse model and that combination with TMZ is likely to enhance its antitumor potency. © 2016 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

  8. Proteolysis of MDA5 and IPS-1 is not required for inhibition of the type I IFN response by poliovirus.

    Science.gov (United States)

    Kotla, Swathi; Gustin, Kurt E

    2015-10-06

    The type I interferon (IFN) response is a critical component of the innate immune response to infection by RNA viruses and is initiated via recognition of viral nucleic acids by RIG-like receptors (RLR). Engagement of these receptors in the cytoplasm initiates a signal transduction pathway leading to activation of the transcription factors NF-κB, ATF-2 and IRF-3 that coordinately upregulate transcription of type I IFN genes, such as that encoding IFN-β. In this study the impact of poliovirus infection on the type I interferon response has been examined. The type I IFN response was assessed by measuring IFN-β mRNA levels using qRT-PCR and normalizing to levels of β-actin mRNA. The status of host factors involved in activation of the type I IFN response was examined by immunoblot, immunofluorescence microcopy and qRT-PCR. The results show that poliovirus infection results in induction of very low levels of IFN-β mRNA despite clear activation of NF-κB and ATF-2. In contrast, analysis of IRF-3 revealed no transcriptional induction of an IRF-3-responsive promoter or homodimerization of IRF-3 indicating it is not activated in poliovirus-infected cells. Exposure of poliovirus-infected cells to poly(I:C) results in lower levels of IFN-β mRNA synthesis and IRF-3 activation compared to mock-infected cells. Analysis of MDA-5 and IPS-1 revealed that these components of the RLR pathway were largely intact at times when the type I IFN response was suppressed. Collectively, these results demonstrate that poliovirus infection actively suppresses the host type I interferon response by blocking activation of IRF-3 and suggests that this is not mediated by cleavage of MDA-5 or IPS-1.

  9. Critical role of IFN-gamma in CFA-mediated protection of NOD mice from diabetes development.

    Science.gov (United States)

    Mori, Yoshiko; Kodaka, Tetsuro; Kato, Takako; Kanagawa, Edith M; Kanagawa, Osami

    2009-11-01

    IFN-gamma signaling-deficient non-obese diabetic (NOD) mice develop diabetes with similar kinetics to those of wild-type NOD mice. However, the immunization of IFN-gamma signaling-deficient NOD mice with CFA failed to induce long-term protection, whereas wild-type NOD mice receiving CFA remained diabetes-free. CFA also failed to protect IFN-gamma receptor-deficient (IFN-gammaR(-/-)) NOD mice from the autoimmune rejection of transplanted islets, as it does in diabetic NOD mice, and from disease transfer by spleen cells from diabetic NOD mice. These data clearly show that the pro-inflammatory cytokine IFN-gamma is necessary for the CFA-mediated protection of NOD mice from diabetes. There is no difference in the T(h)1/T(h)17 balance between IFN-gammaR(-/-) NOD and wild-type NOD mice. There is also no difference in the total numbers and percentages of regulatory T (Treg) cells in the lymph node CD4(+) T-cell populations between IFN-gammaR(-/-) NOD and wild-type NOD mice. However, pathogenic T cells lacking IFN-gammaR are resistant to the suppressive effect of Treg cells, both in vivo and in vitro. Therefore, it is likely that CFA-mediated protection against diabetes development depends on a change in the balance between Treg cells and pathogenic T cells, and IFN-gamma signaling seems to control the susceptibility of pathogenic T cells to the inhibitory activity of Treg cells.

  10. Functional characterization of duck LSm14A in IFN-β induction.

    Science.gov (United States)

    Hua, Kexin; Li, Huilin; Chen, Huanchun; Foda, Mohamed Frahat; Luo, Rui; Jin, Hui

    2017-11-01

    Human LSm14A is a key component of processing body (P-body) assembly that mediates interferon-β (IFN-β) production by sensing viral RNA or DNA. To the best of our knowledge, we are the first to report duck LSm14A (duLSm14A) cloning from duck embryo fibroblasts (DEFs). Full-length duLSm14A encoded 461 amino acids and was highly homologous with chicken and swan goose sequences. More interestingly, the duLSm14A mRNA was extensively expressed in all the studied tissues. In DEFs, duLSm14A was localized in the cytoplasm as P-body-like dots. Expression of duLSm14A induced IFN-β through the activation of interferon regulatory factor-1 and nuclear factor-κB in DEFs. Furthermore, knockdown of duLSm14A by small interfering RNA notably decreased poly(I:C)- or duck reovirus-induced IFN-β production. The present study results indicate that the duLSm14A is an essential sensor that mediates duck innate immunity against viral infections. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Vitamin D Is Required for IFN-γ–Mediated Antimicrobial Activity of Human Macrophages

    Science.gov (United States)

    Fabri, Mario; Stenger, Steffen; Shin, Dong-Min; Yuk, Jae-Min; Liu, Philip T.; Realegeno, Susan; Lee, Hye-Mi; Krutzik, Stephan R.; Schenk, Mirjam; Sieling, Peter A.; Teles, Rosane; Montoya, Dennis; Iyer, Shankar S.; Bruns, Heiko; Lewinsohn, David M.; Hollis, Bruce W.; Hewison, Martin; Adams, John S.; Steinmeyer, Andreas; Zügel, Ulrich; Cheng, Genhong; Jo, Eun-Kyeong; Bloom, Barry R.; Modlin, Robert L.

    2012-01-01

    Control of tuberculosis worldwide depends on our understanding of human immune mechanisms, which combat the infection. Acquired T cell responses are critical for host defense against microbial pathogens, yet the mechanisms by which they act in humans remain unclear. We report that T cells, by the release of interferon-γ (IFN-γ), induce autophagy, phagosomal maturation, the production of antimicrobial peptides such as cathelicidin, and antimicrobial activity against Mycobacterium tuberculosis in human macrophages via a vitamin D–dependent pathway. IFN-γ induced the antimicrobial pathway in human macrophages cultured in vitamin D–sufficient sera, but not in sera from African-Americans that have lower amounts of vitamin D and who are more susceptible to tuberculosis. In vitro supplementation of vitamin D–deficient serum with 25-hydroxyvitamin D3 restored IFN-γ–induced antimicrobial peptide expression, autophagy, phagosome-lysosome fusion, and antimicrobial activity. These results suggest a mechanism in which vitamin D is required for acquired immunity to overcome the ability of intracellular pathogens to evade macrophage-mediated antimicrobial responses. The present findings underscore the importance of adequate amounts of vitamin D in all human populations for sustaining both innate and acquired immunity against infection. PMID:21998409

  12. PENINGKATAN CD8 DAN IFN-γ PADA HYPERSENSITIVITY PNEUMONITIS (HP AKIBAT PAJANAN DEBU PENGGILINGAN PADI

    Directory of Open Access Journals (Sweden)

    Isa Ma'rufi

    2017-10-01

    Full Text Available Abstrak     Masalah klinis kesehatan kerja pada pekerja penggilingan padi saat ini adalah penyakit saluran pernafasan. Penelitian ini bertujuan untuk menganalisis peningkatan CD8 dan IFN-γ pada Pneumonitis Hipersensitif (HP akibat pajanan debu penggilingan padi pada mencit  (Musmusculus BALB/C. Penelitian yang dilakukan adalah penelitian eksperimental laboratoris dengan hewan coba mencit (Musmusculus BALB/C,  rancangan penelitian yang digunakan adalah Randomized the post test only control group design. Mencit  (Musmusculus BALB/C dipajan dengan debu penggilingan padi selama empat jam/hari selama tiga puluh hari dengan konsentrasi 0.50 mg/m3, 0.75 mg/m3, 1.00 mg/m3. Variabel bebas adalah debu penggilingan padi, sedangkan variabel tergantung adalah   CD8 dan IFN-γ, serta gambaran histopatologis paru mencit, sedangkan variabel kendali adalah strain, berat badan, dan umur. Hasil penelitian menunjukkan bahwa terjadi peningkatan kadar CD8 antara kontrol dengan perlakuan, dan secara statistik  ada perbedaan yang bermakna. Kemudian terjadi peningkatan IFN-γ dan secara statistik ada perbedaan yang bermakna antara kontrol dan perlakuan pada mencit  (Musmusculus BALB/C. Hasil penelitian dapat digunakan sebagai dasar upaya pencegahan dan pemberian terapi penyakit HP lebih dini sehingga dapat meningkatkan kualitas paru.   Kata Kunci: CD8, IFN-γ,  debu penggilingan padi     Abtract   The purpose of this research was to analyze increase of CD8  and IFN-γ of Hypersensitivity Pneumonitis (HP as a result from the exposure of dust from paddy milling on mice (MusmusculusBALB/C. The research done was a laboratory experimental research with mice (MusMusculus as experimental animal.  The research design used was the post only control group design using mice (MusMusculus Balb/c as experimental animal.  Mice (Musmusculus Balb/c were exposed to dust from paddy milling for four (4 hours/day and it was done for thirty (30 days with the exposed

  13. Internal medicine. An illustrated radiological guide

    International Nuclear Information System (INIS)

    Al-Tubaikh, Jarrah Ali; Sabah Hospital, Kuwait

    2010-01-01

    This book explains how radiology can be a powerful tool for establishing the diagnosis of many internal medicine diseases that are usually diagnosed on the basis of their laboratory or clinical presentation. It is organized in the classic fashion for internal medicine books, with eleven chapters covering the different internal medicine specialties. Within these chapters, more than 450 diseases are considered, some of which are rarely encountered but are nonetheless significant. For each disease, radiological and clinical features are displayed in images and high-quality digital medical illustrations, and those differential diagnoses are identified that can be ruled out by imaging alone. In addition, the pathophysiology underlying the radiological features is described, enabling the reader to understand why a particular sign is seen on MR images, CT scans, or plain radiographs. The book will serve as an excellent radiological atlas for internal medicine practitioners and family physicians, showing disease presentations that may be hard to find in standard medical textbooks and explaining which imaging modalities are likely to be most informative in particular patients. (orig.)

  14. The role of Hsp0, CD-8 and IFN-γ in immunopathobiogenesis of periapical granuloma in dental caries

    Directory of Open Access Journals (Sweden)

    Risya Cilmiaty

    2014-03-01

    Full Text Available Background: The incidence of dental caries with periapical granulomas in Indonesia is quite high. However, the mechanism of the formation of periapical granulomas in dental caries caused by bacterial infection in immunopathobiogenesis cannot be explained completely. Thus, this explanation is necessary in order to be used as a basis for diagnostic, preventive and therapeutic measures. Purpose: This research was aimed to determine the role of Hsp60, CD-8 and IFN-γ in immunopatobiogenesis of periapical granuloma in dental caries. Methods: This research was an analytic observational study with cross sectional approach. Samples of this research were 36 teeth of patients with dental caries, consisting of 18 caries teeth with periapical granulomas and 18 caries teeth without periapical granulomas. The variables observed in this research were Hsp60, CD-8 and IFN-γ. Measurements were conducted by using immunohistochemical methods on periapical tissue. Results: The mean of Hsp60, CD-8 and IFN-γ in granuloma group was significantly higher than those in non granuloma group (p<0.05. The positive role of IFN-γ on the incidence of granulomas appeared to be more prominent. Conclusion: The study suggested that in immunopathobiogenesis of periapical granuloma in dental caries, Hsp60, CD-8 and IFN-γ played important roles, but the role of IFN-γ was found to be more prominent.Latar belakang: Angka kejadian gigi karies dengan granuloma periapikal di Indonesia cukup tinggi, Namun mekanisme terbentuknya granuloma periapikal pada gigi karies yang disebabkan oleh infeksi bakteri secara imunopatobiogenesis belum dapat dijelaskan secara tuntas. Adanya penjelasan ini diperlukan agar dapat digunakan sebagai dasar pengembangan diagnosis, langkah preventif dan terapinya. Tujuan: Penelitian ini bertujuan untuk mengetahui peran Hsp60, CD-8 dan IFN-γ dalam immunopatobiogenesis dari granuloma periapikal karies gigi. Metode: Penelitian ini merupakan penelitian observasional

  15. IFN-{gamma} enhances neurogenesis in wild-type mice and in a mouse model of Alzheimer's disease

    DEFF Research Database (Denmark)

    Baron, Rona; Nemirovsky, Anna; Harpaz, Idan

    2008-01-01

    the spatial learning and memory performance of the animals. In older mice, the effect of IFN-gamma is more pronounced in both wild-type mice and mice with Alzheimer's-like disease and is associated with neuroprotection. In addition, IFN-gamma reverses the increase in oligodendrogenesis observed in a mouse...... mechanisms can generate immunity to such deficits in neuronal repair. We demonstrate that in contrast to primarily innate immunity cytokines, such as interleukin-6 and tumor necrosis factor-alpha, the adaptive immunity cytokine IFN-gamma enhances neurogenesis in the dentate gyrus of adult mice and improves...

  16. Bringing Life to Illustration and Illustrating the World in Movement through Visual Literacy

    DEFF Research Database (Denmark)

    Carpe Pérez, Inmaculada Concepción; Pedersen, Hanne

    2016-01-01

    “If a picture is worth a thousand words” as Arthur Brisbane said, journalist of the New York Times in 1911 Fig.1 How many words would equal the hundreds of frames containing in an animation? In this equation as any other, illustration and animation are complex visual expressions, full of shapes c...

  17. Professional representation and the free-lance medical illustrator.

    Science.gov (United States)

    Mount, K N; Daugherty, J

    1994-01-01

    We researched factors related to the success or failure in working relationships between free-lance medical illustrators and artist's representatives. In the fall of 1992, surveys were mailed to 230 medical illustrators; 105 (46%) completed surveys were returned. Respondents were divided into three categories: 1) medical illustrators currently represented, 2) medical illustrators previously represented, and 3) medical illustrators who had never been represented. Comparisons made among illustrators from the three groups included business practices, clientele, experience, and self-promotion techniques. These comparisons revealed notable differences and similarities between the three groups and were subsequently analyzed to identify the characteristics of medical illustrators who would benefit from professional representation.

  18. Sprache als Barriere (Language as a Barrier)

    Science.gov (United States)

    Mattheier, Klaus

    1974-01-01

    The concept of language barrier has its derivations in the fields of dialectology, sociology and psychology. In contemporary usage however, the concept has two meanings i.e. regional-cultural barrier and socio-cultural barrier. (Text is in German.) (DS)

  19. MyD88 and STING signaling pathways are required for IRF3-mediated IFN-β induction in response to Brucella abortus infection.

    Directory of Open Access Journals (Sweden)

    Leonardo A de Almeida

    Full Text Available Type I interferons (IFNs are cytokines that orchestrate diverse immune responses to viral and bacterial infections. Although typically considered to be most important molecules in response to viruses, type I IFNs are also induced by most, if not all, bacterial pathogens. In this study, we addressed the role of type I IFN signaling during Brucella abortus infection, a facultative intracellular bacterial pathogen that causes abortion in domestic animals and undulant fever in humans. Herein, we have shown that B. abortus induced IFN-β in macrophages and splenocytes. Further, IFN-β induction by Brucella was mediated by IRF3 signaling pathway and activates IFN-stimulated genes via STAT1 phosphorylation. In addition, IFN-β expression induced by Brucella is independent of TLRs and TRIF signaling but MyD88-dependent, a pathway not yet described for Gram-negative bacteria. Furthermore, we have identified Brucella DNA as the major bacterial component to induce IFN-β and our study revealed that this molecule operates through a mechanism dependent on RNA polymerase III to be sensed probably by an unknown receptor via the adaptor molecule STING. Finally, we have demonstrated that IFN-αβR KO mice are more resistant to infection suggesting that type I IFN signaling is detrimental to host control of Brucella. This resistance phenotype is accompanied by increased IFN-γ and NO production by IFN-αβR KO spleen cells and reduced apoptosis.

  20. MyD88 and STING Signaling Pathways Are Required for IRF3-Mediated IFN-β Induction in Response to Brucella abortus Infection

    Science.gov (United States)

    de Almeida, Leonardo A.; Carvalho, Natalia B.; Oliveira, Fernanda S.; Lacerda, Thais L. S.; Vasconcelos, Anilton C.; Nogueira, Lucas; Bafica, Andre; Silva, Aristóbolo M.; Oliveira, Sergio C.

    2011-01-01

    Type I interferons (IFNs) are cytokines that orchestrate diverse immune responses to viral and bacterial infections. Although typically considered to be most important molecules in response to viruses, type I IFNs are also induced by most, if not all, bacterial pathogens. In this study, we addressed the role of type I IFN signaling during Brucella abortus infection, a facultative intracellular bacterial pathogen that causes abortion in domestic animals and undulant fever in humans. Herein, we have shown that B. abortus induced IFN-β in macrophages and splenocytes. Further, IFN-β induction by Brucella was mediated by IRF3 signaling pathway and activates IFN-stimulated genes via STAT1 phosphorylation. In addition, IFN-β expression induced by Brucella is independent of TLRs and TRIF signaling but MyD88-dependent, a pathway not yet described for Gram-negative bacteria. Furthermore, we have identified Brucella DNA as the major bacterial component to induce IFN-β and our study revealed that this molecule operates through a mechanism dependent on RNA polymerase III to be sensed probably by an unknown receptor via the adaptor molecule STING. Finally, we have demonstrated that IFN-αβR KO mice are more resistant to infection suggesting that type I IFN signaling is detrimental to host control of Brucella. This resistance phenotype is accompanied by increased IFN-γ and NO production by IFN-αβR KO spleen cells and reduced apoptosis. PMID:21829705

  1. Local therapy with CpG motifs in a murine model of allergic airway inflammation in IFN-beta knock-out mice

    DEFF Research Database (Denmark)

    Matheu, Victor; Treschow, Alexandra; Teige, Ingrid

    2005-01-01

    BACKGROUND: CpG oligodeoxynucleotides (CpG-ODN) are capable of inducing high amounts of type I IFNs with many immunomodulatory properties. Furthermore, type-I IFNs have been proposed to play a key role in mediating effects of CpG-ODN. The precise role of IFN-beta in the immunomodulatory effects o...

  2. Reproducibility of Interferon Gamma (IFN-γ) Release Assays. A Systematic Review

    Science.gov (United States)

    Tagmouti, Saloua; Slater, Madeline; Benedetti, Andrea; Kik, Sandra V.; Banaei, Niaz; Cattamanchi, Adithya; Metcalfe, John; Dowdy, David; van Zyl Smit, Richard; Dendukuri, Nandini

    2014-01-01

    Rationale: Interferon gamma (IFN-γ) release assays for latent tuberculosis infection result in a larger-than-expected number of conversions and reversions in occupational screening programs, and reproducibility of test results is a concern. Objectives: Knowledge of the relative contribution and extent of the individual sources of variability (immunological, preanalytical, or analytical) could help optimize testing protocols. Methods: We performed a systematic review of studies published by October 2013 on all potential sources of variability of commercial IFN-γ release assays (QuantiFERON-TB Gold In-Tube and T-SPOT.TB). The included studies assessed test variability under identical conditions and under different conditions (the latter both overall and stratified by individual sources of variability). Linear mixed effects models were used to estimate within-subject SD. Measurements and Main Results: We identified a total of 26 articles, including 7 studies analyzing variability under the same conditions, 10 studies analyzing variability with repeat testing over time under different conditions, and 19 studies reporting individual sources of variability. Most data were on QuantiFERON (only three studies on T-SPOT.TB). A considerable number of conversions and reversions were seen around the manufacturer-recommended cut-point. The estimated range of variability of IFN-γ response in QuantiFERON under identical conditions was ±0.47 IU/ml (coefficient of variation, 13%) and ±0.26 IU/ml (30%) for individuals with an initial IFN-γ response in the borderline range (0.25–0.80 IU/ml). The estimated range of variability in noncontrolled settings was substantially larger (±1.4 IU/ml; 60%). Blood volume inoculated into QuantiFERON tubes and preanalytic delay were identified as key sources of variability. Conclusions: This systematic review shows substantial variability with repeat IFN-γ release assays testing even under identical conditions, suggesting that reversions

  3. Cytokine-induced depression during IFN-α treatment: the role of IL-6 and sleep quality

    Science.gov (United States)

    Prather, Aric A.; Rabinovitz, Mordechai; Pollock, Bruce G.; Lotrich, Francis E.

    2009-01-01

    Depressive symptoms, poor sleep quality, and systemic markers of inflammation (e.g. interleukin (IL)-6) are frequently associated. Interferon-alpha (IFN-α) therapy results in major depressive disorder (MDD) in some people, offering the possibility to elucidate the relationship of MDD to sleep and inflammation during treatment. In particular, delineating the temporal relations among these factors could help inform their causal relationships. To this end, a cohort of 95 non-depressed hepatitis C patients was followed prospectively for four consecutive months during IFN-α therapy. We found that higher pre-treatment levels of circulating IL-6 predicted incidence of MDD (X2(1)=7.7; psleep quality may be risk factors for IFN-α induced depression. Furthermore, these findings highlight the complex temporal relationships that exist among sleep, depression, and inflammation, and support the need for further prospective investigations to elucidate the dynamics that underlie depression during IFN-α treatment. PMID:19615438

  4. To achieve an earlier IFN-γ response is not sufficient to control Mycobacterium tuberculosis infection in mice.

    Science.gov (United States)

    Vilaplana, Cristina; Prats, Clara; Marzo, Elena; Barril, Carles; Vegué, Marina; Diaz, Jorge; Valls, Joaquim; López, Daniel; Cardona, Pere-Joan

    2014-01-01

    The temporo-spatial relationship between the three organs (lung, spleen and lymph node) involved during the initial stages of Mycobacterium tuberculosis infection has been poorly studied. As such, we performed an experimental study to evaluate the bacillary load in each organ after aerosol or intravenous infection and developed a mathematical approach using the data obtained in order to extract conclusions. The results showed that higher bacillary doses result in an earlier IFN-γ response, that a certain bacillary load (BL) needs to be reached to trigger the IFN-γ response, and that control of the BL is not immediate after onset of the IFN-γ response, which might be a consequence of the spatial dimension. This study may have an important impact when it comes to designing new vaccine candidates as it suggests that triggering an earlier IFN-γ response might not guarantee good infection control, and therefore that additional properties should be considered for these candidates.

  5. Neutralization of IFN-γ reverts clinical and laboratory features in a mouse model of macrophage activation syndrome.

    Science.gov (United States)

    Prencipe, Giusi; Caiello, Ivan; Pascarella, Antonia; Grom, Alexei A; Bracaglia, Claudia; Chatel, Laurence; Ferlin, Walter G; Marasco, Emiliano; Strippoli, Raffaele; de Min, Cristina; De Benedetti, Fabrizio

    2018-04-01

    The pathogenesis of macrophage activation syndrome (MAS) is not clearly understood: a large body of evidence supports the involvement of mechanisms similar to those implicated in the setting of primary hemophagocytic lymphohistiocytosis. We sought to investigate the pathogenic role of IFN-γ and the therapeutic efficacy of IFN-γ neutralization in an animal model of MAS. We used an MAS model established in mice transgenic for human IL-6 (IL-6TG mice) challenged with LPS (MAS mice). Levels of IFN-γ and IFN-γ-inducible chemokines were evaluated by using real-time PCR in the liver and spleen and by means of ELISA in plasma. IFN-γ neutralization was achieved by using the anti-IFN-γ antibody XMG1.2 in vivo. Mice with MAS showed a significant upregulation of the IFN-γ pathway, as demonstrated by increased mRNA levels of Ifng and higher levels of phospho-signal transducer and activator of transcription 1 in the liver and spleen and increased expression of the IFN-γ-inducible chemokines Cxcl9 and Cxcl10 in the liver and spleen, as well as in plasma. A marked increase in Il12a and Il12b expression was also found in livers and spleens of mice with MAS. In addition, mice with MAS had a significant increase in numbers of liver CD68 + macrophages. Mice with MAS treated with an anti-IFN-γ antibody showed a significant improvement in survival and body weight recovery associated with a significant amelioration of ferritin, fibrinogen, and alanine aminotransferase levels. In mice with MAS, treatment with the anti-IFN-γ antibody significantly decreased circulating levels of CXCL9, CXCL10, and downstream proinflammatory cytokines. The decrease in CXCL9 and CXCL10 levels paralleled the decrease in serum levels of proinflammatory cytokines and ferritin. These results provide evidence for a pathogenic role of IFN-γ in the setting of MAS. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  6. Coordinate induction of IFN-α and -γ by SARS-CoV also in the absence of virus replication

    International Nuclear Information System (INIS)

    Castilletti, Concetta; Bordi, Licia; Lalle, Eleonora; Rozera, Gabriella; Poccia, Fabrizio; Agrati, Chiara; Abbate, Isabella; Capobianchi, Maria R.

    2005-01-01

    Background:: Severe acute respiratory syndrome (SARS) is an emerging infection caused by a novel coronavirus known as SARS-CoV, characterized by an over-exuberant immune response with lung lymphomononuclear cells infiltration and proliferation that may account for tissue damage more than the direct effect of viral replication. This study is aimed at investigating the capability of SARS-CoV to activate IFN-α and -γ expression in lymphomonocytes (PBMC) from healthy donors, evaluating whether viral replication is necessary for this activation. Results:: SARS-CoV virus is able to induce both IFN-α and -γ mRNA accumulation and protein release in a dose-dependent manner, MOI 10 being the most effective. The time course curve indicated that IFN-α mRNA induction peaked at 24 h.p.i,. whereas IFN-γ mRNA was still increasing at 48 h.p.i. Released IFN (both types) reached a plateau after 24-48 h.p.i. and remained rather stable over a 5-day period. A transient peak of negative strand viral RNA was detected after 1-2 days of infection, but neither infectious virus progeny yield nor newly produced viral genomic RNA could be evidenced in infected cultures, even after prolonged observation time (up to 13 days). Cocultivation of PBMC with fixed SARS-CoV-infected Vero cells was even more efficient than exposure to live virus in eliciting IFN-α and -γ induction. A combination of IFN-α and -γ strongly inhibited SARS-CoV replication in Vero cells, while the single cytokines were much less effective. Conclusions:: This study provides evidence that SARS-CoV is able to induce in normal PBMC a coordinate induction of IFN-α and -γ gene expression. Virus replication is not necessary for IFN induction since efficient IFN expression could be obtained also by the cocultivation of normal PBMC with fixed SARS-CoV-infected cells. Concomitant activation of IFN-α and -γ gene expression by SARS-CoV in vivo may be relevant for the pathogenesis of the disease, both for the possible

  7. An illustrated landslide handbook for developing nations

    Science.gov (United States)

    Highland, Lynn M.; Bobrowsky, Peter

    2008-01-01

    As landslides continue to be a hazard that account for large numbers of human and animal casualties, property loss, and infrastructure damage, as well as impacts on the natural environment, it is incumbent on developed nations that resources be allocated to educate affected populations in less developed nations, and provide them with tools to effectively manage this hazard. Given that the engineering, planning and zoning, and mitigation techniques for landslide hazard reduction are more accessible to developed nations, it is crucial that such landslide hazard management tools be communicated to less developed nations in a language that is not overly technical, and provides information on basic scientific explanations on where, why and how landslides occur. The experiences of the United States, Canada, and many other nations demonstrate that, landslide science education, and techniques for reducing damaging landslide impacts may be presented in a manner that can be understood by the layperson. There are various methods through which this may be accomplished–community-level education, technology transfer, and active one-on-one outreach to national and local governments, and non-governmental organizations (NGOs), who disseminate information throughout the general population. The population at large can also benefit from the dissemination of landslide information directly to individual community members. The United States Geological Survey and the Geological Survey of Canada have just published and will distribute a universal landslide handbook that can be easily made available to emergency managers, local governments, and individuals. The handbook, “The Landslide Handbook: A Guide to Understanding Landslides” is initially published as U.S. Geological Survey Circular 1325, in English, available in print, and accessible on the internet. It is liberally illustrated with schematics and photographs, and provides the means for a basic understanding of landslides, with

  8. Defining the Roles of IFN-γ and IL-17A in Inflammation and Protection against Helicobacter pylori Infection.

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    Louise Sjökvist Ottsjö

    Full Text Available CD4+ T cells have been shown to be essential for vaccine-induced protection against Helicobacter pylori infection. However, the effector mechanisms leading to reductions in the gastric bacterial loads of vaccinated mice remain unclear. We have investigated the function of IFN-γ and IL-17A for vaccine-induced protection and inflammation (gastritis using IFN-γ-gene-knockout (IFN-γ-/- mice, after sublingual or intragastric immunization with H. pylori lysate antigens and cholera toxin. Bacteria were enumerated in the stomachs of mice and related to the gastritis score and cellular immune responses. We report that sublingually and intragastrically immunized IFN-γ-/- mice had significantly reduced bacterial loads similar to immunized wild-type mice compared to respective unimmunized infection controls. The reduction in bacterial loads in sublingually and intragastrically immunized IFN-γ-/- mice was associated with significantly higher levels of IL-17A in stomach extracts and lower gastritis scores compared with immunized wild-type mice. To study the role of IL-17A for vaccine-induced protection in sublingually immunized IFN-γ-/- mice, IL-17A was neutralized in vivo at the time of infection. Remarkably, the neutralization of IL-17A in sublingually immunized IFN-γ-/- mice completely abolished protection against H. pylori infection and the mild gastritis. In summary, our results suggest that IFN-γ responses in the stomach of sublingually immunized mice promote vaccine-induced gastritis, after infection with H. pylori but that IL-17A primarily functions to reduce the bacterial load.

  9. Clinical trials using IFN-α as a vaccine adjuvant: new strategies for the molecular monitoring of the immune response

    International Nuclear Information System (INIS)

    Belardelli, F.; Arico, E.; Marincola, F.; Wang, E.

    2009-01-01

    The main general objective of this project was to define immunotherapy protocols based on the new concept of using IFN-a as and immune adjuvant, developing innovative methodologies suitable for predicting and monitoring the immunological and clinical responses. Specific aim of developing new micro arrays technologies particularly suitable for a molecular tracking and prediction of the response to IFN of cytokine-treated patients

  10. Role of IFN-gamma and LPS on Neuron/Glial Co-Cultures Infected by Neospora caninum

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    Erica Etelvina Viana De Jesus

    2014-10-01

    Full Text Available Neospora caninum causes cattle abortion and neurological symptoms in dogs. Although infection is usually asymptomatic, classical neurological symptoms of neosporosis may be associated with encephalitis. This parasite can grow in brain endothelial cells without markedly damages, but it can modulate the cellular environment to promote its survival in the brain. In previous studies, we described that IFN-γ decreased the parasite proliferation and down regulated nitric oxide production in astrocyte/microglia cultures. However, it remains unclear how glial cells respond to N. caninum in the presence of neurons. Therefore, we evaluated the effect of 300 IU/mL IFN-γ or 1.0 μg/mL of LPS on infected rat neuron/glial co-cultures. After 72 hours of infection, LPS did not affect the mitochondrial dehydrogenase activity. However, IFN-γ decreased this parameter by 15.5 and 12.0% in uninfected and infected cells, respectively. The number of tachyzoites decreased 54.1 and 44.3% in cells stimulated with IFN-γ and LPS, respectively. Infection or LPS treatment did not change NO production. On the other hand, IFN-γ induced increased nitrite release in 55.7%, but the infection reverted this induction. IL-10 levels increased only in infected cultures (treated or not, meanwhile PGE2 release was improved in IFN-γ/infected or LPS/infected cells. Although IFN-γ significantly reduced the neurite length in uninfected cultures (42.64%; p < 0.001, this inflammatory cytokine reverted the impairment of neurite outgrowth induced by the infection (81.39%. The results suggest a neuroprotective potential response of glia to N. caninum infection under IFN-γ stimulus. This observation contributes to understand the immune mediated mechanisms of neosporosis in CNS

  11. Roles of IFN-γ and γδ T cells in protective immunity against blood-stage malaria

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    Shin-Ichi eInoue

    2013-08-01

    Full Text Available Malaria is caused by infection with Plasmodium parasites. Various studies with knockout mice have indicated that IFN-γ plays essential roles in protective immunity against blood-stage Plasmodium infection. However, after Plasmodium infection, increased IFN-γ production by various types of cells is involved not only in protective immunity, but also in immunopathology. Recent reports have shown that IFN-γ acts as a pro-inflammatory cytokine to induce not only the activation of macrophages, but also the generation of uncommon myelolymphoid progenitor cells after Plasmodium infection. However, the effects of IFN-γ on hematopoietic stem cells and progenitor cells are unclear. Therefore, the regulation of hematopoiesis by IFN-γ during Plasmodium infection remains to be clarified. Although there are conflicting reports concerning the significance of γδ T cells in protective immunity against Plasmodium infection, γδ T cells may respond to infection and produce IFN-γ as innate immune cells in the early phase of blood-stage malaria. Our recent studies have shown that γδ T cells express CD40 ligand and produce IFN-γ after Plasmodium infection, resulting in the enhancement of dendritic cell activation as part of the immune response to eliminate Plasmodium parasites. These data suggest that the function of γδ T cells is similar to that of NK cells. Although several reports suggest that γδ T cells have the potential to act as memory cells for various infections, it remains to be determined whether memory γδ T cells are generated by Plasmodium infection and whether memory γδ T cells can contribute to the host defense against re-infection with Plasmodium. Here, we summarize and discuss the effects of IFN-γ and the various functions of γδ T cells in blood-stage Plasmodium infection.

  12. Association Between IFN-γ Gene Polymorphisms and IgA Nephropathy in a Chinese Han Population

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    Jie Gao

    2017-04-01

    Full Text Available Background/Aims: IFN-γ was reported to be involved in the development and progression of Immunoglobulin A nephropathy (IgAN, however, few studies have investigated the association between IFN-γ polymorphisms and IgAN. Therefore, we performed a case-control study to assess the association between IFN-γ polymorphisms and the risk of IgAN. Methods: Sequenom MassARRAY was used to genotype two SNPs (rs1861494 and rs2430561 in 351 patients with IgAN and 310 healthy controls. Associations were evaluated as odd ratios (OR with 95% confidence intervals (CI. Results: No association was found between IFN-γ rs1861494 and IgAN risk or clinical parameters. For rs2430561, the AA genotype was more common in patients with IgAN, compared with controls (AT vs. AA: OR = 0.57, P = 0.035. IFN-γ-rs2430561 T allele may be a protective factor for IgAN susceptibility (T vs. A: OR = 0.59, P = 0.04. Subgroup analysis based on clinical features revealed no significant association between rs2430561 polymorphism and clinical data such as gender, 24-h urine protein, blood pressure, Oxford classifcation and estimated glomerular fltration rate. IgAN patients had a higher IFN-γ serum level than healthy controls and patients with rs1861494 AA genotype had a higher IFN-γ serum level compared with those with AG/GG genotypes. Conclusions: IFN-γ polymorphisms may be involved in the development and progression of IgAN.

  13. Adenovirus-specific T-cell Subsets in Human Peripheral Blood and After IFN-γ Immunomagnetic Selection.

    Science.gov (United States)

    Qian, Chongsheng; Wang, Yingying; Cai, Huili; Laroye, Caroline; De Carvalho Bittencourt, Marcelo; Clement, Laurence; Stoltz, Jean-François; Decot, Véronique; Reppel, Loïc; Bensoussan, Danièle

    2016-01-01

    Adoptive antiviral cellular immunotherapy by infusion of virus-specific T cells (VSTs) is becoming an alternative treatment for viral infection after hematopoietic stem cell transplantation. The T memory stem cell (TSCM) subset was recently described as exhibiting self-renewal and multipotency properties which are required for sustained efficacy in vivo. We wondered if such a crucial subset for immunotherapy was present in VSTs. We identified, by flow cytometry, TSCM in adenovirus (ADV)-specific interferon (IFN)-γ+ T cells before and after IFN-γ-based immunomagnetic selection, and analyzed the distribution of the main T-cell subsets in VSTs: naive T cells (TN), TSCM, T central memory cells (TCM), T effector memory cell (TEM), and effector T cells (TEFF). In this study all of the different T-cell subsets were observed in the blood sample from healthy donor ADV-VSTs, both before and after IFN-γ-based immunomagnetic selection. As the IFN-γ-based immunomagnetic selection system sorts mainly the most differentiated T-cell subsets, we observed that TEM was always the major T-cell subset of ADV-specific T cells after immunomagnetic isolation and especially after expansion in vitro. Comparing T-cell subpopulation profiles before and after in vitro expansion, we observed that in vitro cell culture with interleukin-2 resulted in a significant expansion of TN-like, TCM, TEM, and TEFF subsets in CD4IFN-γ T cells and of TCM and TEM subsets only in CD8IFN-γ T cells. We demonstrated the presence of all T-cell subsets in IFN-γ VSTs including the TSCM subpopulation, although this was weakly selected by the IFN-γ-based immunomagnetic selection system.

  14. Influenza A virus protein PB1-F2 exacerbates IFN-beta expression of human respiratory epithelial cells.

    Science.gov (United States)

    Le Goffic, Ronan; Bouguyon, Edwige; Chevalier, Christophe; Vidic, Jasmina; Da Costa, Bruno; Leymarie, Olivier; Bourdieu, Christiane; Decamps, Laure; Dhorne-Pollet, Sophie; Delmas, Bernard

    2010-10-15

    The PB1-F2 protein of the influenza A virus (IAV) contributes to viral pathogenesis by a mechanism that is not well understood. PB1-F2 was shown to modulate apoptosis and to be targeted by the CD8(+) T cell response. In this study, we examined the downstream effects of PB1-F2 protein during IAV infection by measuring expression of the cellular genes in response to infection with wild-type WSN/33 and PB1-F2 knockout viruses in human lung epithelial cells. Wild-type virus infection resulted in a significant induction of genes involved in innate immunity. Knocking out the PB1-F2 gene strongly decreased the magnitude of expression of cellular genes implicated in antiviral response and MHC class I Ag presentation, suggesting that PB1-F2 exacerbates innate immune response. Biological network analysis revealed the IFN pathway as a link between PB1-F2 and deregulated genes. Using quantitative RT-PCR and IFN-β gene reporter assay, we determined that PB1-F2 mediates an upregulation of IFN-β expression that is dependent on NF-κB but not on AP-1 and IFN regulatory factor-3 transcription factors. Recombinant viruses knocked out for the PB1-F2 and/or the nonstructural viral protein 1 (the viral antagonist of the IFN response) genes provide further evidence that PB1-F2 increases IFN-β expression and that nonstructural viral protein 1 strongly antagonizes the effect of PB1-F2 on the innate response. Finally, we compared the effect of PB1-F2 variants taken from several IAV strains on IFN-β expression and found that PB1-F2-mediated IFN-β induction is significantly influenced by its amino acid sequence, demonstrating its importance in the host cell response triggered by IAV infection.

  15. Macrophage-expressed IFN-β contributes to apoptotic alveolar epithelial cell injury in severe influenza virus pneumonia.

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    Katrin Högner

    2013-02-01

    Full Text Available Influenza viruses (IV cause pneumonia in humans with progression to lung failure and fatal outcome. Dysregulated release of cytokines including type I interferons (IFNs has been attributed a crucial role in immune-mediated pulmonary injury during severe IV infection. Using ex vivo and in vivo IV infection models, we demonstrate that alveolar macrophage (AM-expressed IFN-β significantly contributes to IV-induced alveolar epithelial cell (AEC injury by autocrine induction of the pro-apoptotic factor TNF-related apoptosis-inducing ligand (TRAIL. Of note, TRAIL was highly upregulated in and released from AM of patients with pandemic H1N1 IV-induced acute lung injury. Elucidating the cell-specific underlying signalling pathways revealed that IV infection induced IFN-β release in AM in a protein kinase R- (PKR- and NF-κB-dependent way. Bone marrow chimeric mice lacking these signalling mediators in resident and lung-recruited AM and mice subjected to alveolar neutralization of IFN-β and TRAIL displayed reduced alveolar epithelial cell apoptosis and attenuated lung injury during severe IV pneumonia. Together, we demonstrate that macrophage-released type I IFNs, apart from their well-known anti-viral properties, contribute to IV-induced AEC damage and lung injury by autocrine induction of the pro-apoptotic factor TRAIL. Our data suggest that therapeutic targeting of the macrophage IFN-β-TRAIL axis might represent a promising strategy to attenuate IV-induced acute lung injury.

  16. Respiratory Syncytial Virus Nonstructural Proteins Upregulate SOCS1 and SOCS3 in the Different Manner from Endogenous IFN Signaling

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    Junwen Zheng

    2015-01-01

    Full Text Available Respiratory syncytial virus (RSV infection upregulates genes of the suppressor of cytokine signaling (SOCS family, which utilize a feedback loop to inhibit type I interferon dependent antiviral signaling pathway. Here, we reconstituted RSV nonstructural (NS protein expression plasmids (pNS1, pNS2, and pNS1/2 and tested whether NS1 or NS2 would trigger SOCS1 and SOCS3 protein expression. These NS proteins inhibited interferon- (IFN- α signaling through a mechanism involving the induction of SOCS1 and SOCS3, which appeared to be different from autocrine IFN dependent. NS1 induced both SOCS1 and SOCS3 upregulation, while NS2 only induced SOCS1 expression. The induced expression of SOCS1 and SOCS3 preceded endogenous IFN-signaling activation and inhibited the IFN-inducible antiviral response as well as chemokine induction. Treatments with INF-α and NS proteins both induced SOCS1 expression; however, they had opposing effects on IFN-α-dependent antiviral gene expression. Our results indicate that NS1 and NS2, which induce the expression of SOCS1 or SOCS3, might represent an independent pathway of stimulating endogenous IFN signaling.

  17. Neutrophils responsive to endogenous IFN-beta regulate tumor angiogenesis and growth in a mouse tumor model.

    Science.gov (United States)

    Jablonska, Jadwiga; Leschner, Sara; Westphal, Kathrin; Lienenklaus, Stefan; Weiss, Siegfried

    2010-04-01

    Angiogenesis is a hallmark of malignant neoplasias, as the formation of new blood vessels is required for tumors to acquire oxygen and nutrients essential for their continued growth and metastasis. However, the signaling pathways leading to tumor vascularization are not fully understood. Here, using a transplantable mouse tumor model, we have demonstrated that endogenous IFN-beta inhibits tumor angiogenesis through repression of genes encoding proangiogenic and homing factors in tumor-infiltrating neutrophils. We determined that IFN-beta-deficient mice injected with B16F10 melanoma or MCA205 fibrosarcoma cells developed faster-growing tumors with better-developed blood vessels than did syngeneic control mice. These tumors displayed enhanced infiltration by CD11b+Gr1+ neutrophils expressing elevated levels of the genes encoding the proangiogenic factors VEGF and MMP9 and the homing receptor CXCR4. They also expressed higher levels of the transcription factors c-myc and STAT3, known regulators of VEGF, MMP9, and CXCR4. In vitro, treatment of these tumor-infiltrating neutrophils with low levels of IFN-beta restored expression of proangiogenic factors to control levels. Moreover, depletion of these neutrophils inhibited tumor growth in both control and IFN-beta-deficient mice. We therefore suggest that constitutively produced endogenous IFN-beta is an important mediator of innate tumor surveillance. Further, we believe our data help to explain the therapeutic effect of IFN treatment during the early stages of cancer development.

  18. Oxidative Stress Facilitates IFN-γ-Induced Mimic Extracellular Trap Cell Death in A549 Lung Epithelial Cancer Cells.

    Science.gov (United States)

    Lin, Chiou-Feng; Chen, Chia-Ling; Chien, Shun-Yi; Tseng, Po-Chun; Wang, Yu-Chih; Tsai, Tsung-Ting

    2016-01-01

    We previously demonstrated that IFN-γ induces an autophagy-regulated mimic extracellular trap cell death (ETosis) in A549 human lung cancer cells. Regarding reactive oxygen species (ROS) are involved in ETosis, this study investigated the role of oxidative stress. After IFN-γ stimulation, a necrosis-like cell death mimic ETosis occurred accompanied by the inhibition of cell growth, aberrant nuclear staining, and nucleosome release. ROS were generated in a time-dependent manner with an increase in NADPH oxidase component protein expression. STAT1-mediated IFN regulatory factor-1 activation was essential for upregulating ROS production. By genetically silencing p47phox, IFN-γ-induced ROS and mimic ETosis were significantly attenuated. This mechanistic study indicated that ROS may mediate DNA damage followed by histone H3 citrullination. Furthermore, ROS promoted IFN-γ-induced mimic ETosis in cooperation with autophagy. These findings further demonstrate that ROS regulates IFN-γ-induced mimic ETosis in lung epithelial malignancy.

  19. THE ANALYSIS OF ILLUSTRATIONS IN THE FOURTH CLASS GEOGRAPHY TEXTBOOKS

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    IOANA CHIRCEV

    2014-01-01

    Full Text Available This study focuses on the analysis of the illustrations found in five different Geography textbooks in Romania. The analysis is based on several criteria: number, size, clarity, pedagogical usefulness. The following conclusions have been drawn: the illustrations are numerous; most of the illustrations are too small and unclear to be efficiently used in the teaching activity; the purpose of some materials is purely illustrative; some illustrations are overcharged with details, which prevent children from understanding them. Authors and publishing houses are advised to choose the illustrations in the fourth class Geography textbooks more carefully.

  20. New World hantaviruses activate IFNlambda production in type I IFN-deficient vero E6 cells.

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    Joseph Prescott

    Full Text Available Hantaviruses indigenous to the New World are the etiologic agents of hantavirus cardiopulmonary syndrome (HCPS. These viruses induce a strong interferon-stimulated gene (ISG response in human endothelial cells. African green monkey-derived Vero E6 cells are used to propagate hantaviruses as well as many other viruses. The utility of the Vero E6 cell line for virus production is thought to owe to their lack of genes encoding type I interferons (IFN, rendering them unable to mount an efficient innate immune response to virus infection. Interferon lambda, a more recently characterized type III IFN, is transcriptionally controlled much like the type I IFNs, and activates the innate immune system in a similar manner.We show that Vero E6 cells respond to hantavirus infection by secreting abundant IFNlambda. Three New World hantaviruses were similarly able to induce IFNlambda expression in this cell line. The IFNlambda contained within virus preparations generated with Vero E6 cells independently activates ISGs when used to infect several non-endothelial cell lines, whereas innate immune responses by endothelial cells are specifically due to viral infection. We show further that Sin Nombre virus replicates to high titer in human hepatoma cells (Huh7 without inducing ISGs.Herein we report that Vero E6 cells respond to viral infection with a highly active antiviral response, including secretion of abundant IFNlambda. This cytokine is biologically active, and when contained within viral preparations and presented to human epithelioid cell lines, results in the robust activation of innate immune responses. We also show that both Huh7 and A549 cell lines do not respond to hantavirus infection, confirming that the cytoplasmic RNA helicase pathways possessed by these cells are not involved in hantavirus recognition. We demonstrate that Vero E6 actively respond to virus infection and inhibiting IFNlambda production in these cells might increase their utility

  1. The chicken TH1 response: potential therapeutic applications of ChIFN-γ.

    Science.gov (United States)

    Guo, Pengju; Thomas, Jesse D; Bruce, Matthew P; Hinton, Tracey M; Bean, Andrew G D; Lowenthal, John W

    2013-11-01

    The outcomes of viral infections are costly in terms of human and animal health and welfare worldwide. The observed increase in the virulence of some viruses and failure of many vaccines to stop these infections has lead to the apparent need to develop new anti-viral strategies. One approach to dealing with viral infection may be to employ the therapeutic administration of recombinant cytokines to act as 'immune boosters' to assist in augmenting the host response to virus. With this in mind, a greater understanding of the immune response, particularly cell mediated T-helper-1 (TH1) type responses, is imperative to the development of new anti-viral and vaccination strategies. Following the release of the chicken genome, a number of TH1-type cytokines have been identified, including chicken interleukin-12 (ChIL-12), ChIL-18 and interferon-γ ChIFN-γ), highlighting the nature of the TH1-type response in this non-mammalian vertebrate. To date a detailed analysis of the in vivo biological function of these cytokines has been somewhat hampered by access to large scale production techniques. This review describes the role of TH-1 cytokines in immune responses to viruses and explores their potential use in enhancing anti-viral treatment strategies in chickens. Furthermore, this review focuses on the example of ChIFN-γ treatment of Chicken Anemia Virus (CAV) infection. CAV causes amongst other things thymocyte depletion and thymus atrophy, as well as immunosuppression in chickens. However, due to vaccination, clinical disease appears less often, nevertheless, the subclinical form of the disease is often associated with secondary complicating infections due to an immunocompromised state. Since CAV-induced immunosuppression can cause a marked decrease in the immune response against other pathogens, understanding this aspect of the disease is critically important, as well as providing insights into developing new control approaches. With increasing emphasis on developing

  2. Modelo de detección de anticuerpos neutralizantes contra IFN-β mediante citometría de flujo

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    Juan Carlos Villa-Camacho

    2012-12-01

    Full Text Available Introducción. El interferón beta (IFN-β se usa para tratar la forma recaída-remisión de la esclerosis múltiple. Sin embargo, el uso de proteínas recombinantes como medicamentos puede generar la producción de anticuerpos, disminuyendo así la efectividad del tratamiento. Objetivo. Estandarizar una técnica de detección de anticuerpos neutralizantes contra IFN-β, mediante citometría de flujo. Materiales y métodos. Se cultivaron dos líneas tumorales humanas (U937 y K562 con IFN-β1a humano recombinante y mediante citometría de flujo se determinó la expresión de la proteína ISG15 intracelular. Los sueros se obtuvieron de un conejo Nueva Zelanda antes y después de la inmunización con 100.000 UI de IFN-β1a en adyuvante de Freund. Para la detección de anticuerpos neutralizantes, se estimularon células K562 con IFN-β1a preincubado con sueros de conejos a una dilución 1:20. Después de 24 horas de incubación se determinó la expresión de la proteína ISG15. Resultados. La expresión de ISG15 fue mayor en células K562 estimuladas. La intensidad media de fluorescencia para la ISG-15 entre células en ausencia IFN-β1a, mostró una mediana de 198 unidades arbitrarias (UA (p25-75= 173-231 UA y, en presencia de IFN-β1a, 430 UA (p25-75 =316-611,5, con una diferencia estadísticamente significativa (p=0,008. La presencia de anticuerpos anti-IFN-β1a en el suero del conejo inmunizado, hizo disminuir de forma acentuada la expresión de la ISG15 en células K562 cultivadas con IFN-β1a, en comparación con el control (mediana=3,040 UA Vs. 43,644 UA, respectivamente. Conclusiones. Este trabajo muestra la detección de anticuerpos neutralizantes contra IFN-β en conejos, utilizando la expresión de la proteína ISG15 por citometría de flujo.   doi: http://dx.doi.org/10.7705/biomedica.v32i4.637

  3. The use of transparent media in medical illustration.

    Science.gov (United States)

    Winn, W M

    1978-03-01

    Transparent media, such as watercolor, acrylic, and dyes, have been used by scientific illustrators for centuries. This article gives one artist's view of the highly complex medium. Materials, techniques, short cuts, and potential problem areas are discussed. Illustrations of specific techniques and a step-by-step development of a medical illustration is provided.

  4. Can Strategies Facilitate Learning from Illustrated Science Texts?

    Science.gov (United States)

    Iding, Marie K.

    2000-01-01

    Examines the effectiveness of schema training in illustration types and text-illustration relations for learning from college level physiology texts and discusses findings that are consistent with prior research on learning from illustrated materials and with dual coding theory. Considers future directions for strategy training research and…

  5. 31 CFR 411.1 - Color illustrations authorized.

    Science.gov (United States)

    2010-07-01

    ... SERVICE, DEPARTMENT OF THE TREASURY COLOR ILLUSTRATIONS OF UNITED STATES CURRENCY § 411.1 Color... necessary plates or items for such printing or publishing, of color illustrations of U.S. currency provided... storage devices, and any other thing used in the making of the illustration that contain an image of the...

  6. Population genetic evidence for positive and purifying selection acting at the human IFN-γ locus in Africa.

    Science.gov (United States)

    Campbell, Michael C; Smith, Lunden T; Harvey, Jayla

    2018-03-29

    Despite its critical role in the defense against microbial infection and tumor development, little is known about the range of nucleotide and haplotype variation at IFN-γ, or the evolutionary forces that have shaped patterns of diversity at this locus. To address this gap in knowledge, we examined sequence data from the IFN-γ gene in 1461 individuals from 15 worldwide populations. Our analyses uncovered novel patterns of variation in distinct African populations, including an excess of high frequency-derived alleles, unusually long haplotype structure surrounding the IFN-γ gene, and a "star-like" genealogy of African-specific haplotypes carrying variants previously associated with infectious disease. We also inferred a deep time to coalescence of variation at IFN-γ (~ 0.8 million years ago) and ancient ages for common polymorphisms predating the evolution of modern humans. Taken together, these results are congruent with a model of positive selection on standing variation in African populations. Furthermore, we inferred that common variants in intron 3 of IFN-γ are the likely targets of selection. In addition, we observed a paucity of non-synonymous substitutions relative to synonymous changes in the exons of IFN-γ in African and non-African populations, suggestive of strong purifying selection. Therefore, we contend that positive and purifying selection have influenced levels of diversity in different regions of IFN-γ, implying that these distinct genic regions are, or have been, functionally important. Overall, this study provides additional insights into the evolutionary events that have contributed to the frequency and distribution of alleles having a role in human health and disease.

  7. Smart parking barrier

    KAUST Repository

    Alharbi, Abdulrazaq M.

    2016-05-06

    Various methods and systems are provided for smart parking barriers. In one example, among others, a smart parking barrier system includes a movable parking barrier located at one end of a parking space, a barrier drive configured to control positioning of the movable parking barrier, and a parking controller configured to initiate movement of the parking barrier, via the barrier drive. The movable parking barrier can be positioned between a first position that restricts access to the parking space and a second position that allows access to the parking space. The parking controller can initiate movement of the movable parking barrier in response to a positive identification of an individual allowed to use the parking space. The parking controller can identify the individual through, e.g., a RFID tag, a mobile device (e.g., a remote control, smartphone, tablet, etc.), an access card, biometric information, or other appropriate identifier.

  8. Cucurbita ficifolia (Cucurbitaceae) modulates inflammatory cytokines and IFN-γ in obese mice.

    Science.gov (United States)

    Fortis-Barrera, Á; García-Macedo, R; Almanza-Perez, J C; Blancas-Flores, G; Zamilpa-Alvarez, A; Flores-Sáenz, J L; Cruz, M; Román-Ramos, R; Alarcón-Aguilar, F J

    2017-02-01

    This study investigated the effect of aqueous extract of Cucurbita ficifolia Bouché on systemic chronic inflammation in an obesity model induced by monosodium glutamate (MSG) via modulating the expression of adipokines (TNF-α, IL-6, resistin, and adiponectin) and immune-regulatory cytokines (IFN-γ and IL-10). Cucurbita ficifolia extract was administered daily by gavage to lean and MSG-obese mice for 30 days. At the end of treatment, cytokine mRNA expression in adipose tissue was determined by real-time polymerase chain reaction (PCR), and the protein levels of these cytokines were also quantified by enzyme-linked immunosorbent assay (ELISA). Cucurbita ficifolia extract decreased body mass and inflammation in MSG-obese mice by reducing the expression of TNF-α and IL-6; these decreases were parallel to significant reductions in protein levels. The extract also increased protein levels of IL-10 in lean mice and IFN-γ in both lean and MSG-obese mice. In conclusion, C. ficifolia extract modulates systemic chronic inflammation in MSG-obese mice and could have a beneficial effect on the adaptive immune system in obesity.

  9. Suppression of type I and type III IFN signalling by NSs protein of severe fever with thrombocytopenia syndrome virus through inhibition of STAT1 phosphorylation and activation.

    Science.gov (United States)

    Chaudhary, Vidyanath; Zhang, Shuo; Yuen, Kit-San; Li, Chuan; Lui, Pak-Yin; Fung, Sin-Yee; Wang, Pei-Hui; Chan, Chi-Ping; Li, Dexin; Kok, Kin-Hang; Liang, Mifang; Jin, Dong-Yan

    2015-11-01

    Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne pathogen causing significant morbidity and mortality in Asia. NSs protein of SFTSV is known to perturb type I IFN induction and signalling, but the mechanism remains to be fully understood. Here, we showed the suppression of both type I and type III IFN signalling by SFTSV NSs protein is mediated through inhibition of STAT1 phosphorylation and activation. Infection with live SFTSV or expression of NSs potently suppressed IFN-stimulated genes but not NFkB activation. NSs was capable of counteracting the activity of IFN-α1, IFN-β, IFN-λ1 and IFN-λ2. Mechanistically, NSs associated with STAT1 and STAT2, mitigated IFN-β-induced phosphorylation of STAT1 at S727, and reduced the expression and activity of STAT1 protein in IFN-β-treated cells, resulting in the inhibition of STAT1 and STAT2 recruitment to IFNstimulated promoters. Taken together, SFTSV NSs protein is an IFN antagonist that suppresses phosphorylation and activation of STAT1.

  10. Preassembly and ligand-induced restructuring of the chains of the IFN-gamma receptor complex: the roles of Jak kinases, Stat1 and the receptor chains.

    Science.gov (United States)

    Krause, Christopher D; Lavnikova, Natasha; Xie, Junxia; Mei, Erwen; Mirochnitchenko, Olga V; Jia, Yiwei; Hochstrasser, Robin M; Pestka, Sidney

    2006-01-01

    We previously demonstrated using noninvasive technologies that the interferon-gamma (IFN-gamma) receptor complex is preassembled (1). In this report we determined how the receptor complex is preassembled and how the ligand-mediated conformational changes occur. The interaction of Stat1 with IFN-gammaR1 results in a conformational change localized to IFN-gammaR1. Jak1 but not Jak2 is required for the two chains of the IFN-gamma receptor complex (IFN-gammaR1 and IFN-gammaR2) to interact; however, the presence of both Jak1 and Jak2 is required to see any ligand-dependant conformational change. Two IFN-gammaR2 chains interact through species-specific determinants in their extracellular domains. Finally, these determinants also participate in the interaction of IFN-gammaR2 with IFN-gammaR1. These results agree with a detailed model of the IFN-gamma receptor that requires the receptor chains to be pre-associated constitutively for the receptor to be active.

  11. Andrographolide Restores Steroid Sensitivity To Block Lipopolysaccharide/IFN-γ-Induced IL-27 and Airway Hyperresponsiveness in Mice.

    Science.gov (United States)

    Liao, Wupeng; Tan, W S Daniel; Wong, W S Fred

    2016-06-01

    LPS and IFN-γ alone or in combination have been implicated in the development of steroid resistance. Combined LPS/IFN-γ strongly upregulates IL-27 production, which has been linked to steroid-resistant airway hyperresponsiveness (AHR). Andrographolide, a bioactive molecule isolated from the plant Andrographis paniculata, has demonstrated anti-inflammatory and antioxidant properties. The present study investigated whether andrographolide could restore steroid sensitivity to block LPS/IFN-γ-induced IL-27 production and AHR via its antioxidative property. The mouse macrophage cell line Raw 264.7, mouse primary lung monocytes/macrophages, and BALB/c mice were treated with LPS/IFN-γ, in the presence and absence of dexamethasone and/or andrographolide. Levels of IL-27 in vitro and in vivo were examined and mouse AHR was assessed. Dexamethasone alone failed to inhibit LPS/IFN-γ-induced IL-27 production and AHR in mice. Andrographolide significantly restored the suppressive effect of dexamethasone on LPS/IFN-γ-induced IL-27 mRNA and protein levels in the macrophage cell line and primary lung monocytes/macrophages, mouse bronchoalveolar lavage fluid and lung tissues, and AHR in mice. LPS/IFN-γ markedly reduced the nuclear level of histone deacetylase (HDAC)2, an essential epigenetic enzyme that mediates steroid anti-inflammatory action. LPS/IFN-γ also decreased total HDAC activity but increased the total histone acetyltransferase/HDAC activity ratio in mouse lungs. Andrographolide significantly restored nuclear HDAC2 protein levels and total HDAC activity, and it diminished the total histone acetyltransferase/HDAC activity ratio in mouse lungs exposed to LPS/IFN-γ, possibly via suppression of PI3K/Akt/HDAC2 phosphorylation, and upregulation of the antioxidant transcription factor NF erythroid-2-related factor 2 level and DNA binding activity. Our data suggest that andrographolide may have therapeutic value in resensitizing steroid action in respiratory disorders

  12. Efecto de la maca roja (Lepidium meyenii sobre los niveles de IFN-γ en ratas ovariectomizadas

    Directory of Open Access Journals (Sweden)

    Johanna Leiva-Revilla

    Full Text Available Objetivos. Comparar el efecto de diferentes dosis de maca roja sobre los niveles de interferón gamma (IFN-γ en ratas ovariectomizadas (OVX. Materiales y métodos. Ratas hembras adultas fueron divididas al azar en los siguientes seis grupos: Grupo 1: ratas pesudo-ovariectomizadas (PO; Grupo 2: ratas OVX; Grupo 3: ratas OVX tratadas con 4 ug/kg de estradiol, y Grupo 4, 5 y 6: ratas OVX tratadas con extractos de maca con 2,15, 4,3 y 8,6 mg polifenoles/kilogramo de peso corporal, respectivamente. Resultados. Las ratas OVX mostraron niveles bajos de IFN-γ en comparación con las ratas PO. El estradiol y la maca roja revirtieron el efecto de la ovariectomía sobre los niveles de IFN-γ. La maca roja presenta un incremento dosis-respuesta de los niveles de IFN-γ (r=0,57, p<0,05. Conclusiones. La administración de la maca roja incrementa los niveles de IFN-γ en ratas ovariectomizadas.

  13. Dendritic Cell Stimulation by IFN-β Alters T Cell Function via Modulation of Cytokine Secretion in Diabetes Type 1

    Directory of Open Access Journals (Sweden)

    Abediankenari Saeid

    2009-10-01

    Full Text Available During antigen capture and processing, mature dendritic cells (DC express large amounts of peptide-MHC complexes and accessory molecules on their surface. We investigated the role of IFN-β in induction HLA-G expression on the monocyte derived DC and cytokine profile in diabetes type 1. We accomplished secretary pattern and total cytokine production of the Th1 cytokine (IL-2, γIFN and Th2 cytokines (IL-4, IL-10 before and after mixed leukocyte reaction (MLR of 30 diabetic patients and 30 normal subjects.   In this study a significant increase of IL-10 and γIFN reduction after IFN-β Therapy in culture in presence of HLA-G bearing DC as compared to control were seen. It is seen that dendritic cell causes IL-10 production of T cell in vitro that reduce T cell activation from diabetes patients and normal subjects resulted to the production and expression of HLA-G on these cells from both groups. Using mixed leukocyte reaction, it was found that IFN-β-treated dendritic cell mediated the inhibition of autologous T cell activation via IL-10 production and level of HLA-G on dendritic cell may be correlated to disease activity in diabetes patients and it could also serve as a useful marker for disease progress and treatment.

  14. Quantification and phenotypic characterisation of peripheral IFN-γ producing leucocytes in chickens vaccinated against Newcastle disease

    DEFF Research Database (Denmark)

    Andersen, Stig Henrik; Vervelde, Lonneke; Sutton, Kate

    2017-01-01

    controls, one group was vaccinated intramuscularly twice with a commercial inactivated ND virus (NDV) vaccine, and the last group was vaccinated orally twice with a commercial live attenuated NDV vaccine. PBMC were ex vivo stimulated with ConA or with NDV antigen. The ICS assay was used to determine...... the phenotype and frequency of IFN-γ positive cells. ConA stimulation induced extensive IFN-γ production in both CD3+TCRγδ+ (γδ T cells) cells and CD3+TCRγδ− cells (αβ T cells), but no significant differences were observed between the experimental groups. Furthermore, a large proportion of the IFN-γ producing...... cells were CD3− indicating that other cells than classic T cells, secreted this cytokine. NDV antigen stimulation induced IFN-γ production but to a lower extent than ConA and with a large variation between individuals. The CD3+TCR1γδ−CD8α+ (CTL) population produced the highest NDV specific IFN...

  15. The combination of IL-21 and IFN-alpha boosts STAT3 activation, cytotoxicity and experimental tumor therapy

    DEFF Research Database (Denmark)

    Eriksen, Karsten W; Søndergaard, Henrik; Woetmann, Anders

    2008-01-01

    such as IFN-alpha and IL-2 have multiple and severe side effects. Accordingly, they are generally used at sub-optimal doses, which limit their clinical efficacy. Here we hypothesized that a combination of IFN-alpha and IL-21, a novel cytokine of the IL-2 family with anti-cancer effects, will increase the anti......-cancer efficacy at sub-optimal cytokine doses. We show that the combined stimulation of target-cells with IFN-alpha and IL-21 triggers an increased STAT3 activation whereas the activation of other STATs including STAT1/2 is unaffected. In parallel, the combined stimulation with IFN-alpha and IL-21 triggers...... a selective increase in MHC class I expression and NK- and CD8(+) T-cell-mediated cytotoxicity. In an experimental in vivo model of renal carcinoma, the combined treatment of IFN-alpha and IL-21 also produces a significant anti-cancer effect as judged by an inhibition of tumor growth and an increased survival...

  16. Antigen presentation by small intestinal epithelial cells uniquely enhances IFN-γ secretion from CD4{sup +} intestinal intraepithelial lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Hatano, Ryo; Yamada, Kiyoshi; Iwamoto, Taku; Maeda, Nana; Emoto, Tetsuro; Shimizu, Makoto; Totsuka, Mamoru, E-mail: atotuka@mail.ecc.u-tokyo.ac.jp

    2013-06-14

    Highlights: •Small intestinal epithelial cells (sIECs). •sIECs are able to induce antigen specific proliferation of CD4{sup +} IELs. •sIECs induce markedly enhanced IFN-γ secretion by CD4{sup +} IELs. •Induction of enhanced IFN-γ secretion by sIECs is uniquely observed in CD4{sup +} IELs. -- Abstract: Small intestinal epithelial cells (sIECs) express major histocompatibility complex class II molecules even in a normal condition, and are known to function as antigen presenting cells (APCs) at least in vitro. These findings raised the possibility that sIECs play an important role in inducing immune responses against luminal antigens, especially those of intestinal intraepithelial lymphocytes (IELs) and lamina propria lymphocytes (LPLs). We herein showed that antigenic stimulation with sIECs induced markedly greater secretion of interferon-gamma (IFN-γ) by CD4{sup +} IELs, but not interleukin (IL)-4, IL-10 and IL-17 although the proliferative response was prominently lower than that with T cell-depleted splenic APCs. In contrast, no enhanced IFN-γ secretion by CD4{sup +} LPLs and primed splenic CD4{sup +} T cells was observed when stimulated with sIECs. Taken together, these results suggest that sIECs uniquely activate CD4{sup +} IELs and induce remarkable IFN-γ secretion upon antigenic stimulation in vivo.

  17. Antigen presentation by small intestinal epithelial cells uniquely enhances IFN-γ secretion from CD4+ intestinal intraepithelial lymphocytes

    International Nuclear Information System (INIS)

    Hatano, Ryo; Yamada, Kiyoshi; Iwamoto, Taku; Maeda, Nana; Emoto, Tetsuro; Shimizu, Makoto; Totsuka, Mamoru

    2013-01-01

    Highlights: •Small intestinal epithelial cells (sIECs). •sIECs are able to induce antigen specific proliferation of CD4 + IELs. •sIECs induce markedly enhanced IFN-γ secretion by CD4 + IELs. •Induction of enhanced IFN-γ secretion by sIECs is uniquely observed in CD4 + IELs. -- Abstract: Small intestinal epithelial cells (sIECs) express major histocompatibility complex class II molecules even in a normal condition, and are known to function as antigen presenting cells (APCs) at least in vitro. These findings raised the possibility that sIECs play an important role in inducing immune responses against luminal antigens, especially those of intestinal intraepithelial lymphocytes (IELs) and lamina propria lymphocytes (LPLs). We herein showed that antigenic stimulation with sIECs induced markedly greater secretion of interferon-gamma (IFN-γ) by CD4 + IELs, but not interleukin (IL)-4, IL-10 and IL-17 although the proliferative response was prominently lower than that with T cell-depleted splenic APCs. In contrast, no enhanced IFN-γ secretion by CD4 + LPLs and primed splenic CD4 + T cells was observed when stimulated with sIECs. Taken together, these results suggest that sIECs uniquely activate CD4 + IELs and induce remarkable IFN-γ secretion upon antigenic stimulation in vivo

  18. Detection of IFN-γ Secretion by T Cells Collected Before and After Successful Treatment of Early Lyme Disease.

    Science.gov (United States)

    Callister, Steven M; Jobe, Dean A; Stuparic-Stancic, Aleksandra; Miyamasu, Misato; Boyle, Jeff; Dattwyler, Raymond J; Arnaboldi, Paul M

    2016-05-15

    Current serodiagnostics for Lyme disease lack sensitivity during early disease, and cannot determine treatment response. We evaluated an assay based on QuantiFERON technology utilizing peptide antigens derived from Borrelia burgdorferi to stimulate interferon-gamma (IFN-γ) release as an alternative to serodiagnosis for the laboratory detection of Lyme disease. Blood was obtained from patients with erythema migrans before (n = 29) and 2 months after (n = 27) antibiotic therapy. IFN-γ release was measured by enzyme-linked immunosorbent assay (ELISA) following overnight stimulation of whole blood with the peptide antigens, and compared to the results of standard serological assays (C6, ELISA, and Western blot). IFN-γ release was observed in pretreatment blood of 20 of 29 (69%) patients with Lyme disease. Following antibiotic treatment, IFN-γ was significantly reduced (P = .0002), and was detectable in only 4 of 20 (20%) initially positive patients. By contrast, anti-C6 antibodies were detected in pretreatment sera from 17 of 29 (59%) subjects, whereas only 5 of 29 (17%) patients had positive Western blot seroreactivity. Antibody responses persisted and expanded following treatment. Our findings suggest that measurement of IFN-γ after incubating blood with Borrelia antigens could be useful in the laboratory diagnosis of early Lyme disease. Also, after antibiotic treatment, this response appears to be short lived. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  19. Decrease of PECAM-1-gene-expression induced by proinflammatory cytokines IFN-γ and IFN-α is reversed by TGF-β in sinusoidal endothelial cells and hepatic mononuclear phagocytes

    Directory of Open Access Journals (Sweden)

    Ramadori Giuliano

    2008-05-01

    Full Text Available Abstract Background and aim The mechanisms of transmigration of inflammatory cells through the sinusoids are still poorly understood. This study aims to identify in vitro conditions (cytokine treatment which may allow a better understanding of the changes in PECAM (platelet endothelial cell adhesion molecule-1-gene-expression observed in vivo. Methods and results In this study we show by immunohistochemistry, that there is an accumulation of ICAM-1 (intercellular cell adhesion molecule-1 and ED1 positive cells in necrotic areas of livers of CCl4-treated rats, whereas there are few PECAM-1 positive cells observable. After the administration of CCl4, we could detect an early rise of levels of IFN-γ followed by an enhanced TGF-β protein level. As shown by Northern blot analysis and surface protein expression analysed by flow cytometry, IFN-γ-treatment decreased PECAM-1-gene-expression in isolated SECs (sinusoidal endothelial cells and mononuclear phagocytes (MNPs in parallel with an increase in ICAM-1-gene-expression in a dose and time dependent manner. In contrast, TGF-β-treatment increased PECAM-1-expression. Additional administration of IFN-γ to CCl4-treated rats and observations in IFN-γ-/- mice confirmed the effect of IFN-γ on PECAM-1 and ICAM-1-expression observed in vitro and increased the number of ED1-expressing cells 12 h after administration of the toxin. Conclusion The early decrease of PECAM-1-expression and the parallel increase of ICAM-1-expression following CCl4-treatment is induced by elevated levels of IFN-γ in livers and may facilitate adhesion and transmigration of inflammatory cells. The up-regulation of PECAM-1-expression in SECs and MNPs after TGF-β-treatment suggests the involvement of PECAM-1 during the recovery after liver damage.

  20. Ebi3 Prevents Trypanosoma cruzi-Induced Myocarditis by Dampening IFN-γ-Driven Inflammation

    Directory of Open Access Journals (Sweden)

    Tiago Silva Medina

    2017-09-01

    Full Text Available The identification of anti-inflammatory mediators can reveal important targetable molecules capable of counterbalancing Trypanosoma cruzi-induced myocarditis. Composed of Ebi3 and IL-27p28 subunits, IL-27 is produced by myeloid cells and is able to suppress inflammation by inducing IL-10-producing Tr1 cells, thus emerging as a potential candidate to ameliorate cardiac inflammation induced by T. cruzi. Although IL-27 has been extensively characterized as a suppressive cytokine that prevents liver immunopathogenesis after T. cruzi infection, the mechanisms underlying its effects on T. cruzi-induced myocarditis remain largely unknown. Here, wild-type (WT and Ebi3-deficient animals were intraperitoneally infected with trypomastigotes of T. cruzi Y strain and used to evaluate the potential anti-inflammatory properties of Ebi3 during T. cruzi infection. The survival rates of mice were daily recorded, the frequency of inflammatory cells was analyzed by flow cytometry and inflammatory mediators were measured by ELISA, real-time PCR and PCR array. We reported that T. cruzi-induced myocarditis was prevented by Ebi3. Stressors mainly recognized by TLR2 and TLR4 receptors on myeloid cells were essential to trigger IL-27p28 production. In addition, Ebi3 regulated IFN-γ-mediated myocarditis by promoting an anti-inflammatory environment through IL-10, which was most likely produced by Tr1 cells rather than classical regulatory T cells (Tregs, in the heart tissue of T. cruzi-infected animals. Furthermore, in vivo IFN-γ blockade ameliorated the host survival without compromising the parasite control in the bloodstream. In humans, IL-27p28 was correlated with cardiac protection during Chagas disease. Patients with mild clinical forms of the disease produced high levels of IL-27p28, whereas lower levels were found in those with severe forms. In addition, polymorphic sites at Ebi3 gene were associated with severe cardiomyopathy in patients with Chagas disease

  1. Ebi3 Prevents Trypanosoma cruzi-Induced Myocarditis by Dampening IFN-γ-Driven Inflammation

    Science.gov (United States)

    Medina, Tiago Silva; Oliveira, Gabriela Gonçalves; Silva, Maria Cláudia; David, Bruna Araújo; Silva, Grace Kelly; Fonseca, Denise Morais; Sesti-Costa, Renata; Frade, Amanda Farage; Baron, Monique Andrade; Ianni, Barbara; Pereira, Alexandre Costa; Chevillard, Christophe; Cunha-Neto, Edécio; Marin-Neto, José Antonio; Silva, João Santana

    2017-01-01

    The identification of anti-inflammatory mediators can reveal important targetable molecules capable of counterbalancing Trypanosoma cruzi-induced myocarditis. Composed of Ebi3 and IL-27p28 subunits, IL-27 is produced by myeloid cells and is able to suppress inflammation by inducing IL-10-producing Tr1 cells, thus emerging as a potential candidate to ameliorate cardiac inflammation induced by T. cruzi. Although IL-27 has been extensively characterized as a suppressive cytokine that prevents liver immunopathogenesis after T. cruzi infection, the mechanisms underlying its effects on T. cruzi-induced myocarditis remain largely unknown. Here, wild-type (WT) and Ebi3-deficient animals were intraperitoneally infected with trypomastigotes of T. cruzi Y strain and used to evaluate the potential anti-inflammatory properties of Ebi3 during T. cruzi infection. The survival rates of mice were daily recorded, the frequency of inflammatory cells was analyzed by flow cytometry and inflammatory mediators were measured by ELISA, real-time PCR and PCR array. We reported that T. cruzi-induced myocarditis was prevented by Ebi3. Stressors mainly recognized by TLR2 and TLR4 receptors on myeloid cells were essential to trigger IL-27p28 production. In addition, Ebi3 regulated IFN-γ-mediated myocarditis by promoting an anti-inflammatory environment through IL-10, which was most likely produced by Tr1 cells rather than classical regulatory T cells (Tregs), in the heart tissue of T. cruzi-infected animals. Furthermore, in vivo IFN-γ blockade ameliorated the host survival without compromising the parasite control in the bloodstream. In humans, IL-27p28 was correlated with cardiac protection during Chagas disease. Patients with mild clinical forms of the disease produced high levels of IL-27p28, whereas lower levels were found in those with severe forms. In addition, polymorphic sites at Ebi3 gene were associated with severe cardiomyopathy in patients with Chagas disease. Collectively, we

  2. Barrier cell sheath formation

    International Nuclear Information System (INIS)

    Kesner, J.

    1980-04-01

    The solution for electrostatic potential within a simply modeled tandem mirror thermal barrier is seen to exhibit a sheath at each edge of the cell. The formation of the sheath requires ion collisionality and the analysis assmes that the collisional trapping rate into the barrier is considerably slower than the barrier pump rate

  3. Dynamic monitoring of serum IFN-γ, IL-2, and IL-6 contents in patients with Graves' disease

    International Nuclear Information System (INIS)

    Zou Jianwen; Li Weiguo

    2006-01-01

    Objective: To investigate the possible role of cytokines (IFN-γ, IL-2, IL-6) in the pathogenesis of Graves' disease. Methods: Serum FT 3 , FT 4 , TSH (with CLIA), IL-2, IL-6 (with RIA) and IFN-γ (with ELISA) contents were measured in the following subjects: (1) 42 patients with Graves' disease before any treatment, (2) 40 patients in remission after successful treatment with antithyroid drugs (ATD), (3) 25 patients in relapse (around 6 months after cessation of two years' ATD treatment, (4) 40 controls. Results: The serum IFN-γ and IL-6 contents in the patients before treatment and patients in relapse were significantly higher than those in the controls (P 3 , FT 4 levels while the serum IL-2 contents were linearly negatively correlated with FT 3 , FT 4 levels before treatment. Conclusion: Contents of these cytokines fluctuated dynamically along with the status of Graves' disease and might be related to the pathogenesis in some way. (authors)

  4. Does IFN-γ play a role on the pathogenesis of non-atopic asthma in Latin America children?

    Directory of Open Access Journals (Sweden)

    Figueiredo Camila Alexandrina

    2012-12-01

    Full Text Available Abstract In this work we explore differences in blood cells and cytokine profiles in children according to atopic status and asthma (atopic or non-atopic. The study involved measurement of Th1(IFN-γ and Th2 (IL-5 and IL-13 cytokines in Dermatophagoides pteronyssinus stimulated peripheral blood leukocytes, blood cell count, skin prick test and specific IgE against common aeroallergens. Atopic status was associated with eosinophilia and production of Th2 type cytokines. Atopic asthma was associated with eosinophilia and non-atopic asthma was associated with IFN-γ and elevated monocytes in blood. IFN-γ and monocytes might play a role in immunopathology of non-atopic asthma in Latin American children.

  5. Does IFN-γ play a role on the pathogenesis of non-atopic asthma in Latin America children?

    Science.gov (United States)

    Figueiredo, Camila Alexandrina; Rodrigues, Laura Cunha; Alcantara-Neves, Neuza Maria; Cooper, Philip J; Amorim, Leila Denise; Silva, Nivea Bispo; Cruz, Alvaro A; Barreto, Mauricio Lima

    2012-12-19

    In this work we explore differences in blood cells and cytokine profiles in children according to atopic status and asthma (atopic or non-atopic). The study involved measurement of Th1(IFN-γ) and Th2 (IL-5 and IL-13) cytokines in Dermatophagoides pteronyssinus stimulated peripheral blood leukocytes, blood cell count, skin prick test and specific IgE against common aeroallergens. Atopic status was associated with eosinophilia and production of Th2 type cytokines. Atopic asthma was associated with eosinophilia and non-atopic asthma was associated with IFN-γ and elevated monocytes in blood. IFN-γ and monocytes might play a role in immunopathology of non-atopic asthma in Latin American children.

  6. Compromised virus control and augmented perforin-mediated immunopathology in IFN-gamma-deficient mice infected with lymphocytic choriomeningitis virus

    DEFF Research Database (Denmark)

    Nansen, A; Jensen, Teis; Christensen, Jan Pravsgaard

    1999-01-01

    To define the role of IFN-gamma in the control of acute infection with a noncytopathogenic virus, mice with targeted defects of the genes encoding IFN-gamma, perforin, or both were infected i.v. with two strains of lymphocytic choriomeningitis virus differing markedly in their capacity to spread...... in wild-type mice. Our results reveal that IFN-gamma is pivotal to T cell-mediated control of a rapidly invasive stain, whereas it is less important in the acute elimination of a slowly invasive strain. Moreover, the majority of mice infected with the rapidly invasive strain succumb to a wasting syndrome...... mediated by CD8+ effector cells. The primary effector mechanism underlying this disease is perforin-dependent lysis, but other mechanisms are also involved. Wasting disease can be prevented if naive CD8+ cells from mice transgenic for an MHC class I-restricted lymphocytic choriomeningitis virus...

  7. Development of monoclonal antibodies (MAbs) to feline interferon (fIFN)-γ as tools to evaluate cellular immune responses to feline infectious peritonitis virus (FIPV).

    Science.gov (United States)

    Satoh, Ryoichi; Kaku, Ayumi; Satomura, Megumi; Kohori, Michiyo; Noura, Kanako; Furukawa, Tomoko; Kotake, Masako; Takano, Tomomi; Hohdatsu, Tsutomu

    2011-06-01

    Feline infectious peritonitis virus (FIPV) can cause a lethal disease in cats, feline infectious peritonitis (FIP). The antibody-dependent enhancement (ADE) of FIPV infection has been recognised in experimentally infected cats, and cellular immunity is considered to play an important role in preventing the onset of FIP. To evaluate the importance of cellular immunity for FIPV infection, monoclonal antibodies (MAbs) against feline interferon (fIFN)-γ were first created to establish fIFN-γ detection systems using the MAbs. Six anti-fIFN-γ MAbs were created. Then, the difference in epitope which those MAbs recognise was demonstrated by competitive enzyme-linked immunosorbent assay (ELISA) and IFN-γ neutralisation tests. Detection systems for fIFN-γ (sandwich ELISA, ELISpot assay, and two-colour flow cytometry) were established using anti-fIFN-γ MAbs that recognise different epitopes. In all tests, fIFN-γ production from peripheral blood mononuclear cells (PBMCs) obtained from cats experimentally infected with an FIPV isolate that did not develop the disease was significantly increased by heat-inactivated FIPV stimulation in comparison with medium alone. Especially, CD8(+)fIFN-γ(+) cells, but not CD4(+)fIFN-γ(+) cells, were increased. In contrast, fIFN-γ production from PBMCs isolated from cats that had developed FIP and specific pathogen-free (SPF) cats was not increased by heat-inactivated FIPV stimulation. These results suggest that cellular immunity plays an important role in preventing the development of FIP. Measurement of fIFN-γ production with the anti-fIFN-γ MAbs created in this study appeared to be useful in evaluating cellular immunity in cats. Copyright © 2011 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.

  8. In Vivo Visualizing the IFN-β Response Required for Tumor Growth Control in a Therapeutic Model of Polyadenylic-Polyuridylic Acid Administration.

    Science.gov (United States)

    Nocera, David Andrés; Roselli, Emiliano; Araya, Paula; Nuñez, Nicolás Gonzalo; Lienenklaus, Stefan; Jablonska, Jadwiga; Weiss, Siegfried; Gatti, Gerardo; Brinkmann, Melanie M; Kröger, Andrea; Morón, Gabriel; Maccioni, Mariana

    2016-03-15

    The crucial role that endogenously produced IFN-β plays in eliciting an immune response against cancer has recently started to be elucidated. Endogenous IFN-β has an important role in immune surveillance and control of tumor development. Accordingly, the role of TLR agonists as cancer therapeutic agents is being revisited via the strategy of intra/peritumoral injection with the idea of stimulating the production of endogenous type I IFN inside the tumor. Polyadenylic-polyuridylic acid (poly A:U) is a dsRNA mimetic explored empirically in cancer immunotherapy a long time ago with little knowledge regarding its mechanisms of action. In this work, we have in vivo visualized the IFN-β required for the antitumor immune response elicited in a therapeutic model of poly A:U administration. In this study, we have identified the role of host type I IFNs, cell populations that are sources of IFN-β in the tumor microenvironment, and other host requirements for tumor control in this model. One single peritumoral dose of poly A:U was sufficient to induce IFN-β, readily visualized in vivo. IFN-β production relied mainly on the activation of the transcription factor IFN regulatory factor 3 and the molecule UNC93B1, indicating that TLR3 is required for recognizing poly A:U. CD11c(+) cells were an important, but not the only source of IFN-β. Host type I IFN signaling was absolutely required for the reduced tumor growth, prolonged mice survival, and the strong antitumor-specific immune response elicited upon poly A:U administration. These findings add new perspectives to the use of IFN-β-inducing compounds in tumor therapy. Copyright © 2016 by The American Association of Immunologists, Inc.

  9. Evaluation of IL-4, IL-17, and IFN-γ Levels in PatientsWith Breast Cancer

    Directory of Open Access Journals (Sweden)

    Mina Rohani Borj

    2017-03-01

    Full Text Available Introduction: Tumor growth depends on intrinsic properties of malignant tumor and tumor microenvironment. Cytokines are secreted substances of the tumor microenvironment which are widely produced by tumor and immune cells. The aim of this research was to evaluate concentrations of interleukin 4 (IL-4, interleukin 7 (IL-17 and interferon gamma (IFN-γ in the breast cancer microenvironment. Methods: One hundred sixteen women between 18-73 years of age (61.15 ± 24.39 were enrolled in this study. Based on pathologic diagnostic assessment, patients were divided into 2 categories: those affected with benign breast tumor, and the subjects suffering from malignant breast tumors. Biopsy specimens were collected. Following homogenization, IFN-γ, IL-17, and IL-4 concentrations were determined in tumor tissues, adjacent tissues of the tumor, and blood serum samples of these 2 groups of patients by enzyme-linked immunosorbent assay (ELISA method. Results: Concentrations of IFN-γ, IL-17, and IL-4 were measured in tumor tissue samples, adjacent tissues of the tumor, and blood serum samples in both groups. Malignant breast tumor samples had significantly higher concentrations of IL-4 and IL-17 compared with benign breast tumor samples. And also the concentration of IFN-γ in adjacent tissues of the tumor and in blood serums in patients with malignant breast tumors was significantly higher than that in the benign breast tumor samples. However, there was no significant difference between the concentration of IFN-γ in neoplastic breast tumor tissues and that in the benign breast tumor tissues (P > 0. 05. Conclusion: Our data indicated that IL-17 and IL-4 cytokines but not IFN-γ had higher concentrations in the subjects with malignant tumor compared with those with benign tumor. The present findings indicated that the concentrations of IL-4 and IL-17 in tumor tissues may be associated with the severity of breast malignancy.

  10. Calcium/Calmodulin-Dependent Protein Kinase IV Mediates IFN-γ-Induced Immune Behaviors in Skeletal Muscle Cells

    Directory of Open Access Journals (Sweden)

    RuiCai Gu

    2018-03-01

    Full Text Available Background/Aims: Whether calcium/calmodulin-dependent protein kinase IV (CaMKIV plays a role in regulating immunologic features of muscle cells in inflammatory environment, as it does for immune cells, remains mostly unknown. In this study, we investigated the influence of endogenous CaMKIV on the immunological characteristics of myoblasts and myotubes received IFN-γ stimulation. Methods: C2C12 and murine myogenic precursor cells (MPCs were cultured and differentiated in vitro, in the presence of pro-inflammatory IFN-γ. CaMKIV shRNA lentivirus transfection was performed to knockdown CaMKIV gene in C2C12 cells. pEGFP-N1-CaMKIV plasmid was delivered into knockout cells for recovering intracellular CaMKIV gene level. CREB1 antagonist KG-501 was used to block CREB signal. qPCR, immunoblot analysis, or immunofluorescence was used to detect mRNA and protein levels of CaMKIV, immuno-molecules, or pro-inflammatory cytokines and chemokines. Co-stimulatory molecules expression was assessed by FACS analysis. Results: IFN-γ induces the expression or up-regulation of MHC-I/II and TLR3, and the up-regulation of CaMKIV level in muscle cells. In contrast, CaMKIV knockdown in myoblasts and myotubes leads to expression inhibition of the above immuno-molecules. As well, CaMKIV knockdown selectively inhibits pro-inflammatory cytokines/chemokines, and co-stimulatory molecules expression in IFN-γ treated myoblasts and myotubes. Finally, CaMKIV knockdown abolishes IFN-γ induced CREB pathway molecules accumulation in differentiated myotubes. Conclusions: CaMKIV can be induced to up-regulate in muscle cells under inflammatory condition, and positively mediates intrinsic immune behaviors of muscle cells triggered by IFN-γ.

  11. Melanoma cells treated with GGTI and IFN-gamma allow murine vaccination and enhance cytotoxic response against human melanoma cells.

    Directory of Open Access Journals (Sweden)

    Guillaume Sarrabayrouse

    Full Text Available BACKGROUND: Suboptimal activation of T lymphocytes by melanoma cells is often due to the defective expression of class I major histocompatibility antigens (MHC-I and costimulatory molecules. We have previously shown that geranylgeranyl transferase inhibition (done with GGTI-298 stimulates anti-melanoma immune response through MHC-I and costimulatory molecule expression in the B16F10 murine model [1]. METHODOLOGY/PRINCIPAL FINDINGS: In this study, it is shown that vaccination with mIFN-gand GGTI-298 pretreated B16F10 cells induces a protection against untreated tumor growth and pulmonary metastases implantation. Furthermore, using a human melanoma model (LB1319-MEL, we demonstrated that in vitro treatment with hIFN-gamma and GGTI-298 led to the up regulation of MHC-I and a costimulatory molecule CD86 and down regulation of an inhibitory molecule PD-1L. Co-culture experiments with peripheral blood mononuclear cells (PBMC revealed that modifications induced by hIFN-gamma and GGTI-298 on the selected melanoma cells, enables the stimulation of lymphocytes from HLA compatible healthy donors. Indeed, as compared with untreated melanoma cells, pretreatment with hIFN-gamma and GGTI-298 together rendered the melanoma cells more efficient at inducing the: i activation of CD8 T lymphocytes (CD8+/CD69+; ii proliferation of tumor-specific CD8 T cells (MelanA-MART1/TCR+; iii secretion of hIFN-gamma; and iv anti-melanoma specific cytotoxic cells. CONCLUSIONS/SIGNIFICANCE: These data indicate that pharmacological treatment of melanoma cell lines with IFN-gamma and GGTI-298 stimulates their immunogenicity and could be a novel approach to produce tumor cells suitable for vaccination and for stimulation of anti-melanoma effector cells.

  12. TLR2-dependent inhibition of macrophage responses to IFN-gamma is mediated by distinct, gene-specific mechanisms.

    Directory of Open Access Journals (Sweden)

    Sarah A Benson

    2009-07-01

    Full Text Available Mycobacterium tuberculosis uses multiple mechanisms to avoid elimination by the immune system. We have previously shown that M. tuberculosis can inhibit selected macrophage responses to IFN-gamma through TLR2-dependent and -independent mechanisms. To specifically address the role of TLR2 signaling in mediating this inhibition, we stimulated macrophages with the specific TLR2/1 ligand Pam(3CSK(4 and assayed responses to IFN-gamma. Pam(3CSK(4 stimulation prior to IFN-gamma inhibited transcription of the unrelated IFN-gamma-inducible genes, CIITA and CXCL11. Surface expression of MHC class II and secretion of CXCL11 were greatly reduced as well, indicating that the reduction in transcripts had downstream effects. Inhibition of both genes required new protein synthesis. Using chromatin immunoprecipitation, we found that TLR2 stimulation inhibited IFN-gamma-induced RNA polymerase II binding to the CIITA and CXCL11 promoters. Furthermore, TATA binding protein was unable to bind the TATA box of the CXCL11 promoter, suggesting that assembly of transcriptional machinery was disrupted. However, TLR2 stimulation affected chromatin modifications differently at each of the inhibited promoters. Histone H3 and H4 acetylation was reduced at the CIITA promoter but unaffected at the CXCL11 promoter. In addition, NF-kappaB signaling was required for inhibition of CXCL11 transcription, but not for inhibition of CIITA. Taken together, these results indicate that TLR2-dependent inhibition of IFN-gamma-induced gene expression is mediated by distinct, gene-specific mechanisms that disrupt binding of the transcriptional machinery to the promoters.

  13. IFN-γ fails to overcome inhibition of selected macrophage activation events in response to pathogenic mycobacteria.

    Directory of Open Access Journals (Sweden)

    Shyamala Thirunavukkarasu

    Full Text Available According to most models of mycobacterial infection, inhibition of the pro-inflammatory macrophage immune responses contributes to the persistence of bacteria. Mycobacterium avium subsp. paratuberculosis (MAP is a highly successful pathogen in cattle and sheep and is also implicated as the causative agent of Crohn's disease in humans. Pathogenic mycobacteria such as MAP have developed multiple strategies to evade host defence mechanisms including interfering with the macrophages' capacity to respond to IFN-γ, a feature which might be lacking in non-pathogenic mycobacteria such as M. smegmatis. We hypothesized that pre-sensitisation of macrophages with the pro-inflammatory cytokine IFN-γ would help in overcoming the inhibitory effect of MAP or its antigens on macrophage inflammatory responses. Herein we have compared a series of macrophage activation parameters in response to MAP and M. smegmatis as well as mycobacterial antigens. While IFN-γ did overcome the inhibition in immune suppressive mechanisms in response to MAP antigen as well as M. smegmatis, we could not find a clear role for IFN-γ in overcoming the inhibition of macrophage inflammatory responses to the pathogenic mycobacterium, MAP. We demonstrate that suppression of macrophage defence mechanisms by pathogenic mycobacteria is unlikely to be overcome by prior sensitization with IFN-γ alone. This indicates that IFN-γ signaling pathway-independent mechanisms may exist for overcoming inhibition of macrophage effector functions in response to pathogenic mycobacteria. These findings have important implications in understanding the survival mechanisms of pathogenic mycobacteria directed towards finding better therapeutics and vaccination strategies.

  14. Association study of interferon gamma (IFN-γ) +874T/A gene polymorphism in patients with paranoid schizophrenia.

    Science.gov (United States)

    Paul-Samojedny, Monika; Owczarek, Aleksander; Suchanek, Renata; Kowalczyk, Malgorzata; Fila-Danilow, Anna; Borkowska, Paulina; Kucia, Krzysztof; Kowalski, Jan

    2011-03-01

    Schizophrenia is a multifactorial disease with changes affecting the immune system. Dysregulation of the cytokine network in schizophrenia has been well documented. Such changes may occur due to disturbances in cytokine levels that are linked to polymorphisms of cytokine genes. However, research in the role of cytokine gene polymorphisms in schizophrenia has been surprisingly scanty. The aim of this study was to identify, in a case control study, whether polymorphism of IFN-γ gene is a risk factor for the development of paranoid schizophrenia. To the best of our knowledge, this is the first study that examines the association between the IFN-γ gene polymorphism and psychopathological symptoms in patients with paranoid schizophrenia. Polymorphism of IFN-γ (+874T/A, rs 62559044) in schizophrenic patients (n=179), as well as healthy individuals (n=196), both Polish residents, was genotyped using AS-PCR method. Of note, when analyzing the results, we took into consideration the gender of studied individuals. Surprisingly, a single-nucleotide polymorphism in the first intron of the IFN-γ gene was found to be associated with paranoid schizophrenia in males, but not in females. The presence of allele A at position +874 in the IFN-γ gene correlates with 1.66-fold higher risk of paranoid schizophrenia development in males. Differences in the genotypes may have an important role in determining the level of I gene transcription. Because other polymorphisms have been demonstrated to influence IFN-γ transcription, further analysis is necessary to clarify the role of this gene in the pathogenesis of paranoid schizophrenia.

  15. Association of the IFN-γ (+874A/T) Genetic Polymorphism with Paranoid Schizophrenia in Tunisian Population.

    Science.gov (United States)

    Jemli, Achraf; Eshili, Awatef; Trifa, Fatma; Mechri, Anouar; Zaafrane, Ferid; Gaha, Lotfi; Juckel, George; Tensaout, Besma Bel Hadj Jrad

    2017-02-01

    Since growing evidence suggests a significant role of chronic low-grade inflammation in the physiopathology of schizophrenia, we have hypothesized that functional genetic variant of the IFN gamma (IFN-γ; +874A/T; rs2430561) gene may be involved in the predisposition to schizophrenia. This research is based on a case-control study which aims to identify whether polymorphism of the IFN-γ gene is a risk factor for the development of schizophrenia. The RFLP-PCR genotyping of the IFN-γ gene was conducted on a Tunisian population composed of 218 patients and 162 controls. The IFN-γ (+874A/T) polymorphism analysis showed higher frequencies of minor homozygous genotype (TT) and allele (T) in all patients compared with controls (11.5 vs. 4.9%; p = 0.03, OR = 2.64 and 30.7 vs. 24.1%, p = 0.04, OR = 1.4, respectively). This correlation was confirmed for male but not for female patients. Also, the T allele was significantly more common among patients with paranoid schizophrenia when compared with controls (25.8 vs. 4.9%, p = 0.0001; OR = 6.7). Using the binary regression analysis to eliminate confounding factors as age and sex, only this last association remained significant (p = 0.03; OR = 1.76, CI = 1.05-2.93). In conclusion, our results showed a significant association between +874A/T polymorphism of IFN-γ and paranoid schizophrenia, suggesting that this single nucleotide polymorphism (SNP) or another at proximity could predispose to paranoid schizophrenia. Since the minor allele of this polymorphism was correlated with an increased expression of their product, our study validates the hypothesis of excessive pro-inflammatory cytokine in the physiopathology of paranoid schizophrenia.

  16. Roles of Illustrators in Visual Communication of Scientific Knowledge

    Directory of Open Access Journals (Sweden)

    Kana Okawa

    2011-10-01

    Full Text Available Scientific knowledge is the knowledge accumulated by systematic studies and organized by general principles. Visual, verbal, numeric, and other types of representation are used to communicate scientific knowledge. Scientific illustration is the visual representation of objects and concepts in order to record and to convey scientific knowledge(Ford, 1993. There are some discussions on scientific illustrations in history, philosophy and the sociology of science(Burri & Dumit, 2008, but little has been done on the creation of scientific illustrations by illustrators. This study focuses on the creation of scientific illustrations by illustrators. The purpose is to show how illustrators create the visual messages in communications of scientific knowledge. Through analysis of semi-structured interviews with 6 professional illustrators, creators and art directors, it is showed that illustrators select and edit scientific information, add non-scientific information, and organize information into one visual representation of scientific knowledge. The implication of this research will provide a new perspective to multisensory communication of scientific knowledge.

  17. Alveolar macrophages and type I IFN in airway homeostasis and immunity.

    Science.gov (United States)

    Divangahi, Maziar; King, Irah L; Pernet, Erwan

    2015-05-01

    Globally, respiratory infections cause more than 4 million deaths per year, with influenza and tuberculosis (TB) in particular being major causes of mortality and morbidity. Although immune cell activation is critical for killing respiratory pathogens, this response must be tightly regulated to effectively control and eliminate invading microorganisms while minimizing immunopathology and maintaining pulmonary function. The distinct microenvironment of the lung is constantly patrolled by alveolar macrophages (Mφ), which are essential for tissue homeostasis, early pathogen recognition, initiation of the local immune response, and resolution of inflammation. Here, we focus on recent advances that have provided insight into the relation between pulmonary Mφ, type I interferon (IFN) signaling, and the delicate balance between protective and pathological immune responses in the lung. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Barriers to fusion

    International Nuclear Information System (INIS)

    Berriman, A.C.; Butt, R.D.; Dasgupta, M.; Hinde, D.J.; Morton, C.R.; Newton, J.O.

    1999-01-01

    The fusion barrier is formed by the combination of the repulsive Coulomb and attractive nuclear forces. Recent research at the Australian National University has shown that when heavy nuclei collide, instead of a single fusion barrier, there is a set of fusion barriers. These arise due to intrinsic properties of the interacting nuclei such deformation, rotations and vibrations. Thus the range of barrier energies depends on the properties of both nuclei. The transfer of matter between nuclei, forming a neck, can also affect the fusion process. High precision data have been used to determine fusion barrier distributions for many nuclear reactions, leading to new insights into the fusion process

  19. Extremal surface barriers

    International Nuclear Information System (INIS)

    Engelhardt, Netta; Wall, Aron C.

    2014-01-01

    We present a generic condition for Lorentzian manifolds to have a barrier that limits the reach of boundary-anchored extremal surfaces of arbitrary dimension. We show that any surface with nonpositive extrinsic curvature is a barrier, in the sense that extremal surfaces cannot be continuously deformed past it. Furthermore, the outermost barrier surface has nonnegative extrinsic curvature. Under certain conditions, we show that the existence of trapped surfaces implies a barrier, and conversely. In the context of AdS/CFT, these barriers imply that it is impossible to reconstruct the entire bulk using extremal surfaces. We comment on the implications for the firewall controversy

  20. Safety- barrier diagrams

    DEFF Research Database (Denmark)

    Duijm, Nijs Jan

    2008-01-01

    Safety-barrier diagrams and the related so-called 'bow-tie' diagrams have become popular methods in risk analysis. This paper describes the syntax and principles for constructing consistent and valid safety-barrier diagrams. The relation of safety-barrier diagrams to other methods such as fault...... trees and Bayesian networks is discussed. A simple method for quantification of safety-barrier diagrams is proposed. It is concluded that safety-barrier diagrams provide a useful framework for an electronic data structure that integrates information from risk analysis with operational safety management....

  1. Safety-barrier diagrams

    DEFF Research Database (Denmark)

    Duijm, Nijs Jan

    2007-01-01

    Safety-barrier diagrams and the related so-called "bow-tie" diagrams have become popular methods in risk analysis. This paper describes the syntax and principles for constructing consistent and valid safety-barrier diagrams. The relation with other methods such as fault trees and Bayesian networks...... are discussed. A simple method for quantification of safety-barrier diagrams is proposed, including situations where safety barriers depend on shared common elements. It is concluded that safety-barrier diagrams provide a useful framework for an electronic data structure that integrates information from risk...... analysis with operational safety management....

  2. IL-15 Superagonist–Mediated Immunotoxicity: Role of NK Cells and IFN

    Science.gov (United States)

    Guo, Yin; Luan, Liming; Rabacal, Whitney; Bohannon, Julia K.; Fensterheim, Benjamin A.; Hernandez, Antonio

    2015-01-01

    IL-15 is currently undergoing clinical trials to assess its efficacy for treatment of advanced cancers. The combination of IL-15 with soluble IL-15Rα generates a complex termed IL-15 superagonist (IL-15 SA) that possesses greater biological activity than IL-15 alone. IL-15 SA is considered an attractive antitumor and antiviral agent because of its ability to selectively expand NK and memory CD8+ T (mCD8+ T) lymphocytes. However, the adverse consequences of IL-15 SA treatment have not been defined. In this study, the effect of IL-15 SA on physiologic and immunologic functions of mice was evaluated. IL-15 SA caused dose- and time-dependent hypothermia, weight loss, liver injury, and mortality. NK (especially the proinflammatory NK subset), NKT, and mCD8+ T cells were preferentially expanded in spleen and liver upon IL-15 SA treatment. IL-15 SA caused NK cell activation as indicated by increased CD69 expression and IFN-γ, perforin, and granzyme B production, whereas NKT and mCD8+ T cells showed minimal, if any, activation. Cell depletion and adoptive transfer studies showed that the systemic toxicity of IL-15 SA was mediated by hyperproliferation of activated NK cells. Production of the proinflammatory cytokine IFN-γ, but not TNF-α or perforin, was essential to IL-15 SA–induced immunotoxicity. The toxicity and immunological alterations shown in this study are comparable to those reported in recent clinical trials of IL-15 in patients with refractory cancers and advance current knowledge by providing mechanistic insights into IL-15 SA–mediated immunotoxicity. PMID:26216888

  3. Evasion of IFN-γ signaling by Francisella novicida is dependent upon Francisella outer membrane protein C.

    Directory of Open Access Journals (Sweden)

    Kalyan C Nallaparaju

    2011-03-01

    Full Text Available Francisella tularensis is a Gram-negative facultative intracellular bacterium and the causative agent of the lethal disease tularemia. An outer membrane protein (FTT0918 of F. tularensis subsp. tularensis has been identified as a virulence factor. We generated a F. novicida (F. tularensis subsp. novicida FTN_0444 (homolog of FTT0918 fopC mutant to study the virulence-associated mechanism(s of FTT0918.The ΔfopC strain phenotype was characterized using immunological and biochemical assays. Attenuated virulence via the pulmonary route in wildtype C57BL/6 and BALB/c mice, as well as in knockout (KO mice, including MHC I, MHC II, and µmT (B cell deficient, but not in IFN-γ or IFN-γR KO mice was observed. Primary bone marrow derived macrophages (BMDM prepared from C57BL/6 mice treated with rIFN-γ exhibited greater inhibition of intracellular ΔfopC than wildtype U112 strain replication; whereas, IFN-γR KO macrophages showed no IFN-γ-dependent inhibition of ΔfopC replication. Moreover, phosphorylation of STAT1 was downregulated by the wildtype strain, but not the fopC mutant, in rIFN-γ treated macrophages. Addition of NG-monomethyl-L-arginine, an NOS inhibitor, led to an increase of ΔfopC replication to that seen in the BMDM unstimulated with rIFN-γ. Enzymatic screening of ΔfopC revealed aberrant acid phosphatase activity and localization. Furthermore, a greater abundance of different proteins in the culture supernatants of ΔfopC than that in the wildtype U112 strain was observed.F. novicida FopC protein facilitates evasion of IFN-γ-mediated immune defense(s by down-regulation of STAT1 phosphorylation and nitric oxide production, thereby promoting virulence. Additionally, the FopC protein also may play a role in maintaining outer membrane stability (integrity facilitating the activity and localization of acid phosphatases and other F. novicida cell components.

  4. Specific Oral Tolerance Induction Using IFN-Gamma in 2 Cases of Food-Dependent Exercise-Induced Anaphylaxis

    Directory of Open Access Journals (Sweden)

    Geunwoong Noh

    2013-01-01

    Full Text Available Anaphylaxis induced by exercise after the intake of certain foods is referred to as food-dependent exercise-induced anaphylaxis (FDEIA. Only the preventive medication such as oral sodium cromoglycate and oral combined cetirizine-montelukast was tried in FDEIA. Specific oral tolerance induction (SOTI using IFN-gamma was tried in 2 cases of FDEIA for wheat. Merely, exercise accompanied every treatment just after the intake of allergenic foods during treatment. Patients acquired tolerance for wheat in both cases successfully. After treatment, two patients take wheat in their food living freely. Conclusively, SOTI using IFN-gamma was effective as the causative treatment for allergenic foods in FDEIA.

  5. Upregulation of B7 molecules (CD80 and CD86) and exacerbated eosinophilic pulmonary inflammatory response in mice lacking the IFN-beta gene

    DEFF Research Database (Denmark)

    Matheu, Victor; Treschow, Alexandra; Navikas, Vaidrius

    2003-01-01

    . OBJECTIVE: We sought to define the differential role of endogenous IFN-beta in controlling the development of allergic inflammation. METHODS: We assessed whether deletion of the gene encoding IFN-beta (IFNB) with knockout mice participated in the development of allergic response in ovalbumin (OVA......BACKGROUND: IFN-beta has been shown to be effective as therapy for multiple sclerosis. Some reports attributed its beneficial effects to the capacity to induce a T(H)2 response. However, other studies have suggested that endogenous type I IFN might downregulate the allergic response in mice...

  6. Dimethyl Sulfoxide (DMSO) Decreases Cell Proliferation and TNF-α, IFN-γ, and IL-2 Cytokines Production in Cultures of Peripheral Blood Lymphocytes.

    Science.gov (United States)

    de Abreu Costa, Lucas; Henrique Fernandes Ottoni, Marcelo; Dos Santos, Michaelle Geralda; Meireles, Agnes Batista; Gomes de Almeida, Valéria; de Fátima Pereira, Wagner; Alves de Avelar-Freitas, Bethânia; Eustáquio Alvim Brito-Melo, Gustavo

    2017-11-10

    Dimethylsulfoxide (DMSO) is an amphipathic molecule composed of a polar domain characterized by the sulfinyl and two nonpolar methyl groups, for this reason it is able to solubilize polar and nonpolar substances and transpose hydrophobic barriers. DMSO is widely used to solubilize drugs of therapeutic applications and studies indicated that 10% v/v concentration did not modify culture viability when used to treat human peripheral blood mononuclear cells (PBMC). However, some DMSO concentrations could influence lymphocyte activation and present anti-inflammatory effects. Therefore, the objective of this study was to evaluate the effect of DMSO on lymphocyte activation parameters. Cell viability analysis, proliferation, and cytokine production were performed on PBMC from six healthy subjects by flow cytometry. The results indicated that 2.5% v/v DMSO concentrations did not modify lymphocytes viability. DMSO at 1% and 2% v/v concentrations reduced the relative proliferation index of lymphocytes and at 5% and 10% v/v concentrations reduced the percentage of total lymphocytes, cluster of differentiation 4⁺ (CD4⁺) T lymphocytes and CD8⁺ T lymphocytes interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2) producers. Thus, it was concluded that DMSO has an in vitro anti-inflammatory effect by reducing lymphocyte activation demonstrated with proliferation reduction and the decrease of cytokine production.

  7. Dorothea Mantzel and Bernd Schulz. Francolin Illustrated School Dic

    African Journals Online (AJOL)

    rbr

    and wonder whether the Francolin Illustrated School Dictionary for Southern. Africa makes this distinction. I wonder ... The dictionary, the editors claim, is aimed at senior primary school learners who do not speak English as ... illustration of someone shooting with a bow and arrow at a target. When one turns to the headword ...

  8. Automatic Generation of Stippling Illustrations from two Photographs

    Directory of Open Access Journals (Sweden)

    Germán Arroyo

    2012-05-01

    This tool needs almost no user interaction. The user simply has to align both photographs and indicate the level of detail according to the distance. The rest is decided by our software. Whereas a professional illustrator needs more than 20 hours to finish a similar illustration, our software is able to do it in just few seconds.

  9. Mental Imagery, Text Illustrations, and Children's Story Comprehension and Recall.

    Science.gov (United States)

    Gambrell, Linda B.; Jawitz, Paula Brooks

    1993-01-01

    Investigates the effects of instructions to induce mental imagery and attend to text illustrations on fourth graders' reading comprehension and recall of narrative text. Finds that images and illustrations independently enhanced reading performance and that, in combination, these two strategies resulted in impressive increases in children's…

  10. The Effect of Illustrations on Second Graders' Reading Comprehension.

    Science.gov (United States)

    Parisi, Gina

    A study investigated whether text illustrations improve the reading comprehension of second graders. Subjects, 14 second-grade students, read five stories from a basal reader. The control group read each story with accompanying illustrations, while the experimental group was exposed to only the written version of the same stories. Questions based…

  11. The Influence of Illustrations on Children's Comprehension of Written Stories.

    Science.gov (United States)

    O'Keefe, Elizabeth J.; Solman, Robert T.

    1987-01-01

    Examines the effect of a variety of picture-text conditions on third and fifth grade average readers' comprehension. Concludes that the advantage of presenting children of normal reading ability with illustrated text is small and primarily dependent on the placement of illustrations adjacent to related textual materials. (RS)

  12. 26 CFR 1.941-3 - Illustration of principles.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 10 2010-04-01 2010-04-01 false Illustration of principles. 1.941-3 Section 1.941-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES China Trade Act Corporations § 1.941-3 Illustration of principles. The application...

  13. IFN-γ priming of macrophages represses a part of the inflammatory program and attenuates neutrophil recruitment

    NARCIS (Netherlands)

    Hoeksema, Marten A.; Scicluna, Brendon P.; Boshuizen, Marieke C. S.; van der Velden, Saskia; Neele, Annette E.; van den Bossche, Jan; Matlung, Hanke L.; van den Berg, Timo K.; Goossens, Pieter; de Winther, Menno P. J.

    2015-01-01

    Macrophages form a heterogeneous population of immune cells, which is critical for both the initiation and resolution of inflammation. They can be skewed to a proinflammatory subtype by the Th1 cytokine IFN-γ and further activated with TLR triggers, such as LPS. In this work, we investigated the

  14. Benefit of adjuvant interferon alfa-2b (IFN-α) therapy in melanoma patients with high serum MMP-8 levels

    DEFF Research Database (Denmark)

    Vihinen, Pia; Tervahartiala, Taina; Sorsa, Timo

    2015-01-01

    Matrix metalloproteinases (MMPs) are important enzymes in tissue turnover and various inflammatory processes. In this study, it was evaluated whether serum MMP-8 can predict the response to adjuvant interferon alfa-2b (IFN-α) therapy in patients with operated high-risk cutaneous melanoma. Pre......-treatment sera from 460 patients with stage IIB-IIIC melanoma were analyzed for MMP-8. The patients were randomized after surgery to adjuvant IFN-α for 12 or 24 months (n = 313) or observation only (n = 147). The median serum MMP-8 level was used to classify the patients into a low MMP-8 (n = 232) and a high MMP......-8 (n = 228) group. In the high MMP-8 subgroup, IFN-α therapy significantly improved relapse-free survival (RFS). RFS was 36.8 months in patients with high MMP-8 levels receiving IFN-α therapy, whereas RFS for those with high MMP-8 levels with observation only was 10.6 months (P = 0.027). Median...

  15. In vivo IFN-γ secretion by NK cells in response to Salmonella typhimurium requires NLRC4 inflammasomes.

    Directory of Open Access Journals (Sweden)

    Andreas Kupz

    Full Text Available Natural killer (NK cells are a critical part of the innate immune defense against viral infections and for the control of tumors. Much less is known about how NK cells contribute to anti-bacterial immunity. NK cell-produced interferon gamma (IFN-γ contributes to the control of early exponential replication of bacterial pathogens, however the regulation of these events remains poorly resolved. Using a mouse model of invasive Salmonellosis, here we report that the activation of the intracellular danger sensor NLRC4 by Salmonella-derived flagellin within CD11c+ cells regulates early IFN-γ secretion by NK cells through the provision of interleukin 18 (IL-18, independently of Toll-like receptor (TLR-signaling. Although IL18-signalling deficient NK cells improved host protection during S. Typhimurium infection, this increased resistance was inferior to that provided by wild-type NK cells. These findings suggest that although NLRC4 inflammasome-driven secretion of IL18 serves as a potent activator of NK cell mediated IFN-γ secretion, IL18-independent NK cell-mediated mechanisms of IFN-γ secretion contribute to in vivo control of Salmonella replication.

  16. DMPD: TLR pathways and IFN-regulatory factors: to each its own. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available Immunol. 2007 Feb;37(2):306-9. (.png) (.svg) (.html) (.csml) Show TLR pathways and IFN-regulatory factors: ...ng) SVG File (.svg) HTML File (.html) CSML File (.csml) Open .csml file with CIOPlayer Open .csml file with

  17. Mycobacterium tuberculosis decreases human macrophage IFN-γ responsiveness through miR-132 and miR-26a.

    Science.gov (United States)

    Ni, Bin; Rajaram, Murugesan V S; Lafuse, William P; Landes, Michelle B; Schlesinger, Larry S

    2014-11-01

    IFN-γ-activated macrophages play an essential role in controlling intracellular pathogens; however, macrophages also serve as the cellular home for the intracellular pathogen Mycobacterium tuberculosis. Based on previous evidence that M. tuberculosis can modulate host microRNA (miRNA) expression, we examined the miRNA expression profile of M. tuberculosis-infected primary human macrophages. We identified 31 differentially expressed miRNAs in primary human macrophages during M. tuberculosis infection by NanoString and confirmed our findings by quantitative real-time RT-PCR. In addition, we determined a role for two miRNAs upregulated upon M. tuberculosis infection, miR-132 and miR-26a, as negative regulators of transcriptional coactivator p300, a component of the IFN-γ signaling cascade. Knockdown expression of miR-132 and miR-26a increased p300 protein levels and improved transcriptional, translational, and functional responses to IFN-γ in human macrophages. Collectively, these data validate p300 as a target of miR-132 and miR-26a, and demonstrate a mechanism by which M. tuberculosis can limit macrophage responses to IFN-γ by altering host miRNA expression. Copyright © 2014 by The American Association of Immunologists, Inc.

  18. Enhanced Dendritic Cell-Mediated Antigen-Specific CD4+ T Cell Responses: IFN-Gamma Aids TLR Stimulation

    Directory of Open Access Journals (Sweden)

    Kuo-Ching Sheng

    2013-01-01

    Full Text Available Phenotypic maturation and T cell stimulation are two functional attributes of DCs critical for immune induction. The combination of antigens, including those from cancer, with Toll-like receptor (TLR ligands induces far superior cellular immune responses compared to antigen alone. In this study, IFN-gamma treatment of bone marrow-derived DC, followed by incubation with the TLR2, TLR4, or TLR9 agonists, enhanced DC activation compared to TLR ligation alone. Most notably, the upregulation of CD40 with LPS stimulation and CD86 with CpG stimulation was observed in in vitro cultures. Similarly, IFN-gamma coinjected with TLR ligands was able to promote DC activation in vivo, with DCs migrating from the site of immunization to the popliteal lymph nodes demonstrating increased expression of CD80 and CD86. The heightened DC activation translated to a drastic increase in T cell stimulatory capacity in both antigen independent and antigen dependent fashions. This is the first time that IFN-gamma has been shown to have a combined effect with TLR ligation to enhance DC activation and function. The results demonstrate the novel use of IFN-gamma together with TLR agonists to enhance antigen-specific T cell responses, for applications in the development of enhanced vaccines and drug targets against diseases including cancer.

  19. Manual de control de calidad del Inventario Forestal Nacional (IFN) [Quality control manual of the National Forest Inventory (NFI)

    Science.gov (United States)

    P. Barbosa; F. Herrera; S. Goeking; V. Nieto; M. Pena; S. Ortiz

    2014-01-01

    El Inventario Forestal Nacional de Colombia (IFN) incluye un programa de Aseguramiento de Calidad (AC) para garantizar la confiabilidad de todos los datos recogidos y generados en la etapa de muestreo. El objetivo de este programa; es proporcionar un marco que asegure que la información compilada acerca de los bosques es completa, exacta, imparcial y de calidad...

  20. Interferon-gamma (IFN-gamma) treatment decreases the inflammatory response in chronic Pseudomonas aeruginosa pneumonia in rats

    DEFF Research Database (Denmark)

    Johansen, H K; Hougen, H P; Rygaard, J

    1996-01-01

    In a rat model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis (CF), we studied whether the inflammatory response could be altered by intraperitoneal treatment with recombinant rat interferon-gamma (rrIFN-gamma). Rats were treated either before or after intratracheal ch...

  1. Analysis of IL-12 p40 subunit gene and IFN-γ G5644A polymorphisms in Idiopathic Pulmonary Fibrosis

    Directory of Open Access Journals (Sweden)

    Welsh Kenneth I

    2003-06-01

    Full Text Available Abstract Background Genes encoding cytokine mediators are prime candidates for genetic analysis in conditions with T-helper (Th cell disease driven imbalance. Idiopathic Pulmonary Fibrosis (IPF is a predominantly Th2 mediated disease associated with a paucity of interferon-gamma (IFN-γ. The paucity of IFN-γ may favor the development of progressive fibrosis in IPF. Interleukin-12 (IL-12 plays a key role in inducing IFN-γ production. The aim of the current study was to assess whether the 1188 (A/C 3'UTR single nucleotide polymorphism (SNP in the IL-12 p40 subunit gene which was recently found to be functional and the 5644 (G/A 3' UTR SNP of the IFN-γ gene were associated with susceptibility to IPF. Methods We investigated the allelic distribution in these loci in UK white Caucasoid subjects comprising 73 patients with IPF and 157 healthy controls. The SNPs were determined using the polymerase chain reaction in association with sequence-specific primers incorporating mismatches at the 3'-end. Results Our results showed that these polymorphisms were distributed similarly in the IPF and control groups Conclusion We conclude that these two potentially important candidate gene single nucleotide polymorphisms are not associated with susceptibility to IPF.

  2. Nocardia brasiliensis Modulates IFN-gamma, IL-10, and IL-12 cytokine production by macrophages from BALB/c Mice.

    Science.gov (United States)

    Salinas-Carmona, Mario C; Zúñiga, Juan M; Pérez-Rivera, Luz I; Segoviano-Ramírez, Juan C; Vázquez-Marmolejo, Anna V

    2009-05-01

    Interferon-gamma (IFN-gamma) is a critical cytokine involved in control of different infections. Actinomycetoma is a chronic infectious disease mainly caused by the bacterium Nocardia brasiliensis, which destroys subcutaneous tissue, including bone. Currently, the mechanism of pathogenesis in N. brasiliensis infection is not known. Here, we demonstrate that N. brasiliensis induced an IFN-gamma response in serum after 24 h of infection, while, in infected tissue, positive cells to IFN-gamma appeared in 2 early peaks: the first was present only 3 h after infection, then transiently decreased; and the second peak appeared 12 h after infection and was independent of interleukin-10. Resident macrophages produced an immediate IFN-gamma response 1 h after in vitro infection, and spleen-positive cells began later. The phase of growth of N. brasiliensis affected cytokine production, and exposure of macrophages to Nocardia opsonized with either polyclonal anti-Nocardia antibodies or anti-P61 monoclonal antibody led to a suppression of cytokine production. Our report provides evidence that N. brasiliensis as an intracellular bacterium modulates macrophage cytokine production, which helps survival of the pathogen. Modulation of these cytokines may contribute to pathogenesis once this bacterium is inside the macrophage.

  3. A new era for IFN-α in the treatment of Philadelphia-negative chronic myeloproliferative neoplasms

    DEFF Research Database (Denmark)

    Hasselbalch, H.C.

    2011-01-01

    In recent years, several studies have shown that IFN-α2 is able to induce molecular remissions with undetectable JAK2V617F in a subset of patients with essential thrombocythemia (ET) and polycythemia vera (PV), even with normalization of the bone marrow and sustained molecular remissions after...

  4. Endogenous IL-22 Plays a Dual Role in Arthritis: Regulation of Established Arthritis via IFN-γ Responses

    Science.gov (United States)

    Justa, Shivali; Zhou, Xiaoqun; Sarkar, Sujata

    2014-01-01

    Objective IL-22 is elevated in patients with inflammatory arthritis and correlates with disease activity. IL-22 deficient mice have reduced incidence of arthritis. Recombinant IL-22 restrains progression of arthritis via increase in IL-10 responses when administered prior to onset of arthritis. These findings imply a possible dual role of IL-22 in inflammatory arthritis depending on the phase of arthritis. Experiments outlined here were designed to elucidate the contribution of endogenous IL-22 before and after the onset of arthritis. Methods Collagen induced arthritis (CIA) was induced in DBA1 or IFN-γ deficient mice following immunization with collagen and complete Freund's adjuvant. Anti-IL-22 antibody or isotype control were administered prior to or after onset of arthritis and disease progression assessed by clinical scoring and histopathology. IL-22, IL-17 and IFN-γ responses were measured by ELISA and flowcytometry. Anti-collagen antibody responses were analyzed by ELISA. Expression of IL-22R1 in CD4+ cells was elucidated by flowcytometry and real time PCR. Results Collagen specific IL-22 responses were expanded during arthritis and IL-22 producing cells were discrete from IL-17 or IFN-γ producing cells. Neutralization of IL-22 after onset of arthritis resulted in significant increase in Th1 responses and significantly reduced severity of arthritis. CD4+ cells from arthritic mice showed increased surface expression of IL-22R1. In vitro, CD4+T cells cultured with antigen presenting cells in the presence or absence of IL-22 suppressed or induced IFN-γ, respectively. The protective effect of anti-IL-22 was reversed in IFN-γ deficient mice. Moreover, administration of anti-IL-22 prior to onset of arthritis augmented arthritis severity. Conclusion We show for the first time that IL-22 plays a dual role: protective prior to the onset of arthritis and pathogenic after onset of arthritis. The pathogenic effect of IL-22 is dependent on suppression of IFN

  5. Multilayer moisture barrier

    Science.gov (United States)

    Pankow, Joel W; Jorgensen, Gary J; Terwilliger, Kent M; Glick, Stephen H; Isomaki, Nora; Harkonen, Kari; Turkulainen, Tommy

    2015-04-21

    A moisture barrier, device or product having a moisture barrier or a method of fabricating a moisture barrier having at least a polymer layer, and interfacial layer, and a barrier layer. The polymer layer may be fabricated from any suitable polymer including, but not limited to, fluoropolymers such as polyethylene terephthalate (PET) or polyethylene naphthalate (PEN), or ethylene-tetrafluoroethylene (ETFE). The interfacial layer may be formed by atomic layer deposition (ALD). In embodiments featuring an ALD interfacial layer, the deposited interfacial substance may be, but is not limited to, Al.sub.2O.sub.3, AlSiO.sub.x, TiO.sub.2, and an Al.sub.2O.sub.3/TiO.sub.2 laminate. The barrier layer associated with the interfacial layer may be deposited by plasma enhanced chemical vapor deposition (PECVD). The barrier layer may be a SiO.sub.xN.sub.y film.

  6. Barrier penetration database

    International Nuclear Information System (INIS)

    Fainberg, A.; Bieber, A.M. Jr.

    1978-11-01

    This document is intended to supply the NRC and nuclear power plant licensees with basic data on the times required to penetrate forcibly the types of barriers commonly found in nuclear plants. These times are necessary for design and evaluation of the physical protection system required under 10CFR73.55. Each barrier listed is described in detail. Minor variations in basic barrier construction that result in the same penetration time, are also described

  7. Role of IFN-gamma and IL-6 in a protective immune response to Yersinia enterocolitica in mice

    Directory of Open Access Journals (Sweden)

    Autenrieth Ingo B

    2008-09-01

    Full Text Available Abstract Background Yersinia outer protein (Yop H is a secreted virulence factor of Yersinia enterocolitica (Ye, which inhibits phagocytosis of Ye and contributes to the virulence of Ye in mice. The aim of this study was to address whether and how YopH affects the innate immune response to Ye in mice. Results For this purpose, mice were infected with wild type Ye (pYV+ or a YopH-deficient Ye mutant strain (ΔyopH. CD11b+ cells were isolated from the infected spleen and subjected to gene expression analysis using microarrays. Despite the attenuation of ΔyopH in vivo, by variation of infection doses we were able to achieve conditions that allow comparison of gene expression in pYV+ and ΔyopH infection, using either comparable infection courses or splenic bacterial burden. Gene expression analysis provided evidence that expression levels of several immune response genes, including IFN-γ and IL-6, are high after pYV+ infection but low after sublethal ΔyopH infection. In line with these findings, infection of IFN-γR-/- and IL-6-/- mice with pYV+ or ΔyopH revealed that these cytokines are not necessarily required for control of ΔyopH, but are essential for defense against infection with the more virulent pYV+. Consistently, IFN-γ pretreatment of bone marrow derived macrophages (BMDM strongly enhanced their ability in killing intracellular Ye bacteria. Conclusion In conclusion, this data suggests that IFN-γ-mediated effector mechanisms can partially compensate virulence exerted by YopH. These results shed new light on the protective role of IFN-γ in Ye wild type infections.

  8. Interaction of TLR-IFN and HLA polymorphisms on susceptibility of chronic HBV infection in Southwest Han Chinese.

    Science.gov (United States)

    He, Dengming; Tao, Shiqi; Guo, Shimin; Li, Maoshi; Wu, Junqiu; Huang, Hongfei; Guo, Xinwu; Yan, Guohua; Zhu, Peng; Wang, Yuming

    2015-08-01

    The toll-like receptor-interferon (TLR-IFN) signalling pathway plays a crucial role in HBV infection. Human leucocyte antigen (HLA) polymorphisms are associated with chronic HBV infection by genome wide association study (GWAS). We aimed to explore interaction between TLR-IFN and HLA gene polymorphisms in susceptibility of chronic HBV infection. In the Chinese Southwest Han population, 1191 chronic HBV infection patients and 273 HBV clearance were selected. A total of 39 single nucleotide polymorphism loci in 23 genes of the TLR-IFN pathway and four HLA polymorphism loci associated with chronic HBV infection identified by GWAS were selected for genotyping. SNPStats, QVALUE, and multifactor dimensionality reduction were used for statistical analysis. A significant association was seen in several of the TLR-IFN pathway genes, TLR9 rs352140 (OR = 0.70, P = 0.0088), IL1B rs16944 (OR = 0.67, P = 0.016), IL12B rs3212227 (OR = 1.38, P = 0.021), IFNGR1 rs3799488 (OR = 1.48, P = 0.0048), IFNGR2 rs1059293 (OR = 0.27, P = 0.011), MX1 rs467960 (OR = 0.68, P = 0.022), as well as four loci in HLA, rs3077 (OR = 0.55, P rs16944 (0.13%), rs1143623 and rs6613 (0.10%). The combination of rs9277535 in HLA and rs16944 in IL1B was the best model to predict chronic HBV infection (testing accuracy = 0.6040, P = 0.0010, cross-validation consistency = 10/10). TLR-IFN pathway gene polymorphisms are associated with chronic HBV infection. Interactions with polymorphisms in these genes may be one mechanism by which HLA polymorphisms influence susceptibility to chronic HBV infection, as specific single nucleotide polymorphism combinations are highly predictive of chronic HBV infection. © 2014 The Authors. Liver International Published by John Wiley & Sons Ltd.

  9. Transport barriers in plasmas

    International Nuclear Information System (INIS)

    Caldas, I L; Szezech, J D Jr; Kroetz, T; Marcus, F A; Roberto, M; Viana, R L; Lopes, S R

    2012-01-01

    We discuss the creation of transport barriers in magnetically confined plasmas with non monotonic equilibrium radial profiles. These barriers reduce the transport in the shearless region (i.e., where the twist condition does not hold). For the chaotic motion of particles in an equilibrium electric field with a nonmonotonic radial profile, perturbed by electrostatic waves, we show that a nontwist transport barrier can be created in the plasma by modifying the electric field radial profile. We also show non twist barriers in chaotic magnetic field line transport in the plasma near to the tokamak wall with resonant modes due to electric currents in external coils.

  10. Children’s Book Illustrations: Visual Language of Picture Books

    Directory of Open Access Journals (Sweden)

    Hladíková Hana

    2014-01-01

    Full Text Available High-quality picture books that merge text and illustration together in order to tell a story are eminent for healthy mental and social growth of children. This paper is to outline the benefits picture books bring to children between the ages three to eight, determine functions of its illustrative language, examine the process of its production, and point out a set of elements that, according to number of professional children's book illustrators, significantly contribute to the success of a picture book

  11. Developing hospital identity manuals: a reference tool for illustrators.

    Science.gov (United States)

    Schaffer, J A; Zimmerman, S B

    1990-01-01

    Because of an increase in hospital marketing efforts, medical illustrators may be asked to assist in developing and implementing hospital identity manuals, which specify the graphic standards for visual communications media. A checklist survey of existing identity manuals and a literature review were conducted by one of the authors, a medical illustrator, to help her to develop a manual for her hospital employer. This article documents the literature review, the study, and the identity manual development, and presents recommendations to help other medical illustrators who might become involved in similar assignments.

  12. Daily intake of probiotics with high IFN-γ/IL-10 ratio increases the cytotoxicity of human natural killer cells: a personalized probiotic approach.

    Science.gov (United States)

    Ho, Yu-Hsuan; Lu, Yu-Chiu; Chang, Hung-Cheng; Lee, Shin-Yi; Tsai, Min-Fen; Huang, Yu-Ting; Hsu, Ting-Yuan

    2014-01-01

    A personalized probiotic microfluidic chip system has been established and used to screen the probiotics which had the highest value of IFN-γ/IL-10 or IL-10/IFN-γ among six probiotics, including L. paracasei BRAP01, L. acidophilus AD300, B. longum BA100, E. faecium BR0085, L. rhamnosus AD500, and L. reuteri BR101. One hundred volunteers were included and their PBMCs were collected and stimulated by the six probiotics. People who belonged to the IFN-γ group took the probiotics that exerted the highest ratio of IFN-γ/IL-10 and vice versa in IL-10 group. A significant increase in NK cytotoxicity of 69 volunteers in the IFN-γ group was observed compared to the IL-10 group (n = 21) and control group (n = 10). The result also showed that L. paracasei BRAP01 and L. acidophilus AD300 were the two dominant inducers in IFN-γ group which yielded higher value of IFN-γ/IL-10 than the other 4 probiotics, while L. reuteri BR101 was the most effective agent on the ratio of IL-10/IFN-γ in the IL-10 group. Our finding highlighted the concept of personalized probiotics and also provided a good foundation to investigate the probiotics with NK activity.

  13. Clinical evaluation of determination the changes on serum IL-2, IL-4 and IFN-γ levels after treatment in pediatric patients with acute nephritis

    International Nuclear Information System (INIS)

    Zhou Hong; Hu Yan; Wei Guoyu; Liu Ya

    2011-01-01

    Objective: To explore the clinical evaluation of the changes of determination of serum IL-2, IL-4 and IFN-γ levels after treatment in pediatric patients with acute nephritis. Methods: Serum IL-2 (with RIA), IL-4, IFN-γ (with ELISA) levels were determined both before and after treatment in 32 pediatric patients with acute nephritis and 35 normal controls. Results: The serum IL-4, IFN-γ levels were significantly higher in the patients than those in controls before treatment (P 0.05). Serum IL-2 levels were negatively correlated with IL-4, IFN-γ levels (r=-0.5536, -0.6012, P<0.01). Conclusion: Interaction of the serum IL-2, IL-4 and IFN-γ also participated in the pathogenesis of acute nephritis in pediatric patients, monitoring the changes of their serum levels was helpful for the management of the diseases and provider important clinical value. (authors)

  14. Enhancement of ceramide formation increases endocytosis of Lactobacillus acidophilus and leads to increased IFN-β and IL-12 production in dendritic cells

    DEFF Research Database (Denmark)

    Fuglsang, Eva; Boye, Louise; Frøkiær, Hanne

    2017-01-01

    , and induced macropinocytosis in the bmDCs. Addition of SMase increased the phagocytosis of L. acidophilus and L. acidophilus-induced IL-12/IFN-β but showed no effect on the uptake of E. coli nor on E.coli induced IL-12/IFN-β production. Also, SMase did not affect Pam3CSK4-induced macropinocytosis of FITC......-dextran. Inhibition of both acid SMase and ceramidase by CPZ increased constitutive macropinocytosis of dextran and slightly increased L.acidophilus induced Il12/Ifn-β expression and E.coli induced Ifnβ expression. Our results confirm a role for ceramide in the L.acidophilus induced IL-12/IFN-β production but also...

  15. Combination of pegylated IFN-α2b with imatinib increases molecular response rates in patients with low- or intermediate-risk chronic myeloid leukemia

    DEFF Research Database (Denmark)

    Simonsson, Bengt; Gedde-Dahl, Tobias; Markevärn, Berit

    2011-01-01

    Biologic and clinical observations suggest that combining imatinib with IFN-a may improve treatment outcome in chronic myeloid leukemia (CML). We randomized newly diagnosed chronic-phase CML patients with a low or intermediate Sokal risk score and in imatinib-induced complete hematologic remission......%) discontinued imatinib treatment (1 because of blastic transformation in imatinib arm). In addition, in the combination arm, 34 patients (61%) discontinued Peg-IFN-a2b, most because of toxicity. The MMR rate at 12 months was significantly higher in the imatinib plus Peg-IFN-a2b arm (82%) compared...... with the imatinib monotherapy arm (54%; intention-to-treat, P = .002). The MMR rate increased with the duration of Peg-IFN-a2b treatment ( 12-week MMR rate 91%). Thus, the addition of even relatively short periods of Peg-IFN-a2b to imatinib markedly increased the MMR rate at 12 months...

  16. Learning hatching for pen-and-ink illustration of surfaces

    KAUST Repository

    Kalogerakis, Evangelos; Nowrouzezahrai, Derek; Breslav, Simon; Hertzmann, Aaron

    2012-01-01

    This article presents an algorithm for learning hatching styles from line drawings. An artist draws a single hatching illustration of a 3D object. Her strokes are analyzed to extract the following per-pixel properties: hatching level (hatching

  17. Congenital diseases and syndromes. An illustrated radiological guide

    Energy Technology Data Exchange (ETDEWEB)

    Al-Tubaikh, Jarrah Ali [Universitaetsklinikum Muenchen, Klinikum Grosshadern (Germany). Inst. fuer Klinische Radiologie; Sabah Hospital (Kuwait). Dept. of Diagnostic Radiology; Reiser, Maximilian F. [Universitaetsklinikum Muenchen, Klinikum Grosshadern (Germany). Inst. fuer Klinische Radiologie

    2009-07-01

    Congenital Diseases and Syndromes - An Illustrated Radiological Guide is designed to serve the radiologist as an easy-to-use visual guide that illustrates the typical diagnostic radiological features of the most common congenital diseases and syndromes. The book is organised according to body system, with chapters focusing on the CNS, the head and neck, the chest and heart, the abdomen and pelvis, and the musculoskeletal system. A final chapter is devoted to phakomatosis. Each syndrome or disease is illustrated by multiple images as well as by high-quality digital medical illustrations depicting those radiological signs that are difficult to detect. The reader is thereby familiarised with the various congenital anomalies from the radiological point of view. In addition, etiology, diagnostic criteria, and main symptoms are described, and potential differential diagnoses highlighted. This book will be immensely useful for junior radiologists, radiology students, and doctors in any specialty who are interested in congenital malformations and syndromes. (orig.)

  18. Alkylation of Chlorobenzene. An Experiment Illustrating Kinetic versus Thermodynamic Control.

    Science.gov (United States)

    Kolb, Kenneth; And Others

    1988-01-01

    Describes an experiment which illustrates the kinetic versus thermodynamic control of chemical reactions for organic chemistry students. Considers the laboratory procedures including the isolation of both the kinetic and thermodynamic products. (CW)

  19. Illustrative examples in a bilingual decoding dictionary: An (un ...

    African Journals Online (AJOL)

    Keywords: Illustrative Examples, Bilingual Decoding Dictionary, Semantic Differences Between Source Language (Sl) And Target Language (Tl), Grammatical Differences Between Sl And Tl, Translation Of Examples, Transposition, Context-Dependent Translation, One-Word Equivalent, Zero Equivalent, Idiomatic ...

  20. Physics with illustrative examples from medicine and biology

    CERN Document Server

    Benedek, George B

    Physics: with illustrative examples from medicine and biology is a three-volume set of textbooks in introductory physics written at the calculus level and designed primarily for students with career objectives in the life sciences.

  1. Research on Illustrations in Text: Issues and Perspectives.

    Science.gov (United States)

    Duchastel, Philippe C.

    1980-01-01

    Explores the problems of research on the effects of illustrations in text and other teaching materials. Several research frameworks are described, and a functional approach is suggested as a method of improvement. (BK)

  2. The seismic analyzer: interpreting and illustrating 2D seismic data.

    Science.gov (United States)

    Patel, Daniel; Giertsen, Christopher; Thurmond, John; Gjelberg, John; Gröller, M Eduard

    2008-01-01

    We present a toolbox for quickly interpreting and illustrating 2D slices of seismic volumetric reflection data. Searching for oil and gas involves creating a structural overview of seismic reflection data to identify hydrocarbon reservoirs. We improve the search of seismic structures by precalculating the horizon structures of the seismic data prior to interpretation. We improve the annotation of seismic structures by applying novel illustrative rendering algorithms tailored to seismic data, such as deformed texturing and line and texture transfer functions. The illustrative rendering results in multi-attribute and scale invariant visualizations where features are represented clearly in both highly zoomed in and zoomed out views. Thumbnail views in combination with interactive appearance control allows for a quick overview of the data before detailed interpretation takes place. These techniques help reduce the work of seismic illustrators and interpreters.

  3. Congenital diseases and syndromes. An illustrated radiological guide

    International Nuclear Information System (INIS)

    Al-Tubaikh, Jarrah Ali; Sabah Hospital; Reiser, Maximilian F.

    2009-01-01

    Congenital Diseases and Syndromes - An Illustrated Radiological Guide is designed to serve the radiologist as an easy-to-use visual guide that illustrates the typical diagnostic radiological features of the most common congenital diseases and syndromes. The book is organised according to body system, with chapters focusing on the CNS, the head and neck, the chest and heart, the abdomen and pelvis, and the musculoskeletal system. A final chapter is devoted to phakomatosis. Each syndrome or disease is illustrated by multiple images as well as by high-quality digital medical illustrations depicting those radiological signs that are difficult to detect. The reader is thereby familiarised with the various congenital anomalies from the radiological point of view. In addition, etiology, diagnostic criteria, and main symptoms are described, and potential differential diagnoses highlighted. This book will be immensely useful for junior radiologists, radiology students, and doctors in any specialty who are interested in congenital malformations and syndromes. (orig.)

  4. La proteína asociada a SLAM (SAP regula la expresión de IFN-g en lepra The SLAM-associated protein (SAP regulates IFN-g expression in leprosy

    Directory of Open Access Journals (Sweden)

    María F. Quiroga

    2004-10-01

    Full Text Available La inmunidad protectora contra Mycobacterium leprae requiere IFN-g. Los pacientes con lepra tuberculoide producen localmente citoquinas Th1, mientras que los pacientes lepromatosos producen citoquinas Th2. La molécula linfocitaria activadora de señales (SLAM y la proteína asociada a SLAM (SAP participan en la diferenciación celular que conduce a producción de patrones específicos de citoquinas. A fin de investigar la vía SLAM/SAP en la infección por M. leprae, determinamos expresión de ARN mensajero (ARNm de SAP, IFN-g y SLAM en pacientes con lepra. Observamos que la expresión de SLAM correlacionó en forma directa con la expresión de IFN-g, mientras que la expresión de SAP correlacionó inversamente con la expresión de ambas proteínas. Así, nuestros resultados indican que SAP interferiría con las respuestas de citoquinas Th1 mientras que SLAM contribuiría con la respuesta Th1 en lepra, señalando a la vía SLAM/SAP como potencial blanco modulador de citoquinas en enfermedades con respuestas Th2 disfuncionales.Tuberculoid leprosy patients locally produce Th1 cytokines, while lepromatous patients produce Th2 cytokines. Signaling lymphocytic activation molecule (SLAM and the SLAM-associated protein (SAP participate in the differentiation process that leads to the production of specific patterns of cytokines by activated T cells. To investigate the SLAM/SAP pathway in M. leprae infection, we determined the expression of SAP, IFN-g and SLAM RNA messenger in leprosy patients. We found a direct correlation of SLAM expression with IFN-g expression, whereas the expression of SAP was inversely correlated with the expression of both SLAM and IFN-g. Therefore, our data indicate that SAP might interfere with Th1 cytokine responses while SLAM expression may contribute to Th1 responses in leprosy. This study further suggests that the SLAM/SAP pathway might be a focal point for therapeutic modulation of T cell cytokine responses in diseases

  5. ADVERTISING AND AN ACCIDENTAL CLASSIC: ILLUSTRATED SKETCHES OF DFATH VALLEY

    Directory of Open Access Journals (Sweden)

    Douglas Steeples

    2001-01-01

    Full Text Available Illustrated Sketches of Death Valley (1891 originated as a hastily-written series of journalistic sketches of our Western borax deserts. They were written on commission to supplement their authors income. Conceived as a means subtly to promote the borax industry the Sketches in time won unintended recognition as a classic source for their subject. They also assumed unforeseen importance as an illustration of the role of advertising in America’s changing economy.

  6. Illustration of reaction mechanism in polyatomic systems via computer movies

    International Nuclear Information System (INIS)

    Raff, L.M.

    1974-01-01

    The CD 4 + T* systems is suited for classroom illustration of reaction dynamics. Questions about the system can be illustrated by reducing selected many-body trajectories to a 16 mm color movie that represents the six-body motion in projected coordinates. Such a movie has been produced for this system. The production procedure used is reported, and a detailed description of the contents of the movie is given. (U.S.)

  7. The Seismic Analyzer: Interpreting and Illustrating 2D Seismic Data

    OpenAIRE

    Patel, Daniel; Giertsen, Christopher; Thurmond, John; Gjelberg, John; Gröller, Eduard

    2008-01-01

    We present a toolbox for quickly interpreting and illustrating 2D slices of seismic volumetric reflection data. Searching for oil and gas involves creating a structural overview of seismic reflection data to identify hydrocarbon reservoirs. We improve the search of seismic structures by precalculating the horizon structures of the seismic data prior to interpretation. We improve the annotation of seismic structures by applying novel illustrative rendering algorithms tailored to seism...

  8. Dogville or an illustration of some properties of general equilibrium

    OpenAIRE

    Harmgart, H.; Huck, S.

    2008-01-01

    In this note we argue that Lars von Trier’s movie Dogville can be viewed as an illustration of a simple economy where one agent has only her body as initial endowment. The movie illustrates some interesting comparative statics of equilibrium allocations. It shows how life would be like in a world where, in the absence of constitutional or legal constraints, economic forces reign freely and raises some fundamental issues of voluntary exchange versus force that apply to a number ...

  9. Serum IFN neutralizing antibodies and neopterin levels in a cross-section of MS patients.

    Science.gov (United States)

    Cook, S D; Quinless, J R; Jotkowitz, A; Beaton, P

    2001-09-25

    To determine levels of serum interferon beta (IFNbeta) neutralizing antibody (NAb) and neopterin-an IFN biologic response marker-in patients with MS treated with Betaseron or Avonex. Controversy exists over the relative immunogenicity of IFNbeta-1a and IFNbeta-1b and the reasons for any such difference. To determine the role of patient profile and test methodology in IFNbeta, NAb levels need to be measured blindly and simultaneously in a predefined closely matched MS patient cohort. Serum NAb and neopterin levels were measured in closely matched patients on Avonex (n = 98) or Betaseron (n = 64). NAb were determined by Athena Diagnostics and serum neopterin levels by Covance Laboratories using a competitive binding radioimmunoassay. More patients taking Betaseron (22%) than Avonex (7%) had elevated titers of NAb (p = 0.008). Mean serum neopterin levels were lower in patients with high as compared to low NAb titers (p = 0.0002). No difference in mean neopterin levels was found comparing the total Betaseron group to the Avonex group; however, in the subset of patients with low NAb titers, mean neopterin levels were higher in the Betaseron than in the Avonex group (p = 0.027). A random cross-sectional sampling of patients on Avonex showed a decrease in neopterin levels over time between weekly doses. NAb are more commonly found with Betaseron than Avonex. More studies are needed to determine the correlation among serum neopterin levels, other biologic response markers, NAb, and disease activity in patients with MS being treated with IFNbeta.

  10. IFN-γ expression in placenta is associated to resistance to Chlamydia abortus after intragastric infection.

    Science.gov (United States)

    del Rio, L; Barberá-Cremades, M; Navarro, J A; Buendía, A J; Cuello, F; Ortega, N; Gallego, M C; Salinas, J; Caro, M R

    2013-03-01

    Intragastric infection mimics the natural route of infection of Chlamydia abortus (etiological agent of ovine enzootic abortion). In the mouse model, intragastric experimental infection induces very mild signs of infection followed by late term abortions, as it is shown by the natural ovine host. In order to evaluate the immune mechanisms associated to the dissemination of the pathogen from the gastrointestinal tract, we have administered an intragastric dose of C. abortus to pregnant mice. Systemic and local expression of cytokines, tissue colonization and excretion of bacteria after parturition were monitored during pregnancy. Susceptible CBA/J mice showed a higher bacterial colonization of the placenta and excretion of live bacteria after parturition that were related to a higher local IL-10 expression. By contrast, resistant C57BL/6 mouse strain had higher local IFN-γ mRNA expression in the placenta just before parturition and a transient bacterial colonization of the reproductive tract, with no excretion of C. abortus after parturition. In summary, intragastric infection not only mimics the natural route of infection of C. abortus, but can also be useful in order to understand the immunopathogenesis of chlamydial abortion in the mouse. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Analyses of the pathways involved in early- and late-phase induction of IFN-beta during C. muridarum infection of oviduct epithelial cells.

    Directory of Open Access Journals (Sweden)

    Sishun Hu

    Full Text Available We previously reported that the IFN-β secreted by Chlamydia muridarum-infected murine oviduct epithelial cells (OE cells was mostly dependent on the TLR3 signaling pathway. To further characterize the mechanisms of IFN-β synthesis during Chlamydia infection of OE cells in vitro, we utilized specific inhibitory drugs to clarify the roles of IRF3 and NF-κB on both early- and late-phase C. muridarum infections. Our results showed that the pathways involved in the early-phase of IFN-β production were distinct from that in the late-phase of IFN-β production. Disruption of IRF3 activation using an inhibitor of TBK-1 at early-phase Chlamydia infection had a significant impact on the overall synthesis of IFN-β; however, disruption of IRF3 activation at late times during infection had no effect. Interestingly, inhibition of NF-κB early during Chlamydia infection also had a negative effect on IFN-β production; however, its impact was not significant. Our data show that the transcription factor IRF7 was induced late during Chlamydia infection, which is indicative of a positive feedback mechanism of IFN-β synthesis late during infection. In contrast, IRF7 appears to play little or no role in the early synthesis of IFN-β during Chlamydia infection. Finally, we demonstrate that antibiotics that target chlamydial DNA replication are much more effective at reducing IFN-β synthesis during infection versus antibiotics that target chlamydial transcription. These results provide evidence that early- and late-phase IFN-β production have distinct signaling pathways in Chlamydia-infected OE cells, and suggest that Chlamydia DNA replication might provide a link to the currently unknown chlamydial PAMP for TLR3.

  12. Converse Barrier Certificate Theorems

    DEFF Research Database (Denmark)

    Wisniewski, Rafael; Sloth, Christoffer

    2016-01-01

    This paper shows that a barrier certificate exists for any safe dynamical system. Specifically, we prove converse barrier certificate theorems for a class of structurally stable dynamical systems. Other authors have developed a related result by assuming that the dynamical system has neither...

  13. Skin barrier function

    DEFF Research Database (Denmark)

    2016-01-01

    Renowned experts present the latest knowledge Although a very fragile structure, the skin barrier is probably one of the most important organs of the body. Inward/out it is responsible for body integrity and outward/in for keeping microbes, chemicals, and allergens from penetrating the skin. Since...... the role of barrier integrity in atopic dermatitis and the relationship to filaggrin mutations was discovered a decade ago, research focus has been on the skin barrier, and numerous new publications have become available. This book is an interdisciplinary update offering a wide range of information...... on the subject. It covers new basic research on skin markers, including results on filaggrin and on methods for the assessment of the barrier function. Biological variation and aspects of skin barrier function restoration are discussed as well. Further sections are dedicated to clinical implications of skin...

  14. Barriers to the future

    Energy Technology Data Exchange (ETDEWEB)

    Massey, C T

    1986-09-01

    Opportunities for the British coal industry seem vast yet there are still barriers to progress. Seven areas are identified and discussed: mining mobility (for example, longwall mining systems are rigid and inflexible compared with American stall and pillar working); mine structure (many mines are more suitable to pit ponies than to large pieces of equipment); financial barriers (Government requires the industry to break even in 1987/88); personnel barriers (less specialization, better use of skills); safety barriers (increased use of remote control, ergonomics and robotics to protect workers); microelectronic management (nationalization has cushioned management from the market place; there is a need for a more multidisciplinary approach to the industry); and legal barriers (most legislation in the past has been in response to accidents; legislation external to the industry but affecting it is more fundamental).

  15. HCV-specific immune responses induced by CIGB-230 in combination with IFN-α plus ribavirin

    Science.gov (United States)

    Amador-Cañizares, Yalena; Martínez-Donato, Gillian; Álvarez-Lajonchere, Liz; Vasallo, Claudia; Dausá, Mariacarla; Aguilar-Noriega, Daylen; Valenzuela, Carmen; Raíces, Ivette; Dubuisson, Jean; Wychowski, Czeslaw; Cinza-Estévez, Zurina; Castellanos, Marlén; Núñez, Magdalys; Armas, Anny; González, Yaimé; Revé, Ismariley; Guerra, Ivis; Pérez Aguiar, Ángel; Dueñas-Carrera, Santiago

    2014-01-01

    AIM: To analyze hepatitis C virus (HCV)-specific immune responses in chronically infected patients under triple therapy with interferon-α (IFN-α) plus ribavirin and CIGB-230. METHODS: CIGB-230 was administered in different schedules with respect to IFN-α plus ribavirin therapy. Paired serum and peripheral blood mononuclear cells (PBMC) samples from baseline and end of treatment were analyzed. The HCV-specific humoral response was tested by enzyme-linked immunosorbent assay, neutralizing antibodies were evaluated by cell culture HCV neutralization assays, PBMC proliferation was assayed by carboxyfluorescein succinimidyl ester staining and IFN-γ secretion was assessed by enzyme-linked immunospot. Data on virological and histological response and their association with immune variables are also provided. RESULTS: From week 12 to week 48, all groups of patients showed a significant reduction in mean leukocyte counts. Statistically significant reductions in antibody titers were frequent, but only individuals immunized with CIGB-230 as early add-on treatment sustained the core-IgG response, and the neutralizing antibody response was enhanced only in patients receiving CIGB-230. Cell-mediated immune responses also tended to decline, but significant reductions in IFN-γ secretion and total absence of core-specific lymphoproliferation were exclusive of the control group. Only CIGB-230-immunized individuals showed de novo induced lymphoproliferative responses against the structural antigens. Importantly, it was demonstrated that the quality of the CIGB-230-induced immune response depended on the number of doses and timing of administration in relation to the antiviral therapy. Specifically, the administration of 6 doses of CIGB-230 as late add-on to therapy increased the neutralizing antibody activity and the de novo core-specific IFN-γ secretion, both of which were associated with the sustained virological response. CONCLUSION: CIGB-230, combined with IFN

  16. Impaired chromatin remodelling at STAT1-regulated promoters leads to global unresponsiveness of Toxoplasma gondii-infected macrophages to IFN-γ.

    Directory of Open Access Journals (Sweden)

    Christine Lang

    2012-01-01

    Full Text Available Intracellular pathogens including the apicomplexan and opportunistic parasite Toxoplasma gondii profoundly modify their host cells in order to establish infection. We have shown previously that intracellular T. gondii inhibit up-regulation of regulatory and effector functions in murine macrophages (MΦ stimulated with interferon (IFN-γ, which is the cytokine crucial for controlling the parasites' replication. Using genome-wide transcriptome analysis we show herein that infection with T. gondii leads to global unresponsiveness of murine macrophages to IFN-γ. More than 61% and 89% of the transcripts, which were induced or repressed by IFN-γ in non-infected MΦ, respectively, were not altered after stimulation of T. gondii-infected cells with IFN-γ. These genes are involved in a variety of biological processes, which are mostly but not exclusively related to immune responses. Analyses of the underlying mechanisms revealed that IFN-γ-triggered nuclear translocation of STAT1 still occurred in Toxoplasma-infected MΦ. However, STAT1 bound aberrantly to oligonucleotides containing the IFN-γ-responsive gamma-activated site (GAS consensus sequence. Conversely, IFN-γ did not induce formation of active GAS-STAT1 complexes in nuclear extracts from infected MΦ. Mass spectrometry of protein complexes bound to GAS oligonucleotides showed that T. gondii-infected MΦ are unable to recruit non-muscle actin to IFN-γ-responsive DNA sequences, which appeared to be independent of stimulation with IFN-γ and of STAT1 binding. IFN-γ-induced recruitment of BRG-1 and acetylation of core histones at the IFN-γ-regulated CIITA promoter IV, but not β-actin was diminished by >90% in Toxoplasma-infected MΦ as compared to non-infected control cells. Remarkably, treatment with histone deacetylase inhibitors restored the ability of infected macrophages to express the IFN-γ regulated genes H2-A/E and CIITA. Taken together, these results indicate that Toxoplasma

  17. The Use of Pictorial Illustrations in African Language Dictionaries

    Directory of Open Access Journals (Sweden)

    Lilian Gangla-Birir

    2011-10-01

    Full Text Available

    ABSTRACT: This article examines the use of pictorial illustrations in African language dictionar-ies, with particular reference to items generally included in dictionaries based on Stein's (1991 categories. It argues for the need to include more illustrations of cultural items specific to a par-ticular community and language group in dictionaries. A corpus analytic survey is done to deter-mine if African language dictionaries employ pictorial illustrations and, if so, which items are illus-trated. The results of this survey indicate that only a few African language dictionaries employ pictorial illustrations, even those that do correspond to Stein's categories. Of the dictionaries exam-ined, only one uses illustrations in the form of full-colour photographs, namely of different kinds of cattle, a very important cultural item within that specific community.


    Keywords: PICTORIAL ILLUSTRATIONS, CULTURE, LEXICOGRAPHY, BILINGUAL DIC-TIONARY, MONOLINGUAL DICTIONARY, AFRICAN LANGUAGE

    *****

    OPSOMMING: Die gebruik van beeldillustrasies in Afrikataalwoordeboeke. Hierdie artikel ondersoek die gebruik van beeldillustrasies in Afrikataalwoordeboeke met spesiale verwysing na items wat gewoonlik in woordeboeke ingesluit word, gebaseer op Stein (1991 se kategorieë. Dit betoog vir die noodsaaklikheid om meer illustrasies van kulturele items eie aan 'n besondere gemeenskap of taalgroep in woordeboeke in te sluit. 'n Analitiese oorsig van 'n korpus is gedoen om te bepaal of Afrikataalwoordeboeke beeldillustrasies gebruik, en, indien wel, watter items geïllustreer word. Die resultate van hierdie oorsig toon aan dat slegs 'n paar Afrikataalwoor-deboeke beeldillustrasies gebruik, selfs dié wat met Stein se kategorieë ooreenstem. Van die woor-deboeke wat ondersoek is, gebruik net een illustrasies in die vorm van volkleurfoto's, naamlik van verskillende soorte beeste, 'n baie belangrike kulturele item binne daardie spesifieke gemeenskap

  18. Increased TNF-alpha/IFN-gamma/IL-2 and decreased TNF-alpha/IFN-gamma production by central memory T cells are associated with protective responses against bovine tuberculosis following BCG vaccination

    Directory of Open Access Journals (Sweden)

    Mayara Fernanda Maggioli

    2016-10-01

    Full Text Available Central memory T cells (Tcm and polyfunctional CD4 T cell responses contribute to vaccine-elicited protection with both human and bovine tuberculosis (TB; however, their combined role in protective immunity to TB is unclear. To address this question, we evaluated polyfunctional cytokine responses by CD4 T cell effector / memory populations from bacille Calmette Guerin (BCG vaccinated and non-vaccinated calves prior to and after aerosol challenge with virulent Mycobacterium bovis. Polyfunctional cytokine expression patterns in the response by Tcm, effector memory, and effector T cell subsets were similar between BCG-vaccinated and M. bovis-infected calves; only differing in magnitude (i.e., infected > vaccinated. BCG vaccination, however, did alter the kinetics of the ensuing response to virulent M. bovis infection. Early after challenge (three weeks post-infection, non-vaccinates had greater antigen-specific IFN-γ/TNF-α and lesser IFN-γ/TNF-α/IL-2 responses by Tcm cells than did vaccinated animals. Importantly, these differences were also associated with mycobacterial burden upon necropsy. Polyfunctional responses to ESAT-6:CFP10 (antigens not synthesized by BCG strains were detected in memory subsets, as well as in effector cells, as early as three weeks after challenge. These findings suggest that cell fate divergence may occur early after antigen priming in the response to bovine TB and that memory and effector T cells may expand concurrently during the initial phase of the immune response. In summary, robust IFN-γ/TNF-α response by Tcm cells is associated with greater mycobacterial burden while IFN-γ/TNF-α/IL-2 response by Tcm cells are indicative of a protective response to bovine TB.

  19. HPV18 Persistence Impairs Basal and DNA Ligand-Mediated IFN-β and IFN-λ1 Production through Transcriptional Repression of Multiple Downstream Effectors of Pattern Recognition Receptor Signaling.

    Science.gov (United States)

    Albertini, Silvia; Lo Cigno, Irene; Calati, Federica; De Andrea, Marco; Borgogna, Cinzia; Dell'Oste, Valentina; Landolfo, Santo; Gariglio, Marisa

    2018-03-15

    Although it is clear that high-risk human papillomaviruses (HPVs) can selectively infect keratinocytes and persist in the host, it still remains to be unequivocally determined whether they can escape antiviral innate immunity by interfering with pattern recognition receptor (PRR) signaling. In this study, we have assessed the innate immune response in monolayer and organotypic raft cultures of NIKS cells harboring multiple copies of episomal HPV18 (NIKSmcHPV18), which fully recapitulates the persistent state of infection. We show for the first time, to our knowledge, that NIKSmcHPV18, as well as HeLa cells (a cervical carcinoma-derived cell line harboring integrated HPV18 DNA), display marked downregulation of several PRRs, as well as other PRR downstream effectors, such as the adaptor protein stimulator of IFN genes and the transcription factors IRF1 and 7. Importantly, we provide evidence that downregulation of stimulator of IFN genes, cyclic GMP-AMP synthase, and retinoic acid-inducible gene I mRNA levels occurs at the transcriptional level through a novel epigenetic silencing mechanism, as documented by the accumulation of repressive heterochromatin markers seen at the promoter region of these genes. Furthermore, stimulation of NIKSmcHPV18 cells with salmon sperm DNA or poly(deoxyadenylic-deoxythymidylic) acid, two potent inducers of PRR signaling, only partially restored PRR protein expression. Accordingly, the production of IFN-β and IFN-λ 1 was significantly reduced in comparison with the parental NIKS cells, indicating that HPV18 exerts its immunosuppressive activity through downregulation of PRR signaling. Altogether, our findings indicate that high-risk human papillomaviruses have evolved broad-spectrum mechanisms that allow simultaneous depletion of multiple effectors of the innate immunity network, thereby creating an unreactive cellular milieu suitable for viral persistence. Copyright © 2018 by The American Association of Immunologists, Inc.

  20. The history and illustration of anatomy in the Middle Ages.

    Science.gov (United States)

    Gurunluoglu, Raffi; Gurunluoglu, Aslin; Williams, Susan A; Cavdar, Safiye

    2013-11-01

    This article reviews the influence of key figures on the pictorial representation of anatomy and the evolution of anatomical illustration during the Middle Ages until the time of the Renaissance, based on medical history books, journals and ancient medical books. During the early period in the Middle Ages, most illustrations were traditional drawings of emblematic nature, oftentimes unrealistic, not only because the precise knowledge of anatomy was lacking but also because the objective was to elucidate certain principles for teaching purposes. Five figure-series that came down to us through ancient manuscripts and textbooks represent the best examples of such traditional illustrations. With the advent of human dissection in the 13th and 14th centuries, a significant transformation in the depiction of anatomy began to project the practice of human dissection, as we see in the works of Mondino de Luzzi, Henri de Mondeville and Guido de Vigevano. After the invention of book printing in the second half of the 15th century, the reproduction of books was commonly practised and the woodcut made multiplication of pictures easier. Peter of Abano, Hieronymous Brunschwig, Johannes de Ketham, Johannes Peyligk, Gregory Reisch, Magnus Hundt, Laurentius Phryesen and many more included several anatomical illustrations in their treatises that demonstrated the development of anatomical illustration during the later Middle Ages.

  1. Volume illustration of muscle from diffusion tensor images.

    Science.gov (United States)

    Chen, Wei; Yan, Zhicheng; Zhang, Song; Crow, John Allen; Ebert, David S; McLaughlin, Ronald M; Mullins, Katie B; Cooper, Robert; Ding, Zi'ang; Liao, Jun

    2009-01-01

    Medical illustration has demonstrated its effectiveness to depict salient anatomical features while hiding the irrelevant details. Current solutions are ineffective for visualizing fibrous structures such as muscle, because typical datasets (CT or MRI) do not contain directional details. In this paper, we introduce a new muscle illustration approach that leverages diffusion tensor imaging (DTI) data and example-based texture synthesis techniques. Beginning with a volumetric diffusion tensor image, we reformulate it into a scalar field and an auxiliary guidance vector field to represent the structure and orientation of a muscle bundle. A muscle mask derived from the input diffusion tensor image is used to classify the muscle structure. The guidance vector field is further refined to remove noise and clarify structure. To simulate the internal appearance of the muscle, we propose a new two-dimensional example based solid texture synthesis algorithm that builds a solid texture constrained by the guidance vector field. Illustrating the constructed scalar field and solid texture efficiently highlights the global appearance of the muscle as well as the local shape and structure of the muscle fibers in an illustrative fashion. We have applied the proposed approach to five example datasets (four pig hearts and a pig leg), demonstrating plausible illustration and expressiveness.

  2. Vehicle barrier systems

    International Nuclear Information System (INIS)

    Sena, P.A.

    1986-01-01

    The ground vehicle is one of the most effective tools available to an adversary force. Vehicles can be used to penetrate many types of perimeter barriers, transport equipment and personnel rapidly over long distances, and deliver large amounts of explosives directly to facilities in suicide missions. The function of a vehicle barrier system is to detain or disable a defined threat vehicle at a selected distance from a protected facility. Numerous facilities are installing, or planning to install, vehicle barrier systems and many of these facilities are requesting guidance to do so adequately. Therefore, vehicle barriers are being evaluated to determine their stopping capabilities so that systems can be designed that are both balanced and capable of providing a desired degree of protection. Equally important, many of the considerations that should be taken into account when establishing a vehicle barrier system have been identified. These considerations which pertain to site preparation, barrier selection, system integration and operation, and vehicle/barrier interaction, are discussed in this paper

  3. Impedance model for quantum-mechanical barrier problems

    International Nuclear Information System (INIS)

    Nelin, Evgenii A

    2007-01-01

    Application of the impedance model to typical quantum-mechanical barrier problems, including those for structures with resonant electron tunneling, is discussed. The efficiency of the approach is illustrated. The physical transparency and compactness of the model and its potential as a teaching and learning tool are discussed. (methodological notes)

  4. Three distinct developmental pathways for adaptive and two IFN-γ-producing γδ T subsets in adult thymus

    DEFF Research Database (Denmark)

    Buus, Terkild Brink; Ødum, Niels; Geisler, Carsten

    2017-01-01

    -producing γδ T cells (γδNKT). Developmental progression towards both IFN-γ-producing subsets can be induced by TCR signalling, and each pathway results in thymic emigration at a different stage. Finally, we show that γδT1 cells are the predominating IFN-γ-producing subset developing in the adult thymus. Thus......, this study maps out three distinct development pathways that result in the programming of γδTn, γδT1 and γδNKT cells.......Murine γδ T cells include subsets that are programmed for distinct effector functions during their development in the thymus. Under pathological conditions, different γδ T cell subsets can be protective or can exacerbate a disease. Here we show that CD117, CD200 and CD371, together with other...

  5. Exoenzyme T Plays a Pivotal Role in the IFN-γ Production after Pseudomonas Challenge in IL-12 Primed Natural Killer Cells

    Directory of Open Access Journals (Sweden)

    Mickael Vourc’h

    2017-10-01

    Full Text Available Pseudomonas aeruginosa (PA expresses the type III secretion system (T3SS and effector exoenzymes that interfere with intracellular pathways. Natural killer (NK cells play a key role in antibacterial immunity and their activation is highly dependent on IL-12 produced by myeloid cells. We studied PA and NK cell interactions and the role of IL-12 using human peripheral blood mononuclear cells, sorted human NK cells, and a human NK cell line (NK92. We used a wild-type (WT strain of PA (PAO1 or isogenic PA-deleted strains to delineate the role of T3SS and exoenzymes. Our hypotheses were tested in vivo in a PA-pneumonia mouse model. Human NK cells or NK92 cell line produced low levels of IFN-γ in response to PA without IL-12 stimulation, whereas PA significantly increased IFN-γ after IL-12 priming. The modulation of IFN-γ production by PA required bacteria-to-cell contact. Among T3SS effectors, exoenzyme T (ExoT upregulates IFN-γ production and control ERK activation. In vivo, ExoT also increases IFN-γ levels and the percentage of IFN-γ+ NK cells in lungs during PA pneumonia, confirming in vitro data. In conclusion, our results suggest that T3SS could modulate the production of IFN-γ by NK cells after PA infection through ERK activation.

  6. Development and Validation of a Novel Dual Luciferase Reporter Gene Assay to Quantify Ebola Virus VP24 Inhibition of IFN Signaling

    Directory of Open Access Journals (Sweden)

    Elisa Fanunza

    2018-02-01

    Full Text Available The interferon (IFN system is the first line of defense against viral infections. Evasion of IFN signaling by Ebola viral protein 24 (VP24 is a critical event in the pathogenesis of the infection and, hence, VP24 is a potential target for drug development. Since no drugs target VP24, the identification of molecules able to inhibit VP24, restoring and possibly enhancing the IFN response, is a goal of concern. Accordingly, we developed a dual signal firefly and Renilla luciferase cell-based drug screening assay able to quantify IFN-mediated induction of Interferon Stimulated Genes (ISGs and its inhibition by VP24. Human Embryonic Kidney 293T (HEK293T cells were transiently transfected with a luciferase reporter gene construct driven by the promoter of ISGs, Interferon-Stimulated Response Element (ISRE. Stimulation of cells with IFN-α activated the IFN cascade leading to the expression of ISRE. Cotransfection of cells with a plasmid expressing VP24 cloned from a virus isolated during the last 2014 outbreak led to the inhibition of ISRE transcription, quantified by a luminescent signal. To adapt this system to test a large number of compounds, we performed it in 96-well plates; optimized the assay analyzing different parameters; and validated the system by calculating the Z′- and Z-factor, which showed values of 0.62 and 0.53 for IFN-α stimulation assay and VP24 inhibition assay, respectively, indicative of robust assay performance.

  7. ORF7-encoded accessory protein 7a of feline infectious peritonitis virus as a counteragent against IFN-α-induced antiviral response.

    Science.gov (United States)

    Dedeurwaerder, Annelike; Olyslaegers, Dominique A J; Desmarets, Lowiese M B; Roukaerts, Inge D M; Theuns, Sebastiaan; Nauwynck, Hans J

    2014-02-01

    The type I IFN-mediated immune response is the first line of antiviral defence. Coronaviruses, like many other viruses, have evolved mechanisms to evade this innate response, ensuring their survival. Several coronavirus accessory genes play a central role in these pathways, but for feline coronaviruses this has never to our knowledge been studied. As it has been demonstrated previously that ORF7 is essential for efficient replication in vitro and virulence in vivo of feline infectious peritonitis virus (FIPV), the role of this ORF in the evasion of the IFN-α antiviral response was investigated. Deletion of ORF7 from FIPV strain 79-1146 (FIPV-Δ7) rendered the virus more susceptible to IFN-α treatment. Given that ORF7 encodes two proteins, 7a and 7b, it was further explored which of these proteins is active in this mechanism. Providing 7a protein in trans rescued the mutant FIPV-Δ7 from IFN sensitivity, which was not achieved by addition of 7b protein. Nevertheless, addition of protein 7a to FIPV-Δ3Δ7, a FIPV mutant deleted in both ORF3 and ORF7, could no longer increase the replication capacity of this mutant in the presence of IFN. These results indicate that FIPV 7a protein is a type I IFN antagonist and protects the virus from the antiviral state induced by IFN, but it needs the presence of ORF3-encoded proteins to exert its antagonistic function.

  8. Peripheral blood CD161+ T cells from asthmatic patients are activated during asthma attack and predominantly produce IFN-gamma.

    Science.gov (United States)

    González-Hernández, Y; Pedraza-Sánchez, S; Blandón-Vijil, V; del Río-Navarro, B E; Vaughan, G; Moreno-Lafont, M; Escobar-Gutiérrez, A

    2007-04-01

    In humans, T cells expressing the CD161 molecule NKR-P1A constitute around 20% of the circulating CD3(+) cells and are potentially immunoregulatory in several diseases. Their role in asthma is not well known, but they could participate in asthma attacks. To determinate whether activation of CD161(+) T cells and their cytokine production correlate with clinical status of asthma, we analysed blood samples from asthma attack patients (AAP) and stable asthma patients (SAP) in comparison with healthy non-atopic controls (HC). There was a significant higher baseline expression of CD69 on T cells from AAP and the difference was more notorious on CD161(+) T cells; upregulation of CD69 was observed on both CD161(-) and CD161(+) T cells driven by Dermatophagoides pteronyssinus crude extract, whereas polyclonal stimulation with phorbol 12-myristate 13-acetate plus ionomycin predominantly induced IFN-gamma but no IL-4, IL-5 and IL-13 by CD161(+) T cells in all groups; upon polyclonal stimulation, there were more CD161(+) T cells producing IFN-gamma and less CD161(-) T cells producing this cytokine, contrasting with the opposite results observed in SAP and HC groups. Our results indicate that, during asthma attack, CD161(+) T cells are activated and are able to produce predominantly IFN-gamma but no Th2 cytokines. We hypothesize that during an asthma attack, IFN-gamma produced by CD161(+) T cells could help to reestablish the Th1/Th2 equilibrium. These observations may contribute to the understanding of the immune mechanisms involved in asthma attacks.

  9. Does IFN-γ play a role on the pathogenesis of non-atopic asthma in Latin America children?

    OpenAIRE

    Figueiredo Camila Alexandrina; Rodrigues Laura Cunha; Alcantara-Neves Neuza Maria; Cooper Philip J; Amorim Leila Denise; Silva Nivea Bispo; Cruz Alvaro A; Barreto Mauricio Lima

    2012-01-01

    Abstract In this work we explore differences in blood cells and cytokine profiles in children according to atopic status and asthma (atopic or non-atopic). The study involved measurement of Th1(IFN-γ) and Th2 (IL-5 and IL-13) cytokines in Dermatophagoides pteronyssinus stimulated peripheral blood leukocytes, blood cell count, skin prick test and specific IgE against common aeroallergens. Atopic status was associated with eosinophilia and production of Th2 type cytokines. Atopic asthma was a...

  10. JAK inhibitor has the amelioration effect in lupus-prone mice: the involvement of IFN signature gene downregulation.

    Science.gov (United States)

    Ikeda, Keigo; Hayakawa, Kunihiro; Fujishiro, Maki; Kawasaki, Mikiko; Hirai, Takuya; Tsushima, Hiroshi; Miyashita, Tomoko; Suzuki, Satoshi; Morimoto, Shinji; Tamura, Naoto; Takamori, Kenji; Ogawa, Hideoki; Sekigawa, Iwao

    2017-08-22

    We previously reported that JAK-STAT-pathway mediated regulation of IFN-regulatory factor genes could play an important role in SLE pathogenesis. Here, we evaluated the efficacy of the JAK inhibitor tofacitinib (TOFA) for controlling IFN signalling via the JAK-STAT pathway and as a therapeutic for SLE. We treated NZB/NZW F1 mice with TOFA and assessed alterations in their disease, pathological, and immunological conditions. Gene-expression results obtained from CD4 + T cells (SLE mice) and CD3 + T cells (human SLE patients) were measured by DNA microarray and qRT-PCR. TOFA treatment resulted in reduced levels of anti-dsDNA antibodies, decreased proteinuria, and amelioration of nephritis as compared with those observed in control animals. Moreover, we observed the rebalance in the populations of naïve CD4 + T cells and effector/memory cells in TOFA-treated mice; however, treatment with a combination of TOFA and dexamethasone (DEXA) elicited a stronger inhibitory effect toward the effector/memory cells than did TOFA or DEXA monotherapy. We also detected decreased expression of several IFN-signature genes Ifit3 and Isg15 in CD4 + from SLE-prone mice following TOFA and DEXA treatment, and IFIT3 in CD3 + T cells from human patients following immunosuppressant therapy including steroid, respectively. Modulation of type I IFN signalling via JAK-STAT inhibition may exert a beneficial effect in SLE patients, and our results suggest that TOFA could be utilised for the development of new SLE-specific therapeutic strategies.

  11. In the Artist's Studio with L'Illustration

    Directory of Open Access Journals (Sweden)

    Esner, Rachel

    2013-03-01

    Full Text Available This article explores the two series of visits to the artist's studio that appeared in the famed French illustrated magazine L'Illustration in the 1850s and in 1886. An in-depth examination of both the texts and images reveals the verbal and visual tropes used to characterize the artists and their spaces, linking these to broader notions of "the artist" – his moral characteristics, behaviors, and artistic practice – as well as to the politics of the art world and the (bourgeois ideology of L'Illustration. The aim is to uncover not only the language but also the mechanics of the "mediatization" of the image of the artist in this crucial period.

  12. Presenting a Model for Setting in Narrative Fiction Illustration

    Directory of Open Access Journals (Sweden)

    Hajar Salimi Namin

    2017-12-01

    Full Text Available The present research aims at presenting a model for evaluating and enhancing training the setting in illustration for narrative fictions for undergraduate students of graphic design who are weak in setting. The research utilized expert’s opinions through a survey. The designed model was submitted to eight experts, and their opinions were used to have the model adjusted and improved. Used as research instruments were notes, materials in text books, papers, and related websites, as well as questionnaires. Results indicated that, for evaluating and enhancing the level of training the setting in illustration for narrative fiction to students, one needs to extract sub-indexes of setting. Moreover, definition and recognition of the model of setting helps undergraduate students of graphic design enhance the level of setting in their works skill by recognizing details of setting. Accordingly, it is recommended to design training packages to enhance these sub-indexes and hence improve the setting for narrative fiction illustration.

  13. Learning hatching for pen-and-ink illustration of surfaces

    KAUST Repository

    Kalogerakis, Evangelos

    2012-01-01

    This article presents an algorithm for learning hatching styles from line drawings. An artist draws a single hatching illustration of a 3D object. Her strokes are analyzed to extract the following per-pixel properties: hatching level (hatching, cross-hatching, or no strokes), stroke orientation, spacing, intensity, length, and thickness. A mapping is learned from input geometric, contextual, and shading features of the 3D object to these hatching properties, using classification, regression, and clustering techniques. Then, a new illustration can be generated in the artist\\'s style, as follows. First, given a new view of a 3D object, the learned mapping is applied to synthesize target stroke properties for each pixel. A new illustration is then generated by synthesizing hatching strokes according to the target properties. © 2012 ACM.

  14. Modified vaccinia virus Ankara triggers type I IFN production in murine conventional dendritic cells via a cGAS/STING-mediated cytosolic DNA-sensing pathway.

    Directory of Open Access Journals (Sweden)

    Peihong Dai

    2014-04-01

    Full Text Available Modified vaccinia virus Ankara (MVA is an attenuated poxvirus that has been engineered as a vaccine against infectious agents and cancers. Our goal is to understand how MVA modulates innate immunity in dendritic cells (DCs, which can provide insights to vaccine design. In this study, using murine bone marrow-derived dendritic cells, we assessed type I interferon (IFN gene induction and protein secretion in response to MVA infection. We report that MVA infection elicits the production of type I IFN in murine conventional dendritic cells (cDCs, but not in plasmacytoid dendritic cells (pDCs. Transcription factors IRF3 (IFN regulatory factor 3 and IRF7, and the positive feedback loop mediated by IFNAR1 (IFN alpha/beta receptor 1, are required for the induction. MVA induction of type I IFN is fully dependent on STING (stimulator of IFN genes and the newly discovered cytosolic DNA sensor cGAS (cyclic guanosine monophosphate-adenosine monophosphate synthase. MVA infection of cDCs triggers phosphorylation of TBK1 (Tank-binding kinase 1 and IRF3, which is abolished in the absence of cGAS and STING. Furthermore, intravenous delivery of MVA induces type I IFN in wild-type mice, but not in mice lacking STING or IRF3. Treatment of cDCs with inhibitors of endosomal and lysosomal acidification or the lysosomal enzyme Cathepsin B attenuated MVA-induced type I IFN production, indicating that lysosomal enzymatic processing of virions is important for MVA sensing. Taken together, our results demonstrate a critical role of the cGAS/STING-mediated cytosolic DNA-sensing pathway for type I IFN induction in cDCs by MVA. We present evidence that vaccinia virulence factors E3 and N1 inhibit the activation of IRF3 and the induction of IFNB gene in MVA-infected cDCs.

  15. Inflammation in the CNS and Th17 Responses Are Inhibited by IFN-{gamma}-Induced IL-18 Binding Protein

    DEFF Research Database (Denmark)

    Millward, Jason M; Pedersen, Morten Løbner; Wheeler, Rachel D

    2010-01-01

    Inflammatory responses are essential for immune protection but may also cause pathology and must be regulated. Both Th1 and Th17 cells are implicated in the pathogenesis of autoimmune inflammatory diseases, such as multiple sclerosis. We show in this study that IL-18-binding protein (IL-18bp......), the endogenous inhibitor of the Th1-promoting cytokine IL-18, is upregulated by IFN-gamma in resident microglial cells in the CNS during multiple sclerosis-like disease in mice. Test of function by overexpression of IL-18bp in the CNS using a viral vector led to marked reduction in Th17 responses and robust...... inhibition of incidence, severity, and histopathology of disease, independently of IFN-gamma. The disease-limiting action of IL-18bp included suppression of APC-derived Th17-polarizing cytokines. IL-18bp thus acts as a sensor for IFN-gamma and can regulate both Th1 and Th17 responses in the CNS....

  16. HTLV-1 Tax protein recruitment into IKKε and TBK1 kinase complexes enhances IFN-I expression.

    Science.gov (United States)

    Diani, Erica; Avesani, Francesca; Bergamo, Elisa; Cremonese, Giorgia; Bertazzoni, Umberto; Romanelli, Maria Grazia

    2015-02-01

    The Tax protein expressed by human T-cell leukemia virus type 1 (HTLV-1) plays a pivotal role in the deregulation of cellular pathways involved in the immune response, inflammation, cell survival, and cancer. Many of these effects derive from Tax multiple interactions with host factors, including the subunits of the IKK-complex that are required for NF-κB activation. IKKɛ and TBK1 are two IKK-related kinases that allow the phosphorylation of interferon regulatory factors that trigger IFN type I gene expression. We observed that IKKɛ and TBK1 recruit Tax into cellular immunocomplexes. We also found that TRAF3, which regulates cell receptor signaling effectors, forms complexes with Tax. Transactivation analyses revealed that expression of Tax, in presence of IKKɛ and TBK1, enhances IFN-β promoter activity, whereas the activation of NF-κB promoter is not modified. We propose that Tax may be recruited into the TBK1/IKKɛ complexes as a scaffolding-adaptor protein that enhances IFN-I gene expression. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Pan-viral specificity of IFN-induced genes reveals new roles for cGAS in innate immunity

    Science.gov (United States)

    Schoggins, John W.; MacDuff, Donna A.; Imanaka, Naoko; Gainey, Maria D.; Shrestha, Bimmi; Eitson, Jennifer L.; Mar, Katrina B.; Richardson, R. Blake; Ratushny, Alexander V.; Litvak, Vladimir; Dabelic, Rea; Manicassamy, Balaji; Aitchison, John D.; Aderem, Alan; Elliott, Richard M.; García-Sastre, Adolfo; Racaniello, Vincent; Snijder, Eric J.; Yokoyama, Wayne M.; Diamond, Michael S.; Virgin, Herbert W.; Rice, Charles M.

    2014-01-01

    The type I interferon (IFN) response protects cells from viral infection by inducing hundreds of interferon-stimulated genes (ISGs), some of which encode direct antiviral effectors. Recent screening studies have begun to catalogue ISGs with antiviral activity against several RNA and DNA viruses. However, antiviral ISG specificity across multiple distinct classes of viruses remains largely unexplored. Here we used an ectopic expression assay to screen a library of more than 350 human ISGs for effects on 14 viruses representing 7 families and 11 genera. We show that 47 genes inhibit one or more viruses, and 25 genes enhance virus infectivity. Comparative analysis reveals that the screened ISGs target positive-sense single-stranded RNA viruses more effectively than negative-sense single-stranded RNA viruses. Gene clustering highlights the cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS, also known as MB21D1) as a gene whose expression also broadly inhibits several RNA viruses. In vitro, lentiviral delivery of enzymatically active cGAS triggers a STING-dependent, IRF3-mediated antiviral program that functions independently of canonical IFN/STAT1 signalling. In vivo, genetic ablation of murine cGAS reveals its requirement in the antiviral response to two DNA viruses, and an unappreciated contribution to the innate control of an RNA virus. These studies uncover new paradigms for the preferential specificity of IFN-mediated antiviral pathways spanning several virus families.

  18. Cutting edge: Antimalarial drugs inhibit IFN-β production through blockade of cyclic GMP-AMP synthase-DNA interaction.

    Science.gov (United States)

    An, Jie; Woodward, Joshua J; Sasaki, Tomikazu; Minie, Mark; Elkon, Keith B

    2015-05-01

    Type I IFN is strongly implicated in the pathogenesis of systemic autoimmune diseases, such as lupus, and rare monogenic IFNopathies, including Aicardi-Goutières syndrome. Recently, a new DNA-activated pathway involving the enzyme cyclic GMP-AMP synthase (cGAS) was described and potentially linked to Aicardi-Goutières syndrome. To identify drugs that could potentially inhibit cGAS activity, we performed in silico screening of drug libraries. By computational analysis, we identified several antimalarial drugs (AMDs) that were predicted to interact with the cGAS/dsDNA complex. Our studies validated that several AMDs were effective inhibitors of IFN-β production and that they functioned by inhibiting dsDNA stimulation of cGAS. Because AMDs have been widely used in human diseases and have an excellent safety profile, our findings suggest new therapeutic strategies for the treatment of severe debilitating diseases associated with type I IFNs due to cGAS activation. Copyright © 2015 by The American Association of Immunologists, Inc.

  19. Clozapine inhibits Th1 cell differentiation and causes the suppression of IFN-γ production in peripheral blood mononuclear cells.

    Science.gov (United States)

    Chen, Mao-Liang; Tsai, Tzung-Chieh; Wang, Lu-Kai; Lin, Yi-Yin; Tsai, Ya-Min; Lee, Ming-Cheng; Tsai, Fu-Ming

    2012-08-01

    Antipsychotic drugs (APDs) are widely used to alleviate a number of psychic disorders and may have immunomodulatory effects. However, the previous studies of cytokine and immune regulation in APDs are quite inconsistent. The aim of this study was to examine the in vitro effects of different ADPs on cytokine production by peripheral blood mononuclear cells (PBMCs). We examined the effects of risperidone, clozapine, and haloperidol on the production of phorbol myristate acetate and ionomycin-induced interferon-γ (IFN-γ)/interleukin (IL)-4 in PBMCs by using intracellular staining. Real-time quantitative PCR and Western blot were used to further examine the expression changes of some critical transcription factors related to T-cell differentiation in antipsychotic-treated PBMCs. Our results indicated that clozapine can suppress the stimulated production of IFN-γ by 30.62%, whereas haloperidol weakly enhances the expression of IFN-γ. Differences in IL-4 production or in the number of CD4+ T cells were not observed in cells treated with different APDs. Furthermore, clozapine and risperidone inhibited the T-bet mRNA and protein expression, which are critical to Th1 differentiation. Also, clozapine can enhance the expression of Signal Transducer and Activator of Transcription 6 and GATA3, which are critical for the differentiation of Th2 cells. The results suggested that clozapine and haloperidol may induce different immunomodulatory effects on the immune system.

  20. Mendelian susceptibility to mycobacterial disease: genetic, immunological, and clinical features of inborn errors of IFN-γ immunity

    Science.gov (United States)

    Bustamante, Jacinta; Boisson-Dupuis, Stéphanie; Abel, Laurent; Casanova, Jean-Laurent

    2014-01-01

    Mendelian susceptibility to mycobacterial disease (MSMD) is a rare condition characterized by predisposition to clinical disease caused by weakly virulent mycobacteria, such as BCG vaccines and environmental mycobacteria, in otherwise healthy individuals with no overt abnormalities in routine hematological and immunological tests. MSMD designation does not recapitulate all the clinical features, as patients are also prone to salmonellosis, candidiasis and tuberculosis, and more rarely to infections with other intramacrophagic bacteria, fungi, or parasites, and even, perhaps, a few viruses. Since 1996, nine MSMD-causing genes, including seven autosomal (IFNGR1, IFNGR2, STAT1, IL12B, IL12RB1, ISG15, and IRF8) and two X-linked (NEMO, CYBB) genes have been discovered. The high level of allelic heterogeneity has already led to the definition of 18 different disorders. The nine gene products are physiologically related, as all are involved in IFN-γ-dependent immunity. These disorders impair the production of (IL12B, IL12RB1, IRF8, ISG15, NEMO) or the response to (IFNGR1, IFNGR2, STAT1, IRF8, CYBB) IFN-γ. These defects account for only about half the known MSMD cases. Patients with MSMD-causing genetic defects may display other infectious diseases, or even remain asymptomatic. Most of these inborn errors do not show complete clinical penetrance for the case-definition phenotype of MSMD. We review here the genetic, immunological, and clinical features of patients with inborn errors of IFN-γ-dependent immunity. PMID:25453225

  1. S100A7 (Psoriasin), highly expressed in Ductal Carcinoma In Situ (DCIS), is regulated by IFN-gamma in mammary epithelial cells

    International Nuclear Information System (INIS)

    Petersson, Stina; Bylander, Anna; Yhr, Maria; Enerbäck, Charlotta

    2007-01-01

    The aim of the present work was to explore signal transduction pathways used in the regulation of S100A7 (psoriasin). Members of the S100 gene family participate in many important cellular functions. Psoriasin, S100A8 (calgranulin A) and S100A9 (calgranulin B) are expressed in ductal carcinoma in situ (DCIS), as well as in the hyperproliferative skin disease, psoriasis. In the latter condition, a disturbance in the STAT pathway has recently been reported. This pathway is implicated in the regulation of IFN-gamma, widely recognized as a key cytokine in psoriasis. IFN-gamma also exerts anti-tumor action in a number of tumor cell types, including breast cancer. We therefore examined the effect of IFN-gamma and STAT-signaling on the psoriasin expression. We established a TAC2 mouse mammary epithelial cell line with tetracycline-inducible psoriasin expression (Tet-Off). Viability in cell culture was estimated using MTS assay. Protein and gene expression were evaluated by Western blotting and quantitative real-time PCR. Statistical analyses were assessed using a one-tailed, paired t-test. We report the downregulation of psoriasin by IFN-gamma in the MDA-MB-468 breast cancer cell line, as well as the downregulation of psoriasin induced by anoikis in cell lines derived from different epithelial tissues. In contrast, IFN-gamma had no suppressive effect on calgranulin A or calgranulin B. IFN-gamma is an important activator of the STAT1 pathway and we confirmed an active signaling pathway in the cell lines that responded to IFN-gamma treatment. In contrast, in the SUM190 breast carcinoma cell line, IFN-gamma did not suppress the expression of endogenous psoriasin. Moreover, a reduced phosphorylation of the STAT1 protein was observed. We showed that IFN-gamma treatment and the inhibition of the transcription factor NFkappaB had a synergistic effect on psoriasin levels. Finally, in TAC2 cells with tetracycline-induced psoriasin expression, we observed the increased viability of

  2. Information barriers and authentication

    International Nuclear Information System (INIS)

    MacArthur, D.W.; Wolford, J.K.

    2001-01-01

    Acceptance of nuclear materials into a monitoring regime is complicated if the materials are in classified shapes or have classified composition. An attribute measurement system with an information barrier can be emplo,yed to generate an unclassified display from classified measurements. This information barrier must meet two criteria: (1) classified information cannot be released to the monitoring party, and (2) the monitoring party must be convinced that the unclassified output accurately represents the classified input. Criterion 1 is critical to the host country to protect the classified information. Criterion 2 is critical to the monitoring party and is often termed the 'authentication problem.' Thus, the necessity for authentication of a measurement system with an information barrier stems directly from the description of a useful information barrier. Authentication issues must be continually addressed during the entire development lifecycle of the measurement system as opposed to being applied only after the system is built.

  3. Barrier Infrared Detector (BIRD)

    Data.gov (United States)

    National Aeronautics and Space Administration — A recent breakthrough in MWIR detector design, has resulted in a high operating temperature (HOT) barrier infrared detector (BIRD) that is capable of spectral...

  4. Protective barrier development: Overview

    International Nuclear Information System (INIS)

    Wing, N.R.; Gee, G.W.

    1990-01-01

    Protective barrier and warning marker systems are being developed to isolate wastes disposed of near the earth's surface at the Hanford Site. The barrier is designed to function in an arid to semiarid climate, to limit infiltration and percolation of water through the waste zone to near-zero, to be maintenance free, and to last up to 10,000 yr. Natural materials (e.g., fine soil, sand, gravel, riprap, clay, asphalt) have been selected to optimize barrier performance and longevity and to create an integrated structure with redundant features. These materials isolate wastes by limiting water drainage; reducing the likelihood of plant, animal, and human intrusion; controlling emission of noxious gases; and minimizing erosion. Westinghouse Hanford Company and Pacific Northwest Laboratory efforts to assess the performance of various barrier and marker designs will be discussed

  5. Engineered barriers: current status

    International Nuclear Information System (INIS)

    Atkinson, A.; Marsh, G.P.

    1988-01-01

    This report summarises the current state of research relevant to assessing the performance of engineered barriers made of steel and concrete in radioactive waste repositories. The objective of these barriers is to contain the radionuclides within them by providing both physical and chemical impediment to their release. The physical barriers are of most value for highly soluble isotopes with relatively short half-lives (eg 137 Cs), since they can provide containment until a large fraction of the activity has decayed. In addition they can facilitate retrievability for some period after disposal. The chemical barriers operate by beneficial conditioning of the near field groundwater and providing sites for sorption of radionuclides. Both of these reduce the aqueous concentration of radionuclides in the near field. (author)

  6. Skin barrier composition

    International Nuclear Information System (INIS)

    Osburn, F.G.

    1985-01-01

    A skin barrier composition comprises a mixture of a copolymer resin of ethylene and vinyl acetate (EVA), and a water-insoluble dry tack-providing elastomer such as polyisobutylene. The composition after mixing and molding, is subjected to ionizing irradiation to form cross-linked polymer networks of the EVA. The compositions have exceptional properties for use as barrier sheets, rings, or strips in ostomy, wound drainage, and incontinence devices. (author)

  7. Skin barrier composition

    Energy Technology Data Exchange (ETDEWEB)

    Osburn, F G

    1985-06-12

    A skin barrier composition comprises a mixture of a copolymer resin of ethylene and vinyl acetate (EVA), and a water-insoluble dry tack-providing elastomer such as polyisobutylene. The composition after mixing and molding, is subjected to ionizing irradiation to form cross-linked polymer networks of the EVA. The compositions have exceptional properties for use as barrier sheets, rings, or strips in ostomy, wound drainage, and incontinence devices.

  8. IPR Barriers in Collaboration between University and Engineering Industry in Sweden

    OpenAIRE

    Huang, Wenting

    2011-01-01

    This thesis examines the barriers, especially intellectual property rights concerned that inhibit industry academia collaboration. By analyzing Swedish firms in the engineering industry, I explore the influence of IPR barrier on firms’ benefits, short- and long-term respectively from university-industry interaction. Three hypotheses are suggested to investigate the relationship between IPR barriers, firm categories, short-term benefits and long-term benefits. The results illustrate different ...

  9. Activation of ERα signaling differentially modulates IFN-γ induced HLA-class II expression in breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Ahmed A Mostafa

    Full Text Available The coordinate regulation of HLA class II (HLA-II is controlled by the class II transactivator, CIITA, and is crucial for the development of anti-tumor immunity. HLA-II in breast carcinoma is associated with increased IFN-γ levels, reduced expression of the estrogen receptor (ER and reduced age at diagnosis. Here, we tested the hypothesis that estradiol (E₂ and ERα signaling contribute to the regulation of IFN-γ inducible HLA-II in breast cancer cells. Using a panel of established ER⁻ and ER⁺ breast cancer cell lines, we showed that E₂ attenuated HLA-DR in two ER⁺ lines (MCF-7 and BT-474, but not in T47D, while it augmented expression in ER⁻ lines, SK-BR-3 and MDA-MB-231. To further study the mechanism(s, we used paired transfectants: ERα⁺ MC2 (MDA-MB-231 c10A transfected with the wild type ERα gene and ERα⁻ VC5 (MDA-MB-231 c10A transfected with the empty vector, treated or not with E₂ and IFN-γ. HLA-II and CIITA were severely reduced in MC2 compared to VC5 and were further exacerbated by E₂ treatment. Reduced expression occurred at the level of the IFN-γ inducible CIITA promoter IV. The anti-estrogen ICI 182,780 and gene silencing with ESR1 siRNA reversed the E2 inhibitory effects, signifying an antagonistic role for activated ERα on CIITA pIV activity. Moreover, STAT1 signaling, necessary for CIITA pIV activation, and selected STAT1 regulated genes were variably downregulated by E₂ in transfected and endogenous ERα positive breast cancer cells, whereas STAT1 signaling was noticeably augmented in ERα⁻ breast cancer cells. Collectively, these results imply immune escape mechanisms in ERα⁺ breast cancer may be facilitated through an ERα suppressive mechanism on IFN-γ signaling.

  10. Different patterns of cytokines and chemokines combined with IFN-γ production reflect Mycobacterium tuberculosis infection and disease.

    Directory of Open Access Journals (Sweden)

    Yang Yu

    Full Text Available BACKGROUND: IFN-γ is presently the only soluble immunological marker used to help diagnose latent Mycobacterium tuberculosis (M.tb infection. However, IFN-γ is not available to distinguish latent from active TB infection. Moreover, extrapulmonary tuberculosis, such as tuberculous pleurisy, cannot be properly diagnosed by IFN-γ release assay. As a result, other disease- or infection-related immunological biomarkers that would be more effective need to be screened and identified. METHODOLOGY: A panel of 41 soluble immunological molecules (17 cytokines and 24 chemokines was tested using Luminex liquid array-based multiplexed immunoassays. Samples, including plasma and pleural effusions, from healthy donors (HD, n = 12 or patients with latent tuberculosis infection (LTBI, n = 20, pulmonary tuberculosis (TB, n = 12, tuberculous pleurisy (TP, n = 15 or lung cancer (LC, n = 15 were collected and screened for soluble markers. Peripheral blood mononuclear cells (PBMCs and pleural fluid mononuclear cells (PFMCs were also isolated to investigate antigen-specific immune factors. PRINCIPAL FINDINGS: For the 41 examined factors, our results indicated that three patterns were closely associated with infection and disease. (1 Significantly elevated plasma levels of IL-2, IP-10, CXCL11 and CXCL12 were present in both patients with tuberculosis and in a sub-group participant with latent tuberculosis infection who showed a higher level of IFN-γ producing cells by ELISPOT assay compared with other latently infected individuals. (2 IL-6 and IL-9 were only significantly increased in plasma from active TB patients, and the two factors were consistently highly secreted after M.tb antigen stimulation. (3 When patients developed tuberculous pleurisy, CCL1, CCL21 and IL-6 were specifically increased in the pleural effusions. In particular, these three factors were consistently highly secreted by pleural fluid mononuclear cells following M

  11. Interferon-gamma (IFN-γ-mediated retinal ganglion cell death in human tyrosinase T cell receptor transgenic mouse.

    Directory of Open Access Journals (Sweden)

    Shahid Husain

    Full Text Available We have recently demonstrated the characterization of human tyrosinase TCR bearing h3T-A2 transgenic mouse model, which exhibits spontaneous autoimmune vitiligo and retinal dysfunction. The purpose of current study was to determine the role of T cells and IFN-γ in retina dysfunction and retinal ganglion cell (RGC death using this model. RGC function was measured by pattern electroretinograms (ERGs in response to contrast reversal of patterned visual stimuli. RGCs were visualized by fluorogold retrograde-labeling. Expression of CD3, IFN-γ, GFAP, and caspases was measured by immunohistochemistry and Western blotting. All functional and structural changes were measured in 12-month-old h3T-A2 mice and compared with age-matched HLA-A2 wild-type mice. Both pattern-ERGs (42%, p = 0.03 and RGC numbers (37%, p = 0.0001 were reduced in h3T-A2 mice when compared with wild-type mice. The level of CD3 expression was increased in h3T-A2 mice (h3T-A2: 174 ± 27% vs. HLA-A2: 100%; p = 0.04. The levels of effector cytokine IFN-γ were also increased significantly in h3T-A2 mice (h3T-A2: 189 ± 11% vs. HLA-A2: 100%; p = 0.023. Both CD3 and IFN-γ immunostaining were increased in nerve fiber (NF and RGC layers of h3T-A2 mice. In addition, we have seen a robust increase in GFAP staining in h3T-A2 mice (mainly localized to NF layer, which was substantially reduced in IFN-γ ((-/- knockout h3T-A2 mice. We also have seen an up-regulation of caspase-3 and -9 in h3T-A2 mice. Based on our data we conclude that h3T-A2 transgenic mice exhibit visual defects that are mostly associated with the inner retinal layers and RGC function. This novel h3T-A2 transgenic mouse model provides opportunity to understand RGC pathology and test neuroprotective strategies to rescue RGCs.

  12. [Knockdown of STAT3 inhibits proliferation and migration of HepG2 hepatoma cells induced by IFN1].

    Science.gov (United States)

    Li, Xiaofang; Wang, Yuqi; Yan, Ben; Fang, Peipei; Ma, Chao; Xu, Ning; Fu, Xiaoyan; Liang, Shujuan

    2018-02-01

    Objective To prepare lentiviruses expressing shRNA sequences targeting human signal transducer and activator of transcription 3 (STAT3) and detect the effect of STAT3 knockdown on type I interferon (IFN1)-induced proliferation and migration in HepG2 cells. Methods Four STAT3-targeting shRNA sequences (shRNA1-shRNA4) and one control sequence (Ctrl shRNA) were selected and cloned respectively into pLKO.1-sp6-pgk-GFP to construct shRNA-expressing vectors. Along with backbone psPAX2 and pMD2.G vectors, they were separately transfected into HEK293T cells to prepare lentiviruses. HepG2 cells were infected with the lentiviruses. Cytoplastic STAT3 level was detected by Western blotting to screen effective shRNA sequence(s) targeting STAT3. Proliferation and migration of HepG2 cells were analyzed by CCK-8 assay and Transwell TM migration and scratching assay, respectively. To detect the effect of IFN1 on cell proliferation and migration of HepG2 cells, the cells were treated with 2000 U/mL IFNα2b for indicated time and the activation of IFN-triggered STAT1 signal transduction was assayed by Western blotting. Results Two most effective STAT3-targeting shRNA sequences shRNA1 and shRNA2 were selected, and the expression of both STAT3 shRNA significantly decreased proliferation and migration of HepG2 cells. When treated with IFNα2b, 2000 U/mL of IFN1 showed more competent in attenuating growth and migration of HepG2 cells. Our data further proved that knockdown of STAT3 increased the phosphorylation of STAT1, and IFNα2b further enhanced the activation of STAT1 signaling in HepG2 cells. Conclusion Knockdown of STAT3 inhibits cell migration and growth, and rescues IFN response through up-regulating STAT1 signal transduction in HepG2 hepatoma cells.

  13. Influenza A virus inhibits type I IFN signaling via NF-kappaB-dependent induction of SOCS-3 expression.

    Directory of Open Access Journals (Sweden)

    Eva-K Pauli

    2008-11-01

    Full Text Available The type I interferon (IFN system is a first line of defense against viral infections. Viruses have developed various mechanisms to counteract this response. So far, the interferon antagonistic activity of influenza A viruses was mainly observed on the level of IFNbeta gene induction via action of the viral non-structural protein 1 (NS1. Here we present data indicating that influenza A viruses not only suppress IFNbeta gene induction but also inhibit type I IFN signaling through a mechanism involving induction of the suppressor of cytokine signaling-3 (SOCS-3 protein. Our study was based on the observation that in cells that were infected with influenza A virus and subsequently stimulated with IFNalpha/beta, phosphorylation of the signal transducer and activator of transcription protein 1 (STAT1 was strongly reduced. This impaired STAT1 activation was not due to the action of viral proteins but rather appeared to be induced by accumulation of viral 5' triphosphate RNA in the cell. SOCS proteins are potent endogenous inhibitors of Janus kinase (JAK/STAT signaling. Closer examination revealed that SOCS-3 but not SOCS-1 mRNA levels increase in an RNA- and nuclear factor kappa B (NF-kappaB-dependent but type I IFN-independent manner early in the viral replication cycle. This direct viral induction of SOCS-3 mRNA and protein expression appears to be relevant for suppression of the antiviral response since in SOCS-3 deficient cells a sustained phosphorylation of STAT1 correlated with elevated expression of type I IFN-dependent genes. As a consequence, progeny virus titers were reduced in SOCS-3 deficient cells or in cells were SOCS-3 expression was knocked-down by siRNA. These data provide the first evidence that influenza A viruses suppress type I IFN signaling on the level of JAK/STAT activation. The inhibitory effect is at least in part due to the induction of SOCS-3 gene expression, which results in an impaired antiviral response.

  14. An Empirical Illustration of Positive Stigma towards Child Labor

    OpenAIRE

    Harry A Patrinos; Najeeb Shafiq

    2010-01-01

    This empirical note complements the qualitative and theoretical research on positive household stigma towards child labor. We use data from Guatemala and two instruments for measuring stigma: a child's indigenous background and household head's childhood work experience. We then adopt binomial probit regression methods to illustrate that positive stigma has a large effect on child labor practices, and a modest effect on school enrollment.

  15. Using the Screened Coulomb Potential to Illustrate the Variational Method

    Science.gov (United States)

    Zuniga, Jose; Bastida, Adolfo; Requena, Alberto

    2012-01-01

    The screened Coulomb potential, or Yukawa potential, is used to illustrate the application of the single and linear variational methods. The trial variational functions are expressed in terms of Slater-type functions, for which the integrals needed to carry out the variational calculations are easily evaluated in closed form. The variational…

  16. Can Questions Facilitate Learning from Illustrated Science Texts?

    Science.gov (United States)

    Iding, Marie K.

    1997-01-01

    Examines the effectiveness of using questions to facilitate processing of diagrams in science texts. Investigates three different elements in experiments on college students. Finds that questions about illustrations do not facilitate learning. Discusses findings with reference to cognitive load theory, the dual coding perspective, and the…

  17. [The Prague school of anatomy and its illustrators].

    Science.gov (United States)

    Linc, R

    1997-01-01

    The centennial commemorial of the birthday of Ladislav Borovanský gives us an incentive for describing a short history of Czech anatomy in Medical Faculty of Charles University with their textbooks and painters. Parallelly with them are presented some other distinguished painters active in anatomical aspect of illustration.

  18. Promoting Self-Questioning through Picture Book Illustrations

    Science.gov (United States)

    Lohfink, Gayla

    2013-01-01

    This teaching tip manuscript demonstrates how picture book illustrations can be used as an inquiry tool that facilitates one's connecting of visual investigations in a picture to the process of generating self-questions. Techniques suggested to promote self-questioning are (1) introducing young readers to an interactive picture book read aloud…

  19. Child Illustrators: Making Meaning through Visual Art in Picture Books

    Science.gov (United States)

    Villarreal, Alicia; Minton, Sylvia; Martinez, Miriam

    2015-01-01

    In picture books, illustrations often play a critical role in helping authors tell stories. Instruction in the elements of composition including visual, textual, and peritextual features enhances meaning for children when they are given the opportunity to become authors of their own picturebooks. This study was conducted in a fourth grade…

  20. Contemporary Psychoanalytic Perspectives on Eating Disorders: A Case Illustration.

    Science.gov (United States)

    Lerner, Howard D.

    This paper examines recent formulations derived from different lines of conceptual development within psychoanalytic theory in relation to the anorexic and bulimic syndromes. The case history, clinical picture, and course of treatment of a bulimic adolescent girl are reviewed. This discussion illustrates the profound consequences upon cognition of…

  1. A short illustrated history of magnetic resonance imaging

    International Nuclear Information System (INIS)

    Vaughan, B.

    1989-01-01

    The principles of magnetic resonance imaging (MRI) evolved during the late 1970s and the early 1980s. Many of the pioneering research projects and their roles in the evolution of the present technology are described and illustrated. 34 refs., ills

  2. Commentary on "Education, Employment and Human Development: Illustrations from Mexico"

    Science.gov (United States)

    Strathdee, Rob

    2007-01-01

    Flores-Crespo has written a timely paper, "Education, employment and human development: illustrations from Mexico". Flores-Crespo uses Amartya Sen's ideas to bring a fresh perspective to bear on the relationship between higher education and human development. Although there is growing interest in applying Sen's ideas in a range of…

  3. A DIGITAL APPROACH TO LARGE FORMAT ILLUSTRATIONS ON ...

    African Journals Online (AJOL)

    user

    is simply computer illustration or digital drawing and painting. This is ... of computers in the 80s, the traditional tools were represented by digital tools on the user interface for ...... Edwards, B. (1989) Drawing on the right side of the Brain.

  4. Illustrated Plant Identification Keys: An Interactive Tool to Learn Botany

    Science.gov (United States)

    Silva, Helena; Pinho, Rosa; Lopes, Lisia; Nogueira, Antonio J. A.; Silveira, Paulo

    2011-01-01

    An Interactive Dichotomous Key (IDK) for 390 "taxa" of vascular plants from the Ria de Aveiro, available on a website, was developed to help teach botany to school and universitary students. This multimedia tool includes several links to Descriptive and Illustrated Glossaries. Questionnaires answered by high-school and undergraduate students about…

  5. A Brief Illustrated Guide to Understanding Islam. Second Edition.

    Science.gov (United States)

    Ibrahim, I. A.

    This book is a brief guide to understanding Islam, intended to help individuals better understand Islamic culture, Muslims, and the Holy Quran. It consists of the following three chapters: (1) Some Evidence for the Truth of Islam; (2) Some Benefits of Islam; and (3) General Information on Islam. The book is extensively illustrated with photographs…

  6. 12 CFR Appendix B to Part 363 - Illustrative Management Reports

    Science.gov (United States)

    2010-01-01

    .... General. The reporting scenarios, illustrative management reports, and the cover letter (when complying at... management reports and cover letter is not required. The managements of insured depository institutions are encouraged to tailor the wording of their management reports and cover letters to fit their particular...

  7. Using Illustrations from American Novels to Teach about Labor Markets

    Science.gov (United States)

    Vachris, Michelle Albert; Bohanon, Cecil E.

    2012-01-01

    This article illustrates how literature can bring models to life in undergraduate courses on labor market economics. The authors argue that economics instructors and students can benefit from even small doses of literature. The authors examine excerpts from five American novels: "Sister Carrie" by Theodore Drieser (1900/2005); "The Grapes of…

  8. Illustrative Examples in a Bilingual Decoding Dictionary: An (Un ...

    African Journals Online (AJOL)

    user

    not have the status of a phraseological unit in English, it cannot be in- cluded and treated in the idioms section. Therefore, we can find such word combinations mostly included as illustrative examples, and it can often be observed that their translations into Slovene are also idiomatic: tired prid. sit: sick and tired of sth do vrh ...

  9. The Effects of Technical Illustrations on Cognitive Load.

    Science.gov (United States)

    Purnell, Kenneth N.; And Others

    1992-01-01

    Outlines two theories of cognitive science that are relevant for instructional design, i.e., schema theory and cognitive load theory; and describes four experiments with Australian secondary school geography students that used these theories to examine the effects of splitting attention between technical illustrations and related text. (20…

  10. Effects of Text Illustrations: A Review of Research.

    Science.gov (United States)

    Levie, W. Howard; Lentz, Richard

    1982-01-01

    Reviews results of 55 experiments comparing learning from illustrated text and learning from text alone. Research in closely related fields--nonrepresentational pictures (maps, diagrams, graphic organizers), learner-produced drawings, mental imagery, and oral prose--is also examined, and guidelines for practice are offered. A 160-item reference…

  11. Graph Theory to Pure Mathematics: Some Illustrative Examples

    Indian Academy of Sciences (India)

    Graph Theory to Pure Mathematics: Some. Illustrative Examples v Yegnanarayanan is a. Professor of Mathematics at MNM Jain Engineering. College, Chennai. His research interests include graph theory and its applications to both pure maths and theoretical computer science. Keywords. Graph theory, matching theory,.

  12. A Simple Inexpensive Procedure for Illustrating Some Principles of Tomography

    Science.gov (United States)

    Darvey, Ivan G.

    2013-01-01

    The experiment proposed here illustrates some concepts of tomography via a qualitative determination of the relative concentration of various dilutions of food dye without "a priori" knowledge of the concentration of each dye mixture. This is performed in a manner analogous to computed tomography (CT) scans. In order to determine the…

  13. Using Telestrations™ to Illustrate Small Group Communication Principles

    Science.gov (United States)

    Fedesco, Heather Noel

    2014-01-01

    This single class activity described here: (1) illustrates the importance of interdependence in groups; (2) can be used to measure group productivity and performance; (3) can encourage groups to engage in group learning; and (4) can facilitate group cohesion for newly formed groups. Students will be working in groups for the majority of their…

  14. Towards a Digital Infrastructure for Illustrated Handwritten Archives

    NARCIS (Netherlands)

    Weber, Andreas; Ameryan, Mahya; Wolstencroft, Katherine; Stork, Lise; Heerlien, Maarten; Schomaker, Lambert; Ioannides, Marinos

    Large and important parts of cultural heritage are stored in archives that are difficult to access, even after digitization. Documents and notes are written in hard-to-read historical handwriting and are often interspersed with illustrations. Such collections are weakly structured and largely

  15. Evaluation of School Psychological Services: A Case Illustration.

    Science.gov (United States)

    Fairchild, Thomas N.; Seeley, Tracey J.

    1996-01-01

    Illustrates how school psychological services were evaluated in two elementary schools. Questionnaires were used to solicit input from students regarding individual counseling and classroom guidance activities. Rating scales were used to solicit input from parents regarding the assessment service and from building staff regarding their perception…

  16. Introduction to Numerical Computation - analysis and Matlab illustrations

    DEFF Research Database (Denmark)

    Elden, Lars; Wittmeyer-Koch, Linde; Nielsen, Hans Bruun

    In a modern programming environment like eg MATLAB it is possible by simple commands to perform advanced calculations on a personal computer. In order to use such a powerful tool efiiciently it is necessary to have an overview of available numerical methods and algorithms and to know about...... are illustrated by examples in MATLAB....

  17. Dancing Crystals: A Dramatic Illustration of Intermolecular Forces

    Science.gov (United States)

    Mundell, Donald W.

    2007-01-01

    Crystals of naphthalene form on the surface of an acetone solution and dance about in an animated fashion illustrating surface tension, crystallization, and intermolecular forces. Additional experiments reveal the properties of the solution. Flows within the solutions can be visualized by various means. Previous demonstrations of surface motion…

  18. Introductory Level Problems Illustrating Concepts in Pharmaceutical Engineering

    Science.gov (United States)

    McIver, Keith; Whitaker, Kathryn; De Delva, Vladimir; Farrell, Stephanie; Savelski, Mariano J.; Slater, C. Stewart

    2012-01-01

    Textbook style problems including detailed solutions introducing pharmaceutical topics at the level of an introductory chemical engineering course have been created. The problems illustrate and teach subjects which students would learn if they were to pursue a career in pharmaceutical engineering, including the unique terminology of the field,…

  19. Scaling up depot medroxyprogesterone acetate (DMPA): a systematic literature review illustrating the AIDED model.

    Science.gov (United States)

    Curry, Leslie; Taylor, Lauren; Pallas, Sarah Wood; Cherlin, Emily; Pérez-Escamilla, Rafael; Bradley, Elizabeth H

    2013-08-02

    Use of depot medroxyprogesterone acetate (DMPA), often known by the brand name Depo-Provera, has increased globally, particularly in multiple low- and middle-income countries (LMICs). As a reproductive health technology that has scaled up in diverse contexts, DMPA is an exemplar product innovation with which to illustrate the utility of the AIDED model for scaling up family health innovations. We conducted a systematic review of the enabling factors and barriers to scaling up DMPA use in LMICs. We searched 11 electronic databases for academic literature published through January 2013 (n = 284 articles), and grey literature from major health organizations. We applied exclusion criteria to identify relevant articles from peer-reviewed (n = 10) and grey literature (n = 9), extracting data on scale up of DMPA in 13 countries. We then mapped the resulting factors to the five AIDED model components: ASSESS, INNOVATE, DEVELOP, ENGAGE, and DEVOLVE. The final sample of sources included studies representing variation in geographies and methodologies. We identified 15 enabling factors and 10 barriers to dissemination, diffusion, scale up, and/or sustainability of DMPA use. The greatest number of factors were mapped to the ASSESS, DEVELOP, and ENGAGE components. Findings offer early empirical support for the AIDED model, and provide insights into scale up of DMPA that may be relevant for other family planning product innovations.

  20. Spectroscopic criteria for identification of nuclear tetrahedral and octahedral symmetries: Illustration on a rare earth nucleus

    Science.gov (United States)

    Dudek, J.; Curien, D.; Dedes, I.; Mazurek, K.; Tagami, S.; Shimizu, Y. R.; Bhattacharjee, T.

    2018-02-01

    We formulate criteria for identification of the nuclear tetrahedral and octahedral symmetries and illustrate for the first time their possible realization in a rare earth nucleus 152Sm. We use realistic nuclear mean-field theory calculations with the phenomenological macroscopic-microscopic method, the Gogny-Hartree-Fock-Bogoliubov approach, and general point-group theory considerations to guide the experimental identification method as illustrated on published experimental data. Following group theory the examined symmetries imply the existence of exotic rotational bands on whose properties the spectroscopic identification criteria are based. These bands may contain simultaneously states of even and odd spins, of both parities and parity doublets at well-defined spins. In the exact-symmetry limit those bands involve no E 2 transitions. We show that coexistence of tetrahedral and octahedral deformations is essential when calculating the corresponding energy minima and surrounding barriers, and that it has a characteristic impact on the rotational bands. The symmetries in question imply the existence of long-lived shape isomers and, possibly, new waiting point nuclei—impacting the nucleosynthesis processes in astrophysics—and an existence of 16-fold degenerate particle-hole excitations. Specifically designed experiments which aim at strengthening the identification arguments are briefly discussed.

  1. IFN-γ and TNF-α producing CD4+ T-cells in the blood after Mycoplasma hyosynoviae challenge of vaccinated pigs

    DEFF Research Database (Denmark)

    Riber, Ulla; Hansen, Mette Sif; Lauritsen, Klara Tølbøll

    In a vaccine trial against Mycoplasma hyosynoviae infection, pigs were vaccinated with formalin fixed whole-cell-antigen formulated with adjuvant DDA/TDB (SSI). Placebo pigs received adjuvant with saline. Vaccinations were performed at five and eight weeks of age, followed by an intranasal M....... hyosynoviae challenge inoculation three weeks later. Vaccination induced both antibodies and a cell-mediated immune response (CMI) in vaccinated pigs compared to placebo pigs as shown by M. hyosynoviae antigen (Ag) specific IFN-γ response in an IL-18 potentiated whole-blood IFN-γ stimulation assay (mean IFN......-γ level 1936 pg/ml vs. 82 pg/ml (p=0.0001)). A central memory T cell phenotype with polyfunctional capacity to produce all three cytokines IFN-γ, TNF-α and IL-2 has recently been linked to development of vaccine induced protection in several infections. In a subset of seven vaccinated pigs and four...

  2. Clinical significance of measurement of changes of serum IL-2, TNF-α and IFN-γ levels after treatment in patients with psoriasis

    International Nuclear Information System (INIS)

    Mou Xudong; Ren Hong; Xie Chuntao

    2010-01-01

    Objective: To study the significance of changes of serum IL-2, TNF-α and IFN-γ levels after treatment in patients with psoriasis. Methods: Serum levels of IL-2, TNF-α (with RIA) and IFN-γ (with ELISA) were measured both before and after treatment in 37 patients with psoriasis and 35 controls. Results: Before treatment, the serum IL-2 levels in patients were significantly lower than those in controls (P<0.01), while the serum TNF-α and IFN-γ levels were significantly higher (P<0.01). After treatment for 3 months, the levels though markedly corrected, were still significantly different from those in controls (P<0.05). Conclusion: The levels of serum IL-2, TNF-α and IFN-γ increased significantly in patients with psoriasis especially in those advanced cases. (authors)

  3. In vitro activated CD4+ T cells from interferon-gamma (IFN-gamma)-deficient mice induce intestinal inflammation in immunodeficient hosts

    DEFF Research Database (Denmark)

    Bregenholt, S; Brimnes, J; Nissen, Mogens Holst

    1999-01-01

    To investigate the role of IFN-gamma in the immunopathogenesis of inflammatory bowel disease (IBD), severe combined immunodeficient (SCID) mice were transplanted with in vitro activated CD4+ T cells from either wild-type (WT) or IFN-gamma-deficient (IFN-gammaKO) BALB/c mice. In vitro, the two types...... of T cells displayed comparable proliferation rates and production of tumour necrosis factor-alpha (TNF-alpha), IL-2, IL-4 and IL-10 after concanavalin A (Con A) stimulation. When transplanted into SCID mice, WT CD4+ blasts induced a lethal IBD, whereas IFN-gammaKO blasts induced a less severe...... intestinal inflammation with moderate weight loss. Intracellular cytokine staining of lamina propria lymphocytes (LPL) revealed comparable fractions of CD4+ T cells positive for TNF-alpha, IL-2 and IL-10 in the two groups of transplanted SCID mice, whereas a two-to-three-fold increase in the fraction of IL-4...

  4. Clinical significance of determination of changes of serum TNF-α, IFN-γ and T-cell subsets distribution pattern in pediatric patients with aplastic anemia

    International Nuclear Information System (INIS)

    Feng Yue

    2008-01-01

    Objective: To explore the changes of serum TNF-α, IFN-γ and T-cell subsets distribution pattern in pediatric patients with aplastic anemia. Methods: Serum TNF-α levels (with RIA), IFN-γ levels (with ELISA), peripheral blood T-cell subsets distribution pattern (with monoclonal antibody technique) were determined in 33 pediatric patients with aplastic anemia, as well as in 35 controls. Results: The serum levels of TNF-α and IFN-γ in the patients with aplastic anemia were significantly higher than those in the controls (P<0.01), while the CD3, CD4 percentages and CD4/CD8 ratio were significantly lower (P<0.01). Conclusion: Detection of changes of serum TNF-α, IFN-γ levels and T-cell subsets ratio was clinically useful for outcome prediction in pediatric patients with aplastic anemia. (authors)

  5. Les Anglo-americanismes du "Petit Larousse Illustre 1979" (Anglo-Americanisms in the 1979 "Petit Larousse Illustre").

    Science.gov (United States)

    Trescases, Pierre

    1979-01-01

    Based on the 1979 edition of the "Petit Larousse Illustre," English or American loan words are evaluated as to their actual usage in modern French. It is concluded that anglo-americanisms have a greater impact on technical French than on everyday French. A list of 57 words that have become part of French usage is provided for pedagogical…

  6. OX40+ T lymphocytes and IFN-γ are associated with American tegumentary leishmaniasis pathogenesis Linfócitos T OX40+ e IFN-γ estão associados com a patogênese da leishmaniose tegumentar americana

    Directory of Open Access Journals (Sweden)

    Patrícia Luciana Batista Domingos

    2012-12-01

    Full Text Available BACKGROUND: Leishmaniases are zoonoses considered a public health problem, representing a complex group of diseases with a broad clinical spectrum and epidemiological diversity. Leishmaniasis is caused by several species of protozoa of the genus Leishmania. The evolution of the pathology and the resolution of the leishmaniasis are dependent mainly on the Leishmania species involved, although the cytokine profile plays an important role in the development of the immune response. OBJECTIVES: The purpose of our study was to evaluate the immune response of patients affected by lesions of cutaneous leishmaniasis by immunostaining of the OX40, CD20, IFN-γ and IL-4 proteins. METHODS: The tissue samples were collected from indolent skin ulcers confirmed as cutaneous leishmaniasis of 41 patients aged between six and 90 years. The lesions were submitted to OX40, CD20, INF-γ and IL-4 immunolabeling. RESULTS: We observed a statistically significant higher expression of IFN-γ compared with IL-4 (p=0.009. Besides, OX40 had higher expression when compared with CD20 (pFUNDAMENTOS: As leishmanioses são zoonoses consideradas um problema de saúde pública, representando um grupo de doenças complexas, com uma diversidade de amplo espectro clínico e epidemiológico. A leishmaniose é uma doença causada por várias espécies de protozoários do gênero Leishmania spp. A evolução da patologia e a resolução da leishmaniose são dependentes principalmente da espécie de Leishmania envolvida; embora o perfil das citocinas tenha um importante papel no desenvolvimento da resposta imune. OBJETIVOS: Proporcionar mais conhecimentos sobre os eventos inflamatórios na leishmaniose tegumentar através da avaliação da imunoexpressão de OX40, CD20, IFN-γ e IL-4. MÉTODOS: Foram coletadas amostras de tecido de 41 pacientes, com idade variando entre 6 a 90 anos, com úlceras indolentes na pele confirmados através de exames de diagnóstico como leishmaniose

  7. Modulation of inflammasome-mediated pulmonary immune activation by type I IFNs protects bone marrow homeostasis during systemic responses to Pneumocystis lung infection.

    Science.gov (United States)

    Searles, Steve; Gauss, Katherine; Wilkison, Michelle; Hoyt, Teri R; Dobrinen, Erin; Meissner, Nicole

    2013-10-01

    Although acquired bone marrow failure (BMF) is considered a T cell-mediated autoimmune disease, possible innate immune defects as a cause for systemic immune deviations in response to otherwise innocuous infections have not been extensively explored. In this regard, we recently demonstrated an important role of type I IFNs in protecting hematopoiesis during systemic stress responses to the opportunistic fungal pathogen Pneumocystis in lymphocyte-deficient mice. Mice deficient in both lymphocytes and type I IFN receptor (IFrag(-/-) mice) develop rapidly progressing BMF due to accelerated bone marrow (BM) cell apoptosis associated with innate immune deviations in the BM in response to Pneumocystis lung infection. However, the communication pathway between lung and BM eliciting the induction of BMF in response to this strictly pulmonary infection has been unclear. In this study, we report that absence of an intact type I IFN system during Pneumocystis lung infection not only causes BMF in lymphocyte-deficient mice but also transient BM stress in lymphocyte-competent mice. This is associated with an exuberant systemic IFN-γ response. IFN-γ neutralization prevented Pneumocystis lung infection-induced BM depression in type I IFN receptor-deficient mice and prolonged neutrophil survival time in BM from IFrag(-/-) mice. IL-1β and upstream regulators of IFN-γ, IL-12, and IL-18 were also upregulated in lung and serum of IFrag(-/-) mice. In conjunction, there was exuberant inflammasome-mediated caspase-1 activation in pulmonary innate immune cells required for processing of IL-18 and IL-1β. Thus, absence of type I IFN signaling during Pneumocystis lung infection may result in deregulation of inflammasome-mediated pulmonary immune activation, causing systemic immune deviations triggering BMF in this model.

  8. Changes in growth hormone (GH) messenger RNA (GH mRNA) expression in the rat anterior pituitary after single interferon (IFN) alpha administration

    International Nuclear Information System (INIS)

    Romanowski, W.; Braczkowski, R.; Nowakowska-Zajdel, E.; Muc-Wierzgon, M.; Zubelewicz-Szkodzinska, B.; Kosiewicz, J.; Korzonek, I.

    2006-01-01

    Introduction: Interferon a (IFN-a) is a cytokine with pleiotropic effects which, via different pathways, influences the secretion of certain cytokines and hormones. Growth hormone (GH) secreted from the pituitary has physiological effects on various target tissues. The question is how IFN-a administered in various types of disease influences GH secretion. This study investigated the acute effect of IFN-a on GH mRNA expression in the rat anterior pituitary. Objective: The aim of the study was to measure the cellular expression of GH mRNA by in situ hybridisation in the anterior pituitary after a single administration of IFN-a. Material and methods: Rats were administered an intraperitoneal injection of IFN-a or saline. The rat pituitaries were taken 2 and 4 hours after IFN/saline administration and kept frozen until in situ hybridisation histochemistry. A 31 - base 35S -labelled oligonucleotide probe complementary to part of the exonic mRNA sequence coding for GH mRNA was used. All control and experimental sections were hybridised in the same hybridisation reaction. Results: Acute administration of interferon a increased GH mRNA expression in the anterior pituitary in the 4-hour group in comparison with the control group, and there was no difference between the control group and the 2-hour rats. Conclusion: A single IFN-a administration was found to exert an influence on anterior pituitary GH mRNA expression. These observations may pave the way for presenting a possible new action of IFN-a. (author) GH mRNA, anterior pituitary, interferon

  9. Effect of the γ-IFN on radiation damage and radiation fibrosis of the rabbit rectum after cavitas pelvisrute fractionated irradiation

    International Nuclear Information System (INIS)

    Yang Yunyi; Zhang Li; Wang Juan; Zhao Hengfang; Dai Li; Liu Zi

    2009-01-01

    Objective: To investigate the effect of γ-IFN on the radiation-induced injury and fibrosis of the rabbit rectum after the fractionated irradiation to pelvic cavity. Methods: The animal model of radiation rectum injury was established. 52 New Zealand rabbits were divided into 3 groups as the normal control group, the conventional radiation group, and γ-IFN group. Except the normal control group, the pelvic cavity of the two other groups were irradiated with 6 MV X-rays. At 5 d post-irradiatio the γ-IFN group was administered with 250 000 U/kg of γ-IFN once a week, while the conventional radiation group with 5 ml of saline solution. The rabbits were executed after 4, 8, 12 and 16 weeks, and the recta in the irradiated field were taken out. HE dyeing, in-situ hybridization and immuno-histochemical methods were used to analyze the radiation-induced rectrum injury and fibrosis. Results: At 4, 8, and 12 weeks post-irradiation, the radiation rectum injury and fibrosis were significantly different between the conventional radiation group and γ-IFN group(P 0.05) . At 4, 8, 12 and 16 weeks post-irradiation, the expression of TGF-β1 mRNA in-situ hybridization in the γ-IFN group were significantly different compared to the conventional radiation group and the normal control group (P <0.05) . The immuno-histochemical results of Col III showed the significant difference among the γ-IFN group and both the normal control group and conventional radiation group ( P < 0.05). Conclusions: γ-IFN could reduce the radiation rectum injury, suppress the expression of TGF-β1 mRNA in the rectum mucosa, inhibit the expression of Col III, and delay the formation of radiation-induced fibrosis. (authors)

  10. Cytokines affecting CD4+T regulatory cells in transplant tolerance. II. Interferon gamma (IFN-γ) promotes survival of alloantigen-specific CD4+T regulatory cells.

    Science.gov (United States)

    Nomura, Masaru; Hodgkinson, Suzanne J; Tran, Giang T; Verma, Nirupama D; Robinson, Catherine; Plain, Karren M; Boyd, Rochelle; Hall, Bruce M

    2017-06-01

    CD4 + T cells that transfer alloantigen-specific transplant tolerance are short lived in culture unless stimulated with specific-donor alloantigen and lymphocyte derived cytokines. Here, we examined if IFN-γ maintained survival of tolerance transferring CD4 + T cells. Alloantigen-specific transplant tolerance was induced in DA rats with heterotopic adult PVG heart allografts by a short course of immunosuppression and these grafts functioned for >100days with no further immunosuppression. In previous studies, we found the CD4 + T cells from tolerant rats that transfer tolerance to an irradiated DA host grafted with a PVG heart, lose their tolerance transferring ability after 3days of culture, either with or without donor alloantigen, and effect rejection of specific-donor grafts. If cultures with specific-donor alloantigen are supplemented by supernatant from ConA activated lymphocytes the tolerance transferring cells survive, suggesting these cells depend on cytokines for their survival. In this study, we found addition of rIFN-γ to MLC with specific-donor alloantigen maintained the capacity of tolerant CD4 + T cells to transfer alloantigen-specific tolerance and their ability to suppress PVG allograft rejection mediated by co-administered naïve CD4 + T cells. IFN-γ suppressed the in vitro proliferation of tolerant CD4 + T cells. Tolerant CD4 + CD25 + T cells did not proliferate in MLC to PVG stimulator cells with no cytokine added, but did when IFN-γ was present. IFN-γ did not alter proliferation of tolerant CD4 + CD25 + T cells to third-party Lewis. Tolerant CD4 + CD25 + T cells' expression of IFN-γ receptor (IFNGR) was maintained in culture when IFN-γ was present. This study suggested that IFN-γ maintained tolerance mediating alloantigen-specific CD4 + CD25 + T cells. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  11. Dengue Virus Infection Differentially Regulates Endothelial Barrier Function over Time through Type I Interferon Effects

    Science.gov (United States)

    Liu, Ping; Woda, Marcia; Ennis, Francis A.; Libraty, Daniel H.

    2013-01-01

    Background The morbidity and mortality resulting from dengue hemorrhagic fever (DHF) are largely caused by endothelial barrier dysfunction and a unique vascular leakage syndrome. The mechanisms that lead to the location and timing of vascular leakage in DHF are poorly understood. We hypothesized that direct viral effects on endothelial responsiveness to inflammatory and angiogenesis mediators can explain the DHF vascular leakage syndrome. Methods We used an in vitro model of human endothelium to study the combined effects of dengue virus (DENV) type 2 (DENV2) infection and inflammatory mediators on paracellular macromolecule permeability over time. Results Over the initial 72 h after infection, DENV2 suppressed tumor necrosis factor (TNF)–α–mediated hyperpermeability in human umbilical vein endothelial cell (HUVEC) monolayers. This suppressive effect was mediated by type I interferon (IFN). By 1 week, TNF-α stimulation of DENV2-infected HUVECs synergistically increased cell cycling, angiogenic changes, and macromolecule permeability. This late effect could be prevented by the addition of exogenous type I IFN. Conclusions DENV infection of primary human endothelial cells differentially modulates TNF-α–driven angiogenesis and hyperpermeability over time. Type I IFN plays a central role in this process. Our findings suggest a rational model for the DHF vascular leakage syndrome. PMID:19530939

  12. Illustrative comparison of one utility's coal and nuclear choices

    International Nuclear Information System (INIS)

    Keeney, R.L.; Sicherman, A.

    1983-01-01

    The technology choices facing an individual utility are complex decision problems. The paper illustrates a method designed to assist an individual utility company in making the choices in a logically consisnt manner. The resulting evaluation model, based on the principles of decision analysis, explicitly addresses the complexity to provide a basis for decision making and support for defending the decision before reviewers. The model, which incorporates economic, environmental, social, safety, and regulatory effects, is demonstrated using a coal/nuclear choice which may be faced by Utah Power and Light Company in the near future. This analysis is meant to be illustrative; more effort would be needed to gather information to support a policy decision

  13. Optical character recognition: an illustrated guide to the frontier

    Science.gov (United States)

    Nagy, George; Nartker, Thomas A.; Rice, Stephen V.

    1999-12-01

    We offer a perspective on the performance of current OCR systems by illustrating and explaining actual OCR errors made by three commercial devices. After discussing briefly the character recognition abilities of humans and computers, we present illustrated examples of recognition errors. The top level of our taxonomy of the causes of errors consists of Imaging Defects, Similar Symbols, Punctuation, and Typography. The analysis of a series of 'snippets' from this perspective provides insight into the strengths and weaknesses of current systems, and perhaps a road map to future progress. The examples were drawn from the large-scale tests conducted by the authors at the Information Science Research Institute of the University of Nevada, Las Vegas. By way of conclusion, we point to possible approaches for improving the accuracy of today's systems. The talk is based on our eponymous monograph, recently published in The Kluwer International Series in Engineering and Computer Science, Kluwer Academic Publishers, 1999.

  14. Scientific and technical reports how to write and illustrate

    CERN Document Server

    Sharma, B C

    2014-01-01

    Scientific and technical reports: How to Write and Illustrate provides step-by-step advice on tackling various tasks associated with report writing like gathering information, analyzing information, preparing an outline, writing a rough draft and revising. Many examples illustrate the processes involved at various steps. A stepwise approach to computer-assisted preparation of tables and various types of figures like line drawings, bar charts, histograms, flowcharts, etc., is provided. Also presented are suggestions about how to use commonly available computer programs to give visual shape to ideas, concepts, processes and cause and effect relations described in the text. Use of readability tests is explained as a screening system for checking comprehensibility of language used. Readers are alerted to some of the common pitfalls in science writing like redundancy, overuse of nouns, noun chains, excessive use of passive voice, use of overlong sentences and ambiguity. Checklist at the end of each chapter sums up...

  15. STS-49 ASEM activity illustrated with PLAID computer graphics

    Science.gov (United States)

    1992-01-01

    STS-49 Endeavour, Orbiter Vehicle (OV) 105, Assembly of Station by Extravehicular Activity (EVA) Methods (ASEM) activity is illustrated with PLAID computer graphics. An extravehicular mobility unit (EMU) suited crewmember, positioned on the remote manipulator system (RMS) manipulator foot restraint (MFR), grabs and maneuvers the multipurpose experiment support structure (MPESS) with truss assembly attached above OV-105's payload bay (PLB) using the steer wheel assembly. The MPESS/ASEM truss structure has been lifted out the sill-mounted payload retention latch assemblies (PRLAs) and will be repositioned in the PRLAs upon completion of handling procedures. Also seen in this illustration are the empty INTELSAT perigee stage cradle structure (aft PLB) and the capture bar grapple fixture stowed on the port side sill longeron.

  16. Both CD4+ and CD8+ Lymphocytes Participate in the IFN-γ Response to Filamentous Hemagglutinin from Bordetella pertussis in Infants, Children, and Adults

    Directory of Open Access Journals (Sweden)

    Violette Dirix

    2012-01-01

    Full Text Available Infant CD4+ T-cell responses to bacterial infections or vaccines have been extensively studied, whereas studies on CD8+ T-cell responses focused mainly on viral and intracellular parasite infections. Here we investigated CD8+ T-cell responses upon Bordetella pertussis infection in infants, children, and adults and pertussis vaccination in infants. Filamentous hemagglutinin-specific IFN-γ secretion by circulating lymphocytes was blocked by anti-MHC-I or -MHC-II antibodies, suggesting that CD4+ and CD8+ T lymphocytes are involved in IFN-γ production. Flow cytometry analyses confirmed that both cell types synthesized antigen-specific IFN-γ, although CD4+ lymphocytes were the major source of this cytokine. IFN-γ synthesis by CD8+ cells was CD4+ T cell dependent, as evidenced by selective depletion experiments. Furthermore, IFN-γ synthesis by CD4+ cells was sometimes inhibited by CD8+ lymphocytes, suggesting the presence of CD8+ regulatory T cells. The role of this dual IFN-γ secretion by CD4+ and CD8+ T lymphocytes in pertussis remains to be investigated.

  17. NOD1 contributes to mouse host defense against Helicobacter pylori via induction of type I IFN and activation of the ISGF3 signaling pathway

    Science.gov (United States)

    Watanabe, Tomohiro; Asano, Naoki; Fichtner-Feigl, Stefan; Gorelick, Peter L.; Tsuji, Yoshihisa; Matsumoto, Yuko; Chiba, Tsutomu; Fuss, Ivan J.; Kitani, Atsushi; Strober, Warren

    2010-01-01

    Nucleotide-binding oligomerization domain 1 (NOD1) is an intracellular epithelial cell protein known to play a role in host defense at mucosal surfaces. Here we show that a ligand specific for NOD1, a peptide derived from peptidoglycan, initiates an unexpected signaling pathway in human epithelial cell lines that results in the production of type I IFN. Detailed analysis revealed the components of the signaling pathway. NOD1 binding to its ligand triggered activation of the serine-threonine kinase RICK, which was then able to bind TNF receptor–associated factor 3 (TRAF3). This in turn led to activation of TANK-binding kinase 1 (TBK1) and IκB kinase ε (IKKε) and the subsequent activation of IFN regulatory factor 7 (IRF7). IRF7 induced IFN-β production, which led to activation of a heterotrimeric transcription factor complex known as IFN-stimulated gene factor 3 (ISGF3) and the subsequent production of CXCL10 and additional type I IFN. In vivo studies showed that mice lacking the receptor for IFN-β or subjected to gene silencing of the ISGF3 component Stat1 exhibited decreased CXCL10 responses and increased susceptibility to Helicobacter pylori infection, phenotypes observed in NOD1-deficient mice. These studies thus establish that NOD1 can activate the ISGF3 signaling pathway that is usually associated with protection against viral infection to provide mice with robust type I IFN–mediated protection from H. pylori and possibly other mucosal infections. PMID:20389019

  18. Recombinant IFN-γ from the bank vole Myodes glareolus: a novel tool for research on rodent reservoirs of zoonotic pathogens.

    Science.gov (United States)

    Torelli, Francesca; Zander, Steffen; Ellerbrok, Heinz; Kochs, Georg; Ulrich, Rainer G; Klotz, Christian; Seeber, Frank

    2018-02-12

    Rodent species like Myodes glareolus and Microtus spp. are natural reservoirs for many zoonotic pathogens causing human diseases and are gaining increasing interest in the field of eco-immunology as candidate animal models. Despite their importance the lack of immunological reagents has hampered research in these animal species. Here we report the recombinant production and functional characterization of IFN-γ, a central mediator of host's innate and adaptive immune responses, from the bank vole M. glareolus. Soluble dimeric recMgIFN-γ was purified in high yield from Escherichia coli. Its activity on M. glareolus and Microtus arvalis kidney cell lines was assessed by immunofluorescent detection of nuclear translocation and phosphorylation of the transcription factor STAT1. RecMgIFN-γ also induced expression of an IFN-γ-regulated innate immunity gene. Inhibition of vesicular stomatitis virus replication in vole cells upon recMgIFN-γ treatment provided further evidence of its biological activity. Finally, we established a recMgIFN-γ-responsive bank vole reporter cell line that allows the sensitive titration of the cytokine activity via a bioluminescence reporter assay. Taken together, we report valuable tools for future investigations on the immune response against zoonotic pathogens in their natural animal hosts, which might foster the development of novel animal models.

  19. Genetic Control of Lyme Arthritis by Borrelia burgdorferi Arthritis-Associated Locus 1 Is Dependent on Localized Differential Production of IFN-β and Requires Upregulation of Myostatin.

    Science.gov (United States)

    Paquette, Jackie K; Ma, Ying; Fisher, Colleen; Li, Jinze; Lee, Sang Beum; Zachary, James F; Kim, Yong Soo; Teuscher, Cory; Weis, Janis J

    2017-11-15

    Previously, using a forward genetic approach, we identified differential expression of type I IFN as a positional candidate for an expression quantitative trait locus underlying Borrelia burgdorferi arthritis-associated locus 1 ( Bbaa1 ). In this study, we show that mAb blockade revealed a unique role for IFN-β in Lyme arthritis development in B6.C3- Bbaa1 mice. Genetic control of IFN-β expression was also identified in bone marrow-derived macrophages stimulated with B. burgdorferi , and it was responsible for feed-forward amplification of IFN-stimulated genes. Reciprocal radiation chimeras between B6.C3- Bbaa1 and C57BL/6 mice revealed that arthritis is initiated by radiation-sensitive cells, but orchestrated by radiation-resistant components of joint tissue. Advanced congenic lines were developed to reduce the physical size of the Bbaa1 interval, and confirmed the contribution of type I IFN genes to Lyme arthritis. RNA sequencing of resident CD45 - joint cells from advanced interval-specific recombinant congenic lines identified myostatin as uniquely upregulated in association with Bbaa1 arthritis development, and myostatin expression was linked to IFN-β production. Inhibition of myostatin in vivo suppressed Lyme arthritis in the reduced interval Bbaa1 congenic mice, formally implicating myostatin as a novel downstream mediator of the joint-specific inflammatory response to B. burgdorferi . Copyright © 2017 by The American Association of Immunologists, Inc.

  20. Early Illustrations of Geste Antagoniste in Cervical and Generalized Dystonia

    Science.gov (United States)

    Broussolle, Emmanuel; Laurencin, Chloé; Bernard, Emilien; Thobois, Stéphane; Danaila, Teodor; Krack, Paul

    2015-01-01

    Background Geste antagoniste, or sensory trick, is a voluntary maneuver that temporarily reduces the severity of dystonic postures or movements. We present a historical review of early reports and illustrations of geste antagoniste. Results In 1894, Brissaud described this phenomenon in Paris in patients with torticollis. He noted that a violent muscular contraction could be reversed by a minor voluntary action. He considered the improvement obtained by what he called “simple mannerisms, childish behaviour or fake pathological movements” was proof of the psychogenic origin of what he named mental torticollis. This concept was supported by photographical illustrations of the patients. The term geste antagoniste was used by Brissaud’s pupils, Meige and Feindel, in their 1902 monograph on movement disorders. Other reports and illustrations of this sign were published in Europe between 1894 and 1906. Although not mentioned explicitly, geste antagoniste was also illustrated in a case report of generalized dystonia in Oppenheim’s 1911 seminal description of dystonia musculorum deformans in Berlin. Discussion Brissaud-Meige’s misinterpretation of the geste antagoniste unfortunately anchored the psychogenic origin of dystonia for decades. In New York, Herz brought dystonia back into the realm of organic neurology in 1944. Thereafter, it was given prominence by other authors, notably Fahn and Marsden in the 1970–1980s. Nowadays, neurologists routinely investigate for geste antagoniste when a dystonic syndrome is suspected, because it provides a further argument in favor of dystonia. The term alleviating maneuver was proposed in 2014 to replace sensory trick or geste antagoniste. This major sign is now part of the motor phenomenology of the 2013 Movement Disorder Society’s classification of dystonia. PMID:26417535

  1. I La Galigo Folklore Illustration on Textile Media

    Directory of Open Access Journals (Sweden)

    Yosepin Sri Ningsih

    2014-01-01

    Full Text Available This project was an effort in conserving the I La Galigo epic story while at the same time adding value to silk, the famous textile product from South Sulawesi and the origin of I La Galigo. As a work of literature, I La Galigo is categorized as an epic. It is known locally as Sureq Galigo in Bugis. It is divided in a number of episodes or tereng. The most well-known tereng is the one which describes the relationship between Sawerigading and a princess called I We Cudai. From that relationship I La Galigo, the central character of this epic is born. For this project six of the most well-known episodes were selected because of the amount of available supporting data, both theoretical and visual. The selected episodes were translated from their original narrative form into visual language or images. The illustration technique used in this project was STP (Space Time Plane. With this technique every object is drawn from varying viewpoints in one frame, both in space and time. Hand embroidery was added to the painted images. The silk painting can be used as an interior element with value added by the I La Galigo illustrations. Keywords: I La Galigo; epic; Sulawesi; illustration; silk painting; space time plane.

  2. [An illustrated guide to dental screening: a school survey].

    Science.gov (United States)

    Tenenbaum, Annabelle; Sayada, Mélanie; Azogui-Levy, Sylvie

    2017-12-05

    Marked social inequalities in oral health are observed right from early childhood. A mandatory complete health check-up, including dental screening, is organized at school for 6-year-old children. School healthcare professionals are not well trained in dental health. The aim of this study was to assess the relevance of an illustrated guide as a simple and rapid dental screening training tool in order to ensure effective, standardized and reproducible screening. A cross-sectional study was conducted in the context of the dental examination performed as part of the health check-up. Two examiners (Doctor E1 and Nurse E2) were trained in dental screening by means of the illustrated guide. This reference guide, comprising pictures and legends, presents the main oral pathology observed in children. 109 consent forms for oral screening were delivered, and 102 children agreed to participate (93.57%). The sensitivity of detection of tooth decay by examiners E1 and E2 was 81.48% with a specificity of 96%. No correlation was observed between the child's age (+/- 6 years) and correct detection rates. The illustrated guide is an appropriate and rapid tool for dental screening that can improve the quality of dental check-up and increase the number of children detected.

  3. Explanatory and illustrative visualization of special and general relativity.

    Science.gov (United States)

    Weiskopf, Daniel; Borchers, Marc; Ertl, Thomas; Falk, Martin; Fechtig, Oliver; Frank, Regine; Grave, Frank; King, Andreas; Kraus, Ute; Müller, Thomas; Nollert, Hans-Peter; Rica Mendez, Isabel; Ruder, Hanns; Schafhitzel, Tobias; Schär, Sonja; Zahn, Corvin; Zatloukal, Michael

    2006-01-01

    This paper describes methods for explanatory and illustrative visualizations used to communicate aspects of Einstein's theories of special and general relativity, their geometric structure, and of the related fields of cosmology and astrophysics. Our illustrations target a general audience of laypersons interested in relativity. We discuss visualization strategies, motivated by physics education and the didactics of mathematics, and describe what kind of visualization methods have proven to be useful for different types of media, such as still images in popular science magazines, film contributions to TV shows, oral presentations, or interactive museum installations. Our primary approach is to adopt an egocentric point of view: The recipients of a visualization participate in a visually enriched thought experiment that allows them to experience or explore a relativistic scenario. In addition, we often combine egocentric visualizations with more abstract illustrations based on an outside view in order to provide several presentations of the same phenomenon. Although our visualization tools often build upon existing methods and implementations, the underlying techniques have been improved by several novel technical contributions like image-based special relativistic rendering on GPUs, special relativistic 4D ray tracing for accelerating scene objects, an extension of general relativistic ray tracing to manifolds described by multiple charts, GPU-based interactive visualization of gravitational light deflection, as well as planetary terrain rendering. The usefulness and effectiveness of our visualizations are demonstrated by reporting on experiences with, and feedback from, recipients of visualizations and collaborators.

  4. Fuzzy barrier distributions

    International Nuclear Information System (INIS)

    Piasecki, E.

    2009-01-01

    Heavy-ion collisions often produce a fusion barrier distribution with structures displaying a fingerprint of couplings to highly collective excitations [1]. Basically the same distribution can be obtained from large-angle quasi-elastic scattering, though here the role of the many weak direct-reaction channels is unclear. For 2 0N e + 9 0Z r we have observed the barrier structures expected for the highly deformed neon projectile, but for 2 0N e + 9 2Z r we find completely smooth distribution (see Fig.1). We find that transfer channels in these systems are of similar strength but single particle excitations are significantly stronger in the latter case. They apparently reduce the 'resolving power' of the quasi-elastic channel, what leads to smeared out, or 'fuzzy' barrier distribution. This is the first case when such a phenomenon has been observed.(author)

  5. Health Barriers to Learning

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    Delaney Gracy

    2014-01-01

    Full Text Available This article summarizes the results from a 2013 online survey with 408 principals and assistant principals in New York City public elementary and middle schools. The survey assessed three primary areas: health issues in the school, health issues perceived as barriers to learning for affected students, and resources needed to address these barriers. Eighteen of the 22 health conditions listed in the survey were considered a moderate or serious issue within their schools by at least 10% of respondents. All 22 of the health issues were perceived as a barrier to learning by between 12% and 87% of the respondents. Representatives from schools that serve a higher percentage of low-income students reported significantly higher levels of concern about the extent of health issues and their impact on learning. Respondents most often said they need linkages with organizations that can provide additional services and resources at the school, especially for mental health.

  6. Alopecia of IFN-gamma knockout mouse as a model for disturbance of the hair cycle: a unique arrest of the hair cycle at the anagen phase accompanied by mitosis.

    Science.gov (United States)

    Hirota, Ryuichiro; Tajima, Sadao; Yoneda, Yukio; Tamayama, Takumi; Watanabe, Masahito; Ueda, Kouichi; Kubota, Takahiro; Yoshida, Ryotaro

    2002-09-01

    Interferon-gamma(-/-) (IFN-gamma(-/-)) and IFN-gamma(+/+) C57BL/6 mice (3 weeks of age) completed the production of morphogenesis-derived hair. Around 6 weeks of age, however, most of the IFN-gamma(-/-) but none of the IFN-gamma(+/+) mice began to lose hairs in the dorsal and occipital areas in the absence of inflammatory reactions, and the alopecia was sustained for at least several 10-week periods of observation. A single subcutaneous injection of IFN-gamma to IFN-gamma(-/-) mice at 3, but not 4, 5, or 8 weeks of age could protect all the mice from alopecia, revealing that the lack of IFN-gamma around 3 weeks of age is directly responsible for the alopecia. Histologic features showed that the hair follicles of the IFN-gamma(+/+) mice passed through the anagen (4-5 weeks of age) and catagen/telogen ( approximately 6 weeks of age) phases, whereas those of IFN-gamma(-/-) mice (5 weeks of age or older) stayed in the anagen phase. TUNEL and bromodeoxyuridine experiments suggested that an arrest with unlimited DNA synthesis of the hair cycle in the anagen phase by the lack of IFN-gamma-dependent apoptosis in the midfollicle region and diffuse shedding of previously formed hair induced alopecia in IFN-gamma(-/-) mice.

  7. Comprehensive Antiretroviral Restriction Factor Profiling Reveals the Evolutionary Imprint of the ex Vivo and in Vivo IFN-β Response in HTLV-1-Associated Neuroinflammation

    Directory of Open Access Journals (Sweden)

    Fabio E. Leal

    2018-05-01

    Full Text Available HTLV-1-Associated Myelopathy (HAM/TSP is a progressive neuroinflammatory disorder for which no disease-modifying treatment exists. Modest clinical benefit from type I interferons (IFN-α/β in HAM/TSP contrasts with its recently identified IFN-inducible gene signature. In addition, IFN-α treatment in vivo decreases proviral load and immune activation in HAM/TSP, whereas IFN-β therapy decreases tax mRNA and lymphoproliferation. We hypothesize this “IFN paradox” in HAM/TSP might be explained by both cell type- and gene-specific effects of type I IFN in HTLV-1-associated pathogenesis. Therefore, we analyzed ex vivo transcriptomes of CD4+ T cells, PBMCs and whole blood in healthy controls, HTLV-1-infected individuals, and HAM/TSP patients. First, we used a targeted approach, simultaneously quantifying HTLV-1 mRNA (HBZ, Tax, proviral load and 42 host genes with known antiretroviral (anti-HIV activity in purified CD4+ T cells. This revealed two major clusters (“antiviral/protective” vs. “proviral/deleterious”, as evidenced by significant negative (TRIM5/TRIM22/BST2 vs. positive correlation (ISG15/PAF1/CDKN1A with HTLV-1 viral markers and clinical status. Surprisingly, we found a significant inversion of antiretroviral activity of host restriction factors, as evidenced by opposite correlation to in vivo HIV-1 vs. HTLV-1 RNA levels. The anti-HTLV-1 effect of antiviral cluster genes was significantly correlated to their adaptive chimp/human evolution score, for both Tax mRNA and PVL. Six genes of the proposed antiviral cluster underwent lentivirus-driven purifying selection during primate evolution (TRIM5/TRIM22/BST2/APOBEC3F-G-H, underscoring the cross-retroviral evolutionary imprint. Secondly, we examined the genome-wide type I IFN response in HAM/TSP patients, following short-term ex vivo culture of PBMCs with either IFN-α or IFN-β. Microarray analysis evidenced 12 antiretroviral genes (including TRIM5α/TRIM22/BST2 were significantly

  8. Comprehensive Antiretroviral Restriction Factor Profiling Reveals the Evolutionary Imprint of the ex Vivo and in Vivo IFN-β Response in HTLV-1-Associated Neuroinflammation.

    Science.gov (United States)

    Leal, Fabio E; Menezes, Soraya Maria; Costa, Emanuela A S; Brailey, Phillip M; Gama, Lucio; Segurado, Aluisio C; Kallas, Esper G; Nixon, Douglas F; Dierckx, Tim; Khouri, Ricardo; Vercauteren, Jurgen; Galvão-Castro, Bernardo; Saraiva Raposo, Rui Andre; Van Weyenbergh, Johan

    2018-01-01

    HTLV-1-Associated Myelopathy (HAM/TSP) is a progressive neuroinflammatory disorder for which no disease-modifying treatment exists. Modest clinical benefit from type I interferons (IFN-α/β) in HAM/TSP contrasts with its recently identified IFN-inducible gene signature. In addition, IFN-α treatment in vivo decreases proviral load and immune activation in HAM/TSP, whereas IFN-β therapy decreases tax mRNA and lymphoproliferation. We hypothesize this "IFN paradox" in HAM/TSP might be explained by both cell type- and gene-specific effects of type I IFN in HTLV-1-associated pathogenesis. Therefore, we analyzed ex vivo transcriptomes of CD4 + T cells, PBMCs and whole blood in healthy controls, HTLV-1-infected individuals, and HAM/TSP patients. First, we used a targeted approach, simultaneously quantifying HTLV-1 mRNA (HBZ, Tax), proviral load and 42 host genes with known antiretroviral (anti-HIV) activity in purified CD4 + T cells. This revealed two major clusters ("antiviral/protective" vs. "proviral/deleterious"), as evidenced by significant negative (TRIM5/TRIM22/BST2) vs. positive correlation (ISG15/PAF1/CDKN1A) with HTLV-1 viral markers and clinical status. Surprisingly, we found a significant inversion of antiretroviral activity of host restriction factors, as evidenced by opposite correlation to in vivo HIV-1 vs. HTLV-1 RNA levels. The anti-HTLV-1 effect of antiviral cluster genes was significantly correlated to their adaptive chimp/human evolution score, for both Tax mRNA and PVL. Six genes of the proposed antiviral cluster underwent lentivirus-driven purifying selection during primate evolution (TRIM5/TRIM22/BST2/APOBEC3F-G-H), underscoring the cross-retroviral evolutionary imprint. Secondly, we examined the genome-wide type I IFN response in HAM/TSP patients, following short-term ex vivo culture of PBMCs with either IFN-α or IFN-β. Microarray analysis evidenced 12 antiretroviral genes (including TRIM5α/TRIM22/BST2) were significantly up-regulated by IFN

  9. IFN-γ alters the expression of diverse immunity related genes in a cell culture model designed to represent maturing neutrophils.

    Directory of Open Access Journals (Sweden)

    Michael A Ellison

    Full Text Available The cytokine interferon-γ (IFN-γ is approved as a drug to treat chronic granulomatous disease (CGD and osteopetrosis and is also used in hyperimmunoglobulin E syndromes. Patients with CGD have defects in proteins of the NOX2 NADPH oxidase system. This leads to reduced production of microbicidal ROS by PMNs and recurrent life threatening infections. The goal of this study was to better understand how IFN-γ might support phagocyte function in these diseases, and to obtain information that might expand potential uses for IFN-γ. Neutrophils mature in the bone marrow and then enter the blood where they quickly undergo apoptotic cell death with a half-life of only 5-10 hours. Therefore we reasoned that IFN-γ might exert its effects on neutrophils via prolonged exposure to cells undergoing maturation in the marrow rather than by its brief exposure to short-lived circulating cells. To explore this possibility we made use of PLB-985 cells, a myeloblast-like myeloid cell line that can be differentiated into a mature, neutrophil-like state by treatment with various agents including DMSO. In initial studies we investigated transcription and protein expression in PLB-985 cells undergoing maturation in the presence or absence of IFN-γ. We observed IFN-γ induced differences in expression of genes known to be involved in classical aspects of neutrophil function (transmigration, chemotaxis, phagocytosis, killing and pattern recognition as well as genes involved in apoptosis and other mechanisms that regulating neutrophil number. We also observed differences for genes involved in the major histocompatibility complex I (MHCI and MHCII systems whose involvement in neutrophil function is controversial and not well defined. Finally, we observed significant changes in expression of genes encoding guanylate binding proteins (Gbps that are known to have roles in immunity but which have not as yet been linked to neutrophil function. We propose that changes in the

  10. Innover en illustration jeunesse : les focalisations

    Directory of Open Access Journals (Sweden)

    Anne Guibert-Lassalle

    2010-09-01

    Full Text Available L’activité éditoriale pour la jeunesse est caractérisée en France depuis 1990 par une très forte multiplication du nombre d’acteurs et un accroissement constant du nombre de publications. L’innovation est considérée comme la principale voie de survie. Ces enjeux culturels et économiques contribuent à promouvoir l’originalité de l’illustration. Pourtant le succès commercial ne couronne pas toujours les inventions graphiques. Une enquête sur l’émergence, dans les années 2000, d’une tendance porteuse, fondée sur un usage nouveau des focalisations, révèle le caractère intuitif, étroitement daté et collaboratif, de l’innovation en illustration pour la jeunesse.Innovating in illustration for the youth: the focalisationsSince 1990, publishing for the youth in France is a sector of activity where the number of actors and items produced has been constantly increased. Innovation is considered as the main way for survival. These cultural and economical stakes tend to promote originality in illustration. Since, commercial profit does not always reward graphic inventiveness. A sociological enquiry upon the emerging in the 2000’ of a successful trend, based on a fresh use of focalisations, reveals how intuitive, strictly dated and joint can be innovating in illustration for the youth.La innovación en las revistas ilustradas para jóvenes. La focalizaciónLa actividad editorial para la juventud se ha caracterizado en Francia desde 1990 por un fuerte aumento de agentes y por un crecimiento constante del número de publicaciones. La innovación es la vía esencial para sobrevivir. Las apuestas culturales y económicas contribuyen a promover la originalidad de las ilustraciones. Sin embargo el éxito comercial no siempre subraya la originalidad de estas. A principios de este siglo, una encuesta acerca de la emergencia de una tendencia prometedora, basada en una manera diferente de efectuar las focalizaciones, ha revelado el

  11. Multi-level barriers analysis to promote guideline based nursing care: a leadership strategy from home health care.

    Science.gov (United States)

    Gifford, Wendy A; Graham, Ian D; Davies, Barbara L

    2013-07-01

    Understanding the types of barriers that exist when implementing change can assist healthcare managers to tailor implementation strategies for optimal patient outcomes. The aim of this paper is to present an organising framework, the Barriers Assessment Taxonomy, for understanding barriers to nurses' use of clinical practice guideline recommendations. Barriers to recommendations are illustrated using the Barriers Assessment Taxonomy and insights discussed. As part of a pilot implementation study, semi-structured interviews (n = 26) were conducted to understand barriers to nurses' use of nine guideline recommendations for diabetic foot ulcers. Content analysis of verbatim transcripts included thematic coding and categorising barriers using the Barriers Assessment Taxonomy. Nineteen barriers were associated with nine recommendations, crossing five levels of the health care delivery system. The Barriers Assessment Taxonomy revealed that all recommendations had individual and organisational level barriers, with one recommendation having barriers at all levels. Individual level barriers were most frequent and lack of knowledge and skills was the only barrier that crossed all recommendations. The Barriers Assessment Taxonomy provides a framework for nursing managers to understand the complexity of barriers that exist, and can assist in choosing intervention strategies to support improved quality care and patient outcomes. © 2013 John Wiley & Sons Ltd.

  12. Reduced IFN-γ and IL-10 responses to paternal antigens during and after pregnancy in allergic women.

    Science.gov (United States)

    Persson, Marie; Ekerfelt, Christina; Ernerudh, Jan; Matthiesen, Leif; Abelius, Martina Sandberg; Jonsson, Yvonne; Berg, Göran; Jenmalm, Maria C

    2012-09-01

    Normal pregnancy and allergy are both characterized by a T helper (Th) 2 deviation. In the current study, we hypothesized that paternal antigen-induced cytokine responses during pregnancy would be deviated toward Th2 and an anti-inflammatory profile, and that the Th2 deviation would be more pronounced in allergic pregnant women. Blood samples were collected longitudinally on three occasions during pregnancy and two occasions post partum (pp). Of the 86 women initially included, 54 women had a normal pregnancy and completed the sampling procedures. Twelve women fulfilled the criteria for allergy (allergic symptoms and circulating immunoglobulin [Ig] E antibodies to inhalant allergens) and 20 were non-allergic (nonsensitized without symptoms). The levels of Th1- and Th2-associated cytokines and chemokines, the Th17 cytokine IL-17 and the anti-inflammatory cytokine IL-10 of the groups were compared. Paternal antigen-induced IL-4 and IL-10 responses increased between the first and the third trimester. Allergy was associated with decreased paternal antigen-induced IFN-γ and CXCL10 secretion in the nonpregnant state (one year pp) and also decreased IFN-γ/IL-4 and IFN-γ/IL-13 ratios during pregnancy. We also observed a decreased paternal antigen-induced IL-10 response in allergic compared with non-allergic women during pregnancy, along with a decreased IL-10/IL-13 ratio. In conclusion, our findings support the hypothesis of lower Th1 responses toward paternal antigens in allergic than in non-allergic women, but also indicate that allergy is associated with a lower capacity to induce anti-inflammatory IL-10 responses after paternal antigen stimulation during pregnancy. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  13. Putative endogenous filovirus VP35-like protein potentially functions as an IFN antagonist but not a polymerase cofactor.

    Directory of Open Access Journals (Sweden)

    Tatsunari Kondoh

    Full Text Available It has been proposed that some non-retroviral RNA virus genes are integrated into vertebrate genomes. Endogenous filovirus-like elements (EFLs have been discovered in some mammalian genomes. However, their potential roles in ebolavirus infection are unclear. A filovirus VP35-like element (mlEFL35 is found in the little brown bat (Myotis lucifugus genome. Putative mlEFL35-derived protein (mlEFL35p contains nearly full-length amino acid sequences corresponding to ebolavirus VP35. Ebola virus VP35 has been shown to bind double-stranded RNA, leading to inhibition of type I interferon (IFN production, and is also known as a viral polymerase cofactor that is essential for viral RNA transcription/replication. In this study, we transiently expressed mlEFL35p in human kidney cells and investigated its biological functions. We first found that mlEFL35p was coimmunoprecipitated with itself and ebolavirus VP35s but not with the viral nucleoprotein. Then the biological functions of mlEFL35p were analyzed by comparing it to ebolavirus VP35s. We found that the expression of mlEFL35p significantly inhibited human IFN-β promoter activity as well as VP35s. By contrast, expression of mlEFL35p did not support viral RNA transcription/replication and indeed slightly decrease the reporter gene expression in a minigenome assay. These results suggest that mlEFL35p potentially acts as an IFN antagonist but not a polymerase cofactor.

  14. Duck RIG-I CARD Domain Induces the Chicken IFN-β by Activating NF-κB

    Directory of Open Access Journals (Sweden)

    Yang Chen

    2015-01-01

    Full Text Available Retinoic acid-inducible gene I- (RIG-I- like receptors (RLRs have recently been identified as cytoplasmic sensors for viral RNA. RIG-I, a member of RLRs family, plays an important role in innate immunity. Although previous investigations have proved that RIG-I is absent in chickens, it remains largely unknown whether the chicken can respond to RIG-I ligand. In this study, the eukaryotic expression vectors encoding duRIG-I full length (duck RIG-I, containing all domains, duRIG-I N-terminal (containing the two caspase activation and recruitment domain, CARDs, and duRIG-I C-terminal (containing helicase and regulatory domains labeled with 6*His tags were constructed successfully and detected by western blotting. Luciferase reporter assay and enzyme-linked immunosorbent assay (ELISA detected the duRIG-I significantly activated NF-κB and induced the expression of IFN-β when polyinosinic-polycytidylic acid (poly[I:C], synthetic double-stranded RNA challenges chicken embryonic fibroblasts cells (DF1 cells, while the duRIG-I was inactive in the absence of poly[I:C]. Further analysis revealed that the CARDs (duRIG-I-N induced IFN-β production regardless of the presence of poly[I:C], while the CARD-lacking duRIG-I (duRIG-I-C was not capable of activating downstream signals. These results indicate that duRIG-I CARD domain plays an important role in the induction of IFN-β and provide a basis for further studying the function of RIG-I in avian innate immunity.

  15. IFN-γ, IL-4 and IL-13 modulate responsiveness of human airway smooth muscle cells to IL-13

    Directory of Open Access Journals (Sweden)

    Michoud Marie-Claire

    2008-12-01

    Full Text Available Abstract Background IL-13 is a critical mediator of allergic asthma and associated airway hyperresponsiveness. IL-13 acts through a receptor complex comprised of IL-13Rα1 and IL-4Rα subunits with subsequent activation of signal transducer and activator of transcription 6 (STAT6. The IL-13Rα2 receptor may act as a decoy receptor. In human airway smooth muscle (HASM cells, IL-13 enhances cellular proliferation, calcium responses to agonists and induces eotaxin production. We investigated the effects of pre-treatment with IL-4, IL-13 and IFN-γ on the responses of HASM cells to IL-13. Methods Cultured HASM were examined for expression of IL-13 receptor subunits using polymerase chain reaction, immunofluorescence microscopy and flow cytometry. Effects of cytokine pre-treatment on IL-13-induced cell responses were assessed by looking at STAT6 phosphorylation using Western blot, eotaxin secretion and calcium responses to histamine. Results IL-13Rα1, IL-4Rα and IL-13Rα2 subunits were expressed on HASM cells. IL-13 induced phosphorylation of STAT6 which reached a maximum by 30 minutes. Pre-treatment with IL-4, IL-13 and, to a lesser degree, IFN-γ reduced peak STAT6 phosphorylation in response to IL-13. IL-13, but not IFN-γ, pre-treatment abrogated IL-13-induced eotaxin secretion. Pre-treatment with IL-4 or IL-13 abrogated IL-13-induced augmentation of the calcium transient evoked by histamine. Cytokine pre-treatment did not affect expression of IL-13Rα1 and IL-4Rα but increased expression of IL-13Rα2. An anti-IL-13Rα2 neutralizing antibody did not prevent the cytokine pre-treatment effects on STAT6 phosphorylation. Cytokine pre-treatment increased SOCS-1, but not SOCS-3, mRNA expression which was not associated with significant increases in protein expression. Conclusion Pre-treatment with IL-4 and IL-13, but not IFN-γ, induced desensitization of the HASM cells to IL-13 as measured by eotaxin secretion and calcium transients to histamine

  16. Efecto de la maca roja (Lepidium meyenii) sobre los niveles de IFN-γ en ratas ovariectomizadas

    OpenAIRE

    Leiva-Revilla, Johanna; Laboratorio de Endocrinología y Reproducción, Facultad de Ciencias y Filosofía. Universidad Peruana Cayetano Heredia. Lima-Perú. Departamento de Ciencias Biológicas y Fisiológicas, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia. Lima-Perú.; Guerra-Castañon, Félix; Departamento de Ciencias Biológicas y Fisiológicas, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia. Lima-Perú. Facultad de Medicina, Universidad Peruana Cayetano Heredia. Lima-Perú.; Olcese-Mori, Paola; Laboratorio de Endocrinología y Reproducción, Facultad de Ciencias y Filosofía. Universidad Peruana Cayetano Heredia. Lima-Perú. Departamento de Ciencias Biológicas y Fisiológicas, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia. Lima-Perú.; Lozada, Iván; Laboratorio de Inmunología, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia. Lima-Perú. Departamento de Microbiología, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia. Lima-Perú.; Rubio, Julio; Laboratorio de Endocrinología y Reproducción, Facultad de Ciencias y Filosofía. Universidad Peruana Cayetano Heredia. Lima-Perú. Departamento de Ciencias Biológicas y Fisiológicas, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia. Lima-Perú. Instituto de Investigaciones de la Altura, Universidad Peruana Cayetano Heredia. Lima-Perú.; Gonzales, Carla; Laboratorio de Endocrinología y Reproducción, Facultad de Ciencias y Filosofía. Universidad Peruana Cayetano Heredia. Lima-Perú. Departamento de Ciencias Biológicas y Fisiológicas, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia. Lima-Perú. Instituto de Investigaciones de la Altura, Universidad Peruana Cayetano Heredia. Lima-Perú.; Gonzales, Gustavo F; Laboratorio de Endocrinología y Reproducción, Facultad de Ciencias y Filosofía. Universidad Peruana Cayetano Heredia. Lima-Perú. Departamento de Ciencias Biológicas y Fisiológicas, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia. Lima-Perú. Instituto de Investigaciones de la Altura, Universidad Peruana Cayetano Heredia. Lima-Perú.

    2014-01-01

    Objectives. Compare the effect of different doses of red maca on gamma interferon (IFN-γ) levels in ovariectomized rats (OVX). Materials and methods. Adult female rats were randomly divided into the following six groups: Group 1: pseudo-ovariectomized rats (PO); Group 2: OVX rats; Group 3: OVX rats treated with 4 ug/kg estradiol; and Group 4, 5 and 6: OVX rats treated with red maca extracts with 2.15, 4.3 and 8.6 mg polyphenols/body weight kilogram, respectively. Results. OVX rats showed low ...

  17. IFN-αα induced psoriatic arthritis and HCV-related liver cirrhosis. Therapeutic options and patient’s opinion

    Directory of Open Access Journals (Sweden)

    M. Piga

    2011-09-01

    Full Text Available Hepatitis C virus (HCV infection in the setting of Psoriatic Arthritis is an additional variable to be considered in the therapeutic approach to the disease because of the complications of an immunosuppressive treatment in the course of a chronic infection and the possible hepatotoxicity of many drugs conventionally used to treat psoriatic arthritis. The case reported explores the therapeutic options in a patient with IFN-α induced psoriatic arthritis, characterised by severe arthritis and psoriasis but also the concomitant presence of HCV chronic hepatitis, in light of the patient’s concerns

  18. Application of Mycobacterium Tuberculosis IFN-γresponses in Differential Diagnosis of Tuberculous Meningitis%结核杆菌IFN-γ在结核性脑膜炎鉴别诊断中的应用

    Institute of Scientific and Technical Information of China (English)

    林正豪; 曾剑锋; 刘国辉

    2013-01-01

    Objective To discuss clinical application of Mycobacterium tuberculosis antigen specific IFN-γresponses in antidiastole between tuberculous meningitis and cryptococal neoformans meningitis. Methods IFN-γresponses in peripheral blood of 13 patients with csf positive tuberculous meningitis , 15 patients with csf negative tuberculous meningitis and 11 patients with cryptococal neoformans meningitis were tested and then analyzed retrospectively. Results Positive IFN-γresponses were detected in 69.2%(9/13)of patients with csf positive tuberculous meningitis, 66.7%(10/15)of patients with csf negative tuberculous meningitis and 9.0%(1/11) of patients with cryptococal neoformans meningitis. IFN-γresponses in the three groups is statistically different(χ2=6.78,P=0.001). Through the comparison between the two two groups, IFN-γresponses positive rate between csf positive tuberculous meningitis patients and csf negative tuberculous meningitis patients is not statistically different(χ2=4.31,P=0.07). IFN-γresponses positive rate between csf positive tuberculous meningitis patients and cryptococal neoformans meningitis patients is statistically different(χ2=7.37,P=0.013). IFN-γresponses positive rate between csf negative tuberculous meningitis patients and cryptococal neoformans meningitis patients is statistically different(χ2=8.26,P=0.024).Conclusion IFN-γresponses in peripheral blood can be used as an assistant means to discriminate cryptococal neoformans meningitis from tuberculous meningitis.%  目的探讨外周血结核杆菌抗原特异性γ干扰素水平在结核性脑膜炎与隐球菌性脑膜炎鉴别诊断中的作用。方法回顾性分析本院13例菌阳结核性脑膜炎、15菌阴结核性脑膜炎及11例隐球菌性脑膜炎患者外周血结核杆菌抗原特异性γ干扰素水平差异。结果菌阳结核性脑膜炎患者外周血结核杆菌抗原特异性γ干扰素9例阳性,4例阴性,阳性率69.2%,菌阴结核性脑

  19. An illustration of the explanatory and discovery functions of proof

    Directory of Open Access Journals (Sweden)

    Michael de Villiers

    2012-11-01

    Full Text Available This article provides an illustration of the explanatory and discovery functions of proof with an original geometric conjecture made by a Grade 11 student. After logically explaining (proving the result geometrically and algebraically, the result is generalised to other polygons by further reflection on the proof(s. Different proofs are given, each giving different insights that lead to further generalisations. The underlying heuristic reasoning is carefully described in order to provide an exemplar for designing learning trajectories to engage students with these functions of proof.

  20. Geoillustrator - fast sketching of geological illustrations and animations

    Science.gov (United States)

    Patel, Daniel; Langeland, Tor; Solteszova, Veronika

    2014-05-01

    We present our research results in the Geoillustrator project. The project has been going for four years and is ending in March. It was aimed at developing a rapid sketching tool for generating geological illustrations and animations for understanding the processes that have led to a current subsurface configuration. The sketching tool facilitates effective dissemination of ideas, e.g. through generation of interactive geo-scientific illustrations for interdisciplinary communication and communication to decision makers, media and lay persons. This can improve work processes in early phases of oil and gas exploration where critical decisions have to be taken based on limited information. It is a challenge for involved specialists in early exploration phases to externalize their ideas, and effectively achieve consensus in multidisciplinary working groups. In these work processes, a tool for rapid sketching of geology would be very useful for expressing geological hypotheses and creating and comparing different evolution scenarios. Often, decisions are influenced by factors that are not relevant, e.g. the geologists who produce the most polished illustrations of their hypothesis have a higher probability for getting their theories through to decision makers as it is more clearly communicated. This results in a competitive advantage for geologists who are skilled in creating illustrations. Having a tool that would lift the ability of all geologists to express their ideas to an equal level would result in more alternatives and better foundation for decision making. Digital sketching will also allow capturing otherwise lost material which can constitute a large amount of mental work and ideas. The results of sketching are currently scrapped as paper or erased from the blackboard or exist only as rough personal sketches. By using a digital sketching tool, the sketches can be exported to a form usable in modelling tools used in later phases of exploration. Currently, no

  1. Parathyroid Carcinoma: A Review with Three Illustrative Cases

    Directory of Open Access Journals (Sweden)

    Antoine Digonnet, Adelaïde Carlier, Esther Willemse, Marie Quiriny, Cécile Dekeyser, Nicolas de Saint Aubain, Marc Lemort, Guy Andry

    2011-01-01

    Full Text Available Parathyroid carcinoma is a rare disease, which accounts for less than 1% of all case of primary hyperparathyroidism and is usually not detected until the time of surgery or thereafter. For most patients preoperative staging is not available. A radical excision remains the standard management; the place of adjuvant radiotherapy is not well established yet. Local recurrence and/or the metastases are unfortunately frequent. The present paper presents an up to date review of the literature illustrated by three clinical cases.

  2. Standard classification of uranium resources-an illustrative example

    International Nuclear Information System (INIS)

    Krishna, P.M.; Babitzke, H.R.; Curry, D.; Masters, C.D.; McCammon, R.B.; Noble, R.B.; Rodriguez, J.A.; Schanz, J.J.; Schreiber, H.W.

    1983-01-01

    An example illustrates the use of ASTM Standard E901-82, Classification System for Uranium Resources. The example demonstrates the dynamic nature of the process of classification and attests to the necessity of addressing both the aggregate needs of broad-scale resource planning and the specific needs of individual property evaluation. Problems that remain in fixing the classification of a given uranium resource include the uncertainty in estimating the quantity of undiscovered resources and resolving the differences that may exist in deciding when the drill-hole spacing is adequate to determine the tonnage and grade of discovered resources

  3. Illustrated Guide to Astronomical Wonders From Novice to Master Observer

    CERN Document Server

    Thompson, Robert

    2011-01-01

    With the advent of inexpensive, high-power telescopes priced at under 250, amateur astronomy is now within the reach of anyone, and this is the ideal book to get you started. The Illustrated Guide to Astronomical Wonders offers you a guide to the equipment you need, and shows you how and where to find hundreds of spectacular objects in the deep sky -- double and multiple stars as well as spectacular star clusters, nebulae, and galaxies. You get a solid grounding in the fundamental concepts and terminology of astronomy, and specific advice about choosing, buying, using, and maintaining the eq

  4. Google SketchUp Workshop Modeling, Visualizing, and Illustrating

    CERN Document Server

    Brixius, Laurent

    2010-01-01

    Discover the secrets of the Google SketchUp with the 16 real-world professional-level projects including parks, structures, concept art, and illustration. Google SketchUp Workshop includes all the wide variety of projects that SketchUp can be used for-architectural visualization, landscape design, video game and film conception, and more. SketchUp masters in every field will get you up to speed in this agile and intuitive software and then show you the real uses with through projects in architecture, engineering, and design. * Packed with 16 real-world Go

  5. Some risk factors in trampolining illustrated by six serious injuries.

    Science.gov (United States)

    Hammer, A.; Schwartzbach, A. L.; Paulev, P. E.

    1982-01-01

    Four case histories out of 75 significant trampoline injuries (from a total of 198 injuries re-examined) plus two recent accidents (1979) are presented, illustrating that the trampoline is posing an undue risk of serious injury. It is argued that the only single factor capable of preventing trampoline injuries is a trampoline ban. This is imperative in schools. Trampoline clubs are advised to reconsider the risk factors involved. Images p27-a p27-b p27-c Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 PMID:7066612

  6. Vocabulaire illustré 350 exercices : niveau moyen

    CERN Document Server

    Watcyn-Jones, Peter

    1995-01-01

    Cet ouvrage de vocabulaire illustré est conçu dans le même esprit que le niveau débutant auquel il fait suite. Il propose un travail stimulant et amusant pour approfondir son lexique, soit 1350 mots utiles et courants, rassemblés par thèmes (la maison, les magasins, les métiers, les animaux, le bricolage...) ou par catégories grammaticales. Il comprend des exercices d'apprentissage et d'élargissement, aussi bien pour les jeunes que pour les adultes. Un livret de corrigés est également disponible.

  7. Phylogeny mandalas for illustrating the Tree of Life.

    Science.gov (United States)

    Hasegawa, Masami

    2017-12-01

    A circular phylogeny with photos or drawings of species is named a phylogeny mandala. This is one of the ways for illustrating the Tree of Life, and is suitable to show visually how the biodiversity has developed in the course of evolution as clarified by the molecular phylogenetics. To demonstrate the recent progress of molecular phylogenetics, six phylogeny mandalas for various taxonomic groups of life were presented; i.e., (1) Eukaryota, (2) Metazoa, (3) Hexapoda, (4) Tetrapoda, (5) Eutheria, and (6) Primates. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. STS-49 ASEM activities illustrated with PLAID computer graphics

    Science.gov (United States)

    1992-01-01

    STS-49 Endeavour, Orbiter Vehicle (OV) 105, Assembly of Station by Extravehicular Activity (EVA) Methods (ASEM) activities are illustrated with PLAID computer graphics. Two extravehicular mobility unit (EMU) suited crewmembers work on multipurpose experiment support structure (MPESS) (with legs attached) grappled by remote manipulator system (RMS) end effector and positioned in the over-the-nose location (above OV-105's crew compartment). This position has been designated as the assembly area for Space Station Freedom (SSF). This procedure will evaluate the ability to use the RMS to position MPESS carrier and EVA crewmembers forward and above the PLB.

  9. Barrier Data Base user's guide

    International Nuclear Information System (INIS)

    Worrell, R.B.; Gould, D.J.; Wall, D.W.

    1977-06-01

    A special purpose data base for physical security barriers has been developed. In addition to barriers, the entities accommodated by the Barrier Data Base (BDB) include threats and references. A threat is established as a configuration of people and equipment which has been employed to penetrate (or attempt to penetrate) a barrier. References are used to cite publications pertinent to the barriers and threats in the data base. Utilization and maintenance of the Barrier Data Base is achieved with LIST, QUERY, ENTER, DELETE, and CHANGE commands which are used to manipulate the data base entities

  10. IRF-3, IRF-5, and IRF-7 coordinately regulate the type I IFN response in myeloid dendritic cells downstream of MAVS signaling.

    Directory of Open Access Journals (Sweden)

    Helen M Lazear

    2013-01-01

    Full Text Available Although the transcription factors IRF-3 and IRF-7 are considered master regulators of type I interferon (IFN induction and IFN stimulated gene (ISG expression, Irf3(-/-×Irf7(-/- double knockout (DKO myeloid dendritic cells (mDC produce relatively normal levels of IFN-β after viral infection. We generated Irf3(-/-×Irf5(-/-×Irf7(-/- triple knockout (TKO mice to test whether IRF-5 was the source of the residual induction of IFN-β and ISGs in mDCs. In pathogenesis studies with two unrelated positive-sense RNA viruses (West Nile virus (WNV and murine norovirus, TKO mice succumbed at rates greater than DKO mice and equal to or approaching those of mice lacking the type I IFN receptor (Ifnar(-/-. In ex vivo studies, after WNV infection or exposure to Toll-like receptor agonists, TKO mDCs failed to produce IFN-β or express ISGs. In contrast, this response was sustained in TKO macrophages following WNV infection. To define IRF-regulated gene signatures, we performed microarray analysis on WNV-infected mDC from wild type (WT, DKO, TKO, or Ifnar(-/- mice, as well as from mice lacking the RIG-I like receptor adaptor protein MAVS. Whereas the gene induction pattern in DKO mDC was similar to WT cells, remarkably, almost no ISG induction was detected in TKO or Mavs(-/- mDC. The relative equivalence of TKO and Mavs(-/- responses suggested that MAVS dominantly regulates ISG induction in mDC. Moreover, we showed that MAVS-dependent induction of ISGs can occur through an IRF-5-dependent yet IRF-3 and IRF-7-independent pathway. Our results establish IRF-3, -5, and -7 as the key transcription factors responsible for mediating the type I IFN and ISG response in mDC during WNV infection and suggest a novel signaling link between MAVS and IRF-5.

  11. The C proteins of human parainfluenza virus type 1 block IFN signaling by binding and retaining Stat1 in perinuclear aggregates at the late endosome.

    Directory of Open Access Journals (Sweden)

    Henrick Schomacker

    Full Text Available Interferons (IFNs play a crucial role in the antiviral immune response. Whereas the C proteins of wild-type human parainfluenza virus type 1 (WT HPIV1 inhibit both IFN-β induction and signaling, a HPIV1 mutant encoding a single amino acid substitution (F170S in the C proteins is unable to block either host response. Here, signaling downstream of the type 1 IFN receptor was examined in Vero cells to define at what stage WT HPIV1 can block, and F170S HPIV1 fails to block, IFN signaling. WT HPIV1 inhibited phosphorylation of both Stat1 and Stat2, and this inhibition was only slightly reduced for F170S HPIV1. Degradation of Stat1 or Stat2 was not observed. The HPIV1 C proteins were found to accumulate in the perinuclear space, often forming large granules, and co-localized with Stat1 and the cation-independent mannose 6-phosphate receptor (M6PR that is a marker for late endosomes. Upon stimulation with IFN-β, both the WT and F170S C proteins remained in the perinuclear space, but only the WT C proteins prevented Stat1 translocation to the nucleus. In addition, WT HPIV1 C proteins, but not F170S C proteins, co-immunoprecipitated both phosphorylated and unphosphorylated Stat1. Our findings suggest that the WT HPIV1 C proteins form a stable complex with Stat1 in perinuclear granules that co-localize with M6PR, and that this direct interaction between the WT HPIV1 C proteins and Stat1 is the basis for the ability of HPIV1 to inhibit IFN signaling. The F170S mutation in HPIV1 C did not prevent perinuclear co-localization with Stat1, but apparently weakened this interaction such that, upon IFN stimulation, Stat1 was translocated to the nucleus to induce an antiviral response.

  12. PCBP2 enhances the antiviral activity of IFN-α against HCV by stabilizing the mRNA of STAT1 and STAT2.

    Directory of Open Access Journals (Sweden)

    Zhongshuai Xin

    Full Text Available Interferon-α (IFN-α is a natural choice for the treatment of hepatitis C, but half of the chronically infected individuals do not achieve sustained clearance of hepatitis C virus (HCV during treatment with IFN-α alone. The virus can impair IFN-α signaling and cellular factors that have an effect on the viral life cycles. We found that the protein PCBP2 is down-regulated in HCV-replicon containing cells (R1b. However, the effects and mechanisms of PCBP2 on HCV are unclear. To determine the effect of PCBP2 on HCV, overexpression and knockdown of PCBP2 were performed in R1b cells. Interestingly, we found that PCBP2 can facilitate the antiviral activity of IFN-α against HCV, although the RNA level of HCV was unaffected by either the overexpression or absence of PCBP2 in R1b cells. RIP-qRT-PCR and RNA half-life further revealed that PCBP2 stabilizes the mRNA of STAT1 and STAT2 through binding the 3'Untranslated Region (UTR of these two molecules, which are pivotal for the IFN-α anti-HCV effect. RNA pull-down assay confirmed that there were binding sites located in the C-rich tracts in the 3'UTR of their mRNAs. Stabilization of mRNA by PCBP2 leads to the increased protein expression of STAT1 and STAT2 and a consistent increase of phosphorylated STAT1 and STAT2. These effects, in turn, enhance the antiviral effect of IFN-α. These findings indicate that PCBP2 may play an important role in the IFN-α response against HCV and may benefit the HCV clinical therapy.

  13. Vulnerability of multiple-barrier systems

    International Nuclear Information System (INIS)

    Lind, N.C.

    1996-01-01

    'Vulnerability' is defined as the ratio of the probability of failure of a damaged system to the probability of failure of the undamaged system. This definition applies to all engineered systems and can be specialized to particular system types. Some disastrous failures (e.g., Chernobyl) have shown that systems can be highly vulnerable. open-quotes Defense in depthclose quotes is a powerful design principle, reducing vulnerability when the consequences of failure can be catastrophic. In the nuclear industry, defense in depth is widely used in radiation protection, reactor control, and shutdown systems. A multiple-barrier system is a simple example of a system that has defense in depth. The idea is that the system is not vulnerable. It cannot fail if one barrier fails because there is another to take its place. This idea is untenable in waste management, but a quantified vulnerability of a system can help owners, designers, and regulators decide how much defense in depth is desirable or enough. Many multiple-barrier systems can be modeled as systems of components physically in a series, each individually able to prevent failure. Components typically have bimodal distributions of the service time to failure, as illustrated by an example of application to a hypothetical nuclear fuel waste repository

  14. Silencing of IFN-stimulated gene transcription is regulated by histone H1 and its chaperone TAF-I.

    Science.gov (United States)

    Kadota, Shinichi; Nagata, Kyosuke

    2014-07-01

    Chromatin structure and its alteration play critical roles in the regulation of transcription. However, the transcriptional silencing mechanism with regard to the chromatin structure at an unstimulated state of the interferon (IFN)-stimulated gene (ISG) remains unclear. Here we investigated the role of template activating factor-I (TAF-I, also known as SET) in ISG transcription. Knockdown (KD) of TAF-I increased ISG transcript and simultaneously reduced the histone H1 level on the ISG promoters during the early stages of transcription after IFN stimulation from the unstimulated state. The transcription factor levels on the ISG promoters were increased in TAF-I KD cells only during the early stages of transcription. Furthermore, histone H1 KD also increased ISG transcript. TAF-I and histone H1 double KD did not show the additive effect in ISG transcription, suggesting that TAF-I and histone H1 may act on the same regulatory pathway to control ISG transcription. In addition, TAF-I KD and histone H1 KD affected the chromatin structure near the ISG promoters. On the basis of these findings, we propose that TAF-I and its target histone H1 are key regulators of the chromatin structure at the ISG promoter to maintain the silent state of ISG transcription. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  15. Severe fever with thrombocytopenia syndrome virus inhibits exogenous Type I IFN signaling pathway through its NSs invitro.

    Science.gov (United States)

    Chen, Xu; Ye, Haiyan; Li, Shilin; Jiao, Baihai; Wu, Jianqin; Zeng, Peibin; Chen, Limin

    2017-01-01

    Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus (SFTS virus, SFTSV). At present there is still no specific antiviral treatment for SFTSV; To understand which cells support SFTSV life cycle and whether SFTSV infection activates host innate immunity, four different cell lines (Vero, Hela, Huh7.5.1, and Huh7.0) were infected with SFTSV. Intracellular/extracellular viral RNA and expression of IFNα, and IFNß were detected by real-time RT- PCR following infection. To confirm the role of non-structural protein (NSs) of SFTSV in exogenous IFNα-induced Jak/STAT signaling, p-STAT1 (Western Blot), ISRE activity (Luciferase assay) and ISG expression (real-time PCR) were examined following IFNα stimulation in the presence or absence of over-expression of NSs in Hela cells. Our study showed that all the four cell lines supported SFTSV life cycle and SFTSV activated host innate immunity to produce type I IFNs in Hela cells but not in Huh7.0, Huh7.5.1 or Vero cells. NSs inhibited exogenous IFNα-induced Jak/STAT signaling as shown by decreased p-STAT1 level, suppressed ISRE activity and down-regulated ISG expression. Suppression of the exogenous Type I IFN-induced Jak/STAT signaling by NSs might be one of the mechanisms of SFTSV to evade host immune surveillance.

  16. CYLD Proteolysis Protects Macrophages from TNF-Mediated Auto-necroptosis Induced by LPS and Licensed by Type I IFN

    Directory of Open Access Journals (Sweden)

    Diana Legarda

    2016-06-01

    Full Text Available Tumor necrosis factor (TNF induces necroptosis, a RIPK3/MLKL-dependent form of inflammatory cell death. In response to infection by Gram-negative bacteria, multiple receptors on macrophages, including TLR4, TNF, and type I IFN receptors, are concurrently activated, but it is unclear how they crosstalk to regulate necroptosis. We report that TLR4 activates CASPASE-8 to cleave and remove the deubiquitinase cylindromatosis (CYLD in a TRIF- and RIPK1-dependent manner to disable necroptosis in macrophages. Inhibiting CASPASE-8 leads to CYLD-dependent necroptosis caused by the TNF produced in response to TLR4 ligation. While lipopolysaccharides (LPS-induced necroptosis was abrogated in Tnf−/− macrophages, a soluble TNF antagonist was not able to do so in Tnf+/+ macrophages, indicating that necroptosis occurs in a cell-autonomous manner. Surprisingly, TNF-mediated auto-necroptosis of macrophages requires type I IFN, which primes the expression of key necroptosis-signaling molecules, including TNFR2 and MLKL. Thus, the TNF necroptosis pathway is regulated by both negative and positive crosstalk.

  17. Geophysical characterization of subsurface barriers

    International Nuclear Information System (INIS)

    Borns, D.J.

    1995-08-01

    An option for controlling contaminant migration from plumes and buried waste sites is to construct a subsurface barrier of a low-permeability material. The successful application of subsurface barriers requires processes to verify the emplacement and effectiveness of barrier and to monitor the performance of a barrier after emplacement. Non destructive and remote sensing techniques, such as geophysical methods, are possible technologies to address these needs. The changes in mechanical, hydrologic and chemical properties associated with the emplacement of an engineered barrier will affect geophysical properties such a seismic velocity, electrical conductivity, and dielectric constant. Also, the barrier, once emplaced and interacting with the in situ geologic system, may affect the paths along which electrical current flows in the subsurface. These changes in properties and processes facilitate the detection and monitoring of the barrier. The approaches to characterizing and monitoring engineered barriers can be divided between (1) methods that directly image the barrier using the contrasts in physical properties between the barrier and the host soil or rock and (2) methods that reflect flow processes around or through the barrier. For example, seismic methods that delineate the changes in density and stiffness associated with the barrier represents a direct imaging method. Electrical self potential methods and flow probes based on heat flow methods represent techniques that can delineate the flow path or flow processes around and through a barrier

  18. ADOBE ILLUSTRATOR AND GIMP - AN APPROACH TO GARMENT DESIGN

    Directory of Open Access Journals (Sweden)

    INDRIE Liliana

    2016-05-01

    Full Text Available Designing clothes has become easier with the use of clothing design software. One of the most popular and basic software made for garments design is Adobe Illustrator. It enables designers and small to medium businesses to create clothing designs with easy access to all assets, including images, colors, brushes, and type styles. While Illustrator has all the necessary elements and features that are ideal for creating designer clothing, GIMP provides basic set of tools for image editing. When used in combination with one another, these two programs provide just about all the tools an apparel designer needs to draw fashion design sketches, technical flat sketches, CAD presentations, graphic artworks, design embroideries etc. In this paper we show how to use the instruments of those two software in order to draw a woman jacket’s garments components and to fill with texture the jacket created. By utilizing Illustrator’s Symbol we created libraries of jacket components (puller zipper, label, then the brushes to design the zipper detail. Finally, by a drag and drop we added the zipper, the zipper puller and the label. GIMP gave us access to precise fabric textures which make our output so realistic that you can almost touch the fabric.

  19. DEVELOPING CEFR ILLUSTRATIVE DESCRIPTORS OF ASPECTS OF MEDIATION

    Directory of Open Access Journals (Sweden)

    Brian North

    2016-04-01

    Full Text Available This article reports on a project commissioned and coordinated by the Council of Europe to develop descriptors for the category ‘Mediation’ in the Common European Framework of Reference for Languages. Mediation is the fourth communicative language activity presented in CEFR Chapter 4, complementing reception, interaction and production. Descriptors for mediation had not been developed in the 1993–6 Swiss National Research Project that produced the original set of illustrative descriptors for the CEFR. The work took place in the context of a wider 2013–6 project to provide an extended set of CEFR illustrative descriptors. The article describes the way in which the approach taken to mediation in the project is broader than the one taken in the presentation of mediation in the CEFR text in 2001. In addition to information transfer (conveying received information the new scheme also embraces the construction of meaning and relational mediation: the process of establishing and managing interpersonal relationships in order to create a positive, collaborative environment. Descriptors were also developed for other, related, areas. The article briefly summarises the three phases of validation to which the draft descriptors were subjected before being calibrated to the mathematic scale underlying the CEFR’s levels and descriptors.

  20. The Bobath concept - a model to illustrate clinical practice.

    Science.gov (United States)

    Michielsen, Marc; Vaughan-Graham, Julie; Holland, Ann; Magri, Alba; Suzuki, Mitsuo

    2017-12-17

    The model of Bobath clinical practice provides a framework identifying the unique aspects of the Bobath concept in terms of contemporary neurological rehabilitation. The utilisation of a framework to illustrate the clinical application of the Bobath concept provides the basis for a common understanding with respect to Bobath clinical practice, education, and research. The development process culminating in the model of Bobath clinical practice is described. The use of the model in clinical practice is illustrated using two cases: a client with a chronic incomplete spinal cord injury and a client with a stroke. This article describes the clinical application of the Bobath concept in terms of the integration of posture and movement with respect to the quality of task performance, applying the Model of Bobath Clinical Practice. Facilitation, a key aspect of Bobath clinical practice, was utilised to positively affect motor control and perception in two clients with impairment-related movement problems due to neurological pathology and associated activity limitations and participation restrictions - the outcome measures used to reflect the individual clinical presentation. Implications for Rehabilitation The model of Bobath clinical practice provides a framework identifying the unique aspects of the Bobath-concept. The model of Bobath clinical practice provides the basis for a common understanding with respect to Bobath clinical practice, education, and research. The clinical application of the Bobath-concept highlights the integration of posture and movement with respect to the quality of task performance. Facilitation, a key aspect of Bobath clinical practice, positively affects motor control, and perception.

  1. Practical illustration of the traditional vers. alternative LOCA embrittlement criteria

    International Nuclear Information System (INIS)

    Vrtilkova, V.; Novotny, L.; Hamouz, V.; Doucha, R.; Tinka, I.; Macek, J.; Lahovsky, F.

    2005-01-01

    Evaluation of LOCA time behaviour is usually based on traditional embrittlement criterion, represented by the equivalent cladding reacted (ECR) limit 17 % (18 %) at the peak cladding temperature below 1204 0 C (1200 0 C). From different existing correlations for evaluation the ECR, the correlations of Baker-Just, Cathcart and VNIINM (Bibilashvili) are discussed here. Results, obtained by these correlations, are illustrated for typical and atypical LOCA courses analysed for the WWER 440 plant. An approach to assess these correlations from the viewpoint of violation of the observed criterion is presented. This approach is based on determination of the temperature vers. time of exposition, when the criterion limit is reached. Reasons leading to necessity of alternative criterion proposal are summarised. This criterion for LOCA events evaluation, including corresponding correlation, is proposed on the basis of the long-term experimental research of cladding materials at UJP Praha. The computational results, obtained according to this alternative criterion, are illustrated for the same courses of LOCA events as for traditional criteria and traditional correlations. Proposed criterion is also confronted with the other discussed criteria in accordance with mentioned approach presented in this paper. The characteristic experimental results and key findings are summarised. They substantiate and support the proposed alternative criterion. An advantage of the criterion is its independence on ECR, on hydrogen and oxygen content and on oxidation history, and its applicability to current Zr-based alloy cladding materials as well. This applicability is kept while preserving the simplicity of the criterion using. (author)

  2. Chaotic correlations in barrier billiards with arbitrary barriers

    International Nuclear Information System (INIS)

    Osbaldestin, A H; Adamson, L N C

    2013-01-01

    We study autocorrelation functions in symmetric barrier billiards for golden mean trajectories with arbitrary barriers. Renormalization analysis reveals the presence of a chaotic invariant set and thus that, for a typical barrier, there are chaotic correlations. The chaotic renormalization set is the analogue of the so-called orchid that arises in a generalized Harper equation. (paper)

  3. Limitations of Using IL-17A and IFN-γ-Induced Protein 10 to Detect Bovine Tuberculosis

    Science.gov (United States)

    Xin, Ting; Gao, Xintao; Yang, Hongjun; Li, Pingjun; Liang, Qianqian; Hou, Shaohua; Sui, Xiukun; Guo, Xiaoyu; Yuan, Weifeng; Zhu, Hongfei; Ding, Jiabo; Jia, Hong

    2018-01-01

    Bovine tuberculosis (bTB) is primarily caused by infection with Mycobacterium bovis, which belongs to the Mycobacterium tuberculosis complex. The airborne route is considered the most common for transmission of M. bovis, and more than 15% of cattle with bTB shed the Mycobacterium, which can be detect by nested PCR to amplify mycobacterial mpb70 from a nasal swab from a cow. To screen for cytokines fostering early and accurate detection of bTB, peripheral blood mononuclear cells were isolated from naturally M. bovis-infected, experimentally M. bovis 68002-infected, and uninfected cattle, then these cells were stimulated by PPD-B, CFP-10-ESAT-6 (CE), or phosphate-buffered saline (PBS) for 6 h. The levels of interferon gamma (IFN-γ), IFN-γ-induced protein 10 (IP-10), IL-6, IL-12, IL-17A, and tumor necrosis factor alpha mRNA were measured using real-time PCR. To explore the cytokines associated with different periods of M. bovis infection, cattle were divided into three groups: PCR-positive, PCR-negative, and uninfected using the tuberculin skin test, CFP-10/ESAT-6/TB10.4 protein cocktail-based skin test, IFN-γ release assay (IGRA), CFP-10/ESAT-6 (CE)-based IGRA, and nested PCR. The expression of IP-10, IL-17A, and IFN-γ proteins induced by PPD-B, CE, or PBS was detected by ELISA. The results showed that levels of PPD-B-stimulated IL-17A and IP-10 (mRNA and protein), and CE-induced IP-10 (mRNA and protein) were significantly higher in cattle naturally or experimentally infected with M. bovis than in those that were uninfected. The levels of PPD-B- or CE-induced IL-17A and IP-10 (protein) could be used to differentiate M. bovis-infected calves from uninfected ones for 6 to 30 weeks post-infection, whereas PPD-B- and CE-induced IP-10 and IL-17A mRNA expression could be used to differentiate M. bovis-infected calves from uninfected ones between 6 and 58 weeks post-infection. However, CE-induced IL-17A (protein) was not a reliable indicator of M. bovis infection

  4. Design of engineered sorbent barriers

    International Nuclear Information System (INIS)

    Jones, E.O.; Freeman, H.D.

    1988-08-01

    A sorbent barrier uses sorbent material such as activated carbon or natural zeolites to prevent the migration of radionuclides from a low-level waste site to the aquifer. The sorbent barrier retards the movement of radioactive contaminants, thereby providing time for the radionuclides to decay. Sorbent barriers can be a simple, effective, and inexpensive method for reducing the migration of radionuclides to the environment. Designing a sorbent barrier consists of using soil and sorbent material properties and site conditions as input to a model which will determine the necessary sorbent barrier thickness to meet contaminant limits. The paper will cover the following areas: techniques for measuring sorption properties of barrier materials and underlying soils, use of a radionuclide transport model to determine the required barrier thickness and performance under a variety of site conditions, and cost estimates for applying the barrier. 8 refs., 6 figs., 1 tab

  5. Design of engineered sorbent barriers

    International Nuclear Information System (INIS)

    Jones, E.O.; Freeman, H.D.

    1988-01-01

    A sorbent barrier uses sorbent material such as activated carbon or natural zeolites to prevent the migration of radionuclides from a low-level waste site to the aquifer. The sorbent barrier retards the movement of radioactive contaminants, thereby providing time for the radionuclides to decay. Sorbent barriers can be a simple, effective, and inexpensive method for reducing the migration of radionuclides to the environment. Designing a sorbent barrier consists of using soil and sorbent material properties and site conditions as input to a model which will determine the necessary sorbent barrier thickness to meet contaminant limits. The paper covers the following areas: techniques for measuring sorption properties of barrier materials and underlying soils, use of a radionuclide transport model to determine the required barrier thickness and performance under a variety of site conditions, and cost estimates for applying the barrier

  6. HIV-1 Promotes the Degradation of Components of the Type 1 IFN JAK/STAT Pathway and Blocks Anti-viral ISG Induction.

    Science.gov (United States)

    Gargan, Siobhan; Ahmed, Suaad; Mahony, Rebecca; Bannan, Ciaran; Napoletano, Silvia; O'Farrelly, Cliona; Borrow, Persephone; Bergin, Colm; Stevenson, Nigel J

    2018-04-01

    Anti-retroviral therapy successfully suppresses HIV-1 infection, but fails to provide a cure. During infection Type 1 IFNs normally play an essential role in viral clearance, but in vivo IFN-α only has a modest impact on HIV-1 infection, suggesting its possible targeting by HIV. Here, we report that the HIV protein, Vif, inhibits effective IFN-α signalling via degradation of essential JAK/STAT pathway components. We found that STAT1 and STAT3 are specifically reduced in HEK293T cells expressing Vif and that full length, infectious HIV-1 IIIB strain promotes their degradation in a Vif-dependent manner. HIV-1 IIIB infection of myeloid ThP-1 cells also reduced the IFN-α-mediated induction of the anti-viral gene, ISG15, but not MxA, revealing a functional consequence of this HIV-1-mediated immune evasion strategy. Interestingly, while total STAT levels were not reduced upon in vitro IIIB infection of primary human PBMCs, IFN-α-mediated phosphorylation of STAT1 and STAT3 and ISG induction were starkly reduced, with removal of Vif (IIIBΔVif), partially restoring pSTATs, ISG15 and MxB induction. Similarly, pSTAT1 and pSTAT3 expression and IFN-α-induced ISG15 were reduced in PBMCs from HIV-infected patients, compared to healthy controls. Furthermore, IFN-α pre-treatment of a CEM T lymphoblast cells significantly inhibited HIV infection/replication (measured by cellular p24), only in the absence of Vif (IIIBΔVif), but was unable to suppress full length IIIB infection. When analysing the mechanism by which Vif might target the JAK/STAT pathway, we found Vif interacts with both STAT1 and STAT3, (but not STAT2), and its expression promotes ubiquitination and MG132-sensitive, proteosomal degradation of both proteins. Vif's Elongin-Cullin-SOCS-box binding motif enables the formation of an active E3 ligase complex, which we found to be required for Vif's degradation of STAT1 and STAT3. In fact, the E3 ligase scaffold proteins, Cul5 and Rbx2, were also found to be

  7. ifn-γ-dependent secretion of IL-10 from Th1 cells and microglia/macrophages contributes to functional recovery after spinal cord injury

    Science.gov (United States)

    Ishii, H; Tanabe, S; Ueno, M; Kubo, T; Kayama, H; Serada, S; Fujimoto, M; Takeda, K; Naka, T; Yamashita, T

    2013-01-01

    Transfer of type-1 helper T-conditioned (Th1-conditioned) cells promotes functional recovery with enhanced axonal remodeling after spinal cord injury (SCI). This study explored the molecular mechanisms underlying the beneficial effects of pro-inflammatory Th1-conditioned cells after SCI. The effect of Th1-conditioned cells from interferon-γ (ifn-γ) knockout mice (ifn-γ−/− Th1 cells) on the recovery after SCI was reduced. Transfer of Th1-conditioned cells led to the activation of microglia (MG) and macrophages (MΦs), with interleukin 10 (IL-10) upregulation. This upregulation of IL-10 was reduced when ifn-γ−/− Th1 cells were transferred. Intrathecal neutralization of IL-10 in the spinal cord attenuated the effects of Th1-conditioned cells. Further, IL-10 is robustly secreted from Th1-conditioned cells in an ifn-γ-dependent manner. Th1-conditioned cells from interleukin 10 knockout (il-10−/−) mice had no effects on recovery from SCI. These findings demonstrate that ifn-γ-dependent secretion of IL-10 from Th1 cells, as well as native MG/MΦs, is required for the promotion of motor recovery after SCI. PMID:23828573

  8. Inflammatory impact of IFN-γ in CD8+ T cell-mediated lung injury is mediated by both Stat1-dependent and -independent pathways

    Science.gov (United States)

    Ramana, Chilakamarti V.; DeBerge, Matthew P.; Kumar, Aseem; Alia, Christopher S.; Durbin, Joan E.

    2015-01-01

    Influenza infection results in considerable pulmonary pathology, a significant component of which is mediated by CD8+ T cell effector functions. To isolate the specific contribution of CD8+ T cells to lung immunopathology, we utilized a nonviral murine model in which alveolar epithelial cells express an influenza antigen and injury is initiated by adoptive transfer of influenza-specific CD8+ T cells. We report that IFN-γ production by adoptively transferred influenza-specific CD8+ T cells is a significant contributor to acute lung injury following influenza antigen recognition, in isolation from its impact on viral clearance. CD8+ T cell production of IFN-γ enhanced lung epithelial cell expression of chemokines and the subsequent recruitment of inflammatory cells into the airways. Surprisingly, Stat1 deficiency in the adoptive-transfer recipients exacerbated the lung injury that was mediated by the transferred influenza-specific CD8+ T cells but was still dependent on IFN-γ production by these cells. Loss of Stat1 resulted in sustained activation of Stat3 signaling, dysregulated chemokine expression, and increased infiltration of the airways by inflammatory cells. Taken together, these data identify important roles for IFN-γ signaling and Stat1-independent IFN-γ signaling in regulating CD8+ T cell-mediated acute lung injury. This is the first study to demonstrate an anti-inflammatory effect of Stat1 on CD8+ T cell-mediated lung immunopathology without the complication of differences in viral load. PMID:25617378

  9. Astragalus root and elderberry fruit extracts enhance the IFN-β stimulatory effects of Lactobacillus acidophilus in murine-derived dendritic cells.

    Directory of Open Access Journals (Sweden)

    Hanne Frøkiær

    Full Text Available Many foods and food components boost the immune system, but little data are available regarding the mechanisms by which they do. Bacterial strains have disparate effects in stimulating the immune system. In dendritic cells, the gram-negative bacteria Escherichia coli upregulates proinflammatory cytokines, whereas gram-positive Lactobacillus acidophilus induces a robust interferon (IFN-β response. The immune-modulating effects of astragalus root and elderberry fruit extracts were examined in bone marrow-derived murine dendritic cells that were stimulated with L. acidophilus or E. coli. IFN-β and other cytokines were measured by ELISA and RT-PCR. Endocytosis of fluorescence-labeled dextran and L. acidophilus in the presence of elderberry fruit or astragalus root extract was evaluated in dendritic cells. Our results show that both extracts enhanced L. acidophilus-induced IFN-β production and slightly decreased the proinflammatory response to E. coli. The enhanced IFN-β production was associated with upregulation of toll-like receptor 3 and to a varying degree, the cytokines IL-12, IL-6, IL-1β and TNF-α. Both extracts increased endocytosis in immature dendritic cells, and only slightly influenced the viability of the cells. In conclusion, astragalus root and elderberry fruit extracts increase the IFN-β inducing activity of L. acidophilus in dendritic cells, suggesting that they may exert antiviral and immune-enhancing activity.

  10. Expression of IFN-Inducible Genes with Antiviral Function OAS1 and MX1 in Health and under Conditions of Recurrent Herpes Simplex Infection.

    Science.gov (United States)

    Karaulov, A V; Shulzhenko, A E; Karsonova, A V

    2017-07-01

    We studied the expression of IFN-inducible genes OAS1 and Mx1 in lysates of peripheral blood mononuclear cells from patients suffering from recurrent Herpes simplex infections in comparison with healthy people. To induce the expression of the studied genes, blood mononuclears were incubated with recombinant IFN-α2b in concentrations of 1, 10, and 100 U/ml for 3 h and then the content of the studied transcripts was evaluated. Relative expression of OAS1 and Mx1 in patients with recurrent forms of Herpes simplex both during the acute stage and clinical remission did not differ significantly from that in healthy people after stimulation with IFN-α2b in a concentration of 1 U/ml and in higher concentrations (10 and 100 U/ml). It was concluded that intracellular signal transduction in IFN-α-activated cells in vitro was not disturbed in patients with recurrent forms of Herpes simplex infection. Thus, the reported phenomenon of IFN-signalling distortion by Herpes simplex virus proteins observed in experiments on model cell lines infected with Herpes simplex virus was not confirmed in our experiments on peripheral blood mononuclear cells from patients with Herpes simplex infection.

  11. Characterisation of vaccine-induced, broadly cross-reactive IFN-γ secreting T cell responses that correlate with rapid protection against classical swine fever virus.

    Science.gov (United States)

    Graham, Simon P; Haines, Felicity J; Johns, Helen L; Sosan, Olubukola; La Rocca, S Anna; Lamp, Benjamin; Rümenapf, Till; Everett, Helen E; Crooke, Helen R

    2012-04-05

    Live attenuated C-strain classical swine fever viruses (CSFV) provide a rapid onset of protection, but the lack of a serological test that can differentiate vaccinated from infected animals limits their application in CSF outbreaks. Since immunity may precede antibody responses, we examined the kinetics and specificity of peripheral blood T cell responses from pigs vaccinated with a C-strain vaccine and challenged after five days with a genotypically divergent CSFV isolate. Vaccinated animals displayed virus-specific IFN-γ responses from day 3 post-challenge, whereas, unvaccinated challenge control animals failed to mount a detectable response. Both CD4(+) and cytotoxic CD8(+) T cells were identified as the cellular source of IFN-γ. IFN-γ responses showed extensive cross-reactivity when T cells were stimulated with CSFV isolates spanning the major genotypes. To determine the specificity of these responses, T cells were stimulated with recombinant CSFV proteins and a proteome-wide peptide library from a related virus, BVDV. Major cross-reactive peptides were mapped on the E2 and NS3 proteins. Finally, IFN-γ was shown to exert potent antiviral effects on CSFV in vitro. These data support the involvement of broadly cross-reactive T cell IFN-γ responses in the rapid protection conferred by the C-strain vaccine and this information should aid the development of the next generation of CSFV vaccines. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

  12. Shottky-barrier formation

    International Nuclear Information System (INIS)

    Guines, F.; Sanchez-Dehesa, J.; Flores, F.

    1983-01-01

    In this paper a realistic selfconsistent calculation of an abrupt metal-semiconductor junction is presented by means of a tight-binding approach. A specific Si-Ag junction has been considered, and the charge neutrality level as well as the barrier height have been determined in good agreement with experiments. For a generaljunction it is shown that the interface properties depend essentially on the characteristics of the first metal layer and its interaction with the semiconductor. (Author) [pt

  13. Performance of engineered barriers

    International Nuclear Information System (INIS)

    Rajaram, V.; Dean, P.V.; McLellan, S.A.

    1997-01-01

    Engineered barriers, both vertical and horizontal, have been used to isolate hazardous wastes from contact, precipitation, surface water and groundwater. The primary objective of this study was to determine the performance of subsurface barriers installed throughout the U.S. over the past 20 years to contain hazardous wastes. Evaluation of Resource Conservation and Recovery Act (RCRA) Subtitle C or equivalent caps was a secondary objective. A nationwide search was launched to select hazardous waste sites at which vertical barrier walls and/or caps had been used as the containment method. None of the sites selected had an engineered floor. From an initial list of 130 sites, 34 sites were selected on the basis of availability of monitoring data for detailed analysis of actual field performance. This paper will briefly discuss preliminary findings regarding the design, construction quality assurance/construction quality control (CQA/CQC), and monitoring at the 34 sites. In addition, the short-term performance of these sites (less than 5 years) is presented since very little long-term performance data was available

  14. Fluctuations in Schottky barrier heights

    International Nuclear Information System (INIS)

    Mahan, G.D.

    1984-01-01

    A double Schottky barrier is often formed at the grain boundary in polycrystalline semiconductors. The barrier height is shown to fluctuate in value due to the random nature of the impurity positions. The magnitude of the fluctuations is 0.1 eV, and the fluctuations cause the barrier height measured by capacitance to differ from the one measured by electrical conductivity

  15. Regional migratory osteoporosis: a review illustrated by five cases

    International Nuclear Information System (INIS)

    Toms, A.P.; Marshall, T.J.; Becker, E.; Donell, S.T.; Lobo-Mueller, E.M.; Barker, T.

    2005-01-01

    Regional migratory osteoporosis is an uncommon self-limiting disease characterized by an arthralgia which migrates between the weight-bearing joints of the lower limb. The radiological features of the disease obtained by conventional radiography, CT, MRI and radionuclide scintigraphy are illustrated by means of five case reports. These range from the most common presentation of sequential, proximal to distal spread in the lower limb to the rare intra-articular form, and disease involving the axial skeleton is also recognized. Clinical and radiographical features often overlap with those of diseases such as transient osteoporosis of the hip and transient bone marrow oedema syndrome, which is reflected in confusing terminology. Histological sampling is usually unnecessary; the radiological features are characteristic and the histological findings are not specific. Regional migratory osteoporosis is associated with systemic osteoporosis. This association is probably under-recognized, and has implications for the pathophysiology of the disease and for treatment

  16. Avoidant restrictive food intake disorder: an illustrative case example.

    Science.gov (United States)

    Bryant-Waugh, Rachel

    2013-07-01

    Avoidant/restrictive food intake disorder (ARFID) is a new diagnostic category in DSM-5. Although replacing Feeding Disorder of Infancy or Early Childhood, it is not restricted to childhood presentations. In keeping with the broader aim of revising and updating criteria and text to better reflect lifespan issues and clinical expression across the age range, ARFID is a diagnosis relevant to children, adolescents, and adults. This case example of a 13-year old boy with ARFID illustrates key issues in diagnosis and treatment planning. The issues discussed are not exhaustive, but serve as a guide for central diagnostic and treatment issues to be considered by the clinician. It is anticipated that the inclusion of specific criteria for ARFID as a category within Feeding and Eating Disorders in DSM-5 will stimulate research into its typology, prevalence, and incidence in different populations and facilitate the development of effective, evidence-based interventions for this patient group. Copyright © 2013 Wiley Periodicals, Inc.

  17. Translation Collective and Illustration: aesthetic film creation from Jane Austen

    Directory of Open Access Journals (Sweden)

    Lemuel da Cruz Gandara

    2015-08-01

    Full Text Available http://dx.doi.org/10.5007/2175-7917.2015v20n2p67 From metonymic clippings of the novels Sense and Sensibility (1811, Pride and Prejudice (1813, Emma (1815 and Persuasion (1817, all written by the English author Jane Austen (1775-1817, we propose a comparative analysis among the literary texts, the illustrations by Hugh Thomson at the end of the nineteenth century and the film footage created between 1995 and 2005. Our goal is to confront tickets to find similarities and differences dialogic between them. This perspective reveals the interpretations made by many readers over the years and the receptions of the English writer in different contexts and media. Our critical and theoretical reflection is based on studies of the Russian philosopher Mikhail Bakhtin about the aesthetics of literary creation and amplifies the concepts of literary cinema, collective translation and aesthetics of film creation.

  18. Architecture Views Illustrating the Service Automation Aspect of SOA

    Science.gov (United States)

    Gu, Qing; Cuadrado, Félix; Lago, Patricia; Duenãs, Juan C.

    Earlier in this book, Chapter 8 provided a detailed analysis of service engineering, including a review of service engineering techniques and methodologies. This chapter is closely related to Chapter 8 as shows how such approaches can be used to develop a service, with particular emphasis on the identification of three views (the automation decision view, degree of service automation view and service automation related data view) that structure and ease elicitation and documentation of stakeholders' concerns. This is carried out through two large case studies to learn the industrial needs in illustrating services deployment and configuration automation. This set of views adds to the more traditional notations like UML, the visual power of attracting the attention of their users to the addressed concerns, and assist them in their work. This is especially crucial in service oriented architecting where service automation is highly demanded.

  19. Orthognathic Surgery: Planning and treatment with illustration on six cases

    International Nuclear Information System (INIS)

    AiRuhaimi, K; Nwoku, A. L; Shaikh, H. S

    1991-01-01

    Almost all conferences for plastic and maxillofacial surgery discuss reports on several methods of orthognathic surgery, planning, success results, and complications of the different procedures carried out to correct patient's soft and hard tissues frontal profiles and occlusal discrepancies. Various principles are involved in the diagnosis and treatment of facial deformities. However, the most important consideration, after all, is the final accepted aesthetic and functional requirements and stability of the moved segments. The objective of this paper is to give the basic principles of treatment planning for correcting facial discrepancies, surgical approach to different cases, and the methods to increase stability of the moved segments. Six cases are included to illustrate the different aspects of treatment planning, surgical management, and stabilization methods. (author)

  20. Practical opto-electronics an illustrated guide for the laboratory

    CERN Document Server

    Protopopov, Vladimir

    2014-01-01

    This book explains how to create opto-electronic systems in a most efficient way, avoiding typical mistakes. It covers light detection techniques, imaging, interferometry, spectroscopy, modulation-demodulation, heterodyning, beam steering, and many other topics common to laboratory applications. The focus is made on self-explanatory figures rather than on words. The book guides the reader through the entire process of creating problem-specific opto-electronic systems, starting from optical source, through beam transportation optical arrangement, to photodetector and data acquisition system. The relevant basics of beam propagation and computer-based raytracing routines are also explained, and sample codes are listed. the book teaches important know-how and practical tricks that are never disclosed in scientific publications.  The book can become the reader's personal adviser in the world of opto-electronics and navigator in the ocean of the market of optical components and systems. Succinct, well-illustrate...

  1. Some illustrative examples of Mayer's interference in the path integral

    International Nuclear Information System (INIS)

    Fizichev, P.P.

    1983-01-01

    A new technique is proposed for evaluation of path integrals by means of a discretization procedure. It is based on the previously established necessity to single out the set of classical trajectories along which the summation is performed. The notion of Mayer interference is introduced and is illustrated on a number of simple examples. It is shown that the choice of the set of paths induced a corresponding quantization prosymmetries of the problem. The possibility is shown of extracting information about the space of quantum states from the path integral. A class of paths is established the summation over which in the framework of the suggested approach leads to the well-known results for the motion is a homogeneous field and for the harmonic oscillator

  2. "To Improve upon Hints of Things": Illustrating Isaac Newton.

    Science.gov (United States)

    Schilt, Cornelis J

    2016-01-01

    When Isaac Newton died in 1727 he left a rich legacy in terms of draft manuscripts, encompassing a variety of topics: natural philosophy, mathematics, alchemy, theology, and chronology, as well as papers relating to his career at the Mint. One thing that immediately strikes us is the textuality of Newton's legacy: images are sparse. Regarding his scholarly endeavours we witness the same practice. Newton's extensive drafts on theology and chronology do not contain a single illustration or map. Today we have all of Newton's draft manuscripts as witnesses of his working methods, as well as access to a significant number of books from his own library. Drawing parallels between Newton's reading practices and his natural philosophical and scholarly work, this paper seeks to understand Newton's recondite writing and publishing politics.

  3. To change or not to change? That's the question... On MOOC-success, Barriers and Their Implications

    NARCIS (Netherlands)

    Henderikx, Maartje; Kreijns, Karel; Kalz, Marco

    2017-01-01

    This explorative study aimed to get an understanding of MOOC-success as seen from the perspective of the MOOC-taker and the types of barriers which might stand in the way of this success. Data of two MOOCs was used to illustrate MOOC-success from two perspectives and barriers encountered. Following

  4. Nfkb1 inhibits LPS-induced IFN-β and IL-12 p40 production in macrophages by distinct mechanisms.

    Directory of Open Access Journals (Sweden)

    Xixing Zhao

    Full Text Available Nfkb1-deficient murine macrophages express higher levels of IFN-β and IL-12 p40 following LPS stimulation than control macrophages, but the molecular basis for this phenomenon has not been completely defined. Nfkb1 encodes several gene products including the NF-κB subunit p50 and its precursor p105. p50 is derived from the N-terminal of 105, and p50 homodimers can exhibit suppressive activity when overexpressed. The C-terminal region of p105 is necessary for LPS-induced ERK activation and it has been suggested that ERK activity inhibits both IFN-β and IL-12 p40 following LPS stimulation. However, the contributions of p50 and the C-terminal domain of p105 in regulating endogenous IFN-β(Ifnb and IL-12 p40 (Il12b gene expression in macrophages following LPS stimulation have not been directly compared.We have used recombinant retroviruses to express p105, p50, and the C-terminal domain of p105 (p105ΔN in Nfkb1-deficient murine bone marrow-derived macrophages at near endogenous levels. We found that both p50 and p105ΔN inhibited expression of Ifnb, and that inhibition of Ifnb by p105ΔN depended on ERK activation, because a mutant of p105ΔN (p105ΔNS930A that lacks a key serine necessary to support ERK activation failed to inhibit. In contrast, only p105ΔN but not p50 inhibited Il12b expression. Surprisingly, p105ΔNS930A retained inhibitory activity for Il12b, indicating that ERK activation was not necessary for inhibition. The differential effects of p105ΔNS930A on Ifnb and Il12b expression inversely correlated with the function of one of its binding partners, c-Rel. This raised the possibility that p105ΔNS930A influences gene expression by interfering with the function of c-Rel.These results demonstrate that Nfkb1 exhibits multiple gene-specific inhibitory functions following TLR stimulation of murine macrophages.

  5. Transformation of SV40-immortalized human uroepithelial cells by 3-methylcholanthrene increases IFN- and Large T Antigen-induced transcripts

    Directory of Open Access Journals (Sweden)

    Easton Marilyn J

    2010-02-01

    Full Text Available Abstract Background Simian Virus 40 (SV40 immortalization followed by treatment of cells with 3-methylcholanthrene (3-MC has been used to elicit tumors in athymic mice. 3-MC carcinogenesis has been thoroughly studied, however gene-level interactions between 3-MC and SV40 that could have produced the observed tumors have not been explored. The commercially-available human uroepithelial cell lines were either SV40-immortalized (HUC or SV40-immortalized and then 3-MC-transformed (HUC-TC. Results To characterize the SV40 - 3MC interaction, we compared human gene expression in these cell lines using a human cancer array and confirmed selected changes by RT-PCR. Many viral Large T Antigen (Tag expression-related changes occurred in HUC-TC, and it is concluded that SV40 and 3-MC may act synergistically to transform cells. Changes noted in IFP 9-27, 2'-5' OAS, IF 56, MxA and MxAB were typical of those that occur in response to viral exposure and are part of the innate immune response. Because interferon is crucial to innate immune host defenses and many gene changes were interferon-related, we explored cellular growth responses to exogenous IFN-γ and found that treatment impeded growth in tumor, but not immortalized HUC on days 4 - 7. Cellular metabolism however, was inhibited in both cell types. We conclude that IFN-γ metabolic responses were functional in both cell lines, but IFN-γ anti-proliferative responses functioned only in tumor cells. Conclusions Synergism of SV40 with 3-MC or other environmental carcinogens may be of concern as SV40 is now endemic in 2-5.9% of the U.S. population. In addition, SV40-immortalization is a generally-accepted method used in many research materials, but the possibility of off-target effects in studies carried out using these cells has not been considered. We hope that our work will stimulate further study of this important phenomenon.

  6. Lesional CD4+ IFN-γ+ cytotoxic T lymphocytes in IgG4-related dacryoadenitis and sialoadenitis

    Science.gov (United States)

    Maehara, Takashi; Mattoo, Hamid; Ohta, Miho; Mahajan, Vinay S; Moriyama, Masafumi; Yamauchi, Masaki; Drijvers, Jefte; Nakamura, Seiji; Stone, John H; Pillai, Shiv S

    2017-01-01

    Objectives IgG4-related disease (IgG4-RD) is a chronic, systemic, inflammatory condition of unknown aetiology. We have recently described clonally expanded circulating CD4+ cytotoxic T lymphocytes (CTLs) in IgG4-RD that infiltrate affected tissues where they secrete interleukin (IL)-1β and transforming growth factor -β1 (TGF-β1). In this study, we sought to examine the role of CD4+ CTLs in the pathogenesis of IgG4-related dacryoadenitis and sialoadenitis (IgG4-DS) and to determine whether these cells secrete interferon-gamma (IFN-γ) at lesional sites. Methods Salivary glands of 25 patients with IgG4-DS, 22 patients with Sjögren’s syndrome (SS), 12 patients with chronic sialoadenitis (CS) and 12 healthy controls were analysed in this study. Gene expression analysis was performed on submandibular glands (SMGs) from five patients with IgG4-DS, three with CS and three healthy controls. Infiltrating CD4+ CTLs were examined by quantitative multicolour imaging in tissue samples from 20 patients with IgG4-DS, 22 patients with SS, 9 patients with CS and 9 healthy controls. Results In IgG4-DS tissues, nine genes associated with CD4+ CTLs were overexpressed. The expression of granzyme A (GZMA) mRNA was significantly higher in samples from patients with IgG4-RD compared with corresponding tissues from SS and healthy controls. Quantitative imaging showed that infiltrating CD4+ GZMA+ CTLs were more abundant in patients with IgG4-DS than in the other groups. The ratio of CD4+GZMA+ CTLs in SMGs from patients with IgG4-DS correlated with serum IgG4 concentrations and the number of affected organs. A large fraction of CD4+GZMA+ CTLs in SMGs from patients with IgG4-DS secreted IFN-γ. Conclusions The pathogenesis of IgG4-DS is associated with tissue infiltration by CD4+GZMA+ CTLs that secrete IFN-γ. PMID:27358392

  7. A constrained approximation for nuclear barrier penetration and fission

    International Nuclear Information System (INIS)

    Tang, H.H.K.; Negele, J.W.; Massachusetts Inst. of Tech., Cambridge; Massachusetts Inst. of Tech., Cambridge

    1983-01-01

    An approximation to the time-dependent mean-field theory for barrier penetration by a nucleus is obtained in terms of constrained Hartree-Fock wave functions and a coherent velocity field. A discrete approximation to the continuum theory suitable for practical numerical calculations is presented and applied to three illustrative models. Potential application of the theory to the study of nuclear fission is discussed. (orig.)

  8. Illustrating the Interaction of Nature and People in Ecosystem Services: The Case of Terroir in Wine

    Science.gov (United States)

    Nicholas, K. A.

    2014-12-01

    The ecosystem services (ES) approach is increasingly used in research and policy, with the Common International Framework on Ecosystem Services (CICES) "cascade" gaining traction as a framework for conceptualizing the production of ecosystem services by the natural environment, and then people consuming these services and obtaining benefits depending on their values. However, uptake of the ES concept on the ground by ecosystem managers, and understanding by everyday citizens, is still limited. One barrier is the challenge of providing tangible, examples of everyday benefits and values that people can readily connect with the biophysical structures and functions that underlie their provision. Winegrowing offers one promising case to illustrate the linkages all along the chain of production and consumption of ecosystem services. The sensitive winegrape has long been known for its properties of terroir, where the taste of wine reflects the environmental conditions of the place where it is grown, a feature valued by consumers. Here the CICES framework is illustrated with the case of winegrowing, demonstrating that the current linear model of natural production and human consumption of ES needs to be modified for this case because people influence each of the five stages by shaping and responding to their environment, producing a two-way interaction between people and the environment throughout. For example, while natural drivers such as climate and soils are key to the provision of the service of winegrape yields, landowners modify the biophysical environment through site selection and growers modify plant ecophysiological function through farming practices such as pruning and irrigation in order to influence the final service. Similarly, winemakers' expertise is needed to transform the service of winegrape yields into the product of wine that can be enjoyed and valued by consumers, whose preferences shape wine styles as well. This case illustrates how incorporating

  9. Clinical significance of measurement of changes of serum IL-2, IL-4 and IFN-γ levels after treatment in patients with vitiligo

    International Nuclear Information System (INIS)

    Cheng Junmin; Zhou Xiujuan; Zhang Yuhong

    2010-01-01

    Objective: To explore the changes of serum IL-2, IL-4 and IFN-γ levels after treatment in patients with vitiligo. Methods: Serum IL-2 (with RIA) IL-4, IFN-γ (with ELISA) levels were examined in 37 patients with vitiligo both before and after treatment as well as in 35 controls. Results: Before treatment, serum IL-2 levels in the patients were significantly lower than those in controls (P < 0.01), while the serum IL-4, IFN-γ levels were significantly higher (P < 0.01). After treatment for 6 months, the values were greatly corrected, but remained significantly different from those in controls (P < 0.05). Conclusion: Vitiligo is a kind of auto-immune diseases with abnormal immuno-regulation. (authors)

  10. Investigating the Role of TNF-α and IFN-γ Activation on the Dynamics of iNOS Gene Expression in LPS Stimulated Macrophages.

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    Taha Salim

    Full Text Available Macrophage produced inducible nitric oxide synthase (iNOS is known to play a critical role in the proinflammatory response against intracellular pathogens by promoting the generation of bactericidal reactive nitrogen species. Robust and timely production of nitric oxide (NO by iNOS and analogous production of reactive oxygen species are critical components of an effective immune response. In addition to pathogen associated lipopolysaccharides (LPS, iNOS gene expression is dependent on numerous proinflammatory cytokines in the cellular microenvironment of the macrophage, two of which include interferon gamma (IFN-γ and tumor necrosis factor alpha (TNF-α. To understand the synergistic effect of IFN-γ and TNF-α activation, and LPS stimulation on iNOS expression dynamics and NO production, we developed a systems biology based mathematical model. Using our model, we investigated the impact of pre-infection cytokine exposure, or priming, on the system. We explored the essentiality of IFN-γ priming to the robustness of initial proinflammatory response with respect to the ability of macrophages to produce reactive species needed for pathogen clearance. Results from our theoretical studies indicated that IFN-γ and subsequent activation of IRF1 are essential in consequential production of iNOS upon LPS stimulation. We showed that IFN-γ priming at low concentrations greatly increases the effector response of macrophages against intracellular pathogens. Ultimately the model demonstrated that although TNF-α contributed towards a more rapid response time, measured as time to reach maximum iNOS production, IFN-γ stimulation was significantly more significant in terms of the maximum expression of iNOS and the concentration of NO produced.

  11. The murine cytomegalovirus M35 protein antagonizes type I IFN induction downstream of pattern recognition receptors by targeting NF-κB mediated transcription.

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    Baca Chan

    2017-05-01

    Full Text Available The type I interferon (IFN response is imperative for the establishment of the early antiviral immune response. Here we report the identification of the first type I IFN antagonist encoded by murine cytomegalovirus (MCMV that shuts down signaling following pattern recognition receptor (PRR sensing. Screening of an MCMV open reading frame (ORF library identified M35 as a novel and strong negative modulator of IFNβ promoter induction following activation of both RNA and DNA cytoplasmic PRR. Additionally, M35 inhibits the proinflammatory cytokine response downstream of Toll-like receptors (TLR. Using a series of luciferase-based reporters with specific transcription factor binding sites, we determined that M35 targets NF-κB-, but not IRF-mediated, transcription. Expression of M35 upon retroviral transduction of immortalized bone marrow-derived macrophages (iBMDM led to reduced IFNβ transcription and secretion upon activation of stimulator of IFN genes (STING-dependent signaling. On the other hand, M35 does not antagonize interferon-stimulated gene (ISG 56 promoter induction or ISG transcription upon exogenous stimulation of the type I IFN receptor (IFNAR. M35 is present in the viral particle and, upon MCMV infection of fibroblasts, is immediately shuttled to the nucleus where it exerts its immunomodulatory effects. Deletion of M35 from the MCMV genome and hence from the viral particle resulted in elevated type I IFN transcription and secretion in vitro and in vivo. In the absence of M35, lower viral titers are observed during acute infection of the host, and productive infection in the salivary glands was not detected. In conclusion, the M35 protein is released by MCMV immediately upon infection in order to deftly inhibit the antiviral type I IFN response by targeting NF-κB-mediated transcription. The identification of this novel viral protein reinforces the importance of timely countermeasures in the complex relationship between virus and host.

  12. Investigating the Role of TNF-α and IFN-γ Activation on the Dynamics of iNOS Gene Expression in LPS Stimulated Macrophages.

    Science.gov (United States)

    Salim, Taha; Sershen, Cheryl L; May, Elebeoba E

    2016-01-01

    Macrophage produced inducible nitric oxide synthase (iNOS) is known to play a critical role in the proinflammatory response against intracellular pathogens by promoting the generation of bactericidal reactive nitrogen species. Robust and timely production of nitric oxide (NO) by iNOS and analogous production of reactive oxygen species are critical components of an effective immune response. In addition to pathogen associated lipopolysaccharides (LPS), iNOS gene expression is dependent on numerous proinflammatory cytokines in the cellular microenvironment of the macrophage, two of which include interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α). To understand the synergistic effect of IFN-γ and TNF-α activation, and LPS stimulation on iNOS expression dynamics and NO production, we developed a systems biology based mathematical model. Using our model, we investigated the impact of pre-infection cytokine exposure, or priming, on the system. We explored the essentiality of IFN-γ priming to the robustness of initial proinflammatory response with respect to the ability of macrophages to produce reactive species needed for pathogen clearance. Results from our theoretical studies indicated that IFN-γ and subsequent activation of IRF1 are essential in consequential production of iNOS upon LPS stimulation. We showed that IFN-γ priming at low concentrations greatly increases the effector response of macrophages against intracellular pathogens. Ultimately the model demonstrated that although TNF-α contributed towards a more rapid response time, measured as time to reach maximum iNOS production, IFN-γ stimulation was significantly more significant in terms of the maximum expression of iNOS and the concentration of NO produced.

  13. Macrophage migration inhibitory factor triggers chemotaxis of CD74+CXCR2+ NKT cells in chemically induced IFN-γ-mediated skin inflammation.

    Science.gov (United States)

    Hsieh, Chia-Yuan; Chen, Chia-Ling; Lin, Yee-Shin; Yeh, Trai-Ming; Tsai, Tsung-Ting; Hong, Ming-Yuan; Lin, Chiou-Feng

    2014-10-01

    IFN-γ mediates chemically induced skin inflammation; however, the mechanism by which IFN-γ-producing cells are recruited to the sites of inflammation remains undefined. Secretion of macrophage migration inhibitory factor (MIF), a proinflammatory cytokine, from damaged cells may promote immune cell recruitment. We hypothesized that MIF triggers an initial step in the chemotaxis of IFN-γ-producing cells in chemically induced skin inflammation. Using acute and chronic models of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammation in mouse ears, MIF expression was examined, and its role in this process was investigated pharmacologically. The cell populations targeted by MIF, their receptor expression patterns, and the effects of MIF on cell migration were examined. TPA directly caused cytotoxicity accompanied by MIF release in mouse ear epidermal keratinocytes, as well as in human keratinocytic HaCaT cells. Treatment with the MIF antagonist (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester considerably attenuated TPA-induced ear swelling, leukocyte infiltration, epidermal cell proliferation, and dermal angiogenesis. Inhibition of MIF greatly diminished the dermal infiltration of IFN-γ(+) NKT cells, whereas the addition of exogenous TPA and MIF to NKT cells promoted their IFN-γ production and migration, respectively. MIF specifically triggered the chemotaxis of NKT cells via CD74 and CXCR2, and the resulting depletion of NKT cells abolished TPA-induced skin inflammation. In TPA-induced skin inflammation, MIF is released from damaged keratinocytes and then triggers the chemotaxis of CD74(+)CXCR2(+) NKT cells for IFN-γ production. Copyright © 2014 by The American Association of Immunologists, Inc.

  14. Plasmodium berghei NK65 in Combination with IFN-γ Induces Endothelial Glucocorticoid Resistance via Sustained Activation of p38 and JNK

    Science.gov (United States)

    Zielińska, Karolina A.; de Cauwer, Lode; Knoops, Sofie; Van der Molen, Kristof; Sneyers, Alexander; Thommis, Jonathan; De Souza, J. Brian; Opdenakker, Ghislain; De Bosscher, Karolien; Van den Steen, Philippe E.

    2017-01-01

    Malaria-associated acute respiratory distress syndrome (MA-ARDS) is an often lethal complication of malaria. Currently, no adequate therapy for this syndrome exists. Although glucocorticoids (GCs) have been used to improve clinical outcome of ARDS, their therapeutic benefits remain unclear. We previously developed a mouse model of MA-ARDS, in which dexamethasone treatment revealed GC resistance. In the present study, we investigated GC sensitivity of mouse microvascular lung endothelial cells stimulated with interferon-γ (IFN-γ) and Plasmodium berghei NK65 (PbNK65). Upon challenge with IFN-γ alone, dexamethasone inhibited the expression of CCL5 (RANTES) by 90% and both CCL2 (MCP-1) and CXCL10 (IP-10) by 50%. Accordingly, whole transcriptome analysis revealed that dexamethasone differentially affected several gene clusters and in particular inhibited a large cluster of IFN-γ-induced genes, including chemokines. In contrast, combined stimulation with IFN-γ and PbNK65 extract impaired inhibitory actions of GCs on chemokine release, without affecting the capacity of the GC receptor to accumulate in the nucleus. Subsequently, we investigated the effects of GCs on two signaling pathways activated by IFN-γ. Dexamethasone left phosphorylation and protein levels of signal transducer and activator of transcription 1 (STAT1) unhampered. In contrast, dexamethasone inhibited the IFN-γ-induced activation of two mitogen-activated protein kinases (MAPK), JNK, and p38. However, PbNK65 extract abolished the inhibitory effects of GCs on MAPK signaling, inducing GC resistance. These data provide novel insights into the mechanisms of GC actions in endothelial cells and show how malaria may impair the beneficial effects of GCs. PMID:29033931

  15. Plasmodium berghei NK65 in Combination with IFN-γ Induces Endothelial Glucocorticoid Resistance via Sustained Activation of p38 and JNK

    Directory of Open Access Journals (Sweden)

    Karolina A. Zielińska

    2017-09-01

    Full Text Available Malaria-associated acute respiratory distress syndrome (MA-ARDS is an often lethal complication of malaria. Currently, no adequate therapy for this syndrome exists. Although glucocorticoids (GCs have been used to improve clinical outcome of ARDS, their therapeutic benefits remain unclear. We previously developed a mouse model of MA-ARDS, in which dexamethasone treatment revealed GC resistance. In the present study, we investigated GC sensitivity of mouse microvascular lung endothelial cells stimulated with interferon-γ (IFN-γ and Plasmodium berghei NK65 (PbNK65. Upon challenge with IFN-γ alone, dexamethasone inhibited the expression of CCL5 (RANTES by 90% and both CCL2 (MCP-1 and CXCL10 (IP-10 by 50%. Accordingly, whole transcriptome analysis revealed that dexamethasone differentially affected several gene clusters and in particular inhibited a large cluster of IFN-γ-induced genes, including chemokines. In contrast, combined stimulation with IFN-γ and PbNK65 extract impaired inhibitory actions of GCs on chemokine release, without affecting the capacity of the GC receptor to accumulate in the nucleus. Subsequently, we investigated the effects of GCs on two signaling pathways activated by IFN-γ. Dexamethasone left phosphorylation and protein levels of signal transducer and activator of transcription 1 (STAT1 unhampered. In contrast, dexamethasone inhibited the IFN-γ-induced activation of two mitogen-activated protein kinases (MAPK, JNK, and p38. However, PbNK65 extract abolished the inhibitory effects of GCs on MAPK signaling, inducing GC resistance. These data provide novel insights into the mechanisms of GC actions in endothelial cells and show how malaria may impair the beneficial effects of GCs.

  16. IFNL4 ss469415590 Variant Is Associated with Treatment Response in Japanese HCV Genotype 1 Infected Individuals Treated with IFN-Including Regimens

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    Tatsuo Miyamura

    2014-01-01

    Full Text Available Aim. Eradication of hepatitis C virus (HCV is still challenging even if interferon- (IFN- free regimens with direct-acting antiviral agents (DAAs for HCV-infected individuals are available in clinical practice. IFNL4 is a newly described protein, associated with human antiviral defenses. We investigated whether IFNL4 ss469415590 variant has an effect on the prediction of treatment response in HCV-infected patients treated with IFN-including regimens. Patients and Methods. In all, 185 patients infected with HCV genotype 1 treated with peg-IFN plus ribavirin, with or without telaprevir, were genotyped for IFNL4 ss469415590. We retrospectively investigated whether the role of IFNL4 ss469415590 variant and other factors could predict sustained virological response (SVR in Japanese patients infected with HCV genotype 1. Results. There were 65.7%, 31.5%, and 2.8% patients in the IFNL4 ss469415590 TT/TT, TT/-G, and -G/-G groups, respectively. SVR rates were 82.1% or 49.3% in patients treated with peg-IFN plus ribavirin with or without telaprevir, respectively. IFNL4 ss469415590 variant and HCV viral loads or IFNL4 ss469415590 variant and early virological response were better predictors of SVR in patients treated with peg-IFN plus ribavirin with or without telaprevir, respectively. Conclusion. In the era of DAAs, measurement of IFNL4 ss469415590 variant could help the prediction of SVR in Japanese HCV genotype 1 infected individuals treated with IFN-including regimens.

  17. TPL-2-ERK1/2 signaling promotes host resistance against intracellular bacterial infection by negative regulation of type I IFN production.

    Science.gov (United States)

    McNab, Finlay W; Ewbank, John; Rajsbaum, Ricardo; Stavropoulos, Evangelos; Martirosyan, Anna; Redford, Paul S; Wu, Xuemei; Graham, Christine M; Saraiva, Margarida; Tsichlis, Philip; Chaussabel, Damien; Ley, Steven C; O'Garra, Anne

    2013-08-15

    Tuberculosis, caused by Mycobacterium tuberculosis, remains a leading cause of mortality and morbidity worldwide, causing ≈ 1.4 million deaths per year. Key immune components for host protection during tuberculosis include the cytokines IL-12, IL-1, and TNF-α, as well as IFN-γ and CD4(+) Th1 cells. However, immune factors determining whether individuals control infection or progress to active tuberculosis are incompletely understood. Excess amounts of type I IFN have been linked to exacerbated disease during tuberculosis in mouse models and to active disease in patients, suggesting tight regulation of this family of cytokines is critical to host resistance. In addition, the immunosuppressive cytokine IL-10 is known to inhibit the immune response to M. tuberculosis in murine models through the negative regulation of key proinflammatory cytokines and the subsequent Th1 response. We show in this study, using a combination of transcriptomic analysis, genetics, and pharmacological inhibitors, that the TPL-2-ERK1/2 signaling pathway is important in mediating host resistance to tuberculosis through negative regulation of type I IFN production. The TPL-2-ERK1/2 signaling pathway regulated production by macrophages of several cytokines important in the immune response to M. tuberculosis as well as regulating induction of a large number of additional genes, many in a type I IFN-dependent manner. In the absence of TPL-2 in vivo, excess type I IFN promoted IL-10 production and exacerbated disease. These findings describe an important regulatory mechanism for controlling tuberculosis and reveal mechanisms by which type I IFN may promote susceptibility to this important disease.

  18. Barrier mechanisms in the Drosophila blood-brain barrier

    Directory of Open Access Journals (Sweden)

    Samantha Jane Hindle

    2014-12-01

    Full Text Available The invertebrate blood-brain barrier field is growing at a rapid pace and, in recent years, studies have shown a physiologic and molecular complexity that has begun to rival its vertebrate counterpart. Novel mechanisms of paracellular barrier maintenance through GPCR signaling were the first demonstrations of the complex adaptive mechanisms of barrier physiology. Building upon this work, the integrity of the invertebrate blood-brain barrier has recently been shown to require coordinated function of all layers of the compound barrier structure, analogous to signaling between the layers of the vertebrate neurovascular unit. These findings strengthen the notion that many blood-brain barrier mechanisms are conserved between vertebrates and invertebrates, and suggest that novel findings in invertebrate model organisms will have a significant impact on the understanding of vertebrate BBB functions. In this vein, important roles in coordinating localized and systemic signaling to dictate organism development and growth are beginning to show how the blood-brain barrier can govern whole animal physiologies. This includes novel functions of blood-brain barrier gap junctions in orchestrating synchronized neuroblast proliferation, and of blood-brain barrier secreted antagonists of insulin receptor signaling. These advancements and others are pushing the field forward in exciting new directions. In this review, we provide a synopsis of invertebrate blood-brain barrier anatomy and physiology, with a focus on insights from the past 5 years, and highlight important areas for future study.

  19. Gut microbial markers are associated with diabetes onset, regulatory imbalance, and IFN-γ level in NOD mice

    DEFF Research Database (Denmark)

    Krych, Lukasz; Nielsen, Dennis Sandris; Hansen, Axel Kornerup

    2015-01-01

    Gut microbiota regulated imbalances in the host's immune profile seem to be an important factor in the etiology of type 1 diabetes (T1D), and identifying bacterial markers for T1D may therefore be useful in diagnosis and prevention of T1D. The aim of the present study was to investigate the link...... measured in diabetic and non-diabetic mice at 30 weeks of age. The early gut microbiota composition was found to be different between NOD mice that later in life were classified as diabetic or non-diabetic. Those differences were further associated with changes in FoxP3(+) regulatory T cells, CD11b......(+) dendritic cells, and IFN-γ production. The model proposed in this work suggests that operational taxonomic units classified to S24-7, Prevotella, and an unknown Bacteriodales (all Bacteroidetes) act in favor of diabetes protection whereas members of Lachnospiraceae, Ruminococcus, and Oscillospira (all...

  20. Revisiting the IFN-γ release assay: Whole blood or PBMC cultures? - And other factors of influence

    DEFF Research Database (Denmark)

    Hartmann, Sofie Bruun; Emnéus, Jenny; Wolff, Anders

    2016-01-01

    light on external factors that could influence the read out in terms of IFN-γ levels. It was found that optimal culture conditions varied between individual animals; when polyclonal activated, cells from whole blood cultures were most responsive, but when activated specifically, the optimal cell....... However, there is no consensus whether to use whole blood cultures or purified PBMCs for the assay, and both cell populations are being used and results compared. Therefore the aim of this study was to compare different culture settings using immune cells from previously vaccinated calves, and to shed...... concentration/population varied with whole blood, 10 × 106 cells/ml PBMC and 5 × 106 cells/ml PBMC being the highest performing conditions. A further investigation of the distribution of cell populations in PBMCs compared to whole blood was conducted, and a significant (p

  1. ANALYSIS OF CELLULAR REACTION TO IFN-γ STIMULATION BY A SOFTWARE PACKAGE GeneExpressionAnalyser

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    A. V. Saetchnikov

    2014-01-01

    Full Text Available The software package GeneExpressionAnalyser for analysis of the DNA microarray experi-mental data has been developed. The algorithms of data analysis, differentially expressed genes and biological functions of the cell are described. The efficiency of the developed package is tested on the published experimental data devoted to the time-course research of the changes in the human cell un-der the influence of IFN-γ on melanoma. The developed software has a number of advantages over the existing software: it is free, has a simple and intuitive graphical interface, allows to analyze different types of DNA microarrays, contains a set of methods for complete data analysis and performs effec-tive gene annotation for a selected list of genes.

  2. BING-NEEL SYNDROME: ILLUSTRATIVE CASES AND COMPREHENSIVE REVIEW OF THE LITERATURE

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    Marzia Varettoni

    2017-10-01

    Full Text Available The Bing-Neel syndrome is a rare neurological complication of Waldenström’s Macroglobulinemia which results from a direct involvement of central nervous system by malignant lymphoplasmacytic cells. The clinical suspicion of Bing-Neel syndrome may be difficult because neurologic symptoms are heterogeneous, non specific and sometimes underhand. A definitive diagnosis of Bing-Neel syndrome can be confidently made using brain and spinal cord magnetic resonance imaging as well as histopathology and/or cerebrospinal fluid analysis to confirm the neoplastic infiltration of central nervous system. The detection in the cerebrospinal fluid of patients with Bing-Neel syndrome of the MYD88 (L265P somatic mutation, which is highly recurrent in Waldenström’s Macroglobulinemia, revealed useful for the diagnosis and monitoring of central nervous system involvement. Despite recommendations recently published, there is still no clear consensus on treatment of Bing-Neel syndrome, which includes systemic immunochemotherapy, intrathecal chemotherapy and brain irradiation as possible options. Ibrutinib, a Bruton kinase inhibitor highly active in patients with Waldenström’s Macroglobulinemia, has been recently added to the therapeutic armamentarium of Bing-Neel syndrome due to its ability to pass the blood-brain barrier. However, prospective clinical trials are eagerly awaited with the aim to define the optimal treatment strategy.  Here we describe four illustrative cases of Bing-Neel syndrome diagnosed and treated at our Institution and review the literature on this topic.

  3. Using diffusion of innovations theory to guide diabetes management program development: an illustrative example.

    Science.gov (United States)

    De Civita, Mirella; Dasgupta, Kaberi

    2007-09-01

    Optimal management of type 2 diabetes requires achievement of optimal glucose, blood pressure and lipid targets through promotion of prudent diet, regular physical activity and adherence to necessary medication. This may require the development of new programs for the coordination of required multidisciplinary services. Diffusion of innovations theory offers a conceptual framework that may facilitate the implementation of such programs. To illustrate this, we have re-examined the implementation experiences previously reported by the developers of an actual diabetes management pilot program in Montreal, with an eye toward identifying potentially important process factors that could effectively increase adoption and sustainability. Physician participation in the program appeared to be influenced by perceived advantages of participation, compatibility of the program with own perspective and perceived barriers to participation. Organizational features that may have influenced participation included the extent of the program's integration within the existing health care system. A thorough consideration of process factors that impact system and team integration must equally include a focus on ensuring ongoing partnerships among the producers of the model, governments, nongovernmental organizations, private industry, user professionals and patients. This can only be achieved when a knowledge transfer action plan is developed to guide program development, implementation and sustainability.

  4. What if energy decoupling of emerging economies were not so spontaneous? an illustrative example on India

    International Nuclear Information System (INIS)

    Mathy, S.; Guivarch, C.

    2009-02-01

    Reference GHG emissions scenarios are critical for estimates of the costs of stabilization and for climate policy recommendations. But recently, existing reference scenarios, notably the SRES, have been the target of criticisms that question their relevance in the light of current emissions trends, dispute the suitability, for developing countries, of the modeling methodologies used and suggest they convey too optimistic views on spontaneous energy decoupling of emerging countries economies. This article focuses on an illustrative example on India. It proposes an alternative reference scenario built with a modeling framework representing as realistically as possible the processes driving energy intensity and carbon intensity changes, in particular accounting for the interactions between energy systems and economic constraints and capturing the sub-optimalities of the energy sector. The mechanisms leading to moderate energy decoupling in this alternative scenario are analysed. From a methodological point of view, our results call for the improvement of the realism of modeling tools for scenarios elaboration. From a mitigation point of view, it appears that the challenge for climate policies to lift the barriers to the diffusion of energy efficiency improvement in India is considerable, but we identify a potential for synergies between development policies and climate policies. (authors)

  5. Lean practices for quality results: a case illustration.

    Science.gov (United States)

    Hwang, Pauline; Hwang, David; Hong, Paul

    2014-01-01

    Increasingly, healthcare providers are implementing lean practices to achieve quality results. Implementing lean healthcare practices is unique compared to manufacturing and other service industries. The purpose of this paper is to present a model that identifies and defines the lean implementation key success factors in healthcare organisations. The model is based on an extant literature review and a case illustration that explores actual lean implementation in a major USA hospital located in a Midwestern city (approximately 300,000 people). An exploratory/descriptive study using observation and follow-up interviews was conducted to identify lean practices in the hospital. Lean practice key drivers include growing elderly populations, rising medical expenses, decreasing insurance coverage and decreasing management support. Effectively implementing lean practices to increase bottom-line results and improve organisational integrity requires sharing goals and processes among healthcare managers and professionals. An illustration explains the model and the study provides a sound foundation for empirical work. Practical implications are included. Lean practices minimise waste and unnecessary hospital stays while simultaneously enhancing customer values and deploying resources in supply systems. Leadership requires clear project targets based on sound front-end planning because initial implementation steps involve uncertainty and ambiguity (i.e. fuzzy front-end planning). Since top management support is crucial for implementing lean practices successfully, a heavyweight manager, who communicates well both with top managers and project team members, is an important success factor when implementing lean practices. Increasingly, green orientation and sustainability initiatives are phrases that replaced lean practices. Effective results; e.g. waste reduction, employee satisfaction and customer values are applicable to bigger competitive challenges arising both in specific

  6. An early burst of IFN-γ induced by the pre-erythrocytic stage favours Plasmodium yoelii parasitaemia in B6 mice

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    Barbier Eliane

    2009-06-01

    Full Text Available Abstract Background In murine models of malaria, an early proinflammatory response has been associated with the resolution of blood-stage infection. To dissect the protective immune mechanims that allow the control of parasitaemia, the early immune response of C57BL/6 mice induced during a non-lethal plasmodial infection was analysed. Methods Mice were infected with Plasmodium yoelii 265BY sporozoites, the natural invasive form of the parasite, in order to complete its full life cycle. The concentrations of three proinflammatory cytokines in the sera of mice were determined by ELISA at different time points of infection. The contribution of the liver and the spleen to this cytokinic response was evaluated and the cytokine-producing lymphocytes were identified by flow cytometry. The physiological relevance of these results was tested by monitoring parasitaemia in genetically deficient C57BL/6 mice or wild-type mice treated with anti-cytokine neutralizing antibody. Finally, the cytokinic response in sera of mice infected with parasitized-RBCs was analysed. Results The early immune response of C57BL/6 mice to sporozoite-induced malaria is characterized by a peak of IFN-γ in the serum at day 5 of infection and splenic CD4 T lymphocytes are the major producer of this cytokine at this time point. Somewhat unexpected, the parasitaemia is significantly lower in P. yoelii-infected mice in the absence of IFN-γ. More precisely, at early time points of infection, IFN-γ favours parasitaemia, whereas helping to clear efficiently the blood-stage parasites at later time points. Interestingly, the early IFN-γ burst is induced by the pre-erythrocytic stage. Conclusion These results challenge the current view regarding the role of IFN-γ on the control of parasite growth since they show that IFN-γ is not an essential mediator of protection in P. yoelii-infected C57BL/6 mice. Moreover, the mice parasitaemia is more efficiently controlled in the absence of an

  7. HMGB1 Is Involved in IFN-α Production and TRAIL Expression by HIV-1-Exposed Plasmacytoid Dendritic Cells: Impact of the Crosstalk with NK Cells.

    Directory of Open Access Journals (Sweden)

    Héla Saïdi

    2016-02-01

    Full Text Available Plasmacytoid dendritic cells (pDCs are innate sensors of viral infections and important mediators of antiviral innate immunity through their ability to produce large amounts of IFN-α. Moreover, Toll-like receptor 7 (TLR7 and 9 (TLR9 ligands, such as HIV and CpG respectively, turn pDCs into TRAIL-expressing killer pDCs able to lyse HIV-infected CD4+ T cells. NK cells can regulate antiviral immunity by modulating pDC functions, and pDC production of IFN-α as well as cell-cell contact is required to promote NK cell functions. Impaired pDC-NK cell crosstalk was reported in the setting of HIV-1 infection, but the impact of HIV-1 on TRAIL expression and innate antiviral immunity during this crosstalk is unknown. Here, we report that low concentrations of CCR5-tropic HIV-1Ba-L promote the release of pro-inflammatory cytokines such as IFN-α, TNF-α, IFN-γ and IL-12, and CCR5-interacting chemokines (MIP-1α and MIP-1β in NK-pDCs co-cultures. At high HIV-1BaL concentrations, the addition of NK cells did not promote the release of these mediators, suggesting that once efficiently triggered by the virus, pDCs could not integrate new activating signals delivered by NK cells. However, high HIV-1BaL concentrations were required to trigger IFN-α-mediated TRAIL expression at the surface of both pDCs and NK cells during their crosstalk. Interestingly, we identified the alarmin HMGB1, released at pDC-NK cell synapse, as an essential trigger for the secretion of IFN-α and IFN-related soluble mediators during the interplay of HIV-1 exposed pDCs with NK cells. Moreover, HMGB1 was found crucial for mTRAIL translocation to the plasma membrane of both pDCs and NK cells during their crosstalk following pDC exposure to HIV-1. Data from serum analyses of circulating HMGB1, HMGB1-specific antibodies, sTRAIL and IP-10 in a cohort of 67 HIV-1+ patients argue for the in vivo relevance of these observations. Altogether, these findings identify HMGB1 as a trigger for IFN

  8. HMGB1 Is Involved in IFN-α Production and TRAIL Expression by HIV-1-Exposed Plasmacytoid Dendritic Cells: Impact of the Crosstalk with NK Cells.

    Science.gov (United States)

    Saïdi, Héla; Bras, Marlène; Formaglio, Pauline; Melki, Marie-Thérèse; Charbit, Bruno; Herbeuval, Jean-Philippe; Gougeon, Marie-Lise

    2016-02-01

    Plasmacytoid dendritic cells (pDCs) are innate sensors of viral infections and important mediators of antiviral innate immunity through their ability to produce large amounts of IFN-α. Moreover, Toll-like receptor 7 (TLR7) and 9 (TLR9) ligands, such as HIV and CpG respectively, turn pDCs into TRAIL-expressing killer pDCs able to lyse HIV-infected CD4+ T cells. NK cells can regulate antiviral immunity by modulating pDC functions, and pDC production of IFN-α as well as cell-cell contact is required to promote NK cell functions. Impaired pDC-NK cell crosstalk was reported in the setting of HIV-1 infection, but the impact of HIV-1 on TRAIL expression and innate antiviral immunity during this crosstalk is unknown. Here, we report that low concentrations of CCR5-tropic HIV-1Ba-L promote the release of pro-inflammatory cytokines such as IFN-α, TNF-α, IFN-γ and IL-12, and CCR5-interacting chemokines (MIP-1α and MIP-1β) in NK-pDCs co-cultures. At high HIV-1BaL concentrations, the addition of NK cells did not promote the release of these mediators, suggesting that once efficiently triggered by the virus, pDCs could not integrate new activating signals delivered by NK cells. However, high HIV-1BaL concentrations were required to trigger IFN-α-mediated TRAIL expression at the surface of both pDCs and NK cells during their crosstalk. Interestingly, we identified the alarmin HMGB1, released at pDC-NK cell synapse, as an essential trigger for the secretion of IFN-α and IFN-related soluble mediators during the interplay of HIV-1 exposed pDCs with NK cells. Moreover, HMGB1 was found crucial for mTRAIL translocation to the plasma membrane of both pDCs and NK cells during their crosstalk following pDC exposure to HIV-1. Data from serum analyses of circulating HMGB1, HMGB1-specific antibodies, sTRAIL and IP-10 in a cohort of 67 HIV-1+ patients argue for the in vivo relevance of these observations. Altogether, these findings identify HMGB1 as a trigger for IFN

  9. HMGB1 Is Involved in IFN-α Production and TRAIL Expression by HIV-1-Exposed Plasmacytoid Dendritic Cells: Impact of the Crosstalk with NK Cells.

    OpenAIRE

    Héla Saïdi; Marlène Bras; Pauline Formaglio; Marie-Thérèse Melki; Bruno Charbit; Jean-Philippe Herbeuval; Marie-Lise Gougeon

    2016-01-01

    Plasmacytoid dendritic cells (pDCs) are innate sensors of viral infections and important mediators of antiviral innate immunity through their ability to produce large amounts of IFN-?. Moreover, Toll-like receptor 7 (TLR7) and 9 (TLR9) ligands, such as HIV and CpG respectively, turn pDCs into TRAIL-expressing killer pDCs able to lyse HIV-infected CD4+ T cells. NK cells can regulate antiviral immunity by modulating pDC functions, and pDC production of IFN-? as well as cell?cell contact is requ...

  10. IL-18 potentiated whole blood IFN-γ assay can identify cell-mediated immune responses towards Lawsonia intracellularis in experimentally infected pigs

    DEFF Research Database (Denmark)

    Riber, Ulla; Jakobsen, Jeanne Toft; Hvass, Henriette Cordes

    Lawsonia intracellularis is an obligate intracellular bacteria causing proliferative enteropathy (PE) in pigs. The infection causes diarrhoea, retarded growth and sudden death in pigs and is one of the most economically important diseases in the swine industry worldwide. The infection is one...... indications that cell-mediated immune responses (CMI) are important for the protection against infections with L. intracellularis and in mice models IFN-γ has been shown to play a key role in the host defence against experimental infections . In L. intracellularis infected pigs, IFN-γ is only sparsely...

  11. Increase in circulating CD4CD25Foxp3 T cells in patients with Philadelphia-negative chronic myeloproliferative neoplasms during treatment with IFN

    DEFF Research Database (Denmark)

    Riley, C.H.; Morten Krogh, Jensen; Brimnes, M.K.

    2011-01-01

    Recent reports have described complete or major molecular remission in patients with polycythemia vera after long-term treatment with the immunomodulatory agent IFN-α2. Accordingly, there are reasons to believe that the immune system is a key player in eradicating the JAK2 mutated clone in these ......Recent reports have described complete or major molecular remission in patients with polycythemia vera after long-term treatment with the immunomodulatory agent IFN-α2. Accordingly, there are reasons to believe that the immune system is a key player in eradicating the JAK2 mutated clone...

  12. The STAT4 SLE risk allele rs7574865[T] is associated with increased IL-12-induced IFN-γ production in T cells from patients with SLE.

    Science.gov (United States)

    Hagberg, Niklas; Joelsson, Martin; Leonard, Dag; Reid, Sarah; Eloranta, Maija-Leena; Mo, John; Nilsson, Magnus K; Syvänen, Ann-Christine; Bryceson, Yenan T; Rönnblom, Lars

    2018-02-23

    Genetic variants in the transcription factor STAT4 are associated with increased susceptibility to systemic lupus erythematosus (SLE) and a more severe disease phenotype. This study aimed to clarify how the SLE-associated intronic STAT4 risk allele rs7574865[T] affects the function of immune cells in SLE. Peripheral blood mononuclear cells (PBMCs) were isolated from 52 genotyped patients with SLE. Phosphorylation of STAT4 (pSTAT4) and STAT1 (pSTAT1) in response to interferon (IFN)-α, IFN-γ or interleukin (IL)-12, total levels of STAT4, STAT1 and T-bet, and frequency of IFN-γ + cells on IL-12 stimulation were determined by flow cytometry in subsets of immune cells before and after preactivation of cells with phytohaemagglutinin (PHA) and IL-2. Cellular responses and phenotypes were correlated to STAT4 risk allele carriership. Janus kinase inhibitors (JAKi) selective for TYK2 (TYK2i) or JAK2 (JAK2i) were evaluated for inhibition of IL-12 or IFN-γ-induced activation of SLE PBMCs. In resting PBMCs, the STAT4 risk allele was neither associated with total levels of STAT4 or STAT1, nor cytokine-induced pSTAT4 or pSTAT1. Following PHA/IL-2 activation, CD8 + T cells from STAT4 risk allele carriers displayed increased levels of STAT4 resulting in increased pSTAT4 in response to IL-12 and IFN-α, and an augmented IL-12-induced IFN-γ production in CD8 + and CD4 + T cells. The TYK2i and the JAK2i efficiently blocked IL-12 and IFN-γ-induced activation of PBMCs from STAT4 risk patients, respectively. T cells from patients with SLE carrying the STAT4 risk allele rs7574865[T] display an augmented response to IL-12 and IFN-α. This subset of patients may benefit from JAKi treatment. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  13. [Blood-brain barrier part III: therapeutic approaches to cross the blood-brain barrier and target the brain].

    Science.gov (United States)

    Weiss, N; Miller, F; Cazaubon, S; Couraud, P-O

    2010-03-01

    Over the last few years, the blood-brain barrier has come to be considered as the main limitation for the treatment of neurological diseases caused by inflammatory, tumor or neurodegenerative disorders. In the blood-brain barrier, the close intercellular contact between cerebral endothelial cells due to tight junctions prevents the passive diffusion of hydrophilic components from the bloodstream into the brain. Several specific transport systems (via transporters expressed on cerebral endothelial cells) are implicated in the delivery of nutriments, ions and vitamins to the brain; other transporters expressed on cerebral endothelial cells extrude endogenous substances or xenobiotics, which have crossed the cerebral endothelium, out of the brain and into the bloodstream. Recently, several strategies have been proposed to target the brain, (i) by by-passing the blood-brain barrier by central drug administration, (ii) by increasing permeability of the blood-brain barrier, (iii) by modulating the expression and/or the activity of efflux transporters, (iv) by using the physiological receptor-dependent blood-brain barrier transport, and (v) by creating new viral or chemical vectors to cross the blood-brain barrier. This review focuses on the illustration of these different approaches. Copyright (c) 2009 Elsevier Masson SAS. All rights reserved.

  14. Barriers to accessing urethroplasty.

    Science.gov (United States)

    Consolo, Michael J; Syed, Kirin K; Robison, Christopher; McFadden, Jacob; Shalowitz, David I; Brown, Gordon A; Sussman, David O; Figler, Bradley D

    2016-01-01

    Urethroplasty is an effective treatment for men with anterior urethral strictures, but is utilized less frequently than ineffective treatments such as internal urethrotomy. We sought to identify provider-level barriers to urethroplasty. An anonymous online survey was emailed to all Mid-Atlantic American Urological Association members. Six scenarios in which urethroplasty was the most appropriate treatment were presented. Primary outcome was recommendation for urethroplasty in ≥ three clinical scenarios. Other factors measured include practice zip code, urethroplasty training, and proximity to a urethroplasty surgeon. Multivariate logistic regression identified factors associated with increased likelihood of urethroplasty recommendation. Of 670 members emailed, 109 (16%) completed the survey. Final analysis included 88 respondents. Mean years in practice was 17.2. Most respondents received formal training in urethroplasty: 43 (49%) in residency, 5 (6%) in fellowship, and 10 (11%) in both; 48 respondents (55%) had a urethroplasty surgeon in their practice, whereas 18 (20%) had a urethroplasty surgeon within 45 minutes of his or her primary practice location. The only covariate that was associated with an increased likelihood of recommending urethroplasty in ≥ three scenarios was formal urethroplasty training. Most members (68%) reported no barriers to referring patients for urethroplasty; the most common barriers cited were long distance to urethroplasty surgeon (n 5 13, 15%) and concern about complications (n 5 8, 9%). Urethroplasty continues to be underutilized in men with anterior urethral strictures, potentially due to lack of knowledge dissemination and access to a urethroplasty surgeon. Appropriate urethroplasty utilization may increase with greater exposure to urethroplasty in training.

  15. Knowledge Exchange and Management Research: Barriers and Potentials

    DEFF Research Database (Denmark)

    Bager, Torben

    2018-01-01

    Purpose: The growing involvement of management researchers in knowledge exchange activities and collaborative research does not seem to be reflected in a growing academic output. The purpose of this paper is to explore barriers for academic output from these activities as well as the potential...... for ‘interesting’ papers. Design/methodology/approach: The paper uses secondary data and statistics as well as an illustrative case study to trace knowledge exchange activities and barriers for academic output based on these activities. Findings: The paper identifies a number of barriers for the turning of data...... derived from knowledge exchange activities and Mode 2 research into academic papers such as low priority of case study research in leading management journals, a growing practice orientation in the research funding systems, methodological challenges due to limited researcher control, and disincentives...

  16. Co-incubation with IL-18 potentiates antigen-specific IFN-γ response in a whole-blood stimulation assay for measurement of cell-mediated immune responses in pigs experimentally infected with Lawsonia intracellularis

    DEFF Research Database (Denmark)

    Riber, Ulla; Boesen, Henriette Toft; Jakobsen, Jeanne Toft

    2011-01-01

    The whole-blood interferon-gamma (IFN-γ) assay is a quantitative in-vitro assay for a direct read out of Ag-specific cell-mediated immune (CMI) responses to infectious diseases. The IFN-γ assay is robust in severe intracellular infections like Brucella or mycobacteria, but more difficult to evalu......The whole-blood interferon-gamma (IFN-γ) assay is a quantitative in-vitro assay for a direct read out of Ag-specific cell-mediated immune (CMI) responses to infectious diseases. The IFN-γ assay is robust in severe intracellular infections like Brucella or mycobacteria, but more difficult...

  17. What hinder the further development of wind power in China?—A socio-technical barrier study

    International Nuclear Information System (INIS)

    Zhao, Zhen-Yu; Chang, Rui-Dong; Chen, Yu-Long

    2016-01-01

    Promoting wind power is a long-term strategy of China to respond to both energy shortage and environmental pollution. Stimulated by various incentive policies, wind power generation in China has achieved tremendous growth, with the cumulative installed capacity being the largest worldwide for five consecutive years since 2010. However, obstructed by various barriers, wind power provides only 2.6% of national electricity generation in China, despite the strong support from the government. From a socio-technical transition perspective, this paper aims to systematically analyze the barriers hindering the further development of China's wind power. A wind power niche model is established to illustrate the complex interactions among actors in the wind power industry and electricity supply regime. Then, qualitative content analysis is adopted to process the related evidence and data, and four categories of socio-technical barriers are identified, including technology, governance, infrastructure and culture barriers. The study shows that various interrelated barriers form a blocking mechanism which prohibits the further development of wind power in China. Policy suggestions are proposed to eliminate the barriers and further empower the wind power niche. The lesson learned from China can offer useful references for other economies to promote wind power industries of their own. - Highlights: • Use wind power niche model to illustrate the interactions among actors in the industry. • Analyze technological, governance, infrastructural and cultural barriers. • Multidimensionality and interconnectedness of the barriers are illustrated. • Policy suggestions are proposed to deal with the wind power development barriers.

  18. Racial Trade Barriers?

    DEFF Research Database (Denmark)

    Bjerre, Jacob Halvas

    . This paper analyzes the racial policies pursued in the foreign trade and argues that we need to recognize Aryanization as a world-wide policy in order to fully understand its character and possible consequences. I focus on the pre-war period and analyze the case of Denmark from three different perspectives......: perpetrators, victims and bystanders. The analysis will show that race, economy and foreign trade were combined in an attempt to raise racial trade barriers. This forced the question of German racial policies on the Danish government, Danish-Jewish businesses, and German companies involved in foreign trade...

  19. Support or Barrier?

    DEFF Research Database (Denmark)

    Sanden, Guro Refsum; Lønsmann, Dorte

    This study offers a critical look at how corporate-level language management influences front-line language practices among employees in three multinational corporations (MNCs) headquartered in Scandinavia. Based on interview and document data, we examine, firstly, what front-line practices...... employees use to cross language boundaries in their everyday work, and, secondly, how these practices relate to top-down language management in the case companies. Our findings show that employees are often dependent on ad hoc and informal solutions in cross- language situations, which leads us...... to a discussion of how a company’s language policy may be seen as both support and a barrier....

  20. Illustration of distributed generation effects on protection system coordination

    Science.gov (United States)

    Alawami, Hussain Adnan

    Environmental concerns, market forces, and emergence of new technologies have recently resulted in restructuring electric utility from vertically integrated networks to competitive deregulated entities. Distributed generation (DG) is playing a major role in such deregulated markets. When they are installed in small amounts and small sizes, their impacts on the system may be negligible. When their penetration levels increase as well as their sizes, however, they may start affecting the system performance from more than one aspect. Power system protection needs to be re-assessed after the emergence of DG. This thesis attempts to illustrate the impact of DG on the power system protection coordination. It will study the operation of the impedance relays, fuses, reclosers and overcurrent relays when a DG is added to the distribution network. Different DG sizes, distances from the network and locations within the distribution system will be considered. Power system protection coordination is very sensitive to the DG size where it is not for the DG distance. DG location has direct impact on the operation of the protective devices especially when it is inserted in the middle point of the distribution system. Key Words, Distributed Generation, Impedance relay, fuses, reclosers, overcurrent relays, power system protection coordination.